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Sample records for methylphenidate ritalin concerta

  1. Concerta cf Ritalin Effects on Driving Performance

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    J Gordon Millichap

    2004-03-01

    Full Text Available The effects of different methylphenidate (MPH delivery profiles on driving performance of 6 male ADHD adolescents, aged 16 to 19 years, were evaluated by a randomized, crossover, single-blind study comparing controlled-release (OROS MPH (Concerta given q.d. to immediate-release MPH (Ritalin in equal doses t.i.d. in a study at the University of Virginia, Charlottesville, VA.

  2. Methylphenidate (Ritalin-associated Cataract and Glaucoma

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    Chao-Kung Lu

    2006-12-01

    Full Text Available Methylphenidate hydrochloride (Ritalin is the drug of choice for attention deficit hyperactivity disorder (ADHD. However, an association of Ritalin with glaucoma has been reported. We report a case of Ritalin-associated cataract and glaucoma. A 10-year-old boy was diagnosed with ADHD and had received methylphenidate hydrochloride, 60 mg/day for 2 years. He presented with blurred vision. Best-corrected visual acuity was 6/60 in both eyes. Ocular examinations revealed intraocular pressure (IOP of 30 mmHg under medication, dense posterior subcapsular opacity of lens, pale disc with advanced cupping, and marked constriction of visual field. Despite maximal anti-glaucomatous medication, IOP still could not be controlled. The patient then received combined cataract and glaucoma surgery. Visual acuity improved and IOP was within normal limits in both eyes postoperatively. Large dose of methylphenidate may cause cataract and glaucoma. The mechanism remains unclear. Doctors should be aware of the possible ocular side effects of methylphenidate.

  3. Synthesis of deuterium-labelled methylphenidate, p-hydroxy-methylphenidate, ritalinic acid and p-hydroxyritalinic acid

    International Nuclear Information System (INIS)

    Patrick, K.; Kilts, C.; Breese, G.

    1982-01-01

    The synthesis of threo-dl-methylphenidate (Ritalin 1), threo-dl-p-hydroxy-methylphenidate (3), threo-dl-ritalinic acid (2), and threo-dl-p-hydroxyritalinic acid (4) with deuterium incorporated in the piperidine ring is described. These compounds were synthesized for use as internal standards for mass fragmentographic assays of methylphenidate and its metabolites. The synthetic scheme described resulted in less than 0.05% 2 H 0 in the piperidine ring in any of the preparations. (author)

  4. A randomized, double-blind, cross-over, phase IV trial of oros-methylphenidate (CONCERTA(®)) and generic novo-methylphenidate ER-C (NOVO-generic).

    Science.gov (United States)

    Fallu, Angelo; Dabouz, Farida; Furtado, Melissa; Anand, Leena; Katzman, Martin A

    2016-08-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child's development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA(®) to the same dose of generic Novo-methylphenidate ER-C(®). Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II). Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study. Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.

  5. Severe Recurrent Pancreatitis in a Child with ADHD after Starting Treatment with Methylphenidate (Ritalin

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    Suheil Artul

    2014-01-01

    Full Text Available We present a case of a 10-year-old boy, who had severe relapsing pancreatitis, three times in two months within 3 weeks after starting treatment with methylphenidate (Ritalin due to attention deficit hyperactivity disorder (ADHD. Pancreatitis due to the use of (methylphenidate Ritalin was never published before. Attention must be made by the physicians regarding this possible complication, and this complication should be taken into consideration in every patient with abdominal pain who was newly treated with Ritalin.

  6. High dose methylphenidate treatment in adult attention deficit hyperactivity disorder: a case report

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    Liebrenz Michael

    2012-05-01

    Full Text Available Abstract Introduction Stimulant medication improves hyperactivity, inattention, and impulsivity in both pediatric and adult populations with Attention Deficit Hyperactivity Disorder (ADHD. However, data regarding the optimal dosage in adults is still limited. Case presentation We report the case of a 38-year-old Caucasian patient who was diagnosed with Attention Deficit Hyperactivity Disorder when he was nine years old. He then received up to 10 mg methylphenidate (Ritalin® and 20 mg sustained-release methylphenidate (Ritalin SR® daily. When he was 13, his medication was changed to desipramine (Norpramin®, and both Ritalin® and Ritalin SR® were discontinued; and at age 18, when he developed obsessive-compulsive symptoms, his medication was changed to clomipramine (Anafranil® 75 mg daily. Still suffering from inattention and hyperactivity, the patient began college when he was 19, but did not receive stimulant medication until three years later, when Ritalin® 60 mg daily was re-established. During the 14 months that followed, he began to use Ritalin® excessively, both orally and rectally, in dosages from 4800-6000 mg daily. Four years ago, he was referred to our outpatient service, where his Attention Deficit Hyperactivity Disorder was re-evaluated. At that point, the patient’s daily Ritalin® dosage was reduced to 200 mg daily orally, but he still experienced pronounced symptoms of, Attention Deficit Hyperactivity Disorder so this dosage was raised again. The patient’s plasma levels consistently remained between 60–187 nmol/l—within the recommended range—and signs of his obsessive-compulsive symptoms diminished with fluoxetine 40 mg daily. Finally, on a dosage of 378 mg extended-release methylphenidate (Concerta®, his symptoms of Attention Deficit Hyperactivity Disorder have improved dramatically and no further use of methylphenidate has been recorded during the 24 months preceding this report. Conclusions Symptoms of

  7. Enantioselective determination of methylphenidate and ritalinic acid in whole blood from forensic cases using automated solid-phase extraction and liquid chromatography-tandem mass spectrometry

    DEFF Research Database (Denmark)

    Thomsen, Ragnar; B. Rasmussen, Henrik; Linnet, Kristian

    2012-01-01

    A chiral liquid chromatography tandem mass spectrometry (LC–MS-MS) method was developed and validated for quantifying methylphenidate and its major metabolite ritalinic acid in blood from forensic cases. Blood samples were prepared in a fully automated system by protein precipitation followed...... methylphenidate was not determined to be related to the cause of death, the femoral blood concentration of d-methylphenidate ranged from 5 to 58 ng/g, and from undetected to 48 ng/g for l-methylphenidate (median d/l-ratio 5.9). Ritalinic acid was present at concentrations 10–20 times higher with roughly equal...

  8. Comparative Efficacy of Iranian and Foreign Methylphenidate in Children with Attention Deficit Hyperactive Disorder

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    M Karahmadi

    2008-04-01

    Full Text Available ABSTRACT: Introduction & Objective: Methylphenidate is one of the basic drugs in treating ADHD. According to many clinical studies, the foreign form of methylphenidate (ritalin is more efficient than the Iranian form of the drug (stimidate. This study aimed to compare the efficacy of stimidate and Ritalin in the treatment of attention deficit hyperactive disorder. Materials & Methods: In this double blind, randomized clinical trial, 200 children with attention deficit hyperactive disorder who referred to Isfahan psychiatric clinics were studied. For 100 of these patients ritalin was prescribed while others received stimidate. After 4 weeks, changes in severity of symptoms were evaluated with parental form of Conner's questionnaire. Results: After 4 weeks of treatment, the mean decrease of Conner's number in Ritalin group was 19.63±13.5 and in Stimidate group was 3.29±7.2. Ritalin had effectiveness in treatment of 83.3 percent of the patients ( 6 reduction in Conner's number, but Stimidate was only effective in treating 37.5 percent of the patients. Conclusion: This study showed that foreign methylphenidate (ritalin is more effective than the Iranian form of the medicine (stimidate.

  9. Synthesis of the racemate and individual enantiomers of [11C]methylphenidate for studying presynaptic dopaminergic neutron with positron emission tomography

    International Nuclear Information System (INIS)

    Ding, Y.-S.; Sugano, Y.; Fowler, J.S.; Salata, C.

    1994-01-01

    Carbon-11 labeled dl-threo-methylphenidate (methyl-2-phenyl-2-(2-piperidyl)acetate, Ritalin), a psychostimulant drug widely used to treat attention deficit hyperactivity disorder, was prepared in two steps: O-methylation of the N-protected dl-threo-ritalinic acid derivative with [ 11 C]methyl iodide followed by deprotection. The same strategy was applied for the preparation of C-11 labeled individual enantiomers of threo-methylphenidate from N-protected d-threo-l-threo-ritalinic acid. The subsequent C18 sep-pak and reverse-phase HPLC purification resulted in ca. 40% radiochemical yield with a total synthesis time of 40 minutes and an average specific activity of 1.5 Ci/μmole (at EOB). (author)

  10. A Randomized, Single-Blind, Substitution Study of OROS Methylphenidate (Concerta) in ADHD Adults Receiving Immediate Release Methylphenidate

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    Spencer, Thomas J.; Mick, Eric; Surman, Craig B. H.; Hammerness, Paul; Doyle, Robert; Aleardi, Megan; Kotarski, Meghan; Williams, Courtney G.; Biederman, Joseph

    2011-01-01

    Objective: The main aim of this study was to examine the efficacy, tolerability, and compliance of an extended-release formulation of methylphenidate (OROS-MPH) in adults with ADHD receiving immediate-release methylphenidate (IR-MPH). Method: Participants were outpatient adults with ADHD who were stable on IR-MPH-administered TID. Participants…

  11. Methylphenidate Enhances Extinction of Contextual Fear

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    Abraham, Antony D.; Cunningham, Christopher L.; Lattal, K. Matthew

    2012-01-01

    Methylphenidate (MPH, Ritalin) is a norepinephrine and dopamine transporter blocker that is widely used in humans for treatment of attention deficit disorder and narcolepsy. Although there is some evidence that targeted microinjections of MPH may enhance fear acquisition, little is known about the effect of MPH on fear extinction. Here, we show…

  12. Synthesis of the racemate and individual enantiomers of [[sup 11]C]methylphenidate for studying presynaptic dopaminergic neutron with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y -S; Sugano, Y; Fowler, J S; Salata, C [Brookhaven National Lab., Upton, NY (United States)

    1994-10-01

    Carbon-11 labeled dl-threo-methylphenidate (methyl-2-phenyl-2-(2-piperidyl)acetate, Ritalin), a psychostimulant drug widely used to treat attention deficit hyperactivity disorder, was prepared in two steps: O-methylation of the N-protected dl-threo-ritalinic acid derivative with [[sup 11]C]methyl iodide followed by deprotection. The same strategy was applied for the preparation of C-11 labeled individual enantiomers of threo-methylphenidate from N-protected d-threo-l-threo-ritalinic acid. The subsequent C18 sep-pak and reverse-phase HPLC purification resulted in ca. 40% radiochemical yield with a total synthesis time of 40 minutes and an average specific activity of 1.5 Ci/[mu]mole (at EOB). (author).

  13. A review of OROS methylphenidate (Concerta(®)) in the treatment of attention-deficit/hyperactivity disorder.

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    Katzman, Martin A; Sternat, Tia

    2014-11-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural disorder with onset during childhood. It affects a child's development, both at home and at school, and impacts on social, emotional and cognitive functioning, in both the home and the school environment. Untreated ADHD is very often associated with poor academic achievement, low occupational status, increased risk of substance abuse and delinquency. Current practice guidelines recommend a multimodal approach in the treatment of ADHD, which includes educational, behavioural and mental health interventions, and pharmacological management. Stimulant medications, including methylphenidate (MPH) and amphetamine products, are recommended as first-line pharmacotherapy in the treatment of ADHD. The choice of stimulant is influenced by several factors; the most influential factor is the duration of action. Long-acting medication provides benefits long after school and work. It also increases the likelihood of once-daily dosing, thereby eliminating the need for mid-day dosing, making the treatment more private, avoiding stigma and improving adherence to medication. MPH is the most widely used psychotropic medication in child psychiatry. It was first developed for use in children as an oral, immediate-release formulation and more recently as various extended-release formulations. These latter formulations include the 12 h preparation Concerta(®) (osmotic-release oral system [OROS] MPH), which utilizes an osmotic pump system, designed to overcome the difficulties of multiple daily dosing. Since it received approval from the US Food and Drug Administration in August 2000, OROS MPH has been quickly and widely accepted as one of the preferred treatments for ADHD because of its once-daily dosing. This paper reviews the data in support of long-acting OROS MPH in children, adolescents and adults, both in ADHD and in association with its comorbidities.

  14. Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

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    Chun-Lei Zhang

    Full Text Available Methylphenidate (MPH, commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD. Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC. To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+ increase, but does not require PKA and extracellular Ca(2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

  15. Effect of food on early drug exposure from extended-release stimulants: results from the Concerta, Adderall XR Food Evaluation (CAFE) Study.

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    Auiler, J F; Liu, K; Lynch, J M; Gelotte, C K

    2002-01-01

    Stimulant therapy is the mainstay of treatment for children, adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Once-daily, extended-release oral formulations offer long acting control of symptoms by modifying drug delivery and absorption. In particular, consistency in early drug exposure is important for symptom control during school or work hours. Because these once-daily formulations are usually taken in the morning, the timing of the doses with breakfast is important. This study compared the effect of a high-fat breakfast on early drug exposure from a morning dose of two extended-release stimulant formulations: the osmotic-controlled OROS tablet of methylphenidate HCI (CONCERTA) and the capsule containing extended-release beads of mixed amphetamine salts (ADDERALL XR). The study had a single-dose, open-label, randomised, four-treatment, crossover design in which healthy subjects received either 36 mg CONCERTA or 20 mg ADDERALL XR in the morning after an overnight fast or a high-fat breakfast. Serial blood samples were collected over 28h to determine plasma concentrations of methylphenidate and amphetamine. The food effect on early drug exposure and the pharmacokinetic profiles up to 8 h after dosing of the two extended-release stimulants were directly compared using partial area (AUC(p4h), AUC(p6h) and AUC(p8h)) fed/fasted ratios. Amphetamine concentrations were markedly lower when the subjects had eaten breakfast, resulting in lower early drug exposures (p food, for patients with ADHD.

  16. Methylphenidate enhances extinction of contextual fear

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    Abraham, Antony D.; Cunningham, Christopher L.; Lattal, K. Matthew

    2012-01-01

    Methylphenidate (MPH, Ritalin) is a norepinephrine and dopamine transporter blocker that is widely used in humans for treatment of attention deficit disorder and narcolepsy. Although there is some evidence that targeted microinjections of MPH may enhance fear acquisition, little is known about the effect of MPH on fear extinction. Here, we show that MPH, administered before or immediately following extinction of contextual fear, will enhance extinction retention in C57BL/6 mice. Animals that ...

  17. Alterations in pain response are partially reversed by methylphenidate (Ritalin) in adults with attention deficit hyperactivity disorder (ADHD).

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    Treister, Roi; Eisenberg, Elon; Demeter, Naor; Pud, Dorit

    2015-01-01

    Attention deficit hyperactivity disorder (ADHD) is characterized by dysregulation of sensory processing and neurobiology of dopamine. Although cumulative evidence suggests that dopamine is involved in pain processing, pain perception in ADHD subjects and the effect of dopamine agonists such as methylphenidate (MP, Ritalin) on it have rarely been studied. The aims of this study were to (1) psychophysically assess sensitivity to pain in ADHD subjects as compared to controls and (2) examine the effects of MP on pain response in ADHD subjects. Thirty subjects with ADHD and 30 age- and gender-matched controls participated in a preliminary trial. Pain threshold, intensity, and tolerance in response to cold pain stimulation were measured for both groups (ADHD with no treatment). In addition, the ADHD group was reassessed following a single dose of MP treatment. The ADHD subjects "without MP" in comparison with controls displayed significantly shorter cold pain threshold (2.8 ± 2.1 vs. 5.8 ± 2.5 seconds, respectively, P ADHD subjects increased significantly compared to those with no treatment (3.6 ± 2.5 seconds, P = 0.011, and 46.4 ± 53.3 seconds, P ADHD are more sensitive to pain compared with controls and that MP may exert antinociceptive properties in these subjects. Randomized, controlled trials are warranted to verify these findings. © 2013 World Institute of Pain.

  18. Methylphenidate misuse in adult patients and the impact of therapeutic use

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    Jensen, L S; Pagsberg, Anne Katrine; Dalhoff, Kim

    2015-01-01

    OBJECTIVE: Methylphenidate (MPH) prescription rates for adults increase, but the extent of a parallel rise in toxic exposures and their causes and distribution between different MPH trade names are unexplored. METHOD: We retrospectively analyzed adult MPH exposures reported to the Danish Poison...... Information Centre from January 2006 to July 2012 and the association with MPH sales and the number of patients prescribed MPH. RESULTS: Of the 394 exposures (57% males, median age 27 years) reported, MPH status was available in 249 of whom 65.5% were prescribed MPH. Exposure was in 54% motivated by suicidal...... (particularly Ritalin(®)/Ritalin(®) Uno). Most exposures were intentional and motivated by suicide attempts or recreational use....

  19. Methylphenidate: increased abuse or appropriate use?

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    Llana, M E; Crismon, M L

    1999-01-01

    To address the question of the significant increase in methylphenidate (MPD) prescriptions being written and to make recommendations for health care providers involved in providing care for patients with attention deficit hyperactivity disorder (ADHD) and their families. Medline search 1966-1998 for professional articles using the following search terms--methylphenidate, children, adolescents, abuse; Internet search using MPD, Ritalin, and ADHD; and Paper Chase search using methylphenidate. The available literature regarding potential abuse or diversion of MPD consists of case reports, review articles, newspaper articles, and a Drug Enforcement Administration (DEA) publication. All available literature sources were used. Although the media and DEA report significant abuse and diversion of prescribed MPD, a review of the available literature did not reveal data to substantiate these claims. Nonetheless, there are reasons to suspect that abuse and diversion occur. A potential contributing factor to abuse is the reported similarities in pharmacodynamics and pharmacokinetics between MPD and cocaine. Recommendations are made to decrease the possibility of abuse and diversion of prescribed MPD. A balanced middle ground must be found regarding the benefits of MPD and its abuse potential. Education of clinicians, patients, and family members is key in ensuring that MPD is used appropriately.

  20. The Effects of Methylphenidate Administration on the Histological Alterations of the Lymphatic System in the Mice

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    Ali Louei Monfared

    2016-12-01

    Full Text Available Abstract Background: The lymphatic system as a key component in the organism's body can be affected by used drugs. Methylphenidate or Ritalin is widely used for treatment of behavioral disorders in children and some depressed people. This study carried out to examine the immunotoxic effects of Ritalin. Materials and Methods: A total of 16 healthy adult female mice were selected and randomly divided into a control and three experimental groups. The experimental groups received Ritalin as 0.5,5 and 50 mg/kg body weight and control groups received distillated water by gavage method for 21 consecutive days. At the end of experiment, the structure and function of the lymphoid organs were evaluated. Results were analyzed by ANOVA and Duncan’s test (p<0.05. Results: Significant alterations including a reduction in the size and number of lymphoid follicles, increasing in the megakaryocytes numbers as well as spleen capsular thickens were seen following Ritalin administration. The atrophy of the lymph nodes together with significant reduction in the number and size of lymph follicles but an increasing in the parenchyma hyperemia were seen. Also lymphocyte numbers increased while the monocytes numbers decreased (p<0.05. Conclusion: The consumption of Ritalin could be exerted detrimental effects on the lymphoid organs in the mouse model.

  1. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

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    Jennifer L. Cornish

    2012-09-01

    Full Text Available The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®. With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY rats and in Spontaneously Hypertensive Rats (SHR, a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day or distilled water (dH2O. The effect of chronic treatment on delayed reinforcement tasks (DRT and tyrosine hydroxylase immunoreactivity (TH-ir in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

  2. Disagreements with implications: diverging discourses on the ethics of non-medical use of methylphenidate for performance enhancement

    OpenAIRE

    Forlini, Cynthia; Racine, Eric

    2009-01-01

    Abstract Background There is substantial evidence that methylphenidate (MPH; Ritalin), is being used by healthy university students for non-medical motives such as the improvement of concentration, alertness, and academic performance. The scope and potential consequences of the non-medical use of MPH upon healthcare and society bring about many points of view. Methods To gain insight into key ethical and social issues on the non-medical use of MPH, we examined discourses in the print media, b...

  3. Methylphenidate Modulates Functional Network Connectivity to Enhance Attention

    Science.gov (United States)

    Zhang, Sheng; Hsu, Wei-Ting; Scheinost, Dustin; Finn, Emily S.; Shen, Xilin; Constable, R. Todd; Li, Chiang-Shan R.; Chun, Marvin M.

    2016-01-01

    Recent work has demonstrated that human whole-brain functional connectivity patterns measured with fMRI contain information about cognitive abilities, including sustained attention. To derive behavioral predictions from connectivity patterns, our group developed a connectome-based predictive modeling (CPM) approach (Finn et al., 2015; Rosenberg et al., 2016). Previously using CPM, we defined a high-attention network, comprising connections positively correlated with performance on a sustained attention task, and a low-attention network, comprising connections negatively correlated with performance. Validating the networks as generalizable biomarkers of attention, models based on network strength at rest predicted attention-deficit/hyperactivity disorder (ADHD) symptoms in an independent group of individuals (Rosenberg et al., 2016). To investigate whether these networks play a causal role in attention, here we examined their strength in healthy adults given methylphenidate (Ritalin), a common ADHD treatment, compared with unmedicated controls. As predicted, individuals given methylphenidate showed patterns of connectivity associated with better sustained attention: higher high-attention and lower low-attention network strength than controls. There was significant overlap between the high-attention network and a network with greater strength in the methylphenidate group, and between the low-attention network and a network with greater strength in the control group. Network strength also predicted behavior on a stop-signal task, such that participants with higher go response rates showed higher high-attention and lower low-attention network strength. These results suggest that methylphenidate acts by modulating functional brain networks related to sustained attention, and that changing whole-brain connectivity patterns may help improve attention. SIGNIFICANCE STATEMENT Recent work identified a promising neuromarker of sustained attention based on whole

  4. Melatonin Effects in Methylphenidate Treated Children with Attention Deficit Hyperactivity Disorder: A Randomized Double Blind Clinical Trial

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    Mohammad Reza Mohammadi

    2012-06-01

    Full Text Available Objective: The aim of this study was to determine melatonin effects on sleep patterns, symptoms of hyperactivity and attention deficiency in children with attention-deficit hyperactivity disorder (ADHD.Methods: Children with age range of 7-12 years who had a combined form of ADHD were randomly divided in to 2 groups according to gender blocks. One group took melatonin (3 or 6mg combined with methylphenidate (Ritalin (1mg/kg, and the other group took placebo combined with methylphenidate (1mg/kg. ADHD rating scale and sleep patterns questionnaires were completed. Research hypotheses were assessed at the baseline, the second, fourth and eighth weeks after the treatment.Results: The mean sleep latency and total sleep disturbance scores were reduced in melatonin group, while the scores increased in the placebo group (p≥0.05. Data analysis, using ANOVA with repeated measures, did not show any statistically significant differences between the two groups in ADHD scores.Conclusion: Administration of melatonin along with methylphenidate can partially improve symptoms of sleep disturbance. However, it does not seem to reduce attention deficiency and hyperactivity behavior of children with ADHD.

  5. Cognitive enhancement with methylphenidate and modafinil: conceptual advances and societal implications

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    Dubljević V

    2015-08-01

    Full Text Available Veljko Dubljević,1 Christopher James Ryan2 1Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada; 2Discipline of Psychiatry and the Centre for Values, Ethics and the Law in Medicine, University of Sydney, Sydney, NSW, Australia Abstract: “Cognition enhancement” (CE drugs are pharmaceuticals taken by healthy people with the aim of sustaining attention, augmenting memory, or improving other cognitive capacities. This paper focuses on two CE drugs – methylphenidate and modafinil. It analyzes their mechanism of action, the evidence for their efficacy in nonsleep deprived individuals, and reviews their adverse effects. It then addresses the normative stances and social issues surrounding CE drug use. Currently, there is little evidence that either methylphenidate or modafinil provide any useful cognitive enhancement to well-rested users. However, it is very possible that future research may reveal cognitive benefits for these agents or for other pharmaceuticals. Public attitudes on CE mirror those evident in academic debate. Even though the majority seem to be opposed to enhancement based on issues of authenticity, utility, and fairness, a steady minority take the view that cognitive enhancer usage is both acceptable and fair. Current legal regimes do not adequately address the social phenomenon of CE use. While the United Nations Convention on Psychotropic Substances defines limits of methylphenidate use across the globe, no such guide exists for modafinil. Keywords: cognitive enhancement, psychopharmacological neuroenhancement, Ritalin, Provigil, neuroethics

  6. Development and validation of an UFLC-MS/MS method for enantioselectivity determination of d,l-thero-methylphenidate, d,l-thero-ethylphenidate and d,l-thero-ritalinic acid in rat plasma and its application to pharmacokinetic study.

    Science.gov (United States)

    Zhang, Chenghao; Luo, Huafei; Wu, Yubo; Zhang, Junyun; Zhang, Furong; Lin, Guobei; Wang, Hao

    2016-02-01

    A chiral UFLC-MS/MS method was established and validated for quantifying d-threo-methylphenidate (d-threo-MPH), l-threo-methylphenidate (l-threo-MPH), d-threo-ethylphenidate (d-threo-EPH), l-threo-ethylphenidate (l-threo-EPH) and d,l-threo-ritalinic acid (d,l-threo-RA) in rat plasma over the linearity range of 1-500ng/mL. Chiral separation was performed on an Astec Chirobiotic V2 column (5μm, 250×2.1mm) with isocratic elution using methanol containing 0.003% ammonium acetate (w/v) and 0.003% trifluoroacetic acid (v/v) at a flow of 0.3mL/min. All analytes and IS were extracted from rat plasma by a one-step liquid-liquid extraction (LLE) method. The intra- and inter-run accuracies were within 85-115%, and the intra- and inter-run precision were <10% for all analytes. Extraction recoveries were 55-62% for d-threo-MPH, 54-60% for l-threo-MPH, 55-60% for d-threo-EPH, 53-57% for l-threo-EPH and 25-30% for d,l-threo-RA. The validated UFLC-MS/MS method successfully applied to the pharmacokinetic interaction study of oral d-threo-MPH and l-threo-MPH (alone or in combination) in female Sprague Dawley rats. The EPH was not detected in rat plasma following oral administrated MPH without EtOH. As far as it is known to the authors, this study is the first one step liquid-liquid extraction method to extract and UFLC-MS/MS method to quantify d-threo-MPH, l-threo-MPH, d-threo-EPH, l-threo-EPH and d,l-threo-RA simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Ritalin®: Panic in the USA

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    Toby Miller

    2011-04-01

    Full Text Available Ritalin® is a popular pharmaceutical. It keeps young people quiet and focused, but attracts intense opprobrium. Beginning with an account of the dimensions of Ritalin®’s use in the United States and controversies surrounding it, this article outlines how this might be understood in moral-panic terms and examines the role of the psy-function and various conflicts of interest, coverage in popular culture, and governmental responses. In many cases, progressive academics and activists have criticised moral panics, recuperating moral-panic folk devils as semiotic guerrillas struggling against authority. In this instance, however, the scene is too complex and multifaceted for that heroisation. There are no good guys; there is lots of panic, from all political-economic quarters. Some of it is justified—and none of it is straightforward.

  8. Ritalin®: Panic in the USA

    Directory of Open Access Journals (Sweden)

    Toby Miller

    2011-04-01

    Full Text Available  Ritalin® is a popular pharmaceutical. It keeps young people quiet and focused, but attracts intense opprobrium. Beginning with an account of the dimensions of Ritalin®’s use in the United States and controversies surrounding it, this article outlines how this might be understood in moral-panic terms and examines the role of the psy-function and various conflicts of interest, coverage in popular culture, and governmental responses. In many cases, progressive academics and activists have criticised moral panics, recuperating moral-panic folk devils as semiotic guerrillas struggling against authority. In this instance, however, the scene is too complex and multifaceted for that heroisation. There are no good guys; there is lots of panic, from all political-economic quarters. Some of it is justified—and none of it is straightforward.

  9. Effect of Simultaneous Use of Ritalin with Grape Seed Extract on Passive Avoidance Learning in Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Tooba Karimizadeh Moneh

    2016-10-01

    Full Text Available Background & objectives: Ritalin is one of the drugs used in the treatment of attention-deficit/hyperactivity disorder (ADHD. This study aimed to investigate the comparative effect of Ritalin with grape seed extract on passive avoidance learning in adult male rats. Methods: In this experimental study, 40 adult male Wistar rats divided randomly into 5 groups of 8 rats including control, sham and three experimental groups. The control group received no treatment. The sham group received 1 ml of distilled water per day. At the same time the experimental groups received 100 mg/kg grape seed extract, 1 mg/kg Ritalin or 100 mg/kg grape seed extract together with 1 mg/kg of Ritalin by gavage for 28 days. For measuring the amount of avoidance learning, Shuttle box was used. Data analyzed by ANOVA and consistent Tukey's tests using SPSS-18 software and p>0.05 considered as significant. Results: The results showed that Ritalin decreases the passive avoidance learning, while the grape seed extract alone or together with Ritalin increases passive avoidance learning. Conclusion:  The outcome of this research shows that taking Ritalin leads to decreasing passive avoidance learning. However, the simultaneous taking Ritalin with grape seed extract inhibits the Ritalin effect and increasing the learning.

  10. Panlobular emphysema in young intravenous Ritalin abusers

    International Nuclear Information System (INIS)

    Schmidt, R.A.; Glenny, R.W.; Godwin, J.D.; Hampson, N.B.; Cantino, M.E.; Reichenbach, D.D.

    1991-01-01

    We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated

  11. The effect of methylphenidate on Internet video game play in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Han, Doug Hyun; Lee, Young Sik; Na, Churl; Ahn, Jee Young; Chung, Un Sun; Daniels, Melissa A; Haws, Charlotte A; Renshaw, Perry F

    2009-01-01

    A number of studies about attention-deficit/hyperactivity disorder (ADHD) and Internet video game play have examined the prefrontal cortex and dopaminergic system. Stimulants such as methylphenidate (MPH), given to treat ADHD, and video game play have been found to increase synaptic dopamine. We hypothesized that MPH treatment would reduce Internet use in subjects with co-occurring ADHD and Internet video game addictions. Sixty-two children (52 males and 10 females), drug-naive, diagnosed with ADHD, and Internet video game players, participated in this study. At the beginning of the study and after 8 weeks of treatment with Concerta (OROS methylphenidate HCl, Seoul, Korea), participants were assessed with Young's Internet Addiction Scale, Korean version (YIAS-K), Korean DuPaul's ADHD Rating Scale, and the Visual Continuous Performance Test. Their Internet usage time was also recorded. After 8 weeks of treatment, the YIAS-K scores and Internet usage times were significantly reduced. The changes in the YIAS-K scores between the baseline and 8-week assessments were positively correlated with the changes in total and inattention scores from the Korean DuPaul's ADHD Rating Scale, as well as omission errors from the Visual Continuous Performance Test. There was also a significant difference in the number of omission errors among non-Internet-addicted, mildly Internet addicted, and severely Internet addicted participants. We suggest that Internet video game playing might be a means of self-medication for children with ADHD. In addition, we cautiously suggest that MPH might be evaluated as a potential treatment of Internet addiction.

  12. Does Prolonged Therapy with a Long-Acting Stimulant Suppress Growth in Children with ADHD?

    Science.gov (United States)

    Spencer, Thomas J.; Faraone, Stephen V.; Biederman, Joseph; Lerner, Marc; Cooper, Kimberly M.; Zimmerman, Brenda

    2006-01-01

    Objective: To investigate whether prolonged therapy with a long-acting stimulant affects growth in children with attention-deficit/hyperactivity disorder (ADHD). Method: One hundred seventy-eight children ages 6 to 13 years received OROS methylphenidate (OROS MPH, CONCERTA) for at least 21 months. Height and weight were measured monthly during the…

  13. Pharmacological Management of Treatment-Induced Insomnia in ADHD

    Science.gov (United States)

    Kratochvil, Christopher J.; Lake, Marybeth; Pliszka, Steven R.; Walkup, John T.

    2005-01-01

    A 7-year-old girl with attention-deficit/hyperactivity disorder (ADHD), combined subtype, and oppositional defiant disorder presents with a complaint of marked insomnia. Her parents describe 60 to 90 minutes of nightly initial insomnia that began with the initiation of 36 mg OROS methylphenidate (Concerta) 2 months ago. Behavioral interventions…

  14. Attention Deficit-Hyperactivity Disorder

    Science.gov (United States)

    ... as methylphenidate (Ritalin) or dextroamphetamine (Dexedrine), which are stimulants that decrease impulsivity and hyperactivity and increase attention. The U.S. Food and Drug Administration has approved the generic versions ...

  15. Effects of OROS-MPH Versus Dl-Amphetamine-XR on Driving Performance of ADHD Adolescents

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-10-01

    Full Text Available Driving performance of 35 adolescent ADHD patients (19 boys/16 girls; mean age 17.8 years on a driving simulator was compared while taking OROS methylphenidate (Concerta, 72 mg, mixed dl-amphetamine salts (Adderall XR, 30 mg, or placebo in a randomized, double-blind, crossover study at University of Virginia, Charlottesville.

  16. A Comparative Study of Effectiveness of Neurofeedback and Ritalin on Improving Conduct Problems and Hyperactivity

    Directory of Open Access Journals (Sweden)

    K. Khoushabi

    2012-01-01

    Full Text Available Introduction & Objective: There are varieties of interventions to treatment of ADHD, among which drug therapy, behavior therapy, parental management training and neurofeedback can be cited. The present study designed to investigate and compare the effectiveness of neurofeedback and Ritalin on improving conduct problems and hyperactivity. Materials & Methods: Quasi-experimental research method with pretest-post test design has been applied in the research. Statistical population of the study consisted of ADHD children of Tehran. The study samples of the study were patients referred to children psychiatric clinic. Based on the purpose of the study' 20 children were randomly selected and classified into 2 groups according to random assignment. CPRS-48 (parent form was administered by parents before and after the treatments as research tools. Recruited data was analyzed by SPSS-19 in two sections of descriptive and inferential statistics. ANCOVA revealed some differences in the groups. Results: The findings of the study showed that there was a significant difference between Ritalin and neurofeedback on improving conduct problems; in other words, Ritalin was more effective in alleviating the problems. Also there was no significant difference between the interventions on improving hyperactivity index. Conclusion: With respect to more efficiency of Ritalin than neurofeedback on certain continuum of signs/symptoms of ADHD, as a whole, preferences of interventions should be based on type, magnitude and severity of the syndrome(Sci J Hamadan Univ Med Sci 2012;18(4:53-59

  17. METHYLPHENIDATE (RITALIN) USE AND ABUSE

    African Journals Online (AJOL)

    University ofthe Witwatersrand Medical School and Johannesburg Hospital. James A TemIett, MB BCh, .... other substances such as heroin, cocaine, LSD or cannabis. Intravenous substance ... intractable cancer pain. Attempts to get addicted ...

  18. Methylphenidate Actively Induces Emergence from General Anesthesia

    Science.gov (United States)

    Solt, Ken; Cotten, Joseph F.; Cimenser, Aylin; Wong, Kin F.K.; Chemali, Jessica J.; Brown, Emery N.

    2011-01-01

    Background Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study we tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane anesthesia. Methods Using adult rats we tested the effect of methylphenidate IV on time to emergence from isoflurane anesthesia. We then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate–induced restoration of righting during continuous isoflurane anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Droperidol IV was administered to test for inhibition of methylphenidate's actions. Results Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without compared to with methylphenidate was 200 [155, 331] s (median, [95% confidence interval]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta to theta, and induced an increase in minute ventilation. Administration of droperidol (0.5 mg/kg IV) prior to methylphenidate (5 mg/kg IV) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Conclusions Methylphenidate actively induces emergence from isoflurane anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. Our findings suggest that methylphenidate may be clinically

  19. Pharmacological Interventions for Students with ADD.

    Science.gov (United States)

    Austin, Vance L.

    2003-01-01

    A review of the research on pharmacological interventions for students with attention deficit disorder finds that psychostimulants such as methylphenidate (Ritalin) are effective in improving focus and impulse control, but should be used in conjunction with psychosocial and behavioral interventions. Comprehensive medical screenings and guidelines…

  20. A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) study.

    Science.gov (United States)

    Mattos, Paulo; Louzã, Mário Rodrigues; Palmini, André Luís Fernandes; de Oliveira, Irismar Reis; Rocha, Fábio Lopes

    2013-07-01

    The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. To assess the effectiveness of methylphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. A 12-week, multicenter, open-label trial involving 60 patients was used. The measures used were Adult Self-Rating Scale, Adult ADHD Quality of Life Scale (AAQoL), State and Trait Anxiety Inventory (STAI), Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression (CGI), and safety measures. A significance statistic level of 5% was adopted. Analyses included 60 patients (66.7% male; M age = 31.1 years) for safety and 58 patients for effectiveness. All AAQoL subscales improved from baseline to Week 12 (p < .0001), as well as the Total AAQoL (p < .0001). A significant reduction on Clinical Global Impression-Improvement (CGI-I), HAM-D, STAI, and ASRS scores was observed (p < .0001). No serious adverse event was reported. Treatment of adult ADHD patients with OROS MPH improves QoL.

  1. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

    Directory of Open Access Journals (Sweden)

    Dekel Shlomi

    2008-06-01

    Full Text Available Dekel Shlomi1, David Shitrit1, Daniele Bendayan1, Gidon Sahar2, Yitshak Shechtman3, Mordechai R Kramer11Pulmonary Institute, Departments of 2Cardiothoracic Surgery and 3Pathology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-yearold woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.Keywords: methylphenidate (Ritalin, emphysema

  2. Rebound effects with long-acting amphetamine or methylphenidate stimulant medication preparations among adolescent male drivers with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Cox, Daniel J; Moore, Melissa; Burket, Roger; Merkel, R Lawrence; Mikami, Amori Yee; Kovatchev, Boris

    2008-02-01

    This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.

  3. Methylphenidate alters selective attention by amplifying salience.

    Science.gov (United States)

    ter Huurne, Niels; Fallon, Sean James; van Schouwenburg, Martine; van der Schaaf, Marieke; Buitelaar, Jan; Jensen, Ole; Cools, Roshan

    2015-12-01

    Methylphenidate, the most common treatment of attention deficit hyperactivity disorder (ADHD), is increasingly used by healthy individuals as a "smart drug" to enhance cognitive abilities like attention. A key feature of (selective) attention is the ability to ignore irrelevant but salient information in the environment (distractors). Although crucial for cognitive performance, until now, it is not known how the use of methylphenidate affects resistance to attentional capture by distractors. The present study aims to clarify how methylphenidate affects distractor suppression in healthy individuals. The effect of methylphenidate (20 mg) on distractor suppression was assessed in healthy subjects (N = 20), in a within-subject double-blind placebo-controlled crossover design. We used a visuospatial attention task with target faces flanked by strong (faces) or weak distractors (scrambled faces). Methylphenidate increased accuracy on trials that required gender identification of target face stimuli (methylphenidate 88.9 ± 1.4 [mean ± SEM], placebo 86.0 ± 1.2 %; p = .003), suggesting increased processing of the faces. At the same time, however, methylphenidate increased reaction time when the target face was flanked by a face distractor relative to a scrambled face distractor (methylphenidate 34.9 ± 3.73, placebo 26.7 ± 2.84 ms; p = .027), suggesting enhanced attentional capture by distractors with task-relevant features. We conclude that methylphenidate amplifies salience of task-relevant information at the level of the stimulus category. This leads to enhanced processing of the target (faces) but also increased attentional capture by distractors drawn from the same category as the target.

  4. Methylphenidate-induced erections in a prepubertal child.

    LENUS (Irish Health Repository)

    Kelly, B D

    2013-02-01

    Methylphenidate is a medication used routinely in the management of attention deficit hyperactivity disorder. We report a case of a prepubertal child who developed unwanted erections after commencing a response-adjusted dosing regimen of sustained release methylphenidate. Despite priapism being a rare adverse reaction associated with methylphenidate, physicians and parents need to be aware as it can have significant long-term complications.

  5. Infusion of methylphenidate into the basolateral nucleus of amygdala or anterior cingulate cortex enhances fear memory consolidation in rats

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The psychostimulant methylphenidate (MPD; also called Ritalin) is a blocker of dopamine and norepi-nephrine transporter. It has been clinically used for treatment of Attention Deficit and Hyperactivity Disorder (ADHD). There have been inconsistent reports regarding the effects of systemically adminis-tered MPD on learning and memory, either in animals or humans. In the present study, we investigated the effect of direct infusion of MPD into the basolateral nucleus of amygdala (BLA) or the anterior cin-gulate cortex (ACC) on conditioned fear memory. Rats were trained on a one-trial step-through inhibi-tory avoidance task. MPD was infused bilaterally into the BLA or the ACC, either at ‘0’ or 6 h post-training. Saline was administered as control. Memory retention was tested 48 h post-training. In-tra-BLA or intra-ACC infusion of MPD ‘0’ h but not 6 h post-training significantly improved 48-h memory retention: the MPD-treated rats had significant longer step-through latency than controls. The present results indicate that action of MPD in the BLA or the ACC produces a beneficial effect on the consoli-dation of inhibitory avoidance memory.

  6. [{sup 11}C]d-threo-Methylphenidate, a new radiotracer for the dopamine transporter. Characterization in baboon and human brain

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Y.S.; Volkow, N.D.; Fowler, J.S. [Brookhaven National Laboratory, Upton, NY (United States)] [and others

    1995-05-01

    dl-threo Methylphenidate (MP, Ritalin) is a psychostimulant drug which binds to the dopamine transporter (DAT). We evaluated [{sup 11}C]d-threo-methylphenidate ([{sup 11}C]d-MP), the more active enantiomer, as a radiotracer for the DAT in baboons and human brain. Stereoselectivity, saturability and pharmacological specificity and reproducibility were examined. Stereoselectivity was examined in baboons by comparing [{sup 11C}]d-MP,[{sup 11}C]l-MP and [{sup 11}C]dl-MP. Unlabeled MP was used to assess the reversibility and saturability of the binding. GBR 12909,{beta}-(4-iodophenyl)tropane-2-carboxylic acid methyl ester ({beta}-CIT), tomoxetine and citalopram were used to assess the specificity of the binding. The ratios between the radioactivity in the striatum to that in cerebellum (ST/CB) were 3.3,2.2 and 1.1 for [{sup 11}C]d-MP,[{sup 11}C]dl-MP and [{sup 11}C]l-MP respectively. Most of the striatal binding of [{sup 11}C]d-threo-MP was displaced by injection of nonradioactive MP demonstrating reversibility. Pretreatment with MP (0.5 mg/kg), GBR12909 (1.5 mg/kg) or {beta}-CIT (0.3 mg/kg) reduced ST/CB by about 60% and the ratios of distribution volumes at the steady-state for the triatum to cerebellum (DV{sub st/}DV{sub cb}) by about 50%. Pretreatment with tomoxetine (3.0 mg/kg) or citalopram (2.0 mg/kg), inhibitors of the norepinephrine and serotonin transporter, had no effect. Studies of [{sup 11}C]d-MP in the human brain showed highest uptake in basal ganglia with a half clearance time of about 60 minutes. Repeated studies in 6 normal human subjects showed differences in DV{sub st/}DV{sub cb} between -7% and 8%. MP pretreatment decreased BG but no cortical or cerebellar binding and reduced Bmax/Kd by 91%.

  7. Long Withdrawal of Methylphenidate Induces a Differential Response of the Dopaminergic System and Increases Sensitivity to Cocaine in the Prefrontal Cortex of Spontaneously Hypertensive Rats.

    Directory of Open Access Journals (Sweden)

    Maurício dos Santos Pereira

    Full Text Available Methylphenidate (MPD is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD. However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii to establish the neurochemical consequences of short- (24 hours and long-term (10 days MPD withdrawal after a subchronic treatment (30 days with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally, (iii to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p. presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult

  8. Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.

    Science.gov (United States)

    Hysek, Cédric M; Simmler, Linda D; Schillinger, Nathalie; Meyer, Nicole; Schmid, Yasmin; Donzelli, Massimiliano; Grouzmann, Eric; Liechti, Matthias E

    2014-03-01

    Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).

  9. Pulmonary emphysema induced by methylphenidate: experimental study.

    Science.gov (United States)

    Rapello, Gabriel Victor Guimarães; Antoniolli, Andréia; Pereira, Daniel Martins; Facco, Gilberto; Pêgo-Fernandes, Paulo Manuel; Pazetti, Rogério

    2015-01-01

    Methylphenidate is the most widely used drug for treating attention deficit hyperactivity disorder. However, it has important side effects, such as abdominal pain, insomnia, anorexia and loss of appetite, and also some cases of early severe emphysema after drug abuse have been reported. Our aim was to investigate the development of pulmonary emphysema in rats that were subjected to different doses of methylphenidate. Experimental study carried out at the laboratory of a public university. Eighteen male Wistar rats were divided into three groups: control (0.9% saline solution); MP 0.8 (methylphenidate, 0.8 mg/kg); MP 1.2 (methylphenidate, 1.2 mg/kg). After 90 days of daily gavage, the animals were sacrificed and lung tissue samples were prepared for analysis on the mean alveolar diameter (Lm). The Lm was greater in MP 0.8 (47.91 ± 3.13; P pulmonary emphysema.

  10. Dietary intake, growth and development of children with ADHD in a randomized clinical trial of Ritalin and Melatonin co-administration: Through circadian cycle modification or appetite enhancement?

    Science.gov (United States)

    Mostafavi, Seyed-Ali; Mohammadi, Mohammad Reza; Hosseinzadeh, Payam; Eshraghian, Mohammad Reza; Akhondzadeh, Shahin; Hosseinzadeh-Attar, Mohammad Javad; Ranjbar, Elham; Kooshesh, Seyed Mohammad-Ali; Keshavarz, Seyed-Ali

    2012-01-01

    It is postulated that ritalin may adversely affect sleep, appetite, weight and growth of some children with ADHD. Therefore, we aimed to evaluate melatonin supplementation effects on dietary intake, growth and development of children with ADHD treated with ritalin through circadian cycle modification and appetite mechanisms. After obtaining consent from parents, 50 children aged 7-12 with combined form of AD/HD were randomly divided into two groups based on gender blocks: one received melatonin (3 or 6 mg based on weight) combined with ritalin (1mg/kg) and the other took placebo combined with ritalin (1mg/kg) in a double blind randomized clinical trial. Three-day food record, and standard weight and height of children were evaluated prior to the treatment and 8 weeks after the treatment. Children's appetite and sleep were evaluated in weeks 0, 2, 4 and 8. Hypotheses were then analyzed using SPSS17. Paired sample t-test showed significant changes in sleep latency (23.15±15.25 vs. 17.96±11.66; p=0.047) and total sleep disturbance score (48.84±13.42 vs. 41.30±9.67; p=0.000) before and after melatonin administration, respectively. However, appetite and food intake did not change significantly during the study. Sleep duration and appetite were significantly correlated in melatonin group (Pearson r=0.971, p=0.029). Mean height (138.28±16.24 vs. 141.35±16.78; P=0.000) and weight (36.73±17.82 vs. 38.97±17.93; P=0.005) were significantly increased in melatonin treated children before and after the trial. Administration of melatonin along with ritalin improves height and weight growth of children. These effects may be attributed to circadian cycle modification, increasing sleep duration and the consequent more growth hormone release during sleep.

  11. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats

    Science.gov (United States)

    Andrzejewski, Matthew E.; Spencer, Robert C.; Harris, Rachel L.; Feit, Elizabeth C.; McKee, Brenda L.; Berridge, Craig W.

    2014-01-01

    Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin®) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD. PMID:24467844

  12. Methylphenidate use and school performance among primary school children: a descriptive study.

    Science.gov (United States)

    van der Schans, Jurjen; Çiçek, Rukiye; Vardar, Sefike; Bos, Jens Hj; de Vries, Tjalling W; Hoekstra, Pieter J; Hak, Eelko

    2017-03-29

    There is no conclusive evidence that stimulants have beneficial effects on major associated outcome parameters, particularly school performance. We assessed the differences in school performance among children using methylphenidate at the end of primary school in relation to various parameters of methylphenidate use. We linked children from a pharmacy prescription database with standardized achievement test results at the end of primary school. We explored differences in test scores between current methylphenidate users versus never users and methylphenidate users who stopped treatment at least 6 months before the test, early versus late starters, different dosage of methylphenidate, and concurrent antipsychotic or asthma treatment. Out of the 7736 children, 377 (4.9%) children were treated with methylphenidate at the time of the test. After adjusting for confounders the methylphenidate users (532.58 ± .48) performed significantly lower on the test than never users (534.72 ± .11). Compared with late starters of methylphenidate treatment (536.94 ± 1.51) we found significantly lower test scores for the early starters (532.33 ± .50). Our study indicates that children using methylphenidate still perform less at school compared to their peers. Our study also suggests that earlier start of methylphenidate treatment is associated with a lower school performance compared to children starting later with the treatment. This result could either indicate a limited effect of long term treatment or a more strongly affected group of early starters.

  13. Active Emergence from Propofol General Anesthesia is Induced by Methylphenidate

    Science.gov (United States)

    Chemali, Jessica J.; Van Dort, Christa J.; Brown, Emery N.; Solt, Ken

    2012-01-01

    BACKGROUND A recent study showed that methylphenidate induces emergence from isoflurane general anesthesia. Isoflurane and propofol are general anesthetics that may have distinct molecular mechanisms of action. The objective of this study was to test the hypothesis that methylphenidate actively induces emergence from propofol general anesthesia. METHODS Using adult rats, the effect of methylphenidate on time to emergence after a single bolus of propofol was determined. The ability of methylphenidate to restore righting during a continuous target controlled infusion of propofol was also tested. In a separate group of rats, a target controlled infusion of propofol was established and spectral analysis was performed on electroencephalogram recordings taken before and after methylphenidate administration. RESULTS Methylphenidate decreased median time to emergence after a single dose of propofol from 735 seconds (95% CI: 598 to 897 seconds, n=6) to 448 seconds (95% CI: 371 to 495 seconds, n=6). The difference was statistically significant (p = 0.0051). During continuous propofol anesthesia with a median final target plasma concentration of 4.0 μg/ml (95%CI: 3.2 to 4.6, n=6), none of the rats exhibited purposeful movements after injection of normal saline. After methylphenidate, however, all 6 rats promptly exhibited arousal and had restoration of righting with a median time of 82 seconds (95% CI: 30 to 166 seconds). Spectral analysis of electroencephalogram data demonstrated a shift in peak power from delta (anesthesia in rats. Further study is warranted to test the hypothesis that methylphenidate induces emergence from propofol general anesthesia in humans. PMID:22446983

  14. Methylphenidate produces selective enhancement of declarative memory consolidation in healthy volunteers.

    Science.gov (United States)

    Linssen, A M W; Vuurman, E F P M; Sambeth, A; Riedel, W J

    2012-06-01

    Methylphenidate inhibits the reuptake of dopamine and noradrenaline and is used to treat children with attention deficit hyperactivity disorder (ADHD). Besides reducing behavioral symptoms, it improves their cognitive function. There are also observations of methylphenidate-induced cognition enhancement in healthy adults, although studies in this area are relatively sparse. We assessed the possible memory-enhancing properties of methylphenidate. In the current study, the possible enhancing effects of three doses of methylphenidate on declarative and working memory, attention, response inhibition and planning were investigated in healthy volunteers. In a double blind placebo-controlled crossover study, 19 healthy young male volunteers were tested after a single dose of placebo or 10, 20 or 40 mg of methylphenidate. Cognitive performance testing included a word learning test as a measure of declarative memory, a spatial working memory test, a set-shifting test, a stop signal test and a computerized version of the Tower of London planning test. Declarative memory consolidation was significantly improved relative to placebo after 20 and 40 mg of methylphenidate. Methylphenidate also improved set shifting and stopped signal task performance but did not affect spatial working memory or planning. To the best of our knowledge, this is the first study reporting enhanced declarative memory consolidation after methylphenidate in a dose-related fashion over a dose range that is presumed to reflect a wide range of dopamine reuptake inhibition.

  15. Pharmacogenetics of Methylphenidate Response in Preschoolers with ADHD

    Science.gov (United States)

    McGough, James; McCracken, James; Swanson, James; Riddle, Mark; Kollins, Scott; Greenhill, Laurence; Abikoff, Howard; Davies, Mark; Chuang, Shirley; Wigal, Tim; Wigal, Sharon; Posner, Kelly; Skrobala, Anne; Kastelic, Elizabeth; Ghuman, Jaswinder; Cunningham, Charles; Shigawa, Sharon; Moyzis, Robert; Vitiello, Benedetto

    2006-01-01

    Objective: The authors explored genetic moderators of symptom reduction and side effects in methylphenidate-treated preschool-age children diagnosed with attention-deficit/hyperactivity disorder (ADHD). Method: DNA was isolated from 81 subjects in a double-blind, placebo-controlled, crossover methylphenidate titration. Parents and teachers…

  16. Prevalence of methylphenidate use by university students in Campos dos Goytacazes, RJ

    Directory of Open Access Journals (Sweden)

    Fernanda Fraga Pessanha

    2014-08-01

    Full Text Available Methylphenidate is a central nervous system stimulant commonly prescribed for children with Attention Deficit Hyperactivity Disorder. The aim of this study was to identify the prevalence of methylphenidate users among college students, as well as the main reasons for it, ways of acquisition, and possible side effects. The study demonstrated a 60% prevalence of the use of methylphenidate by university students in Campos dos Goytacazes. We conclude that there is a high rate of use of methylphenidate among students in this city. The authors suggest an awareness campaign on the risks of inappropriate use of methylphenidate.

  17. Perioperative Outcome of Dyssomnia Patients on Chronic Methylphenidate Use

    Directory of Open Access Journals (Sweden)

    Nicoleta Stoicea MD, PhD

    2014-01-01

    Full Text Available Methylphenidate is frequently prescribed for attention deficit hyperactivity disorder, narcolepsy, and other sleep disorders requiring psychostimulants. Our report is based on 2 different clinical experiences of patients with chronic methylphenidate use, undergoing general anesthesia. These cases contrast different strategies of taking versus withholding the drug treatment on the day of surgery. From the standpoint of anesthetic management and patient safety, the concerns for perioperative methylphenidate use are mainly related to cardiovascular stability and possible counteraction of sedatives and anesthetics.

  18. Developmental rates of immatures of three Chrysomya species (Diptera: Calliphoridae) under the effect of methylphenidate hydrochloride, phenobarbital, and methylphenidate hydrochloride associated with phenobarbital.

    Science.gov (United States)

    Rezende, Fábio; Alonso, Marcela A; Souza, Carina M; Thyssen, Patrícia J; Linhares, Arício X

    2014-05-01

    Entomotoxicology is focused on obtaining data on necrophagous entomofauna, for criminal investigations purposes. This study aimed to evaluate the effect of different concentrations of methylphenidate hydrochloride, phenobarbital, and their association on the developmental rate, larval and pupal survivorship, and the interval of emergence of adults of Chrysomya albiceps (Wiedemann), Chrysomya megacephala (Fabricius), and Chrysomya putoria (Wiedemann) (Diptera: Calliphoridae). Considering the therapeutic dose (TD) of methylphenidate hydrochloride (0.29 mg/Kg), the concentrations tested were 10× TD, 50× TD, and 100× TD. For phenobarbital, the concentrations used were 1× TD (=150 mg/Kg), 3.3× TD, and 6.7× TD. For the association of the drugs, the combinations used were 10× TD-methylphenidate hydrochloride plus 1× TD-phenobarbital, 50× TD-methylphenidate hydrochloride plus 3.3× TD-phenobarbital, and 100× TD-methylphenidate hydrochloride plus 6.7× TD-phenobarbital. The control group, without addition of drug, was maintained under the same conditions of temperature (25 ± 1 °C), humidity (70 ± 10%), and photoperiod (12 h). Specimens of each group were weighed every 12 h until pupariation. The developmental rate of the three Chrysomya species immatures was monitored. For C. albiceps the developmental time was delayed in 24 h for methylphenidate hydrochloride group and in 12 h for the phenobarbital and the drugs association groups. The effect was observed only at specific ages for C. megacephala, without altering the developmental time. For C. putoria, the developmental time was delayed in 12 h for methylphenidate hydrochloride group and in 24 h for the phenobarbital and the drugs association groups. The emergence interval was similar among all experimental groups, but larval and pupal viabilities were affected in different ways.

  19. Dietary intake, growth and development of children with ADHD in a randomized clinical trial of Ritalin and Melatonin co-administration: Through circadian cycle modification or appetite enhancement?

    Directory of Open Access Journals (Sweden)

    Seyed-Ali Mostafavi

    2012-09-01

    Full Text Available Objective: It is postulated that ritalin may adversely affect sleep, appetite, weight and growth of some children with ADHD. Therefore, we aimed to evaluate melatonin supplementation effects on dietary intake, growth and development of children with ADHD treated with ritalin through circadian cycle modification and appetite mechanisms.Method: After obtaining consent from parents, 50 children aged 7-12 with combined form of AD/HD were randomly divided into two groups based on gender blocks: one received melatonin (3 or 6 mg based on weight combined with ritalin (1mg/kg and the other took placebo combined with ritalin (1mg/kg in a double blind randomized clinical trial. Three-day food record, and standard weight and height of children were evaluated prior to the treatment and 8 weeks after the treatment. Children’s appetite and sleep were evaluated in weeks 0, 2, 4 and 8. Hypotheses were then analyzed using SPSS17.Results: Paired sample t-test showed significant changes in sleep latency (23.15±15.25 vs. 17.96±11.66; p=0.047 and total sleep disturbance score (48.84±13.42 vs. 41.30±9.67; p=0.000 before and after melatonin administration, respectively. However, appetite and food intake did not change significantly during the study. Sleep duration and appetite were significantly correlated in melatonin group (Pearson r=0.971, p=0.029. Mean height (138.28±16.24 vs. 141.35±16.78; P=0.000 and weight (36.73±17.82 vs. 38.97±17.93; P=0.005 were significantly increased in melatonin treated children before and after the trial.Conclusion: Administration of melatonin along with ritalin improves height and weight growth of children. These effects may be attributed to circadian cycle modification, increasing sleep duration and the consequent more growth hormone release during sleep.

  20. Prescription Stimulant Medication Misuse: Where Are We and Where Do We Go from Here?

    OpenAIRE

    Weyandt, Lisa L.; Oster, Danielle R.; Marraccini, Marisa Ellen; Gudmundsdottir, Bergljot Gyda; Munro, Bailey A.; Rathkey, Emma S.; Mccallum, Alison

    2016-01-01

    Prescription stimulants, including methylphenidate (e.g., Ritalin) and amphetamine compounds (e.g., dextroamphetamine; Adderall), have been approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) and are classified by the United States Drug Enforcement Administration (DEA) as Schedule II medications due to their high potential for abuse and dependence (DEA, U.S. Department of Justice, 2015). Despite the potential health and judici...

  1. Disagreements with implications: diverging discourses on the ethics of non-medical use of methylphenidate for performance enhancement.

    Science.gov (United States)

    Forlini, Cynthia; Racine, Eric

    2009-07-06

    There is substantial evidence that methylphenidate (MPH; Ritalin), is being used by healthy university students for non-medical motives such as the improvement of concentration, alertness, and academic performance. The scope and potential consequences of the non-medical use of MPH upon healthcare and society bring about many points of view. To gain insight into key ethical and social issues on the non-medical use of MPH, we examined discourses in the print media, bioethics literature, and public health literature. Our study identified three diverging paradigms with varying perspectives on the nature of performance enhancement. The beneficial effects of MPH on normal cognition were generally portrayed enthusiastically in the print media and bioethics discourses but supported by scant information on associated risks. Overall, we found a variety of perspectives regarding ethical, legal and social issues related to the non-medical use of MPH for performance enhancement and its impact upon social practices and institutions. The exception to this was public health discourse which took a strong stance against the non-medical use of MPH typically viewed as a form of prescription abuse or misuse. Wide-ranging recommendations for prevention of further non-medical use of MPH included legislation and increased public education. Some positive portrayals of the non-medical use of MPH for performance enhancement in the print media and bioethics discourses could entice further uses. Medicine and society need to prepare for more prevalent non-medical uses of neuropharmaceuticals by fostering better informed public debates.

  2. Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents

    DEFF Research Database (Denmark)

    Storebø, Ole Jakob; Krogh, Helle B; Ramstad, Erica

    2015-01-01

    STUDY QUESTION: Is methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents? METHODS: Electronic databases were searched up to February 2015 for parallel and crossover randomised clinical trials comparing methylphenidate...

  3. Working memory capacity predicts effects of methylphenidate on reversal learning

    NARCIS (Netherlands)

    Schaaf, M.E. van der; Fallon, S.J.; Huurne, N.P. ter; Buitelaar, J.K.; Cools, R.

    2013-01-01

    Increased use of stimulant medication, such as methylphenidate, by healthy college students has raised questions about its cognitive-enhancing effects. Methylphenidate acts by increasing extracellular catecholamine levels and is generally accepted to remediate cognitive and reward deficits in

  4. Methylphenidate for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

    DEFF Research Database (Denmark)

    Storebø, Ole J; Simonsen, Erik; Gluud, Christian

    2016-01-01

    CLINICAL QUESTION: Is treatment with methylphenidate associated with benefits or harms for children and adolescents with attention-deficit/hyperactivity disorder (ADHD)? BOTTOM LINE: Methylphenidate is associated with improvement in ADHD symptoms, general behavior, and quality of life; however, due...

  5. Methylphenidate significantly improves declarative memory functioning of adults with ADHD.

    NARCIS (Netherlands)

    Verster, J.C.; Bekker, E.M.; Kooij, J.J.; Buitelaar, J.K.; Verbaten, M.N.; Volkerts, E.R.; Olivier, B.

    2010-01-01

    BACKGROUND: Declarative memory deficits are common in untreated adults with attention-deficit hyperactivity disorder (ADHD), but limited evidence exists to support improvement after treatment with methylphenidate. The objective of this study was to examine the effects of methylphenidate on memory

  6. Classics in Chemical Neuroscience: Methylphenidate.

    Science.gov (United States)

    Wenthur, Cody J

    2016-08-17

    As the first drug to see widespread use for the treatment of attention deficit hyperactivity disorder (ADHD), methylphenidate was the forerunner and catalyst to the modern era of rapidly increasing diagnosis, treatment, and medication development for this condition. During its often controversial history, it has variously elucidated the importance of dopamine signaling in memory and attention, provoked concerns about pharmaceutical cognitive enhancement, driven innovation in controlled-release technologies and enantiospecific therapeutics, and stimulated debate about the impact of pharmaceutical sales techniques on the practice of medicine. In this Review, we will illustrate the history and importance of methylphenidate to ADHD treatment and neuroscience in general, as well as provide key information about its synthesis, structure-activity relationship, pharmacological activity, metabolism, manufacturing, FDA-approved indications, and adverse effects.

  7. Prevalence of methylphenidate use among Canadian children following parental divorce.

    Science.gov (United States)

    Strohschein, Lisa A

    2007-06-05

    Evidence suggests that children living in single-parent or step-parent households are more likely than children in households with 2 biological parents to be prescribed methylphenidate. I conducted a study of prospective data to investigate parental divorce as a predictor of methylphenidate use. I used data for children who participated in the National Longitudinal Survey of Children and Youth from 1994 to 2000. The sample was restricted to children who remained in the survey in 2000 and who, at initial interview, lived in a household with 2 biological parents (n = 4784). A generalized estimating equation model was used to compare the odds ratios of methylphenidate use among children whose parents obtained a divorce between 1994 and 2000 relative to children whose parents remained married during this period. Between 1994 and 2000, 633 children (13.2%) experienced the divorce of their parents. The proportion of children who received methylphenidate at any time between 1994 and 2000 was 3.3% among those whose parents remained married and 6.1% among those whose parents divorced during this period. After adjustment for age of the mother and sex and age of the child, I found that methylphenidate use was significantly higher among children whose parents subsequently divorced than among those whose parents remained married (odds ratio 1.82, 95% confidence interval 1.01-3.33). The increased risk of children receiving a prescription for methylphenidate in the period following parental divorce raises questions about the causal links in this association. Future research is needed to replicate these findings and to investigate possible explanations.

  8. Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

    Science.gov (United States)

    Roache, J D; Grabowski, J; Schmitz, J M; Creson, D L; Rhoades, H M

    2000-02-01

    Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated

  9. The adolescent outcome of children with attention deficit hyperactivity disorder treated with methylphenidate or methylphenidate combined with multimodal behaviour therapy: Results of a naturalistic follow-up study

    NARCIS (Netherlands)

    van der Oord, S.; Prins, P.J.M.; Oosterlaan, J.; Emmelkamp, P.M.G

    2012-01-01

    Objective: Children with attention deficit hyperactivity disorder (ADHD) who participated in a randomized clinical trial, which compared a brief intensive multimodal behaviour therapy combined with optimally titrated methylphenidate to optimally titrated methylphenidate alone (n=45), were

  10. Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Yang

    Full Text Available A previously presented physiologically-based pharmacokinetic model for immediate release (IR methylphenidate (MPH was extended to characterize the pharmacokinetic behaviors of oral extended release (ER MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations.

  11. Cardiac Arrest following a Myocardial Infarction in a Child Treated with Methylphenidate

    DEFF Research Database (Denmark)

    Munk, Kim; Gormsen, Lise Kirstine; Kim, Won Yong

    2015-01-01

    -years, did not report any cases of myocardial infarction in current users of methylphenidate, and the risk of serious adverse cardiac events was not found to be increased. We present a case with an 11-year-old child, treated with methylphenidate, who suffered cardiac arrest and was diagnosed with a remote...... myocardial infarction. This demonstrates that myocardial infarction can happen due to methylphenidate exposure in a cardiac healthy child, without cardiovascular risk factors....

  12. Methylphenidate as a cognitive enhancer in healthy young people

    Science.gov (United States)

    Batistela, Silmara; Bueno, Orlando Francisco Amodeo; Vaz, Leonardo José; Galduróz, José Carlos Fernandes

    2016-01-01

    ABSTRACT The so-called cognitive enhancers have been widely and increasingly used by healthy individuals who seek improvements in cognitive performance despite having no pathologies. One drug used for this purpose is methylphenidate, a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Objective: The aim of the present study was to test the effect of acute administration of varying doses of methylphenidate (10 mg, 20 mg, 40 mg and placebo) on a wide range of cognitive functions in healthy young people. Methods: A total of 36 young university students and graduates participated in the study. The participants underwent tests of attention and of episodic, and working memory. Results: No differences in performance were observed on any of the tests. There was a dose-dependent (40 mg > placebo) effect on self-reported wellbeing. Conclusions: According to the recent literature, psychostimulant medications, such as methylphenidate, improve performance when cognitive processes are below an optimal level, which was not the case for the subjects of the present study. We suggest the impression that methylphenidate enhances cognitive performance in healthy young people, justifying its use, may be due to improvements in subjective wellbeing promoted by the drug. PMID:29213444

  13. The Safety and Efficacy of Methylphenidate and Dexmethylphenidate in Adults with Attention Deficit/Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Michael A. Sopko

    2010-01-01

    Full Text Available Objective To review the literature on the safety and efficacy of methylphenidate, OROS-methylphenidate, methylphenidate ER, and dexmethylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD. To analyze the effects of different doses of methylphenidate, it's various formulations, and methylphenidate on efficacy and safety in this population. Data Sources Literature retrieval was performed through Pubmed/MEDLINE (Up to May 2010 using the terms methylphenidate, dexmethylphenidate, and attention-deficit hyperactivity disorder. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction Double-blinded, placebo-controlled clinical trials, as well as crossover and open-label trials found using the search criteria listed above were included for review. Case reports were not included in this review. Data Synthesis Attention-deficit/hyperactivity disorder (ADHD is a psychiatric condition that is commonly seen in children and adolescents, that persists into adulthood for about 50% of patients. Methylphenidate and dexmethylphenidate are often prescribed to treat the symptoms associated with ADHD. The literature validating the safety and efficacy of methylphenidate and dexmethylphenidate in children and adolescents with ADHD is substantial. However, the literature specifically addressing the safety and efficacy of these medications in the adult population is less extensive and prescribing is often anecdotal based on child and adolescent data. Understanding the literature regarding methylphenidate and dexmethylphenidate and its effects in adults can enhance evidence-based medicine (EBM and improve treatment outcomes Conclusion Methylphenidate and dexmethylphenidate are safe and effective medications to treat the symptoms of ADHD in adults. Based on the literature, increased doses are associated with better treatment response with moderate safety concerns. The different dosage forms

  14. Prescription, dispensation and marketing patterns of methylphenidate

    Directory of Open Access Journals (Sweden)

    Edson Perini

    2014-12-01

    Full Text Available OBJECTIVE To analyze the patterns and legal requirements of methylphenidate consumption. METHODS We conducted a cross-sectional study of the data from prescription notification forms and balance lists of drugs sales – psychoactive and others – subject to special control in the fifth largest city of Brazil, in 2006. We determined the defined and prescribed daily doses, the average prescription and dispensation periods, and the regional sales distribution in the municipality. In addition, we estimated the costs of drug acquisition and analyzed the individual drug consumption profile using the Lorenz curve. RESULTS The balance lists data covered all notified sales of the drug while data from prescription notification forms covered 50.6% of the pharmacies that sold it, including those with the highest sales volumes. Total methylphenidate consumption was 0.37 DDD/1,000 inhabitants/day. Sales were concentrated in more developed areas, and regular-release tablets were the most commonly prescribed pharmaceutical formulation. In some regions of the city, approximately 20.0% of the prescriptions and dispensation exceeded 30 mg/day and 30 days of treatment. CONCLUSIONS Methylphenidate was widely consumed in the municipality and mainly in the most developed areas. Of note, the consumption of formulations with the higher abuse risk was the most predominant. Both its prescription and dispensation contrasted with current pharmacotherapeutic recommendations and legal requirements. Therefore, the commercialization of methylphenidate should be monitored more closely, and its use in the treatment of behavioral changes of psychological disorders needs to be discussed in detail, in line with the concepts of the quality use of medicines.

  15. Disagreements with implications: diverging discourses on the ethics of non-medical use of methylphenidate for performance enhancement

    Science.gov (United States)

    Forlini, Cynthia; Racine, Eric

    2009-01-01

    Background There is substantial evidence that methylphenidate (MPH; Ritalin), is being used by healthy university students for non-medical motives such as the improvement of concentration, alertness, and academic performance. The scope and potential consequences of the non-medical use of MPH upon healthcare and society bring about many points of view. Methods To gain insight into key ethical and social issues on the non-medical use of MPH, we examined discourses in the print media, bioethics literature, and public health literature. Results Our study identified three diverging paradigms with varying perspectives on the nature of performance enhancement. The beneficial effects of MPH on normal cognition were generally portrayed enthusiastically in the print media and bioethics discourses but supported by scant information on associated risks. Overall, we found a variety of perspectives regarding ethical, legal and social issues related to the non-medical use of MPH for performance enhancement and its impact upon social practices and institutions. The exception to this was public health discourse which took a strong stance against the non-medical use of MPH typically viewed as a form of prescription abuse or misuse. Wide-ranging recommendations for prevention of further non-medical use of MPH included legislation and increased public education. Conclusion Some positive portrayals of the non-medical use of MPH for performance enhancement in the print media and bioethics discourses could entice further uses. Medicine and society need to prepare for more prevalent non-medical uses of neuropharmaceuticals by fostering better informed public debates. PMID:19580661

  16. Disagreements with implications: diverging discourses on the ethics of non-medical use of methylphenidate for performance enhancement

    Directory of Open Access Journals (Sweden)

    Racine Eric

    2009-07-01

    Full Text Available Abstract Background There is substantial evidence that methylphenidate (MPH; Ritalin, is being used by healthy university students for non-medical motives such as the improvement of concentration, alertness, and academic performance. The scope and potential consequences of the non-medical use of MPH upon healthcare and society bring about many points of view. Methods To gain insight into key ethical and social issues on the non-medical use of MPH, we examined discourses in the print media, bioethics literature, and public health literature. Results Our study identified three diverging paradigms with varying perspectives on the nature of performance enhancement. The beneficial effects of MPH on normal cognition were generally portrayed enthusiastically in the print media and bioethics discourses but supported by scant information on associated risks. Overall, we found a variety of perspectives regarding ethical, legal and social issues related to the non-medical use of MPH for performance enhancement and its impact upon social practices and institutions. The exception to this was public health discourse which took a strong stance against the non-medical use of MPH typically viewed as a form of prescription abuse or misuse. Wide-ranging recommendations for prevention of further non-medical use of MPH included legislation and increased public education. Conclusion Some positive portrayals of the non-medical use of MPH for performance enhancement in the print media and bioethics discourses could entice further uses. Medicine and society need to prepare for more prevalent non-medical uses of neuropharmaceuticals by fostering better informed public debates.

  17. Clinical effect of venlafaxine combined with methylphenidate hydrochloride on narcolepsy

    Directory of Open Access Journals (Sweden)

    YAN Bin

    2013-11-01

    Full Text Available This study aims to explore the clinical effect of venlafaxine sustained-release capsules combined with methylphenidate hydrochloride tablets on narcolepsy. Thirty-eight cases of narcoleptic patients were randomly divided into venlafaxine combined with methylphenidate hydrochloride treatment group (observation group, N = 19 and methylphenidate hydrochloride and clomipramine treatment group (control group, N = 19. After a total of 12-week treatment, clinical curative effect and adverse drug reactions were observed in 2 groups of patients. The results showed that effective rate of the treatment for excessive daytime sleepiness (EDS in observation group was higher than that of the control group (15/19 vs 8/19, P = 0.044, and effective rate of the treatment for cataplexy in observation group was higher than that of the control group (13/19 vs 6/19, P = 0.048. The rate of adverse drug reactions in observation group was lower than that in the control group (χ2 = 8.889, P = 0.003. It was indicated that venlafaxine combined with methylphenidate had good curative effect on narcolepsy with EDS and cataplexy symptoms.

  18. Effects of methylphenidate and MDMA on appraisal of erotic stimuli and intimate relationships.

    Science.gov (United States)

    Schmid, Yasmin; Hysek, Cédric M; Preller, Katrin H; Bosch, Oliver G; Bilderbeck, Amy C; Rogers, Robert D; Quednow, Boris B; Liechti, Matthias E

    2015-01-01

    Methylphenidate mainly enhances dopamine neurotransmission whereas 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") mainly enhances serotonin neurotransmission. However, both drugs also induce a weaker increase of cerebral noradrenaline exerting sympathomimetic properties. Dopaminergic psychostimulants are reported to increase sexual drive, while serotonergic drugs typically impair sexual arousal and functions. Additionally, serotonin has also been shown to modulate cognitive perception of romantic relationships. Whether methylphenidate or MDMA alter sexual arousal or cognitive appraisal of intimate relationships is not known. Thus, we evaluated effects of methylphenidate (40 mg) and MDMA (75 mg) on subjective sexual arousal by viewing erotic pictures and on perception of romantic relationships of unknown couples in a double-blind, randomized, placebo-controlled, crossover study in 30 healthy adults. Methylphenidate, but not MDMA, increased ratings of sexual arousal for explicit sexual stimuli. The participants also sought to increase the presentation time of implicit sexual stimuli by button press after methylphenidate treatment compared with placebo. Plasma levels of testosterone, estrogen, and progesterone were not associated with sexual arousal ratings. Neither MDMA nor methylphenidate altered appraisal of romantic relationships of others. The findings indicate that pharmacological stimulation of dopaminergic but not of serotonergic neurotransmission enhances sexual drive. Whether sexual perception is altered in subjects misusing methylphenidate e.g., for cognitive enhancement or as treatment for attention deficit hyperactivity disorder is of high interest and warrants further investigation. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  19. Methylphenidate as a cognitive enhancer in healthy young people

    Directory of Open Access Journals (Sweden)

    Silmara Batistela

    Full Text Available ABSTRACT The so-called cognitive enhancers have been widely and increasingly used by healthy individuals who seek improvements in cognitive performance despite having no pathologies. One drug used for this purpose is methylphenidate, a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD. Objective: The aim of the present study was to test the effect of acute administration of varying doses of methylphenidate (10 mg, 20 mg, 40 mg and placebo on a wide range of cognitive functions in healthy young people. Methods: A total of 36 young university students and graduates participated in the study. The participants underwent tests of attention and of episodic, and working memory. Results: No differences in performance were observed on any of the tests. There was a dose-dependent (40 mg > placebo effect on self-reported wellbeing. Conclusions: According to the recent literature, psychostimulant medications, such as methylphenidate, improve performance when cognitive processes are below an optimal level, which was not the case for the subjects of the present study. We suggest the impression that methylphenidate enhances cognitive performance in healthy young people, justifying its use, may be due to improvements in subjective wellbeing promoted by the drug.

  20. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

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    Nora D Volkow

    2010-07-01

    Full Text Available Dopamine (phasic release is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function was measured with PET and (18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg. The Cocaine-cues video increased craving to the same extent with placebo (68% and with methylphenidate (64%. In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005 in left limbic regions (insula, orbitofrontal, accumbens and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005, amygdala, striatum and middle insula (p<0.05. This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes, which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  1. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2010-01-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18 FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  2. The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder.

    Science.gov (United States)

    Viktorin, Alexander; Rydén, Eleonore; Thase, Michael E; Chang, Zheng; Lundholm, Cecilia; D'Onofrio, Brian M; Almqvist, Catarina; Magnusson, Patrik K E; Lichtenstein, Paul; Larsson, Henrik; Landén, Mikael

    2017-04-01

    The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder. Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods. Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted. No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.

  3. Non-medical use of methylphenidate among medical students of the University of the Free State

    Directory of Open Access Journals (Sweden)

    Roshini Jain

    2017-01-01

    Full Text Available Background: Faced with demanding training programmes, medical students may be more prone to use methylphenidate for non-medical purposes in order to improve concentration, alertness and academic performance. Aim: The study aimed to investigate the prevalence of the non-medical use of methylphenidate and knowledge of this drug among undergraduate medical students of the University of the Free State. Methods: This was a cross-sectional study. A self-administered, anonymous questionnaire was distributed during lectures to all students in the five year groups of the undergraduate medical programme. Results: Of the 643 undergraduate medical students, 541 completed the questionnaire (response rate: 84.1%. Approximately 11.0% of surveyed students were using methylphenidate at the time of the study, of which the majority (67.9% used it for academic purposes and 70.6% received it from a medical health professional. Less than a third of users had been diagnosed with Attention-Deficit/Hyperactivity Disorder. Methylphenidate users’ median knowledge was greater than non-users, and methylphenidate knowledge increased from first-year and second-year students to third-year to fifth-year students. Median knowledge scores per year group ranged from 52.0% to 60.0%. Conclusion: Methylphenidate is mainly used for non-medical purposes by medical students. Students generally have a low level of knowledge on methylphenidate. Specific information on methylphenidate should be included in lectures on stress management and study methods during the course of the medical curriculum.

  4. Differences in methylphenidate abuse rates among methadone maintenance treatment patients in two clinics.

    Science.gov (United States)

    Peles, Einat; Schreiber, Shaul; Linzy, Shirley; Domani, Yoav; Adelson, Miriam

    2015-07-01

    Methylphenidate, an amphetamine-like prescription medication for attention deficit hyperactivity disorder (ADHD) was suspected as being abused among methadone maintenance treatment (MMT) patients. We tested its presence in the routine urine monitoring of all patients in both Tel Aviv and Las Vegas MMT clinics. Data on demographic and addiction history, ADHD (Wender Utah Rating Scale), cognitive impairment (Mini Mental State Exam), and lifetime DSM-IV-TR psychiatric diagnosis from admission were retrieved, and retention following 6 months. None of the 190 patients in Las Vegas tested positive for methylphenidate, while 14.7% (45/306) did in Tel Aviv. Abusers were less educated (p = 0.01), had higher ADHD scores (p = 0.02), lower cognitive scores (p = 0.05), and a higher benzodiazepine (BDZ) abuse rate (p cannabis, opiates, and cocaine abuse and infectious disease. Of the methylphenidate abuse 42.2% have take-home methadone dose privileges. Not like opiate use, being methylphenidate positive did not relate to 6-months retention. Compared to Tel Aviv, Las Vegas patients were more educated, with lower BDZ, and cocaine abuse. The greater abuse of methylphenidate among ADHD subjects might indicate their using it as self-medication, raising a possible indication for its prescription for that subgroup of MMT patients. The high rate of methylphenidate abuse in Israel needs future study. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Methylphenidate and stimulus control of avoidance behavior1

    Science.gov (United States)

    Stretch, Roger; Skinner, Nicholas

    1967-01-01

    The introduction of a warning signal that preceded a scheduled shock modified the temporal distribution of free-operant avoidance responses. With response-shock and shock-shock intervals held constant, response rates increased only slightly when the response-signal interval was reduced. The result is consistent with Sidman's (1955) findings under different conditions, but at variance with Ulrich, Holz, and Azrin's (1964) findings under similar conditions. Methylphenidate in graded doses increased response rates, modifying frequency distributions of interresponse times. Drug treatment may have disrupted a “temporal discrimination” formed within the signal-shock interval. More simply, methylphenidate influenced response rates by increasing short response latencies after signal onset; this effect was more prominent than the drug's tendency to increase the frequency of pre-signal responses. When signal-onset preceded shock by 2 sec, individual differences in performance were marked; methylphenidate suppressed responding in one rat as a function of increasing dose levels to a greater degree than in a second animal, but both subjects received more shocks than under control conditions. PMID:6050059

  6. Effect of Methylphenidate on Retention and Retrieval of Passive Avoidance Memory in Young and Aged Mice

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    Arzi

    2014-10-01

    Full Text Available Background Several studies showed that dopamine and norepinephrine improve retention and retrieval of memory. Methylphenidate is an enhancer of dopamine and norepinephrine in brain. Objectives In the present study, the effect of methylphenidate was evaluated on retention and retrieval of memory in young and aged mice using passive avoidance apparatus. Materials and Methods Animals were divided into groups (n = 8 as follows: test groups received electric shock plus methylphenidate (2.5, 5 and 10mg kg-1, i. P., control group received electric shock plus normal saline and blank group received only electric shock. In all groups, step-down latency for both retention and retrieval test of memory was measured. Methylphenidate was administered immediately after receiving electric shock in the retention test, but methylphenidate was administered 23.5 hours after receiving electric shock in the retrieval test. Results The mean of step-down latency on day 4 was significantly higher compared to day 2 (P < 0.05 in all young and aged groups of mice. The best response was attained with 5 mg/kg of methylphenidate. In memory retention test, the mean of step-down latency in young groups that received 2.5 and 5 mg/kg methylphenidate was significantly longer(P < 0.05 than aged groups. However, this difference was not significant in memory retrieval test. Conclusions Methylphenidate may improve memory retention and retrieval.

  7. Differential effects of MDMA and methylphenidate on social cognition.

    Science.gov (United States)

    Schmid, Yasmin; Hysek, Cédric M; Simmler, Linda D; Crockett, Molly J; Quednow, Boris B; Liechti, Matthias E

    2014-09-01

    Social cognition is important in everyday-life social interactions. The social cognitive effects of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate (both used for neuroenhancement and as party drugs) are largely unknown. We investigated the acute effects of MDMA (75 mg), methylphenidate (40 mg) and placebo using the Facial Emotion Recognition Task, Multifaceted Empathy Test, Movie for the Assessment of Social Cognition, Social Value Orientation Test and the Moral Judgment Task in a cross-over study in 30 healthy subjects. Additionally, subjective, autonomic, pharmacokinetic, endocrine and adverse drug effects were measured. MDMA enhanced emotional empathy for positive emotionally charged situations in the MET and tended to reduce the recognition of sad faces in the Facial Emotion Recognition Task. MDMA had no effects on cognitive empathy in the Multifaceted Empathy Test or social cognitive inferences in the Movie for the Assessment of Social Cognition. MDMA produced subjective 'empathogenic' effects, such as drug liking, closeness to others, openness and trust. In contrast, methylphenidate lacked such subjective effects and did not alter emotional processing, empathy or mental perspective-taking. MDMA but not methylphenidate increased the plasma levels of oxytocin and prolactin. None of the drugs influenced moral judgment. Effects on emotion recognition and emotional empathy were evident at a low dose of MDMA and likely contribute to the popularity of the drug. © The Author(s) 2014.

  8. Adverse reactions of Methylphenidate in children with attention deficit-hyperactivity disorder: Report from a referral center

    Science.gov (United States)

    Khajehpiri, Zahra; Mahmoudi-Gharaei, Javad; Faghihi, Toktam; Karimzadeh, Iman; Khalili, Hossein; Mohammadi, Mostafa

    2014-01-01

    Objective: The aim of the current study was to determine various aspects of methylphenidate adverse reactions in children with attention deficit-hyperactivity disorder (ADHD) in Iran. Methods: During the 6 months period, all children under methylphenidate treatment alone or along with other agents attending a university-affiliated psychology clinic were screened regarding all subjective and objective adverse drug reactions (ADRs) of methylphenidate. Causality and seriousness of detected ADRs were assessed by relevant World Health Organization definitions. The Schumock and Thornton questionnaire was used to determine preventability of ADRs. Findings: Seventy-one patients including 25 girls and 46 boys with ADHD under methylphenidate treatment were enrolled within the study period. All (100%) ADHD children under methylphenidate treatment developed at least one ADR. Anorexia (74.3%), irritability (57.1%), and insomnia (47.2%) were the most frequent methylphenidate-related adverse reactions. Except for one, all other detected ADRs were determined to be mild. In addition, no ADR was considered to be preventable and serious. Conclusion: Our data suggested that although methylphenidate related adverse reactions were common in children with ADHD, but they were mainly mild and nonserious. PMID:25535621

  9. MR imaging of the effects of methylphenidate on brain structure and function in Attention-Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    Schweren, Lizanne J. S.; de Zeeuw, Patrick; Durston, Sarah

    2013-01-01

    Methylphenidate is the first-choice pharmacological intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The pharmacological and behavioral effects of methylphenidate are well described, but less is known about neurochemical brain changes induced by methylphenidate.

  10. Methylphenidate use in children with attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Felipe Salles Neves Machado

    2015-01-01

    Full Text Available A Brazilian Health Technology Assessment Bulletin (BRATS article regarding scientific evidence of the efficacy and safety of methylphenidate for treating attention deficit hyperactivity disorder (ADHD has caused much controversy about its methods. Considering the relevance of BRATS for public health in Brazil, we critically reviewed this article by remaking the BRATS search and discussing its methods and results. Two questions were answered: did BRATS include all references available in the literature? Do the conclusions reflect the reviewed articles? The results indicate that BRATS did not include all the references from the literature on this subject and also that the proposed conclusions are different from the results of the articles chosen by the BRATS authors themselves. The articles selected by the BRATS authors showed that using methylphenidate is safe and effective. However, the BRATS final conclusion does not reflect the aforementioned and should not be used to support decisions on the use of methylphenidate.

  11. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

    Science.gov (United States)

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2017-07-01

    Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Methylphenidate treatment beyond adolescence maintains increased cocaine self-administration in the spontaneously hypertensive rat model of attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Baskin, Britahny M; Dwoskin, Linda P; Kantak, Kathleen M

    2015-04-01

    Past research with the spontaneously hypertensive rat (SHR) model of attention deficit/hyperactivity disorder showed that adolescent methylphenidate treatment enhanced cocaine abuse risk in SHR during adulthood. The acquisition of cocaine self-administration was faster, and cocaine dose-response functions were shifted upward under fixed-ratio and progressive ratio schedules compared to adult SHR that received adolescent vehicle treatment or to control strains that received adolescent methylphenidate treatment. The current study determined if extending treatment beyond adolescence would ameliorate long-term consequences of adolescent methylphenidate treatment on cocaine abuse risk in adult SHR. Treatments (vehicle or 1.5mg/kg/day oral methylphenidate) began on postnatal day 28. Groups of male SHR were treated with vehicle during adolescence and adulthood, with methylphenidate during adolescence and vehicle during adulthood, or with methylphenidate during adolescence and adulthood. The group receiving adolescent-only methylphenidate was switched to vehicle on P56. Cocaine self-administration began on postnatal day 77, and groups receiving methylphenidate during adolescence and adulthood were treated either 1-h before or 1-h after daily sessions. At baseline under a fixed-ratio 1 schedule, cocaine self-administration (2h sessions; 0.3mg/kg unit dose) did not differ among the four treatment groups. Under a progressive ratio schedule (4.5h maximum session length; 0.01-1.0mg/kg unit doses), breakpoints for self-administered cocaine in SHR receiving the adult methylphenidate treatment 1-h pre-session were not different from the vehicle control group. However, compared to the vehicle control group, breakpoints for self-administered cocaine at the 0.3 and 1.0mg/kg unit doses were greater in adult SHR that received adolescent-only methylphenidate or received methylphenidate that was continued into adulthood and administered 1-h post-session. These findings suggest that

  13. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents

    DEFF Research Database (Denmark)

    Simonsen, Erik; Storebø, Ole Jakob; Rosendal, Susanne

    2012-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows:To assess beneficial and harmful effects of methylphenidate for children and adolescents with ADHD.......This is the protocol for a review and there is no abstract. The objectives are as follows:To assess beneficial and harmful effects of methylphenidate for children and adolescents with ADHD....

  14. Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

    OpenAIRE

    Seibert Julia; Hysek Cédric M; Penno Carlos A; Schmid Yasmin; Kratschmar Denise V; Liechti Matthias E; Odermatt Alex

    2014-01-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-h plasma steroid profiles. Sixteen healthy subjects (eight men, eight women) were treated with single doses of M...

  15. Methylphenidate decreased the amount of glucose needed by the brain to perform a cognitive task.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    2008-04-01

    Full Text Available The use of stimulants (methylphenidate and amphetamine as cognitive enhancers by the general public is increasing and is controversial. It is still unclear how they work or why they improve performance in some individuals but impair it in others. To test the hypothesis that stimulants enhance signal to noise ratio of neuronal activity and thereby reduce cerebral activity by increasing efficiency, we measured the effects of methylphenidate on brain glucose utilization in healthy adults. We measured brain glucose metabolism (using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in 23 healthy adults who were tested at baseline and while performing an accuracy-controlled cognitive task (numerical calculations given with and without methylphenidate (20 mg, oral. Sixteen subjects underwent a fourth scan with methylphenidate but without cognitive stimulation. Compared to placebo methylphenidate significantly reduced the amount of glucose utilized by the brain when performing the cognitive task but methylphenidate did not affect brain metabolism when given without cognitive stimulation. Whole brain metabolism when the cognitive task was given with placebo increased 21% whereas with methylphenidate it increased 11% (50% less. This reflected both a decrease in magnitude of activation and in the regions activated by the task. Methylphenidate's reduction of the metabolic increases in regions from the default network (implicated in mind-wandering was associated with improvement in performance only in subjects who activated these regions when the cognitive task was given with placebo. These results corroborate prior findings that stimulant medications reduced the magnitude of regional activation to a task and in addition document a "focusing" of the activation. This effect may be beneficial when neuronal resources are diverted (i.e., mind-wandering or impaired (i.e., attention deficit hyperactivity disorder, but it could be detrimental when

  16. Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain

    International Nuclear Information System (INIS)

    Volkow, N.D.

    1999-01-01

    The reinforcing effects of cocaine and methylphenidate have been linked to their ability to block dopamine transporters (DAT). Though cocaine and methylphenidate have similar in vitro affinities for DAT the abuse of methylphenidate in humans is substantially lower than of cocaine. To test if differences in in vivo potency at the DAT between these two drugs could account for the differences in their abuse liability the authors compared the levels of DAT occupancies that they had previously reported separately for intravenous methylphenidate in controls and for intravenous cocaine in cocaine abusers. DAT occupancies were measured with Positron Emission Tomography using [ 11 C]cocaine, as a DAT ligand, in 8 normal controls for the methylphenidate study and in 17 active cocaine abusers for the cocaine study. The ratio of the distribution volume of [ 11 C]cocaine in striatum to that in cerebellum, which corresponds to Bmax/Kd+1, was used as measure of DAT availability. Parallel measures were obtained to assess the cardiovascular effects of these two drugs. Methylphenidate and cocaine produced comparable dose-dependent blockage of DAT with an estimated ED 50 for methylphenidate of 0.07 mg/kg and for cocaine of 0.13 mg/kg. Both drugs induced similar increases in heart rate and blood pressure but the duration of the effects were significantly longer for methylphenidate than for cocaine

  17. LETTER TO THE EDITOR - COMMENTS ON CYTOGENETIC EFFECTS IN CHILDREN TREATED WITH METHYLPHENIDATE

    Science.gov (United States)

    The recent report by El-Zein et al. suggests that chromosome alterations may be a consequence of short-term methylphenidate use for the treatment of children with Attention Deficit Hyperactivity Disorder (ADHD). The report concludes that 3 months of treatment with methylphenidate...

  18. Core ADHD Symptom Improvement with Atomoxetine versus Methylphenidate: A Direct Comparison Meta-Analysis

    Science.gov (United States)

    Hazell, Philip L.; Kohn, Michael R.; Dickson, Ruth; Walton, Richard J.; Granger, Renee E.; van Wyk, Gregory W.

    2011-01-01

    Objective: Previous studies comparing atomoxetine and methylphenidate to treat ADHD symptoms have been equivocal. This noninferiority meta-analysis compared core ADHD symptom response between atomoxetine and methylphenidate in children and adolescents. Method: Selection criteria included randomized, controlled design; duration 6 weeks; and…

  19. Predictors of treatment outcome in adults with ADHD treated with OROS(R) methylphenidate

    NARCIS (Netherlands)

    Buitelaar, J.K.; Kooij, J.J.; Ramos-Quiroga, J.A.; Dejonckheere, J.; Casas, M.; Oene, J.C. van; Schauble, B.; Trott, G.E.

    2011-01-01

    BACKGROUND: We conducted a post-hoc analysis of the Long-Acting MethylpheniDate in Adult attention-deficit hyperactivity disorder (LAMDA) study to investigate predictors of response in adults with ADHD randomly assigned to Osmotic Release Oral System (OROS)((R))-methylphenidate hydrochloride (MPH)

  20. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Storebø, Ole Jakob; Ramstad, Erica; Krogh, Helle B; Nilausen, Trine Danvad; Skoog, Maria; Holmskov, Mathilde; Rosendal, Susanne; Groth, Camilla; Magnusson, Frederik L; Moreira-Maia, Carlos R; Gillies, Donna; Buch Rasmussen, Kirsten; Gauci, Dorothy; Zwi, Morris; Kirubakaran, Richard; Forsbøl, Bente; Simonsen, Erik; Gluud, Christian

    2015-11-25

    Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children with ADHD find it difficult to pay attention, they are hyperactive and impulsive.Methylphenidate is the drug most often prescribed to treat children and adolescents with ADHD but, despite its widespread use, this is the first comprehensive systematic review of its benefits and harms. To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. In February 2015 we searched six databases (CENTRAL, Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, Conference Proceedings Citations Index), and two trials registers. We checked for additional trials in the reference lists of relevant reviews and included trials. We contacted the pharmaceutical companies that manufacture methylphenidate to request published and unpublished data. We included all randomised controlled trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. At least 75% of participants needed to have an intellectual quotient of at least 70 (i.e. normal intellectual functioning). Outcomes assessed included ADHD symptoms, serious adverse events, non-serious adverse events, general behaviour and quality of life. Seventeen review authors participated in data extraction and risk of bias assessment, and two review authors independently performed all tasks. We used standard methodological procedures expected within Cochrane. Data from parallel-group trials and first period data from cross-over trials formed the basis of our primary analyses; separate analyses were undertaken using post-cross-over data from cross-over trials. We used Trial Sequential Analyses to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE

  1. OROS Methylphenidate in Adolescents with ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-01-01

    Full Text Available The efficacy and tolerability of osmotic-release oral system (OROS methylphenidate in adolescents with attention deficit hyperactivity disorder (ADHD were evaluated in a multisite controlled study at the Massachusetts General Hospital, Boston, and other centers in the United States.

  2. O metifenidato no Brasil: uma década de publicações Methylphenidate in Brazil: a decade of publications

    Directory of Open Access Journals (Sweden)

    Francisco Ortega

    2013-03-01

    Full Text Available O metilfenidato é um estimulante comercializado desde os anos 50 na Suíça, na Alemanha e nos EUA. Mas foi somente a partir de sua associação com o Transtorno do Déficit de Atenção e Hiperatividade (TDAH que suas vendas alavancaram, tornando-se o estimulante mais consumido no mundo. Este artigo tem por objetivo apresentar os resultados de uma análise das publicações brasileiras sobre os usos do metilfenidato no Brasil, ao longo da última década. Com isto, visa compreender como as informações são apresentadas ou omitidas nos diferentes espaços de divulgação impressa. Para tal análise, foram pesquisadas publicações científicas, nos principais periódicos de psiquiatria brasileiros, e reportagens de jornais e revistas nacionais destinados ao público em geral. A pesquisa inclui as publicações do período de 1998 a 2008. Destaca-se como ponto relevante da análise a importante participação dos laboratórios no financiamento dos grupos e pesquisas sobre TDAH. Os achados indicam que a combinação do uso do medicamento com psicoterapias, a dependência do medicamento e a ideia de que existe excesso de prescrição no Brasil são temas controversos nas publicações analisadas.Methylphenidate is frequently associated with Attention Deficit Hyperactivity disorder (ADHD, though this psychostimulant has been on the market in Switzerland, Germany and the US since the 1950s. After its association with ADHD, Ritalin has become the world's most widely used psychostimulant. The scope of this article is to present the results of an analysis of publications concerning the use of Methylphenidate in Brazil over a decade. It seeks to understand how the information is presented or omitted in the different printed materials. For the analysis, the most important Brazilian psychiatric journals as well as major Brazilian newspapers and magazines for the general public for the 1998-2008 period were consulted. One important point that resulted

  3. Acute effects of 3,4-methylenedioxymethamphetamine and methylphenidate on circulating steroid levels in healthy subjects.

    Science.gov (United States)

    Seibert, Julia; Hysek, Cédric M; Penno, Carlos A; Schmid, Yasmin; Kratschmar, Denise V; Liechti, Matthias E; Odermatt, Alex

    2014-01-01

    3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors. © 2014 S. Karger AG, Basel.

  4. Methylphenidate and Atomoxetine Inhibit Social Play Behavior through Prefrontal and Subcortical Limbic Mechanisms in Rats

    Science.gov (United States)

    Achterberg, E.J. Marijke; van Kerkhof, Linda W.M.; Damsteegt, Ruth; Trezza, Viviana

    2015-01-01

    Positive social interactions during the juvenile and adolescent phases of life, in the form of social play behavior, are important for social and cognitive development. However, the neural mechanisms of social play behavior remain incompletely understood. We have previously shown that methylphenidate and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), suppress social play in rats through a noradrenergic mechanism of action. Here, we aimed to identify the neural substrates of the play-suppressant effects of these drugs. Methylphenidate is thought to exert its effects on cognition and emotion through limbic corticostriatal systems. Therefore, methylphenidate was infused into prefrontal and orbitofrontal cortical regions as well as into several subcortical limbic areas implicated in social play. Infusion of methylphenidate into the anterior cingulate cortex, infralimbic cortex, basolateral amygdala, and habenula inhibited social play, but not social exploratory behavior or locomotor activity. Consistent with a noradrenergic mechanism of action of methylphenidate, infusion of the noradrenaline reuptake inhibitor atomoxetine into these same regions also reduced social play. Methylphenidate administration into the prelimbic, medial/ventral orbitofrontal, and ventrolateral orbitofrontal cortex, mediodorsal thalamus, or nucleus accumbens shell was ineffective. Our data show that the inhibitory effects of methylphenidate and atomoxetine on social play are mediated through a distributed network of prefrontal and limbic subcortical regions implicated in cognitive control and emotional processes. These findings increase our understanding of the neural underpinnings of this developmentally important social behavior, as well as the mechanism of action of two widely used treatments for ADHD. PMID:25568111

  5. Methylphenidate and brain activity in a reward/conflict paradigm: role of the insula in task performance.

    Science.gov (United States)

    Ivanov, Iliyan; Liu, Xun; Clerkin, Suzanne; Schulz, Kurt; Fan, Jin; Friston, Karl; London, Edythe D; Schwartz, Jeffrey; Newcorn, Jeffrey H

    2014-06-01

    Psychostimulants, such as methylphenidate, are thought to improve information processing in motivation-reward and attention-activation networks by enhancing the effects of more relevant signals and suppressing those of less relevant ones; however the nature of such reciprocal influences remains poorly understood. To explore this question, we tested the effect of methylphenidate on performance and associated brain activity in the Anticipation, Conflict, Reward (ACR) task. Sixteen healthy adult volunteers, ages 21-45, were scanned twice using functional magnetic resonance imaging (fMRI) as they performed the ACR task under placebo and methylphenidate conditions. A three-way repeated measures analysis of variance, with cue (reward vs. non-reward), target (congruent vs. incongruent) and medication condition (methylphenidate vs. placebo) as the factors, was used to analyze behaviors on the task. Blood oxygen level dependent (BOLD) signals, reflecting task-related neural activity, were evaluated using linear contrasts. Participants exhibited significantly greater accuracy in the methylphenidate condition than the placebo condition. Compared with placebo, the methylphenidate condition also was associated with lesser task-related activity in components of attention-activation systems irrespective of the reward cue, and less task-related activity in components of the reward-motivation system, particularly the insula, during reward trials irrespective of target difficulty. These results suggest that methylphenidate enhances task performance by improving efficiency of information processing in both reward-motivation and in attention-activation systems. Published by Elsevier B.V.

  6. Oral and transdermal DL-methylphenidate-ethanol interactions in C57BL/6J mice: potentiation of locomotor activity with oral delivery.

    Science.gov (United States)

    Bell, Guinevere H; Griffin, William C; Patrick, Kennerly S

    2011-12-01

    Many abusers of dl-methylphenidate co-abuse ethanol. The present animal study examined behavioral effects of oral or transdermal DL-methylphenidate in combination with a high, depressive dose of ethanol to model co-abuse. Locomotor activity of C57BL/6J mice was recorded for 3 h following dosing with either oral DL-methylphenidate (7.5 mg/kg) or transdermal DL-methylphenidate (Daytrana®;1/4 of a 12.5 cm(2) patch; mean dose 7.5 mg/kg), with or without oral ethanol (3 g/kg). Brains were enantiospecifically analyzed for the isomers of methylphenidate and the transesterification metabolite ethylphenidate. An otherwise depressive dose of ethanol significantly potentiated oral DL-methylphenidate induced increases in total distance traveled for the first 100 min (pbrain D-methylphenidate concentrations were significantly elevated by ethanol in both the oral (65% increase) and transdermal (88% increase) groups. The corresponding L-ethylphenidate concentrations were 10 ng/g and 130 ng/g. Stimulant induced motor activity in rodents may correlate with abuse liability. Potentiation of DL-methylphenidate motor effects by concomitant ethanol carries implications regarding increased abuse potential of DL-methylphenidate when combined with ethanol. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Methylphenidate, cognition, and epilepsy: A 1-month open-label trial.

    Science.gov (United States)

    Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford J

    2017-12-01

    Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well-validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention-deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open-label follow-up to a double-blind, placebo-controlled, single-dose study. Thirty epilepsy patients entered a 1-month open-label methylphenidate trial after a double-blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20-40 mg/day. Primary measures included: Conners' Continuous Performance Test (CPT), Symbol-Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI-II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side-Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy-89 (QOLIE-89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently. Twenty-eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20-60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate for SDMT, MCG, CPT (the ability to discriminate between targets and nontargets [d'] hits, hit reaction time standard deviation, omissions, and commissions), and QOLIE subscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002). BDI-II and additional subscales also improved, at a lower level of statistical significance. Effect

  8. Anxiety and methylphenidate in attention deficit hyperactivity disorder: a double-blind placebo-drug trial.

    Science.gov (United States)

    Moshe, Keren; Karni, Avi; Tirosh, Emanuel

    2012-09-01

    To examine the relationship between attention and anxiety and the response to methylphenidate in children with attention deficit hyperactivity disorder (ADHD), a total of 57 boys, between the ages of 7-12 years, were assessed for their attention and level of anxiety. Methylphenidate was administered for a week in a randomized double-blind drug/placebo-drug cross-over design. The levels of anxiety were evenly distributed between the inattentive and hyperactive/impulsive types. Anxiety was significantly correlated with the attention as reported by both teachers and parents. The response to methylphenidate was inversely correlated with the reported anxiety level only in boys with the hyperactive/impulsive and combined types. The higher the level of anxiety, the lower level of response to methylphenidate was observed. In the assessment and treatment of children with ADHD, the level of anxiety should be evaluated and taken into account while planning and monitoring treatment regiment.

  9. An Open-Label, Randomized Trial of Methylphenidate and Atomoxetine Treatment in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Shang, Chi-Yung; Pan, Yi-Lei; Lin, Hsiang-Yuan; Huang, Lin-Wan; Gau, Susan Shur-Fen

    2015-09-01

    The efficacy of both methylphenidate and atomoxetine has been established in placebo-controlled trials. The present study aimed to directly compare the efficacy of methylphenidate and atomoxetine in improving symptoms among children with attention-deficit/hyperactivity disorder (ADHD). The study sample included 160 drug-naïve children and adolescents 7-16 years of age, with DSM-IV-defined ADHD, randomly assigned to osmotic-release oral system methylphenidate (OROS-methylphenidate) (n=80) and atomoxetine (n=80) in a 24 week, open-label, head-to-head clinical trial. The primary efficacy measure was the score of the ADHD Rating Scale-IV Parents Version: Investigator Administered and Scored (ADHD-RS-IV). The secondary efficacy measures included the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) and Chinese Swanson, Nolan, and Pelham IV scale (SNAP-IV), based on the ratings of investigators, parents, teachers, and subjects. At week 24, mean changes in ADHD-RS-IV Inattention scores were 13.58 points (Cohen's d, -3.08) for OROS-methylphenidate and 12.65 points (Cohen's d, -3.05) for atomoxetine; and mean changes in ADHD-RS-IV Hyperactivity-Impulsivity scores were 10.16 points (Cohen's d, -1.75) for OROS-methylphenidate and 10.68 points (Cohen's d, -1.87) for atomoxetine. In terms of parent-, teacher-, and self-ratings on behavioral symptoms, both of the two treatment groups significantly decreased on the SNAP-IV scores at the end-point, with effect sizes ranging from 0.9 to 0.96 on the Inattention subscale and from 0.61 to 0.8 on the Hyperactivity/Impulsivity subscale for OROS-methylphenidate; and from 0.51 to 0.88 on the Inattention subscale and from 0.29 to 0.57 on the Hyperactivity/Impulsivity subscale for atomoxetine. No statistically significant differences between treatment groups were observed on the outcome measures. Vomiting, somnolence, and dizziness were reported more often for atomoxetine than for OROS-methylphenidate, whereas insomnia was reported

  10. Comparison of Stimdate with Ritalin in Children and Adolescents with Attention Deficit Hyperactivity Disorder: a Double-Blind, Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Najmeh Khosrovan Mehr

    2009-02-01

    Full Text Available "nObjectives: The aim of this randomized clinical trial was to assess the efficacy of stimdate compared to ritalin in the treatment of children with attention deficit hyperactivity disorder (ADHD. "nMethod: Sixty four subjects (45 boys and 15 girls aged 5-13 who were diagnosed with ADHD based on (DSM-IV-TR criteria were selected for this study. The subjects were randomly assigned to two groups: one group with 30 subjects received stimdate and the other group of 30 subjects received ritalin for 6 weeks. Treatment outcomes were assessed using the Attention Deficit Hyperactivity Rating Scale administered at baseline and on weeks 2, 4 and 6 following the treatment. A two-way repeated measures analysis of variance (time- treatment interaction was used. "nResults: There were no significant differences between sex, age, weight, and ethnicity of the participants in the 2 groups. Both groups showed a significant improvement during the 6 weeks of the treatment period, and this improvement was due to the parents' ADHD Rating Scale during the treatment. "nConclusion: Based on the results of this study, no significant difference was observed between the two medications, and it seems both drugs behave[M1]  in a similar way. In addition, stimdate appears to be effective and well tolerated for ADHD in children and adolescents in Iran. "n 

  11. Effects of Methylphenidate on Resting-State Functional Connectivity of the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction

    Energy Technology Data Exchange (ETDEWEB)

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

    2013-08-01

    Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems–level effects of methylphenidate in this population have not yet been described. To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction.

  12. Working Memory after Traumatic Brain Injury: The Neural Basis of Improved Performance with Methylphenidate.

    Science.gov (United States)

    Manktelow, Anne E; Menon, David K; Sahakian, Barbara J; Stamatakis, Emmanuel A

    2017-01-01

    Traumatic brain injury (TBI) often results in cognitive impairments for patients. The aim of this proof of concept study was to establish the nature of abnormalities, in terms of activity and connectivity, in the working memory network of TBI patients and how these relate to compromised behavioral outcomes. Further, this study examined the neural correlates of working memory improvement following the administration of methylphenidate. We report behavioral, functional and structural MRI data from a group of 15 Healthy Controls (HC) and a group of 15 TBI patients, acquired during the execution of the N-back task. The patients were studied on two occasions after the administration of either placebo or 30 mg of methylphenidate. Between group tests revealed a significant difference in performance when HCs were compared to TBI patients on placebo [ F (1, 28) = 4.426, p performance demonstrated the most benefit from methylphenidate. Changes in the TBI patient activation levels in the Left Cerebellum significantly and positively correlated with changes in performance ( r = 0.509, df = 13, p = 0.05). Whole-brain connectivity analysis using the Left Cerebellum as a seed revealed widespread negative interactions between the Left Cerebellum and parietal and frontal cortices as well as subcortical areas. Neither the TBI group on methylphenidate nor the HC group demonstrated any significant negative interactions. Our findings indicate that (a) TBI significantly reduces the levels of activation and connectivity strength between key areas of the working memory network and (b) Methylphenidate improves the cognitive outcomes on a working memory task. Therefore, we conclude that methylphenidate may render the working memory network in a TBI group more consistent with that of an intact working memory network.

  13. Deviant patterns of methylphenidate use in adults

    DEFF Research Database (Denmark)

    Rasmussen, Lotte; Zoëga, Helga; Hallas, Jesper

    2015-01-01

    of drugs used in addictive disorders (OR2 2.08) or opioids (OR2 1.75). Sensitivity analyses revealed that the number of different prescribers alone does not seem to effectively identify deviant users of methylphenidate. CONCLUSION: We have identified characteristics associated with deviant patterns...

  14. Prescribing Patterns of Methylphenidate and Atomoxetine for ...

    African Journals Online (AJOL)

    Purpose: To determine the prescribing pattern of methylphenidate and atomoxetine to patients with. Attention-Deficit/Hyperactivity Disorder (ADHD) in South Africa. Methods: A retrospective, cross-sectional pharmacoepidemiological study was conducted based on the data from a medical aid administrator in South Africa for ...

  15. Prescribing Patterns of Methylphenidate and Atomoxetine for ...

    African Journals Online (AJOL)

    Purpose: To determine the prescribing pattern of methylphenidate and atomoxetine to patients with Attention-Deficit/Hyperactivity Disorder (ADHD) in South Africa. Methods: A retrospective, cross-sectional pharmacoepidemiological study was conducted based on the data from a medical aid administrator in South Africa for ...

  16. Methylphenidate Has Superior Efficacy Over Parent-Child Interaction Therapy for Preschool Children with Disruptive Behaviors.

    Science.gov (United States)

    van der Veen-Mulders, Lianne; van den Hoofdakker, Barbara J; Nauta, Maaike H; Emmelkamp, Paul; Hoekstra, Pieter J

    2018-02-01

    To compare the effectiveness between parent-child interaction therapy (PCIT) and methylphenidate in preschool children with attention-deficit/hyperactivity disorder (ADHD) symptoms and disruptive behaviors who had remaining significant behavior problems after previous behavioral parent training. We included 35 preschool children, ranging in age between 3.4 and 6.0 years. Participants were randomized to PCIT (n = 18) or methylphenidate (n = 17). Outcome measures were maternal ratings of the intensity and number of behavior problems and severity of ADHD symptoms. Changes from pretreatment to directly posttreatment were compared between groups using two-way mixed analysis of variance. We also made comparisons of both treatments to a nonrandomized care as usual (CAU) group (n = 17) regarding intensity and number of behavior problems. All children who started one of the treatments were included in the analyses. Mothers reported a significantly more decreased intensity of behavior problems after methylphenidate (pre-post effect size d = 1.50) compared with PCIT (d = 0.64). ADHD symptoms reduced significantly over time only after methylphenidate treatment (d = 0.48) and not after PCIT. Changes over time of children in the CAU treatment were nonsignificant. Although methylphenidate was more effective than PCIT, both interventions may be effective in the treatment of preschool children with disruptive behaviors. Our findings are preliminary as our sample size was small and the use of methylphenidate in preschool children lacks profound safety data as reflected by its off-label status. More empirical support is needed from studies with larger sample sizes.

  17. Atomoxetine/Methylphenidate Effects on Social Play Behavior

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2015-02-01

    Full Text Available Researchers at Utrecht University, The Netherlands, and University “Roma Tre,” Rome, Italy, studied the neural substrates of the previously identified social play-suppressant effects of methylphenidate (MPH and atomoxetine, drugs widely used for the treatment of attention-deficit hyperactivity disorder (ADHD.

  18. Methylphenidate use and poly-substance use among ...

    African Journals Online (AJOL)

    2016-03-22

    Mar 22, 2016 ... Methylphenidate hydrochloride (MPH) is used in the treatment of attention deficit hyperactivity disorder (ADHD). Prescriptions for and usage of MPH products have increased sharply since the early 1990s with accompanying concerns about potential misuse.1,2,3 While peer pressure and experimentation ...

  19. Acute effects of methylphenidate on impulsivity and attentional behavior among adolescents comorbid for ADHD and conduct disorder.

    Science.gov (United States)

    Dougherty, Donald M; Olvera, Rene L; Acheson, Ashley; Hill-Kapturczak, Nathalie; Ryan, Stacy R; Mathias, Charles W

    2016-12-01

    Adolescents with Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) experience deficits in neuropsychological measures of attention, inhibition, and reward processes. Methylphenidate treatment for ADHD and CD has acute effects on these processes. Some of these same aspects of performance are separately described in the Behavioral Model of Impulsivity, which uses a modified approach to measurement. This study characterized the acute effects of methylphenidate attention, initiation, inhibition, and reward processes described in this model of impulsivity. Thirty-one adolescents from the United States of America with comorbid ADHD and CD completed measures of impulsivity (response initiation, response inhibition, and consequence) and attention following placebo, 20 mg, and 40 mg of a long-acting dose of methylphenidate. Methylphenidate effects on attentional performance was more robust than on any of the measures of impulsivity. Adolescent performance from this behavioral perspective is interpreted in the context of divergence from previous neuropsychological tests of acute methylphenidate effects. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  20. Methylphenidate during early consolidation affects long-term associative memory retrieval depending on baseline catecholamines.

    Science.gov (United States)

    Wagner, Isabella C; van Buuren, Mariët; Bovy, Leonore; Morris, Richard G; Fernández, Guillén

    2017-02-01

    Synaptic memory consolidation is thought to rely on catecholaminergic signaling. Eventually, it is followed by systems consolidation, which embeds memories in a neocortical network. Although this sequence was demonstrated in rodents, it is unclear how catecholamines affect memory consolidation in humans. Here, we tested the effects of catecholaminergic modulation on synaptic and subsequent systems consolidation. We expected enhanced memory performance and increased neocortical engagement during delayed retrieval. Additionally, we tested if this effect was modulated by individual differences in a cognitive proxy measure of baseline catecholamine synthesis capacity. Fifty-three healthy males underwent a between-subjects, double-blind, placebo-controlled procedure across 2 days. On day 1, subjects studied and retrieved object-location associations and received 20 mg of methylphenidate or placebo. Drug intake was timed so that methylphenidate was expected to affect early consolidation but not encoding or retrieval. Memory was tested again while subjects were scanned three days later. Methylphenidate did not facilitate memory performance, and there was no significant group difference in activation during delayed retrieval. However, memory representations differed between groups depending on baseline catecholamines. The placebo group showed increased activation in occipito-temporal regions but decreased connectivity with the hippocampus, associated with lower baseline catecholamine synthesis capacity. The methylphenidate group showed stronger activation in the postcentral gyrus, associated with higher baseline catecholamine synthesis capacity. Altogether, methylphenidate during early consolidation did not foster long-term memory performance, but it affected retrieval-related neural processes depending on individual levels of baseline catecholamines.

  1. Metabolism of methylphenidate in dog and rat

    International Nuclear Information System (INIS)

    Egger, H.; Bartlett, F.; Dreyfuss, R.; Karliner, J.

    1981-01-01

    The urinary metabolites of methylphenidate in the dog and rat were investigated. After oral administration of 14C-labeled methylphenidate, approximately 86% and 63% of the dose was recovered in the urine of the dog and rat, respectively. Less than 1% of the dose was excreted as unchanged drug. Metabolism involved oxidation, hydrolysis, and conjugation processes. The primary hydrolytic product was alpha-phenyl-2-piperidineacetic acid (24%, dog; 35-40%, rat). The primary metabolites of oxidation were methyl 6-oxo-alpha-phenyl-2-piperidineacetate (3%, dog; 1.5%, rat) and the glucuronide of alpha-(p-hydroxyphenyl)-2-piperidineacetic acid (10%, rat). The former also underwent extensive biotransformation, including: 1) hydrolysis to the lactam acid (27%, dog; 7-10%, rat) and subsequent carboxylic acid O-glucuronidation (15%, dog); or 2) hydroxylation at the 5-position (1%, dog; 2%, rat) and subsequent hydrolysis (4%, dog; 15-17%, rat); or 3) 5-O-glucuronidation (12%, dog). Additional minor metabolites from methyl-6-oxo-alpha-phenyl-2-piperidineacetate were the phenolic O-glucuronide of methyl alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetate (1%, dog), and the 4-O-glucuronide of methyl 4-hydroxy-6-oxo-alpha-phenyl-2-piperidineacetate (1%, dog), and the taurine amide conjugate of alpha-(p-hydroxyphenyl)-6-oxo-2-piperidineacetic acid (1%, dog). Additional products from methylphenidate conjugation included methyl 1-carbamoyl-alpha-phenyl-2-piperidineacetate (1%, dog or rat) and its carboxylic acid hydrolysis product (1%, rat). The chirality of the major metabolites isolated from dog urine showed that metabolism was partially stereoselective in all investigated cases, except in the formation of alpha-phenyl-2-piperidineacetic acid

  2. Attention-deficit/hyperactivity disorder: the impact of methylphenidate on working memory, inhibition capacity and mental flexibility.

    Science.gov (United States)

    Bolfer, Cristiana; Pacheco, Sandra Pasquali; Tsunemi, Miriam Harumi; Carreira, Walter Souza; Casella, Beatriz Borba; Casella, Erasmo Barbante

    2017-04-01

    To compare children with attention-deficit/hyperactivity disorder (ADHD), before and after the use of methylphenidate, and a control group, using tests of working memory, inhibition capacity and mental flexibility. Neuropsychological tests were administrated to 53 boys, 9-12 years old: the WISC-III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests. The case group included 23 boys with ADHD, who were combined type, treatment-naive, and with normal intelligence without comorbidities. The control group (n = 30) were age and gender matched. After three months on methylphenidate, the ADHD children were retested. The control group was also retested after three months. Before treatment, ADHD children had lower scores than the control group on the tests (p ≤ 0.001) and after methylphenidate had fewer test errors than before (p ≤ 0.001). Methylphenidate treatment improves the working memory, inhibitory control and mental flexibility of ADHD boys.

  3. Management of attention-deficit hyperactivity disorder in adults: focus on methylphenidate hydrochloride

    Directory of Open Access Journals (Sweden)

    Rajasree Nair

    2009-08-01

    Full Text Available Rajasree Nair, Shannon B MossBaylor Family Medicine Residency at Garland, Garland, Texas, USAAbstract: Attention-deficit hyperactivity disorder (ADHD is one of the most common psychiatric disorders in young adults and causes significant psychosocial impairment and economic burden to society. Because of the paucity of long-term evidence and lack of national guidelines for diagnosis and management of adult ADHD, most of the data are based on experience derived from management of childhood ADHD. This article reviews the current evidence for the diagnosis and management of adult ADHD with special emphasis on the role of methylphenidate hydrochloride preparations in its treatment. Methylphenidate hydrochloride, a stimulant that acts through the dopaminergic and adrenergic pathways, has shown more than 75% efficacy in controlling the symptoms of adult ADHD. Although concern for diversion of the drug exists, recent data have shown benefits in preventing substance use disorders in patients with adult ADHD.Keywords: adult ADHD, treatment, stimulants, methylphenidate hydrochloride

  4. Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

    International Nuclear Information System (INIS)

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Kollins, S.H.; Wigal, T.L.; Newcorn, J.H.; Telang, F.W.; Fowler, J.S.; Logan, J.; Wong, C.T.; Swanson, J.M.

    2012-01-01

    Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and ( 11 C)raclopride (D 2 /D 3 receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D 2 /D 3 receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

  5. Methylphenidate-Elicited Dopamine Increases in Ventral Striatum Are Associated with Long-Term Symptom Improvement in Adults with Attention Deficit Hyperactivity Disorder

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Wang G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Kollins, S.H.; Wigal, T.L.; Newcorn, J.H.; Telang, F.W.; Fowler, J.S.; Logan, J.; Wong, C.T.; Swanson, J.M.

    2012-01-18

    Stimulant medications, such as methylphenidate, which are effective treatments for attention deficit hyperactivity disorder (ADHD), enhance brain dopamine signaling. However, the relationship between regional brain dopamine enhancement and treatment response has not been evaluated. Here, we assessed whether the dopamine increases elicited by methylphenidate are associated with long-term clinical response. We used a prospective design to study 20 treatment-naive adults with ADHD who were evaluated before treatment initiation and after 12 months of clinical treatment with a titrated regimen of oral methylphenidate. Methylphenidate-induced dopamine changes were evaluated with positron emission tomography and [{sup 11}C]raclopride (D{sub 2}/D{sub 3} receptor radioligand sensitive to competition with endogenous dopamine). Clinical responses were assessed using the Conners Adult ADHD Rating Scale and revealed a significant reduction in symptoms of inattention and hyperactivity with long-term methylphenidate treatment. A challenge dose of 0.5 mg/kg intravenous methylphenidate significantly increased dopamine in striatum (assessed as decreases in D{sub 2}/D{sub 3} receptor availability). In the ventral striatum, these dopamine increases were associated with the reductions in ratings of symptoms of inattention with clinical treatment. Statistical parametric mapping additionally showed dopamine increases in prefrontal and temporal cortices with intravenous methylphenidate that were also associated with decreases in symptoms of inattention. Our findings indicate that dopamine enhancement in ventral striatum (the brain region involved with reward and motivation) was associated with therapeutic response to methylphenidate, further corroborating the relevance of the dopamine reward/motivation circuitry in ADHD. It also provides preliminary evidence that methylphenidate-elicited dopamine increases in prefrontal and temporal cortices may also contribute to the clinical response.

  6. Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography

    International Nuclear Information System (INIS)

    Booij, J.; Korn, P.; Linszen, D.H.; Royen, E.A. van

    1997-01-01

    This double-blind, placebo-controlled study assessed pharmacologically induced endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in endogenous DA release after injection of the psychostimulant drug methylphenidate were evaluated by single-photon emission tomography (SPET) and constant infusion of iodine-123 iodobenzamide ([ 123 I[IBZM), a D 2 receptor radioligand that is sensitive to endogenous DA release. Methylphenidate induced displacement of striatal [ 123 I[IBZM binding, resulting in a significantly decrease in the specific to non-specific [ 123 I[IBZM uptake ratio (average: 8.6%) in comparison with placebo (average: -1.9%). Moreover, injection of methylphenidate induced significant behavioural responses on the following items: excitement, anxiety, tension, and mannerisms and posturing. The results of this study demonstrate the feasibility of using constant infusion of [ 123 I[IBZM and SPET imaging to measure endogenous DA release after methylphenidate challenge and to investigate neurochemical aspects of behaviour. (orig.). With 2 figs., 1 tab

  7. Methylphenidate intoxications in children and adults: exposure circumstances and evidence-based dose threshold for pre-hospital triage

    NARCIS (Netherlands)

    Hondebrink, Laura; Rietjens, Saskia J; Hunault, Claudine C; Pereira, Rob R; Kelleci, Nuriye; Yasar, Gulhan; Ghebreslasie, Ariam; Lo-A-Foe, Cindy; De Vries, Irma; Meulenbelt, Jan

    2015-01-01

    CONTEXT: Methylphenidate intoxications mostly have a relatively mild course, although serious complications can occur. OBJECTIVE: We aimed to characterize methylphenidate exposures and reassess our current dose threshold for hospital referral (2 mg/kg). METHODS: In a prospective follow-up study, we

  8. Methylphenidate intoxications in children and adults : Exposure circumstances and evidence-based dose threshold for pre-hospital triage

    NARCIS (Netherlands)

    Hondebrink, Laura; Rietjens, Saskia J.; Hunault, Claudine C.; Pereira, Rob R.; Kelleci, Nuriye; Yasar, Gulhan; Ghebreslasie, Ariam; Lo-A-Foe, Cindy; De Vries, Irma; Meulenbelt, Jan

    Context. Methylphenidate intoxications mostly have a relatively mild course, although serious complications can occur. Objective. We aimed to characterize methylphenidate exposures and reassess our current dose threshold for hospital referral (2 mg/kg). Methods. In a prospective follow-up study, we

  9. Early long-term exposure with caffeine induces cross-sensitization to methylphenidate with involvement of DARPP-32 in adulthood of rats.

    Science.gov (United States)

    Boeck, Carina R; Marques, Virgínia B; Valvassori, Samira S; Constantino, Leandra C; Rosa, Daniela V F; Lima, Fabrício F; Romano-Silva, Marco A; Quevedo, João

    2009-09-01

    Chronic ingestion of caffeine causes dependence and sleep disturbance in children and adolescents. In rodents, the administration of caffeine may produce behavioral cross-sensitization to some psychostimulants, such as dopaminergic psychoactive drugs. Methylphenidate (MPH; Ritalin) is a psychostimulant used in pediatric- and adult human populations to manage the symptoms associated with attention-deficit hyperactivity disorder (ADHD). Previous studies have suggested that dopamine- and cAMP-regulated phosphoproteins of 32 kDa (DARPP-32) participate in the manifestation of behavioral activity following ingestion of caffeine or MPH. The aim of the present study was to evaluate whether long-term administration of low doses of caffeine in rodents during their adolescence induces cross-sensitization to MPH challenge in their adulthood and investigate the involvement of DARPP-32 in this model. Young rats (P25) consumed water or caffeine (0.3 g/L; mean consumption was 7.5 mg/day/kg) for 28 days. The caffeine consumption was then suspended for 14 days (washout period) when the animals received saline solution or MPH (1, 2, or 10 mg/kg) (P67) intraperitoneally. The locomotor activity of these rats was assessed using the open-field test, following which the immunocontent of DARPP-32 was evaluated in samples of their prefrontal cortex, striatum, or hippocampus. Rats chronically exposed to caffeine in their adolescent period and to inactive doses of MPH (1mg/kg) in adulthood showed augmented locomotor activity. The behavioral effect observed was accompanied by increased levels of DARPP-32 in the striatum and prefrontal cortex compared to control groups (saline or caffeine). However, no alteration caused by these treatments was noted in the hippocampus. In conclusion, chronic caffeine exposure induces likely long-term cross-sensitization to MPH in a DARPP-32-dependent pathway.

  10. Procedure for the Disposal of Controlled Medication in the School Setting.

    Science.gov (United States)

    Kleinschmidt, Karen A

    2015-09-01

    The disposal of controlled medication left in the school nurse office is problematic for school nurses. Medications are left for a variety of reasons: students transfer out of the district, state, or country; parents and guardians lack transportation to pick up their child's medication; and some families simply forget. The medications of concern are controlled substances, primarily Schedule II medications including Adderall, Concerta, and methylphenidate. Over time, these medications begin to accumulate in a school nurse's office. Schools should establish procedures that address safe disposal of controlled medications as well as liability protection for the school nursing staff. This article will discuss a procedure created for the Christina School District in conjunction with a state board of pharmacy and subsequently shared with other school nurses in the State of Delaware. © 2015 The Author(s).

  11. Use of methylphenidate among medical students: a systematic review

    Directory of Open Access Journals (Sweden)

    Guilherme Finger

    2013-06-01

    Full Text Available OBJECTIVE: To review the effects of methylphenidate on cognitive enhancement, memory, and performance in medical students. METHODS: A review of four databases (LILACS, PubMed, ScienceDirect, and SciELO, analyzing the title and of all articles published between 1990 and 2012 in English, Portuguese, and Spanish. Selected articles were read in entirety, including in the review those that met the established criteria. RESULTS: The prevalence of use among medical students reached 16%, with no gender difference. Most students began using the drug after entering the university, and the reasons cited to justify it are related to enhancing academic performance. CONCLUSION: There is no evidence in the literature that the use of methylphenidate is beneficial in terms of memory or learning. The drug simply increases wakefulness and alertness, reducing the time of sleep.

  12. Cost-Effectiveness of Extended-Release Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder Sub-Optimally Treated with Immediate Release Methylphenidate

    NARCIS (Netherlands)

    van der Schans, Jurjen; Kotsopoulos, Niko; Hoekstra, Pieter J.; Hak, Eelko; Postma, Maarten J.

    2015-01-01

    BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH) is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at

  13. Safety of Methylphenidate and Atomoxetine in Children with Attention-Deficit/Hyperactivity Disorder (ADHD): Data from the Italian National ADHD Registry.

    Science.gov (United States)

    Cortese, Samuele; Panei, Pietro; Arcieri, Romano; Germinario, Elena A P; Capuano, Annalisa; Margari, Lucia; Chiarotti, Flavia; Curatolo, Paolo

    2015-01-01

    The aim of this study was to assess the type and frequency of adverse events (AEs) in children with attention-deficit/hyperactivity disorder (ADHD) treated with methylphenidate or atomoxetine over a 5-year period in a large naturalistic study. We draw on data from the Italian ADHD Registry, a national database for postmarketing phase IV pharmacovigilance of ADHD medications across 90 centers. AEs were defined as severe or mild as per the classification of the Italian Medicines Agency. AE frequency in the two treatment groups was compared using incidence rates per 100 person-years (IR100PY) and incidence rate ratios (IRRs). Mantel-Haenszel adjusted IRRs were calculated to control for psychiatric comorbidity. A total of 1350 and 753 participants (aged 6-18 years, mean age 10.7 ± 2.8) were treated with methylphenidate and atomoxetine, respectively, from 2007 to 2012. Ninety participants (7 %) were switched from methylphenidate to atomoxetine, and 138 (18 %) from atomoxetine to methylphenidate. Thirty-seven children treated with atomoxetine and 12 with methylphenidate had their medication withdrawn. Overall, 645 patients (26.8 %) experienced at least one mild AE (including decreased appetite and irritability, for both drugs) and 95 patients (3.9 %) experienced at least one severe AE (including severe gastrointestinal events). IR100PY were significantly higher in the atomoxetine-treated group compared with the methylphenidate-treated group for a number of mild and severe AEs and for any severe or mild AEs. After controlling for comorbidities, IRR was still significantly higher in the atomoxetine group compared with the methylphenidate group for a number of mild (decreased appetite, weight loss, abdominal pain, dyspepsia, stomach ache, irritability, mood disorder and dizziness) and severe (gastrointestinal, neuropsychiatric, and cardiovascular) AEs. In this naturalistic study, methylphenidate had a better safety profile than atomoxetine.

  14. Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila

    2015-01-01

    Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

  15. Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Padala, Prasad R; Padala, Kalpana P; Lensing, Shelly Y; Ramirez, Daniel; Monga, Varun; Bopp, Melinda M; Roberson, Paula K; Dennis, Richard A; Petty, Frederick; Sullivan, Dennis H; Burke, William J

    2018-02-01

    Apathy is a common behavioral problem in Alzheimer's disease. Apathy has profound consequences, such as functional impairment, higher service utilization, higher caregiver burden, and increased mortality. The authors' objective was to study the effects of methylphenidate on apathy in Alzheimer's disease. A 12-week, prospective, double-blind, randomized, placebo-controlled trial (methylphenidate versus placebo) was conducted in community-dwelling veterans (N=60) with mild Alzheimer's disease. The primary outcome for apathy (Apathy Evaluation Scale-Clinician) and secondary outcomes for cognition (Mini-Mental State Examination, Modified Mini-Mental State Examination), functional status (activities of daily living, instrumental activities of daily living), improvement and severity (Clinical Global Impressions Scale [CGI]), caregiver burden (Zarit Burden Scale), and depression (Cornell Scale for Depression in Dementia) were measured at baseline and at 4, 8, and 12 weeks. Participants were all men (77 years old, SD=8). After adjusting for baseline, the methylphenidate group had significantly greater improvement in apathy than the placebo group at 4 weeks, 8 weeks, and 12 weeks. At 12 weeks, there was also greater improvement in cognition, functional status, caregiver burden, CGI scores, and depression in the methylphenidate group compared with the placebo group. Methylphenidate improved apathy in a group of community-dwelling veterans with mild Alzheimer's disease. Methylphenidate also improved cognition, functional status, caregiver burden, CGI scores, and depression.

  16. Prescribing patterns of methylphenidate in a South African patient ...

    African Journals Online (AJOL)

    ADHD) in children. The primary aim of the study was to investigate the prescribing patterns of methylphenidate of a medical aid patient population in a private sector and to compare the results with previous studies. An exposure cohort drug ...

  17. Comparison of duloxetine and methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Nasrin Dodangi

    2016-06-01

    Full Text Available Background: Attention-deficit/hyperactivity disorder (ADHD is a common and mostly chronic mental health condition that affects children, adolescents, and adults. Stimulants and atomoxetine are first-line agents for the treatment of ADHD. Despite the impressive track record of stimulants in the treatment of ADHD, they fail in 25% of patients due to lack of efficacy or the emergence of unwanted side effects. Accordingly, this study carried out to compare efficacy and safety of duloxetine (a serotonin and norepinephrine reuptake inhibitor and methylphenidate (a short acting stimulant in the treatment of children with attention-deficit/hyperactivity disorder. Methods: Twenty-four children diagnosed with ADHD participated in this 6 weeks open clinical trial. Patients were between 6 to 11 years old that had been referred to psychiatry clinic at Akhavan and Rofide Medical and Rehabilitation Center in Tehran from September 2012 to July 2014. Diagnosis was made by two child psychiatrist according to DSM-IV TR criteria. Thirteen patients received duloxetine and others received methylphenidate. Conner’ parent rating scale-revised-short form (CPRS-RS and ADHD-rating scale (ADHD-RS were used at the beginning and then each two weeks to assess efficacy of treatment. Routine laboratory tests and electrocardiogram (ECG was carried out in the beginning and end of the trial. Results: Twenty children with ADHD completed the study (Ten in methylphenidate and ten in duloxetine group. In both groups, scales of CPRS-RS and ADHD-RS were reduced from baseline to endpoint, but this reduction in methylphenidate group was significantly greater than duloxetine group (P= 0.000. The most common side effect was gastrointestinal problems in duloxetine group and anorexia in methylphenidate group. No serious side effects and no changes in laboratory and ECG indexes were seen in both groups. Conclusion: Duloxetine is not efficacious as well as methylphenidate in treatment of

  18. Dextroamphetamine and Methylphenidate in the Treatment of Hyperactive/Agressive Children

    Science.gov (United States)

    Winsberg, Bertrand G.; And Others

    1974-01-01

    Studied was the comparative effectiveness of dextroamphetamine and methylphenidate for the treatment of severe behavior disorders among 18 children (from 5 to 10 1/2 years of age) hospitalized for neuropsychiatric conditions. (Author)

  19. ADHD in childhood epilepsy: Clinical determinants of severity and of the response to methylphenidate.

    Science.gov (United States)

    Rheims, Sylvain; Herbillon, Vania; Villeneuve, Nathalie; Auvin, Stéphane; Napuri, Silvia; Cances, Claude; Berquin, Patrick; Castelneau, Pierre; Nguyen The Tich, Sylvie; Villega, Frédéric; Isnard, Hervé; Nabbout, Rima; Gaillard, Ségolène; Mercier, Catherine; Kassai, Behrouz; Arzimanoglou, Alexis

    2016-07-01

    Attention-deficit/hyperactivity disorder (ADHD) is commonly observed in children with epilepsy. However, factors associated with the development of ADHD and which might help to guide its therapeutic management, remain an issue of debate. We conducted a multicenter prospective observational study that included children, aged 6-16 years, with both epilepsy and ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. After inclusion, patients entered a 12-16 week follow-up period during which they were either treated with methylphenidate or they did not receive specific ADHD treatment. ADHD was evaluated with the ADHD Rating Scale-IV. One hundred sixty-seven patients were included, of which 91 were seizure-free during the preinclusion baseline period. At inclusion, the ADHD Rating Scale-IV total score was 30.4 ± (standard deviation) 9.2, the inattentive subscore was 17.3 ± 4.4, and the hyperactive subscore was 13.2 ± 6.6. We did not detect any difference of ADHD Rating Scale-IV scores across patients' age or gender, age at epilepsy onset, epilepsy syndrome, seizure frequency, or number of ongoing antiepileptic drugs. Methylphenidate was initiated in 61 patients, including 55 in whom a follow-up evaluation was available. At the last follow-up, 41 patients (75%) treated with methylphenidate and 39 (42%) of those who did not received ADHD therapy demonstrated ≥25% decrease of ADHD Rating Scale-IV total score (p < 0.001). Response to methylphenidate was greater in girls but was not influenced by any epilepsy-related variables. We did not detect any epilepsy-related factor associated with the severity of ADHD. Twenty-five percent of patients did not respond to methylphenidate. A better understanding of the pathologic process that underlies ADHD development in childhood epilepsy might be required to improve therapeutic strategies. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

  20. First-Trimester In Utero Exposure to Methylphenidate

    DEFF Research Database (Denmark)

    Dideriksen, Dorthe; Pottegård, Anton; Hallas, Jesper

    2013-01-01

    published, and safety during pregnancy has not been established. We systematically reviewed available data on birth outcome after human in utero exposure to methylphenidate. Systematic searches in PubMed/Embase were performed from origin to August 2012, and data from Michigan Medicaid recipients...

  1. Non-medical use of methylphenidate among medical students of the University of the Free State

    OpenAIRE

    Jain, Roshini; Chang, Chiech; Koto, Mpho; Geldenhuys, Alden; Nichol, Richard; Joubert, Gina

    2017-01-01

    Background: Faced with demanding training programmes, medical students may be more prone to use methylphenidate for non-medical purposes in order to improve concentration, alertness and academic performance. Aim: The study aimed to investigate the prevalence of the non-medical use of methylphenidate and knowledge of this drug among undergraduate medical students of the University of the Free State. Methods: This was a cross-sectional study. A self-administered, anonymous questionnaire...

  2. The effects of surgical and chemical lesions on striatal [3H]threo-(+-)-methylphenidate binding: correlation with [3H]dopamine uptake

    International Nuclear Information System (INIS)

    Janowsky, A.; Berger, P.; Long, R.; Paul, S.M.; Schweri, M.M.; Skolnick, P.

    1985-01-01

    The specific binding of [ 3 H]threo-(+-)-methylphenidate to membranes prepared from rat striatum was significantly reduced following either surgical lesions of the medial forebrain bundle or intracerebroventricular administration of 6-hydroxydopamine. The decrease in the density of [ 3 H]threo-(+-)-methylphenidate binding sites in striatum following chemical or surgical denervation was highly correlated with the decrease in [ 3 H]dopamine uptake. In contrast, intracerebroventricular administration of 5,7-dihydroxytryptamine, AF64A, or chronic parenteral administration of reserpine did not alter either the number or apparent affinity of [ 3 H]threo-(+-)-methylphenidate binding sites. These data suggest that the specific binding sites for [ 3 H]threo-(+-)-methylphenidate in striatum are localized to dopaminergic nerve terminals, and may be associated with the dopamine transport complex. (orig.)

  3. Effects of methylphenidate on memory functions of adults with ADHD

    NARCIS (Netherlands)

    Fuermaier, Anselm B M; Tucha, Lara; Koerts, Janneke; Weisbrod, Matthias; Lange, Klaus W; Aschenbrenner, Steffen; Tucha, Oliver

    2017-01-01

    Neuropsychological research on adults with attention deficit hyperactivity disorder (ADHD) revealed considerable impairments in memory functions related to executive control. However, only limited evidence exists supporting the effects of pharmacological treatment using methylphenidate (MPH) on

  4. The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities.

    Science.gov (United States)

    Faraone, Stephen V

    2018-04-01

    Psychostimulants, including amphetamines and methylphenidate, are first-line pharmacotherapies for individuals with attention-deficit/hyperactivity disorder (ADHD). This review aims to educate physicians regarding differences in pharmacology and mechanisms of action between amphetamine and methylphenidate, thus enhancing physician understanding of psychostimulants and their use in managing individuals with ADHD who may have comorbid psychiatric conditions. A systematic literature review of PubMed was conducted in April 2017, focusing on cellular- and brain system-level effects of amphetamine and methylphenidate. The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity, which impacts executive and attentional function. Amphetamine actions include dopamine and norepinephrine transporter inhibition, vesicular monoamine transporter 2 (VMAT-2) inhibition, and monoamine oxidase activity inhibition. Methylphenidate actions include dopamine and norepinephrine transporter inhibition, agonist activity at the serotonin type 1A receptor, and redistribution of the VMAT-2. There is also evidence for interactions with glutamate and opioid systems. Clinical implications of these actions in individuals with ADHD with comorbid depression, anxiety, substance use disorder, and sleep disturbances are discussed. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.

  5. Short-Term Effects of Methylphenidate on Math Productivity in Children With Attention-Deficit/Hyperactivity Disorder are Mediated by Symptom Improvements: Evidence From a Placebo-Controlled Trial.

    Science.gov (United States)

    Kortekaas-Rijlaarsdam, Anne Fleur; Luman, Marjolein; Sonuga-Barke, Edmund; Bet, Pierre M; Oosterlaan, Jaap

    2017-04-01

    Although numerous studies report positive effects of methylphenidate on academic performance, the mechanism behind these improvements remains unclear. This study investigates the effects of methylphenidate on academic performance in children with attention-deficit/hyperactivity disorder (ADHD) and the mediating and moderating influence of ADHD severity, academic performance, and ADHD symptom improvement. Sixty-three children with ADHD participated in a double-blind placebo-controlled crossover study comparing the effects of long-acting methylphenidate and placebo. Dependent variables were math, reading, and spelling performance. The ADHD group performance was compared with a group of 67 typically developing children. Methylphenidate improved math productivity and accuracy in children with ADHD. The effect of methylphenidate on math productivity was partly explained by parent-rated symptom improvement, with greater efficacy for children showing more symptom improvement. Further, children showing below-average math performance while on placebo profited more from methylphenidate than children showing above-average math performance. The results from this study indicate positive effects of methylphenidate on academic performance, although these were limited to math abilities. In light of these results, expectations of parents, teachers, and treating physicians about the immediate effects of methylphenidate on academic improvement should be tempered. Moreover, our results implicate that positive effects of methylphenidate on math performance are in part due directly to effects on math ability and in part due to reductions in ADHD symptoms.

  6. Buspirone versus Methylphenidate in the Treatment of Attention Deficit Hyperactivity Disorder: A Double-Blind and Randomized Trial

    Science.gov (United States)

    Davari-Ashtiani, Rozita; Shahrbabaki, Mahin Eslami; Razjouyan, Katayoon; Amini, Homayoun; Mazhabdar, Homa

    2010-01-01

    The efficacy and side effects of buspirone compared with methylphenidate (MPH) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). A total of 34 children with ADHD as defined by DSM-IV-TR were randomized to buspirone or methylphenidate dosed on weight-adjusted basis at buspirone (0.5 mg/kg/day) and methylphenidate…

  7. [Methylphenidate use in dogs with attention deficit hyperactivity disorder (ADHD). A case report of a Weimaraner bitch].

    Science.gov (United States)

    Piturru, P

    2014-04-16

    A 10-month-old Weimaraner bitch was presented at the practice exhibiting agitation, hyperactivity, inability to learn and attention deficit. The diagnostic findings were excessive, long-lasting acoustic and locomotory activity with unexpected inappropriate reactions. Hematological and biochemical blood analyses did not demonstrate abnormal findings. The first attempts at behavioral therapy and fluoxetine application were unsatisfactory. Therefore, a test was conducted with medication for central nervous system stimulation to confirm a diagnosis of hyperkinesis. Following the diagnosis of attention deficit hyperactivity disorder, the therapy was continued with behavioral modifications, with special consideration of rehabituation and resocialization as well as the use of methylphenidate. During the course of the therapy the bitch developed hyperactivity again when on heat. After changing the dosage of methylphenidate and additionally using dog appeasing pheromone, the behavior of the bitch became normal after 8 days. Two months later endoscopic ovarioectomy was performed. Twelve months after the initial use of methylphenidate the medication could be discontinued completely and the dog's behavior was normal. The methylphenidate dosage used during this therapy was much higher than recommended in the literature.

  8. Acute oral administration of low doses of methylphenidate targets calretinin neurons in the rat septal area.

    Directory of Open Access Journals (Sweden)

    Alvaro eGarcía-Aviles

    2015-03-01

    Full Text Available Methylphenidate (MPD is a commonly administered drug to treat children suffering from attention deficit hyperactivity disorder (ADHD. Alterations in septal driven hippocampal theta rhythm may underlie attention deficits observed in these patients. Amongst others, the septo-hippocampal connections have long been acknowledged to be important in preserving hippocampal function. Thus, we wanted to ascertain if methylphenidate administration, which improves attention in patients, could affect septal areas connecting with hippocampus. We used low and orally administered methylphenidate doses (1.3; 2.7 and 5mg/Kg to rats what mimics the dosage range in humans. In our model, we observed no effect when using 1.3mg/Kg methylphenidate; whereas 2.7 and 5 mg/Kg induced a significant increase in c-fos expression specifically in the medial septum, an area intimately connected to the hippocampus. We analyzed dopaminergic areas such as nucleus accumbens and striatum, and found that only 5mg/Kg induced c-fos levels increase. In these areas tyrosine hydroxylase correlated well with c-fos staining, whereas in the medial septum the sparse tyrosine hydroxylase fibres did not overlap with c-fos positive neurons. Double immunofluorescence of c-fos with neuronal markers in the septal area revealed that co-localization with choline acethyl transferase, parvalbumin, and calbindin with c-fos did not change with MPD treatment; whereas, calretinin and c-fos double labeled neurons increased after MPD administration. Altogether, these results suggest that low and acute doses of methylphenidate primary target specific populations of caltretinin medial septal neurons.

  9. Cocaine-seeking behavior in a genetic model of attention-deficit/hyperactivity disorder following adolescent methylphenidate or atomoxetine treatments*

    Science.gov (United States)

    Jordan, Chloe J.; Harvey, Roxann C.; Baskin, Britahny B.; Dwoskin, Linda P.; Kantak, Kathleen M.

    2014-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with cocaine abuse. Controversy exists regarding long-term consequences of ADHD medications on cocaine abuse liability. Whereas childhood methylphenidate treatment may be preventative, methylphenidate in teens appears to further increase later cocaine abuse risk. In rodents, adolescent methylphenidate treatment further increases adult cocaine self-administration in the Spontaneously Hypertensive Rat (SHR) model of ADHD, whereas adolescent atomoxetine treatment does not. Effects of ADHD medications on cocaine cue reactivity, a critical component of addiction, are unknown. Methods To investigate this, SHR, Wistar-Kyoto (inbred control) and Wistar (outbred control) rats received therapeutically relevant doses of methylphenidate (1.5 mg/kg, oral) and atomoxetine (0.3 mg/kg, intraperitoneal), or respective vehicles from post-natal day 28–55. Cocaine seeking, reflecting cue reactivity, was measured in adulthood during self-administration maintenance and cue-induced reinstatement tests conducted under a second-order schedule. Results Compared to control strains, SHR earned more cocaine infusions, emitted more cocaine-seeking responses during maintenance and reinstatement testing, and required more sessions to reach the extinction criterion. Compared to vehicle, adolescent methylphenidate, but not atomoxetine, further increased cocaine intake during maintenance testing in SHR. Adolescent atomoxetine, but not methylphenidate, decreased cocaine seeking during reinstatement testing in SHR. Neither medication had effects on cocaine intake or cue reactivity in control strains. Conclusions The SHR successfully model ADHD and cocaine abuse comorbidity and show differential effects of adolescent ADHD medications on cocaine intake and cue reactivity during adulthood. Thus, SHR have heuristic value for assessing neurobiology underlying the ADHD phenotype and for evaluating pharmacotherapeutics for ADHD

  10. Motivational effects of methylphenidate are associated with GABRA2 variants conferring addiction risk

    Directory of Open Access Journals (Sweden)

    Theodora eDuka

    2015-11-01

    Full Text Available Background: Variations in the GABRA2 gene, encoding α2 subunits of GABAA receptors, have been associated with risk for addiction to several drugs, but the mechanisms by which variations in non-coding regions of GABRA2 increase risk for addictions are not understood. Mice with deletion of Gabra2 show deficits in the ability of psychostimulants to facilitate responding for conditioned reinforcers, offering a potential explanation. Methods: We report human and mouse studies investigating a potential endophenotype underlying this association. Healthy human volunteers carrying either cocaine-addiction risk or protective GABRA2 SNPs were tested for their subjective responses to methylphenidate, and methylphenidate’s ability to facilitate conditioned reinforcement (CRf for visual stimuli (CS+ associated with monetary reward. In parallel, methylphenidate’s ability to facilitate responding for a visual CRf was studied in wildtype and α2 knockout (α2-/- mice. Results: Methylphenidate increased the number of CS+ presentations obtained by human subjects carrying protective, but not risk SNPs. In mice, methylphenidate increased responding for a CS+ in wildtype, but not α2-/- mice. Human subjects carrying protective SNPs felt stimulated, aroused and restless following methylphenidate, while individuals carrying risk SNPs did not. Conclusion: Human risk SNP carriers were insensitive to methylphenidate’s effects on mood or in facilitating CRf. That mice with the gene deletion were also insensitive to methylphenidate’s ability to increase responding for CRf, suggests a potential mechanism whereby low α2-subunit levels increase risk for addictions. Circuits employing GABAA-α2 subunit-containing receptors may protect against risk for addictions.

  11. Chronic methylphenidate-effects over circadian cycle of young and adult rats submitted to open-field and object recognition tests.

    Science.gov (United States)

    Gomes, Karin M; Souza, Renan P; Valvassori, Samira S; Réus, Gislaine Z; Inácio, Cecília G; Martins, Márcio R; Comim, Clarissa M; Quevedo, João

    2009-11-01

    In this study age-, circadian rhythm- and methylphenidate administration- effect on open field habituation and object recognition were analyzed. Young and adult male Wistar rats were treated with saline or methylphenidate 2.0 mg/kg for 28 days. Experiments were performed during the light and the dark cycle. Locomotor activity was significantly altered by circadian cycle and methylphenidate treatment during the training session and by drug treatment during the testing session. Exploratory activity was significantly modulated by age during the training session and by age and drug treatment during the testing session. Object recognition memory was altered by cycle at the training session; by age 1.5 h later and by cycle and age 24 h after the training session. These results show that methylphenidate treatment was the major modulator factor on open-field test while cycle and age had an important effect on object recognition experiment.

  12. Prefrontal cortical and striatal transcriptional responses to the reinforcing effect of repeated methylphenidate treatment in the spontaneously hypertensive rat, animal model of attention-deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    dela Peña, Ike; Kim, Hee Jin; Sohn, Aeree; Kim, Bung-Nyun; Han, Doug Hyun; Ryu, Jong Hoon; Shin, Chan Young; Noh, Minsoo; Cheong, Jae Hoon

    2014-05-06

    Methylphenidate is the most commonly used stimulant drug for the treatment of attention-deficit/hyperactivity disorder (ADHD). Research has found that methylphenidate is a "reinforcer" and that individuals with ADHD also abuse this medication. Nevertheless, the molecular consequences of long-term recreational methylphenidate use or abuse in individuals with ADHD are not yet fully known. Spontaneously hypertensive rats (SHR), the most validated and widely used ADHD animal model, were pretreated with methylphenidate (5 mg/kg, i.p.) during their adolescence (post-natal day [PND] 42-48) and tested for subsequent methylphenidate-induced conditioned place preference (CPP) and self-administration. Thereafter, the differentially expressed genes in the prefrontal cortex (PFC) and striatum of representative methylphenidate-treated SHRs, which showed CPP to and self-administration of methylphenidate, were analyzed. Genome-wide transcriptome profiling analyses revealed 30 differentially expressed genes in the PFC, which include transcripts involved in apoptosis (e.g. S100a9, Angptl4, Nfkbia), transcription (Cebpb, Per3), and neuronal plasticity (Homer1, Jam2, Asap1). In contrast, 306 genes were differentially expressed in the striatum and among them, 252 were downregulated. The main functional categories overrepresented among the downregulated genes include those involved in cell adhesion (e.g. Pcdh10, Ctbbd1, Itgb6), positive regulation of apoptosis (Perp, Taf1, Api5), (Notch3, Nsbp1, Sik1), mitochondrion organization (Prps18c, Letm1, Uqcrc2), and ubiquitin-mediated proteolysis (Nedd4, Usp27x, Ube2d2). Together, these changes indicate methylphenidate-induced neurotoxicity, altered synaptic and neuronal plasticity, energy metabolism and ubiquitin-dependent protein degradation in the brains of methylphenidate-treated SHRs, which showed methylphenidate CPP and self-administration. In addition, these findings may also reflect cognitive impairment associated with chronic

  13. Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD

    Directory of Open Access Journals (Sweden)

    Bhat Venkataramana

    2011-04-01

    Full Text Available Abstract Background The desired (therapeutic and undesired (side effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. Methods One hundred and fifty-seven children with ADHD (6-12 years were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose, each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents and teachers (CGI-Teachers, while side effects were assessed using the Barkley Side Effects Rating Scale (SERS. Results The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p Conclusion The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

  14. Influence of Methylphenidate on Motor Performance and Attention in Children with Developmental Coordination Disorder and Attention Deficit Hyperactive Disorder

    Science.gov (United States)

    Bart, Orit; Daniel, Liron; Dan, Orrie; Bar-Haim, Yair

    2013-01-01

    Individuals with attention deficit hyperactive disorder (ADHD) often have coexisting developmental coordination disorder (DCD). The positive therapeutic effect of methylphenidate on ADHD symptoms is well documented, but its effects on motor coordination are less studied. We assessed the influence of methylphenidate on motor performance in children…

  15. Prescribing of methylphenidate to children and adolescents in South ...

    African Journals Online (AJOL)

    2008-11-13

    Nov 13, 2008 ... Background: Pharmacoepidemiological studies on ADHD are limited in South Africa. The primary aim was to analyse the prescribing of methylphenidate to patients aged 18 years and younger in the private health care sector. Methods: Data for a one-month period in 2004 were obtained from a large ...

  16. Prescribing of methylphenidate to children and adolescents in South ...

    African Journals Online (AJOL)

    Background: Pharmacoepidemiological studies on ADHD are limited in South Africa. The primary aim was to analyse the prescribing of methylphenidate to patients aged 18 years and younger in the private health care sector. Methods: Data for a one-month period in 2004 were obtained from a large medical aid ...

  17. Comparative efficacy and acceptability of methylphenidate and atomoxetine in treatment of attention deficit hyperactivity disorder in children and adolescents: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Hanwella Raveen

    2011-11-01

    Full Text Available Abstract Background Psychostimulants and non stimulants are effective in the treatment of ADHD. Efficacy of both methylphenidate and atomoxetine has been established in placebo controlled trials. Direct comparison of efficacy is now possible due to availability of results from several head-to-head trials of these two medications. Methods All published, randomized, open label or double blind trials, comparing efficacy of methylphenidate with atomoxetine, in treatment of ADHD in children, diagnosed using DSM-IV™ criteria were included. The outcome studied was ADHDRS-IVParent:Inv score. The standardized mean difference (SMD was used as a measure of effect size. Results Nine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included. Meta-analysis did not find a significant difference in efficacy between methylphenidate and atomoxetine (SMD = 0.09, 95% CI -0.08-0.26 (Z = 1.06, p = 0.29. Synthesis of data from eight trials found no significant difference in response rates (RR = 0.93 95% CI 0.76-1.14, p = 0.49. Sub group analysis showed a significant standardized mean difference favouring OROS methylphenidate (SMD = 0.32, 95% CI 0.12-0.53 (Z = 3.05, p I2 = 67%. Subgroup analysis demonstrated the heterogeneity to be due to the open label trials (p = 0.001, I2 = 81%. Conclusions In general atomoxetine and methylphenidate have comparable efficacy and equal acceptability in treatment of ADHD in children and adolescents. However OROS methylphenidate is more effective than atomoxetine and may be considered as first line treatment in treatment of ADHD in children and adolescents.

  18. Effects of methylphenidate on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4).

    Science.gov (United States)

    Hauser, Joachim; Reissmann, Andreas; Sontag, Thomas-A; Tucha, Oliver; Lange, Klaus W

    2017-05-01

    The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats' performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats.

  19. A Comparison of Effectiveness of Parent Behavioral Management Training and Methylphenidate on Reduction of Symptomsof Attention Deficit Hyperactivity Disorder

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Mohammadi

    2016-09-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is one of the most common psychological disorders of childhood. Methylphenidate is highly effective in the treatment of ADHD. This study aimed to determine the effectiveness of combined Parent behavioral management training (PBMT and medication treatment (Methylphenidate in reducing ADHD symptoms in 6-12-year-old children, using randomized sampling. A total of 50 children with ADHD were assigned into two groups: an experimental group of PBMT and a control group of medication treatment (Methylphenidate without other interventions. Conners’ Parent Rating Scale (CPRS-48 was employed before and after interventions to determine the effects. Descriptive Statistics method (consisting of Mean and Standard deviation and Statistical inference method, (including t-test and Levene's Test were used for data analysis.  Findings revealed that the combined behavioral intervention of PBMT and methylphenidate treatment is more effective in reduction of ADHD in children. The difference of means between pre-test and post-test of CPRS in the experimental group was equal to 10.77, and it was equal to 1.88 in the control group. In addition, PBMT was more effective in the case of younger parents (P<0.025. However, parents’ education level did not affect the behavioral intervention (P<0.025.The findings suggest that combined intervention of PBMT and methylphenidate is effective in reducing the symptoms of ADHD in children.

  20. The Effects of Methylphenidate on Goal-Directed Behavior in a Rat Model of ADHD

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    Joman Y. Natsheh

    2015-11-01

    Full Text Available Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR (ADHD rat model and Wistar-Kyoto rats (WKY, the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate, a commonly used ADHD medication, on goal-directed behavior, we injected rats with either Methylphenidate or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, methylphenidate administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how methylphenidate acts differently on SHR and WKY animals to restore or impair this behavior, respectively.

  1. A Comparative Study on the Effectiveness of Stimulant Therapy (Ritalin Neurofeedback, and Parental Management Training and Interaction of the Three Approaches on Improving ADHD and Quality of Mother -Child Communication

    Directory of Open Access Journals (Sweden)

    Sh. Basteh Hoseini

    2013-07-01

    Full Text Available Introduction & Objective: This research was designed to investigate and compare the effective-ness of stimulant therapy (Ritalin, neurofeedback, parental management training and interac-tion of the treatments on the improvement of Attention Deficit Hyperactivity Disorder (ADHD, and quality of mother-child communication. Materials & Methods: This is a pseudo-experimental research with pretest-posttest de-sign including ADHD children living in Tehran; 40 subjects were randomly selected from clients of child psychiatric/psychological clinic, and then placed in 4 intervention groups based on objectives of the research. The subjects were measured by Conner's Parenting Scale-48 and Parental Stress Index before and after the interventions. Recruited data were analyzed by ANCOVA. Results: The findings of the research reveals that there is a significant difference among the treatments on improving conduct and attention/concentrationproblems; in other words, interaction of the treatments caused more therapeutic effect than other treatments. Also, there was no significant difference among the treatments on improving psychosomatic problems, impulsivity, anxiety, parent reinforcement, parental attachment, and parental competency. Conclusion: Finally, interaction of treatments and then ritalin had the most therapeutic effect compared to other treatments. (Sci J Hamadan Univ Med Sci 2013; 20 (2:133-143

  2. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Scherer, Roberta W; Drye, Lea; Mintzer, Jacobo; Lanctôt, Krista; Rosenberg, Paul; Herrmann, Nathan; Padala, Prasad; Brawman-Mintzer, Olga; Burke, William; Craft, Suzanne; Lerner, Alan J; Levey, Allan; Porsteinsson, Anton; van Dyck, Christopher H

    2018-01-18

    Alzheimer's disease (AD) is characterized not only by cognitive and functional decline, but also often by the presence of neuropsychiatric symptoms. Apathy, which can be defined as a lack of motivation, is one of the most prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality of life and greater burden for caregivers. Treatment options for apathy in AD are limited, but studies have examined the use of the amphetamine, methylphenidate. The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of apathy in AD with methylphenidate was associated with significant improvement in apathy in two of three outcome measures, some evidence of improvement in global cognition, and minimal adverse events. However, the trial only enrolled 60 participants who were followed for only 6 weeks. A larger, longer-lasting trial is required to confirm these promising findings. The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6-month, multi-center, randomized clinical trial targeted to enroll 200 participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg methylphenidate per day prepared as four over-encapsulated tablets or to matching placebo. The primary outcomes include (1) the mean difference in the Neuropsychiatric Inventory Apathy subscale scores measured as change from baseline to 6 months, and (2) the odds of having a given rating or better on the modified AD Cooperative Study Clinical Global Impression of Change ratings at month 6 compared with the baseline rating. Other outcomes include change in cognition, safety, and cost-effectiveness measured at monthly follow-up visits up to 6 months. Given the prevalence of apathy in AD and its impact on both patients and caregivers, an intervention to alleviate apathy would be of great benefit to society. ADMET 2 follows on the promising results from the original ADMET to evaluate the efficacy of methylphenidate as a

  3. Effects of Methylphenidate and Atomoxetine on Cortical Inhibition in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-09-01

    Full Text Available The effects of methylphenidate (MPH, a psychostimulant, and atomoxetine (ATX, a selective norepinephrine reuptake inhibitor, on short interval-cortical inhibition (SICI were measured in motor cortex with transcranial magnetic stimulation, in a study at Cincinnati Children’s Medical Center, OH, and other centers.

  4. Combined methylphenidate and atomoxetine pharmacotherapy in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Ozbaran, Burcu; Kose, Sezen; Yuzuguldu, Onur; Atar, Burcu; Aydin, Cahide

    2015-01-01

    Pharmacological treatment of attention deficit hyperactivity disorder (ADHD) includes stimulant and non-stimulant medications. Our purpose in this study is to investigate efficacy, safety and tolerability of combined methylphenidate and atomoxetine pharmacotherapy. We included 12 patients of the 824 patients with ADHD using methylphenidate and atomoxetine combined therapy between the years 2010 and 2014. Kiddie-SADS, Turgay DSM-IV Based Child and Adolescent Behavior Disorders Screening and Rating Scale, Child Behavior Checklist, Clinic Global Impression Scale Severity and Impression (CGIS-S-I) scales were used. Patients were between the ages of 7 and 17 years. Before combined pharmacotherapy the CGIS-S score mean was 5.08. Mean CGIS-S score after the combined pharmacotherapy was 3.08 (P = 0.03; -2,980). The most common side effects were irritability (n = 5, 41.6%), appetite reduction (n = 3, 25%), palpitations (n = 2, 16.7%), headache (n = 1, 8.3%). Nine of these 12 patients showed significant improvement in their symptoms, combined therapy enhanced the effectiveness of monotherapy.

  5. Anxiety and depression symptoms and response to methylphenidate in children with attention-deficit hyperactivity disorder and tic disorder.

    Science.gov (United States)

    Gadow, Kenneth D; Nolan, Edith E; Sverd, Jeffrey; Sprafkin, Joyce; Schwartz, Joseph

    2002-06-01

    This study examined response to methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD) and chronic multiple tic disorder. The primary goal was to determine if children with anxiety or depression symptoms showed a less favorable response to treatment. Subjects were 38 prepubertal children who participated in an 8-week, double-blind, placebo-controlled, methylphenidate crossover evaluation. Treatment effects were assessed with direct observations of child behavior in public school and clinic settings; rating scales completed by parents, teachers, and clinicians; and laboratory analogue tasks. There was little evidence (group data) that children with anxiety or depression symptoms responded in a clinically different manner to methylphenidate than youngsters who did not exhibit these symptoms, particularly in school observations of the core features of ADHD. Seeming differences between children with and without comorbid anxiety or depression symptoms and drug response are likely explained by differences in pretreatment levels of negativistic behaviors (i.e., symptoms of oppositional defiant disorder or conduct disorder). Methylphenidate appears to be effective for the management of ADHD behaviors in children with mild to moderate anxiety or depression symptoms; nevertheless, much research remains to be performed in this area.

  6. The Prevalence of ADHD Patients among Pediatric Dentists in Israel and Knowledge of Dental and Behavioral Aspects of Treating Them.

    Science.gov (United States)

    Blumer, Sigalit; Khoury, Rula Shehadi; Peretz, Benjamin

    2018-01-01

    There are no clear guidelines for managing the dental treatment of children with attention deficit hyperactivity disorder (ADHD). The use of sedation in combination with chronic ADHD medication use is also not well defined. This study surveyed the prevalence of ADHD children, management techniques and knowledge of pharmacologic therapies of these children among Israeli dentists. A specially designed questionnaire was distributed to all Israeli dentists attending a national conference in 2016. Of the 160 dentists who attended the conference, 96 completed the survey (60% response rate), and they included 46 (51%) pediatric dental specialists and 50 (49%) general dental practitioners. The medications Ritalin and Concerta were most familiar to the respondents (98.9%). Eighty-seven (91.1%) of the practitioners responded that their ADHD patients take their usual doses of any drug for treating ADHD symptoms, regardless of whether or not the dentists intended to use sedatives. The practitioners invented their own behavior management techniques with varying degrees of success. There are no specific guidelines for the most effective pharmacologic protocol (co-administration of ADHD drugs and dental sedatives) or behavior management techniques for the provision of optimal dental care to children with ADHD.

  7. Methylphenidate in Treatment of ADHD and Comorbid Chronic Tic Disorder

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-07-01

    Full Text Available The safety and efficacy of immediate-release methylphenidate (MPH-IR for the treatment of attention deficit hyperactivity disorder (ADHD in children (ages 6-12 years with Tourette's syndrome (96% or chronic motor tic disorder (4% were evaluated at State University of New York, Stony Brook.

  8. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD)

    DEFF Research Database (Denmark)

    Storebø, Ole Jakob; Ramstad, Erica; Krogh, Helle B

    2015-01-01

    BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children with ADHD find it difficult to pay attention, they are hyperactive and impulsive.Methylphenidate is the drug most often prescribed...

  9. A network meta-analysis of atomoxetine and osmotic release oral system methylphenidate in the treatment of attention-deficit/hyperactivity disorder in adult patients.

    Science.gov (United States)

    Bushe, Chris; Day, Kathleen; Reed, Victoria; Karlsdotter, Kristina; Berggren, Lovisa; Pitcher, Ashley; Televantou, Foula; Haynes, Virginia

    2016-05-01

    The lack of head-to-head clinical studies powered to compare atomoxetine and osmotic release oral system (OROS) methylphenidate necessitates treatment comparison by methods that include indirect evidence such as network meta-analysis (NMA). A NMA assessing the relative treatment effects of atomoxetine and OROS methylphenidate in adults with attention-deficit/hyperactivity disorder (ADHD) was conducted. Studies were identified by systematic literature review. Analyses summarised improvements in efficacy, measured by ADHD-specific scales, using Cohen'sdto calculate the standardised mean difference (SMD), and all cause discontinuations. Results showed effect sizes (SMD, 95% credible interval (CrI)) relative to placebo that did not differ significantly between atomoxetine (0.46, 0.36-0.56) and OROS methylphenidate (0.51, 0.40-0.63) in clinical studies of up to 12 weeks' duration (SMD, 95% CrI for atomoxetine versus OROS methylphenidate: -0.05, -0.18-0.08). Patients treated with these medications responded better than those given placebo across all analyses. There was also no significant difference in discontinuation rates between atomoxetine and OROS methylphenidate (odds ratio, 95% CrI: 0.85, 0.53-1.35). Between-study heterogeneity was low overall. Results of this NMA suggest that the efficacy of atomoxetine and OROS methylphenidate in adults does not differ significantly. Clinical guidelines may require amendment to reflect these recent data. © The Author(s) 2016.

  10. Hiccup Due to Aripiprazole Plus Methylphenidate Treatment in an Adolescent with Attention Deficit and Hyperactivity Disorder and Conduct Disorder: A Case Report.

    Science.gov (United States)

    Kutuk, Meryem Ozlem; Guler, Gulen; Tufan, Ali Evren; Kutuk, Ozgur

    2017-11-30

    Our case had hiccups arising in an adolescent with the attention deficit and hyperactivity disorder (ADHD) and conduct disorder (CD) after adding aripiprazole treatment to extended-release methylphenidate. Actually, antipsychotics are also used in the treatment of hiccups, but studies suggest that they can cause hiccups as well. Within 12 hours of taking 2.5 mg aripiprazole added to extended-release methylphenidate at a dose of 54 mg/day, 16-year-old boy began having hiccups in the morning, which lasted after 3-4 hours. As a result, aripiprazole was discontinued and methylphenidate was continued alone because we could not convince the patient to use another additional drug due to this side effect. Subsequently, when his behavior got worsened day by day, his mother administered aripiprazole alone again at the dose of 2.5 mg/day at the weekend and continued treatment because hiccup did not occur again. But when it was administered with methylphenidate on Monday, hiccup started again next morning and lasted one hour at this time. In conclusion, we concluded that concurrent use of methylphenidate and aripiprazole in this adolescent led to hiccups.

  11. Reversible Dopamine Transporter Modifications in Response to Methylphenidate Treatment of ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-09-01

    Full Text Available Single-photon emission computed tomography (SPECT was used to monitor the dopamine transporter activity in 5 males, ages 8 to 10, with ADHD, after cessation of methylphenidate (MPH treatment, in a study at the University Hospital Maastricht, The Netherlands.

  12. EEG Brain Wave Activity at Rest and during Evoked Attention in Children with Attention-Deficit/Hyperactivity Disorder and Effects of Methylphenidate.

    Science.gov (United States)

    Thomas, Bianca Lee; Viljoen, Margaretha

    2016-01-01

    The aim of this study was to assess baseline EEG brain wave activity in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of evoked attention and methylphenidate on this activity. Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulant (methylphenidate) medication. Control subjects (n = 18) were tested once. EEG brain wave activity was tested both at baseline and during focussed attention. Attention was evoked and EEG brain wave activity was determined by means of the BioGraph Infiniti biofeedback apparatus. The main finding of this study was that control subjects and stimulant-free children with ADHD exhibited the expected reactivity in high alpha-wave activity (11-12 Hz) from baseline to focussed attention; however, methylphenidate appeared to abolish this reactivity. Methylphenidate attenuates the normal cortical response to a cognitive challenge. © 2016 S. Karger AG, Basel.

  13. Non-medical use of methylphenidate: a review Uso não terapêutico do metilfenidato: uma revisão

    Directory of Open Access Journals (Sweden)

    Luana Freese

    2012-01-01

    Full Text Available INTRODUCTION: Methylphenidate is a psychostimulant medication used for the treatment of attention deficit hyperactivity disorder and narcolepsy. However, it has also been used for non-medical purposes, e.g. to produce euphoria, to increase self-esteem, and to achieve the so-called neurocognitive enhancement, decreasing the feeling of tiredness and increasing focus and attention. OBJECTIVE: To describe, from theoretical and contextual points of view, the potential for abuse and non-medical use of methylphenidate. METHOD: The PubMed, SciELO and Cochrane databases were searched using the following keywords in Portuguese: metilfenidato, transtorno do déficit de atenção com hiperatividade, facilitadores dos processos cognitivos or agentes nootrópicos, and abuso de substâncias; and in English: methylphenidate, attention deficit disorder with hyperactivity, cognitive enhancement or nootropic agents, and substance abuse. Studies published between 1990 and 2010 were selected for review. RESULTS: Non-medical use of methylphenidate is a relevant topic that raises important ethical and scientific questions in several areas, e.g. pharmacological and neurobiological characteristics, evidence of methylphenidate use, forms of non-medical use of methylphenidate, mechanisms of action, and therapeutic application of methylphenidate. According to the review, methylphenidate can generally influence performance as a result of its stimulatory effect. Notwithstanding, evidence does not support the conclusion that it can enhance cognitive performance. CONCLUSION: Health professionals need to acquire expert knowledge and inform patients and their families on the methylphenidate potential for abuse when used with non-medical purposes.INTRODUÇÃO: O metilfenidato é um medicamento psicoestimulante usado no tratamento do transtorno de déficit de atenção e hiperatividade e da narcolepsia. No entanto, a droga também vem sendo utilizada com fins não terap

  14. Methylphenidate-Related Improvements in Math Performance Cannot Be Explained by Better Cognitive Functioning or Higher Academic Motivation : Evidence From a Randomized Controlled Trial

    NARCIS (Netherlands)

    Kortekaas-Rijlaarsdam, Anne Fleur; Luman, Marjolein; Sonuga-Barke, Edmund; Bet, Pierre; Oosterlaan, Jaap

    2017-01-01

    OBJECTIVE: This study investigated whether improvements in working memory, reaction time, lapses of attention, interference control, academic motivation, and perceived competence mediated effects of methylphenidate on math performance. METHOD: Sixty-three children (ADHD diagnosis; methylphenidate

  15. Virtual Remediation Versus Methylphenidate to Improve Distractibility in Children With ADHD: A Controlled Randomized Clinical Trial Study.

    Science.gov (United States)

    Bioulac, Stéphanie; Micoulaud-Franchi, Jean-Arthur; Maire, Jenna; Bouvard, Manuel P; Rizzo, Albert A; Sagaspe, Patricia; Philip, Pierre

    2018-03-01

    Virtual environments have been used to assess children with ADHD but have never been tested as therapeutic tools. We tested a new virtual classroom cognitive remediation program to improve symptoms in children with ADHD. In this randomized clinical trial, 51 children with ADHD (7-11 years) were assigned to a virtual cognitive remediation group, a methylphenidate group, or a psychotherapy group. All children were evaluated before and after therapy with an ADHD Rating Scale, a Continuous Performance Test (CPT), and a virtual classroom task. After therapy by virtual remediation, children exhibited significantly higher numbers of correct hits on the virtual classroom and CPT. These improvements were equivalent to those observed with methylphenidate treatment. Our study demonstrates for the first time that a cognitive remediation program delivered in a virtual classroom reduces distractibility in children with ADHD and could replace methylphenidate treatment in specific cases.

  16. Effects of Methylphenidate on Working Memory Components: Influence of Measurement

    Science.gov (United States)

    Bedard, Anne-Claude; Jain, Umesh; Hogg-Johnson, Sheilah; Tannock, Rosemary

    2007-01-01

    Background: To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in attention-deficit hyperactivity disorder (ADHD) and determine the responsiveness of WM measures to MPH. Methods: Participants were a clinical sample of 50 children and adolescents with ADHD, aged 6 to 16 years old, who participated in an acute…

  17. Animal Model of Methylphenidate's Longterm Memory-Enhancing Effects

    Science.gov (United States)

    Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

    2014-01-01

    Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a…

  18. Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

    2011-01-01

    Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

  19. A pilot study for augmenting atomoxetine with methylphenidate: safety of concomitant therapy in children with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Ball Susan

    2007-09-01

    Full Text Available Abstract Background This study examined augmenting atomoxetine with extended-release methylphenidate in children whose attention-deficit/hyperactivity disorder (ADHD previously failed to respond adequately to stimulant medication. Methods Children with ADHD and prior stimulant treatment (N = 25 received atomoxetine (1.2 mg/kg/day plus placebo. After 4 weeks, patients who were responders (n = 4 were continued on atomoxetine/placebo while remaining patients were randomly assigned to either methylphenidate (ATX/MPH (1.1 mg/kg/day or placebo augmentation (ATX/PB for another 6 weeks. Patients and sites were blind to timing of active augmentation. Safety measures included vital signs, weight, and adverse events. Efficacy was assessed by ADHD rating scales. Results Categorical increases in vital signs occurred for 5 patients (3 patients in ATX/MPH, 2 patients in ATX/PBO. Sixteen percent discontinued the study due to AE, but no difference between augmentation groups. Atomoxetine treatment was efficacious on outcome measures (P ≤ .001, but methylphenidate did not enhance response. Conclusion Methylphenidate appears to be safely combined with atomoxetine, but conclusions limited by small sample. With atomoxetine treatment, 43% of patients achieved normalization on ADHD ratings.

  20. Selegiline in Comparison with Methylphenidate in Treatment of Adults with Attention Deficit yperactivity Disorder: A Double-blind, Randomized Trial

    Directory of Open Access Journals (Sweden)

    Farbod Fadai

    2009-12-01

    Full Text Available  Objective: "n "nAttention-Deficit/Hyperactivity Disorder (ADHD is one of the most common mental disorders in childhood and it continues to adulthood without proper treatment. Stimulants have been used in treatment of ADHD for many years and the efficacy of methylphenidate (MPH in the treatment of adults with ADHD has been proven to be acceptable according to meta-analysis studies. However, there are some concerns about stimulants. Finding other effective medications for the treatment of adult ADHD seems necessary. We tried a monoamine oxidase inhibitor, Selegiline, as there are some theoretical and experimental evidences for the efficacy of this medication . "nMethod: Forty patients were randomized to receive Selegiline or methylphenidate in an equal ratio for an 8-week double-blind clinical trial. Each patient filled the CAARS self report screening form before starting to take the medication and in weeks 2-4-6 and 8. Patients were also assessed by a psychiatrist at the baseline and on each 14 days up to the 8 weeks period. "nResults: The mean score of the two groups- receiving Selegiline or methylphenidate- decreased over the 8 weeks. There was not a significant difference between the two groups. The most prevalent side-effect of methylphenidate was decrease of appetite and for Selegiline change in sleep pattern . "nConclusion: Selegiline is as effective as methylphenidate in the treatment of adults with Attention-Deficit/Hyperactivity Disorder. Selegiline can be an alternative medication for the treatment of adult ADHD If its clinical efficacy is proven by other larger studies .

  1. The effects of methylphenidate on prepulse inhibition during attended and ignored prestimuli among boys with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Hawk, Larry W; Yartz, Andrew R; Pelham, William E; Lock, Thomas M

    2003-01-01

    The present study investigated attentional modification of prepulse inhibition of startle among boys with and without attention-deficit hyperactivity disorder (ADHD). Two hypotheses were tested: (1) whether ADHD is associated with diminished prepulse inhibition during attended prestimuli, but not ignored prestimuli, and (2) whether methylphenidate selectively increases prepulse inhibition to attended prestimuli among boys with ADHD. Participants were 17 boys with ADHD and 14 controls. Participants completed a tone discrimination task in each of two sessions separated by 1 week. ADHD boys were administered methylphenidate (0.3 mg/kg) in one session and placebo in the other session in a randomized, double-blind fashion. During each series of 72 tones (75 dB; half 1200-Hz, half 400-Hz), participants were paid to attend to one pitch and ignore the other. Bilateral eyeblink electromyogram startle responses were recorded in response to acoustic probes (50-ms, 102-dB white noise) presented following the onset of two-thirds of tones, and during one-third of intertrial intervals. Relative to controls, boys with ADHD exhibited diminished prepulse inhibition 120 ms after onset of attended but not ignored prestimuli following placebo administration. Methylphenidate selectively increased prepulse inhibition to attended prestimuli at 120 ms among boys with ADHD to a level comparable to that of controls, who did not receive methylphenidate. These data are consistent with the hypothesis that ADHD involves diminished selective attention and suggest that methylphenidate ameliorates the symptoms of ADHD, at least in part, by altering an early attentional mechanism.

  2. Anxiety, Methylphenidate Response, and Working Memory in Children with ADHD

    Science.gov (United States)

    Bedard, Anne-Claude; Tannock, Rosemary

    2008-01-01

    Objective: To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in children with ADHD and determine whether MPH produces differential effects on WM in children with comorbid anxiety (ANX). Method: Participants were a clinical sample of 130 children with ADHD, aged 6 to 12 years old (32% comorbid ANX). Each child…

  3. A systematic review of randomized controlled trials of bupropion versus methylphenidate in the treatment of attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Maneeton N

    2014-08-01

    Full Text Available Narong Maneeton,1 Benchalak Maneeton,1 Suthi Intaprasert,1 Pakapan Woottiluk2 1Department of Psychiatry, Faculty of Medicine, 2Psychiatric Nursing Division, Faculty of Nursing, Chiang Mai University, Chiang Mai, ThailandBackground: Some trials have suggested that bupropion, as well as methylphenidate, is bene­ficial in the treatment of attention-deficit/hyperactivity disorder (ADHD.Objectives: The purpose of this systematic review was to summarize the efficacy, acceptability, and tolerability of bupropion in comparison with methylphenidate for ADHD treatment. Included studies were randomized controlled trials (RCTs that compared bupropion and methylphenidate. Clinical studies conducted between January 1991 and January 2014 were reviewed.Data sources: MEDLINE®, EMBASE™, CINAHL, PsycINFO®, and the Cochrane Controlled Trials Register were searched in January 2014. Additionally, clinical trials were identified from the databases of ClinicalTrials.gov and the EU Clinical Trials Register.Study eligible criteria, participants, and interventions: All RCTs of bupropion and methylphenidate reporting final outcomes relevant to 1 ADHD severity, 2 response or remission rates, 3 overall discontinuation rate, or 4 discontinuation rate due to adverse events. Language restriction was not applied.Study appraisal and synthesis methods: The relevant clinical trials were examined and the data of interest were extracted. Additionally, the risks of bias were also inspected. The efficacy outcomes were the mean changed scores of ADHD rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate and the discontinuation rate due to adverse events were determined. Relative risks and weighted mean differences or standardized mean differences with 95% confidence intervals were estimated using a random effect model.Results: A total of 146 subjects in four RCTs comparing bupropion with methylphenidate in the treatment of

  4. Methylphenidate use and school performance among primary school children : a descriptive study

    NARCIS (Netherlands)

    van der Schans, Jurjen; Cicek, Rukiye; Vardar, Sefike; Bos, Jens H. J.; de Vries, Tjalling W.; Hoekstra, Pieter J.; Hak, Eelko

    2017-01-01

    Background: There is no conclusive evidence that stimulants have beneficial effects on major associated outcome parameters, particularly school performance. We assessed the differences in school performance among children using methylphenidate at the end of primary school in relation to various

  5. Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clincal Trial

    NARCIS (Netherlands)

    Schrantee, A.; Tamminga, H.G.H.; Bouziane, C.; Bottelier, M.A.; Bron, E.E.; Mutsaerts, H.-J.M.M.; Zwinderman, A.H.; Groote, I.R.; Rombouts, S.A.R.B.; Lindauer, R.J.L.; Klein, S.; Niessen, W.J.; Opmeer, B.C.; Boer, F.; Lucassen, P.J.; Andersen, S.L.; Geurts, H.M.; Reneman, L.

    2016-01-01

    Importance: Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. Objectives: To determine whether

  6. Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder

    DEFF Research Database (Denmark)

    Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R

    2017-01-01

    OBJECTIVES: To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. METHODS AND FINDINGS...... differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. CONCLUSION: Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit...... hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found....

  7. Age-Dependent Effects of Methylphenidate on the Human Dopaminergic System in Young vs Adult Patients With Attention-Deficit/Hyperactivity Disorder: A Randomized Clinical Trial

    NARCIS (Netherlands)

    Schrantee, Anouk; Tamminga, Hyke G. H.; Bouziane, Cheima; Bottelier, Marco A.; Bron, Esther E.; Mutsaerts, Henk-Jan M. M.; Zwinderman, Aeilko H.; Groote, Inge R.; Rombouts, Serge A. R. B.; Lindauer, Ramon J. L.; Klein, Stefan; Niessen, Wiro J.; Opmeer, Brent C.; Boer, Frits; Lucassen, Paul J.; Andersen, Susan L.; Geurts, Hilde M.; Reneman, Liesbeth

    2016-01-01

    Although numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. To determine whether the effects of

  8. Rationalising polymer selection for supersaturated film forming systems produced by an aerosol spray for the transdermal delivery of methylphenidate.

    Science.gov (United States)

    Edwards, A; Qi, S; Liu, F; Brown, M B; McAuley, W J

    2017-05-01

    Film forming systems offer a number of advantages for topical and transdermal drug delivery, in particular enabling production of a supersaturated state which can greatly improve drug absorption and bioavailability. However the suitability of individual film forming polymers to stabilise the supersaturated state and optimise delivery of drugs is not well understood. This study reports the use of differential scanning calorimetry (DSC) to measure the solubility of methylphenidate both as the free base and as the hydrochloride salt in two polymethacrylate copolymers, Eudragit RS (EuRS) and Eudragit E (EuE) and relates this to the ability of films formed using these polymers to deliver methylphenidate across a model membrane. EuRS provided greater methylphenidate delivery when the drug was formulated as the free base in comparison EuE because the lower solubility of the drug in EuRS provided a higher degree of drug saturation in the polymeric film. In contrast EuE provided greater delivery of methylphenidate hydrochloride as EuRS could not prevent its crystallisation from a supersaturated state. Methylphenidate flux across the membrane could be directly related to degree of saturation of the drug in the film formulation as estimated by the drug solubility in the individual polymers demonstrating the importance of drug solubility in the polymer included in film forming systems for topical/transdermal drug delivery. In addition DSC has been demonstrated to be a useful tool for determining the solubility of drugs in polymers used in film forming systems and the approaches outlined here are likely to be useful for predicting the suitability of polymers for particular drugs in film forming transdermal drug delivery systems. Copyright © 2017. Published by Elsevier B.V.

  9. First-Trimester Exposure to Methylphenidate

    DEFF Research Database (Denmark)

    Pottegård, Anton; Hallas, Jesper; Andersen, Jon T

    2014-01-01

    conducted this study to estimate the risk of major congenital malformations following first-trimester in utero exposure to methylphenidate. METHOD: Data from 2005 to 2012 were extracted from the Danish National Patient Register, the Danish National Prescription Registry, the Medical Birth Registry...... subjects with respect to maternal age, smoking status, body mass index, length of education, calendar year of completion of pregnancy, and concomitant use of antipsychotics, antidepressants, anxiolytics, and nonsteroidal anti-inflammatory drugs. RESULTS: We included 222 exposed and 2,220 unexposed...... pregnancies in the analysis. There was no statistically significant increase in major malformations (point prevalence ratio = 0.8; 95% CI, 0.3-1.8) or cardiac malformations (point prevalence ratio = 0.9; 95% CI, 0.2-3.0). Sensitivity analyses using different definitions of exposure or previous users...

  10. Cognitive Improvement of Attention and Inhibition in the Late Afternoon in Children With Attention-Deficit Hyperactivity Disorder (ADHD) Treated With Osmotic-Release Oral System Methylphenidate.

    Science.gov (United States)

    Slama, Hichem; Fery, Patrick; Verheulpen, Denis; Vanzeveren, Nathalie; Van Bogaert, Patrick

    2015-07-01

    Long-acting medications have been developed and approved for use in the treatment of attention-deficit hyperactivity disorder (ADHD). These compounds are intended to optimize and maintain symptoms control throughout the day. We tested prolonged effects of osmotic-release oral system methylphenidate on both attention and inhibition, in the late afternoon. A double-blind, randomized, placebo-controlled study was conducted in 36 boys (7-12 years) with ADHD and 40 typically developing children. The ADHD children received an individualized dose of placebo or osmotic-release oral system methylphenidate. They were tested about 8 hours after taking with 2 continuous performance tests (continuous performance test-X [CPT-X] and continuous performance test-AX [CPT-AX]) and a counting Stroop. A positive effect of osmotic-release oral system methylphenidate was present in CPT-AX with faster and less variable reaction times under osmotic-release oral system methylphenidate than under placebo, and no difference with typically developing children. In the counting Stroop, we found a decreased interference with osmotic-release oral system methylphenidate but no difference between children with ADHD under placebo and typically developing children. © The Author(s) 2014.

  11. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of harmful effects in non-randomised studies

    DEFF Research Database (Denmark)

    Jakob, Storebø Ole; Nadia, Pedersen; Erica, Ramstad

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows:To assess the harmful effects of methylphenidate treatment for children and adolescents with attention deficit hyperactivity disorder (ADHD) in non-randomised studies.......This is the protocol for a review and there is no abstract. The objectives are as follows:To assess the harmful effects of methylphenidate treatment for children and adolescents with attention deficit hyperactivity disorder (ADHD) in non-randomised studies....

  12. Haloperidol attenuates Methylphenidate and Modafinil induced behavioural sensitization and cognitive enhancement.

    Science.gov (United States)

    Alam, Nausheen; Choudhary, Kulsoom

    2018-06-01

    Previous studies have demonstrated that repeated psychostimulant administration produces behavioural sensitization and cognitive tolerance. Brain dopaminergic system and the involvement of dopamine D 2 -receptors are considered to be important in psychostimulant-induced sensitization. Study designed to compared the motor activity by using familiar and novel enviroments and cognitive effects by water maze and passive avoidance test after long term administration of methylphenidate(at the dose 0.6 mg/kg/day, 2.5 mg/kg/day and 10 mg/kg/day) and modafinil (50 mg/kg/day, 64 mg/kg/day and 75 mg/kg/day) in rats. The effects of challenge dose of haloperidol (at the dose of 1 mg/kg i.p.) has monitored to visualize any subsensitization or supersensitization of D 2 receptors. We found that motor activity and cognitive performance was increased in all doses and sensitization effect was more pronounced after 13 days of drug administration were greater at high than low and medium doses.Challenge dose of haloperidol attenuate motor activity in familiar and novel environment and impaired cognition in water maze and passive avoidance test in all treated rats. The effect of Haloperidol in high dose treated rats were however somewhat greater than low and medium dose treated rats following methylphenidate and modafinil administration. Increased response of haloperidol in methylphenidate treated rats can be explained in term of supersensitization of D 2 receptors which is greater in high dose treated rats. The results show that the role of D 2 receptors to develop side effects such as behavioural sensitization and cognitive tolerance by the long term administration of psychostimulants is of sufficient importance and helpful in understanding the mechanisms underlying the undesirable effects of psychostimulants.

  13. Treatment effect of methylphenidate on intrinsic functional brain network in medication-naïve ADHD children: A multivariate analysis.

    Science.gov (United States)

    Yoo, Jae Hyun; Kim, Dohyun; Choi, Jeewook; Jeong, Bumseok

    2018-04-01

    Methylphenidate is a first-line therapeutic option for treating attention-deficit/hyperactivity disorder (ADHD); however, elicited changes on resting-state functional networks (RSFNs) are not well understood. This study investigated the treatment effect of methylphenidate using a variety of RSFN analyses and explored the collaborative influences of treatment-relevant RSFN changes in children with ADHD. Resting-state functional magnetic resonance imaging was acquired from 20 medication-naïve ADHD children before methylphenidate treatment and twelve weeks later. Changes in large-scale functional connectivity were defined using independent component analysis with dual regression and graph theoretical analysis. The amplitude of low frequency fluctuation (ALFF) was measured to investigate local spontaneous activity alteration. Finally, significant findings were recruited to random forest regression to identify the feature subset that best explains symptom improvement. After twelve weeks of methylphenidate administration, large-scale connectivity was increased between the left fronto-parietal RSFN and the left insula cortex and the right fronto-parietal and the brainstem, while the clustering coefficient (CC) of the global network and nodes, the left fronto-parietal, cerebellum, and occipital pole-visual network, were decreased. ALFF was increased in the bilateral superior parietal cortex and decreased in the right inferior fronto-temporal area. The subset of the local and large-scale RSFN changes, including widespread ALFF changes, the CC of the global network and the cerebellum, could explain the 27.1% variance of the ADHD Rating Scale and 13.72% of the Conner's Parent Rating Scale. Our multivariate approach suggests that the neural mechanism of methylphenidate treatment could be associated with alteration of spontaneous activity in the superior parietal cortex or widespread brain regions as well as functional segregation of the large-scale intrinsic functional

  14. Methylphenidate Transdermal System in Adult ADHD and Impact on Emotional and Oppositional Symptoms

    Science.gov (United States)

    Marchant, Barrie K.; Reimherr, Frederick W.; Robison, Reid J.; Olsen, John L.; Kondo, Douglas G.

    2011-01-01

    Objective: This trial evaluated the effect of methylphenidate transdermal system (MTS) on the full spectrum of adult symptoms (attention-disorganization, hyperactivity-impulsivity, emotional dysregulation [ED], and oppositional-defiant disorder [ODD]) found in this disorder. Method: This placebo-controlled, double-blind, flexible-dose, crossover…

  15. Methylphenidate Improves Visual-Spatial Memory in Children with Attention-Deficit- hyperactivity Disorder

    Science.gov (United States)

    Bedard, Anne-Claude; Martinussen, Rhonda; Ickowicz, Abel; Tannock, Rosemary

    2004-01-01

    Objective: To investigate the effect of methylphenidate (MPH) on visual-spatial memory, as measured by subtests of the Cambridge Neuropsychological Testing Automated Battery (CANTAB), in children with attention-deficit/hyperactivity disorder (ADHD). Visual-spatial memory is a core component of working memory that has been shown to be impaired in…

  16. Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment

    International Nuclear Information System (INIS)

    Dresel, S.; LaFougere, C.; Brinkbaeumer, K.; Hahn, K.; Tatsch, K.; Krause, J.; Krause, K.-H.; Kung, H.F.

    2000-01-01

    Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [ 99m Tc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3 x 5 mg/day). All subjects were injected with 800 MBq [ 99m Tc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semi-quantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background [(STR-BKG)/BKG]. Data were compared with an age-matched control group. It was found that untreated patients presented with a significantly increased specific binding of [ 99m Tc]TRODAT-1 to the DAT as compared with normal controls [(STR-BKG)/BKG: 1.43±0.18 vs 1.22±0.06, P<0.001]. Under treatment with methylphenidate, specific binding decreased significantly in all patients [(STR-BKG)/BKG: 1.00±0.14, P<0.001]. Our findings suggest that the number of DAT binding sites is higher in drug-naive patients suffering from ADHD than in normal controls. The decrease in available DAT binding sites under treatment with methylphenidate correlates well with the improvement in clinical symptoms. The data of this study help to elucidate the complex dysregulation of the dopaminergic neurotransmitter system in patients suffering from ADHD and the effect of treatment with psychoactive drugs. (orig.)

  17. 78 FR 40484 - Determination That METADATE ER (Methylphenidate Hydrochloride) Extended-Release Tablet, 10...

    Science.gov (United States)

    2013-07-05

    ... marketing for reasons other than safety or effectiveness. ANDAs that refer to METADATE ER (methylphenidate... Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration, HHS. ACTION... safety or effectiveness. This determination will allow FDA to approve abbreviated new drug applications...

  18. Buspirone Versus Methylphenidate in the Treatment of Children with Attention- Deficit/ Hyperactivity Disorder: Randomized Double-Blind Study

    Directory of Open Access Journals (Sweden)

    Shahin Akhondzadeh

    2012-11-01

    Full Text Available A recent randomized clinical trial showed buspirone efficacy in the treatment of attention-deficit/hyperactivity disorder (ADHD in children. However, results from a recent multi-site controlled clinical trial of transdermal buspirone failed to separate it from placebo in a large sample of children with ADHD. Therefore, due to these inconsistent findings, this study was designed to assess the efficacy of buspirone in the treatment of children with ADHD compared to methylphenidate in a double blind randomized clinical trial. Forty outpatients with a DSM-IV-TR diagnosis of ADHD were study population of this trial. Subjects were recruited from an outpatient child and adolescent clinic for a 6 week double blind, randomized clinical trial. All study subjects were randomly assigned to receive treatment using tablet of buspirone at a dose of 20-30 mg/day depending on weight (20 mg/day for 30kg (group 1 or methylphenidate at a dose of 20-30 mg/day depending on weight (20 mg/day for 30kg (group 2 for a 6 week double blind, randomized clinical trial. The principal measure of outcome was the Teacher and Parent ADHD Rating Scale IV. Patients were assessed at baseline and at 21 and 42 days after the medication started. Significant differences were observed between the two groups on the Parent and Teacher Rating Scale scores. The changes at the endpoint compared to baseline were: -8.95±8.73 (mean±SD and -15.60±7.81 (mean±SD for buspirone and methyphenidate, for Parent ADHD Rating Scale. The changes at the endpoint compared to baseline were: -9.80 ±7.06 (mean±SD and -22.40±9.90 (mean±SD for buspirone and methyphenidate, respectively for Teacher ADHD Rating Scale. The difference between the buspirone and methylphenidate groups in the frequency of side effects was not significant except for decreased appetite, headache and insomnia that were observed more frequently in the methylphenidate group. The results of this study suggest that administration of

  19. Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism.

    Science.gov (United States)

    Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Katashiba, Keisuke; Hasebe, Shigeru; Takano, Erika; Onaka, Yusuke; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

    2016-09-01

    Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA-treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA-treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA-treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA-induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine-D1 receptor antagonist SCH39166 or the dopamine-D2 receptor antagonist raclopride, but not by the α2 -adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA-treated mice via a prefrontal dopaminergic system-dependent mechanism. Autism Res 2016, 9: 926-939. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  20. Treating nicotine dependence by targeting attention-deficit/ hyperactivity disorder (ADHD) with OROS methylphenidate: the role of baseline ADHD severity and treatment response.

    Science.gov (United States)

    Nunes, Edward V; Covey, Lirio S; Brigham, Gregory; Hu, Mei-Chen; Levin, Frances R; Somoza, Eugene C; Winhusen, Theresa M

    2013-10-01

    To determine whether treatment of attention-deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. This is a secondary analysis of data from a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites; the original trial was sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n = 127) or matching placebo (n = 128). All participants received nicotine patches (21 mg/d) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline ADHD Rating Scale-IV (ADHD-RS) score, change in ADHD-RS score during treatment, and their interactions. Treatment interacted with both ADHD-RS score at baseline (P = .01) and change in ADHD-RS score during treatment (P = .008). Among patients with higher ADHD-RS scores (> 36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score ≥ 24), 70.0% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo (P = .02). In contrast, among patients with the lowest ADHD-RS baseline scores (≤ 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo (P = .02). OROS methylphenidate, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD and more robust response of ADHD symptoms to medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD

  1. Predicting Response of ADHD Symptoms to Methylphenidate Treatment Based on Comorbid Anxiety

    Science.gov (United States)

    Blouin, Brittany; Maddeaux, Cindy; Stanley Firestone, Jill; van Stralen, Judy

    2010-01-01

    Objective: In this small pilot study, the association of comorbid anxiety with the treatment of ADHD is studied. Methods: Eighteen volunteers from a pediatric clinic are tested for ADHD and anxiety and assessed for behavioral and cognitive ADHD symptomology. Response to methylphenidate as treatment for ADHD symptoms is measured 2 to 3 weeks, and…

  2. Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder

    DEFF Research Database (Denmark)

    Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R

    2017-01-01

    : We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were...... summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse...... differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. CONCLUSION: Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit...

  3. Methylphenidate poisoning: an evidence-based consensus guideline for out-of-hospital management.

    Science.gov (United States)

    Scharman, Elizabeth J; Erdman, Andrew R; Cobaugh, Daniel J; Olson, Kent R; Woolf, Alan D; Caravati, E Martin; Chyka, Peter A; Booze, Lisa L; Manoguerra, Anthony S; Nelson, Lewis S; Christianson, Gwenn; Troutman, William G

    2007-01-01

    A review of US poison center data for 2004 showed over 8,000 ingestions of methylphenidate. A guideline that determines the conditions for emergency department referral and prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce health care costs, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with suspected ingestions of methylphenidate by 1) describing the process by which a specialist in poison information should evaluate an exposure to methylphenidate, 2) identifying the key decision elements in managing cases of methylphenidate ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This review focuses on the ingestion of more than a single therapeutic dose of methylphenidate and the effects of an overdose and is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in cases in which

  4. Attention deficit hyperactivity disorder: binding of [{sup 99m}Tc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment

    Energy Technology Data Exchange (ETDEWEB)

    Dresel, S; LaFougere, C; Brinkbaeumer, K; Hahn, K; Tatsch, K [Dept. of Nuclear Medicine, Univ. of Munich (Germany); Krause, J; Krause, K -H [Inst. for Psychiatry and Psychotherapy, Ottobrunn (Germany); Friedrich Baur Inst., Univ. of Munich (Germany); Kung, H F [Dept. of Radiology, Univ. of Pennsylvania (United States)

    2000-10-01

    Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [{sup 99m}Tc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3 x 5 mg/day). All subjects were injected with 800 MBq [{sup 99m}Tc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semi-quantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background [(STR-BKG)/BKG]. Data were compared with an age-matched control group. It was found that untreated patients presented with a significantly increased specific binding of [{sup 99m}Tc]TRODAT-1 to the DAT as compared with normal controls [(STR-BKG)/BKG: 1.43{+-}0.18 vs 1.22{+-}0.06, P<0.001]. Under treatment with methylphenidate, specific binding decreased significantly in all patients [(STR-BKG)/BKG: 1.00{+-}0.14, P<0.001]. Our findings suggest that the number of DAT binding sites is higher in drug-naive patients suffering from ADHD than in normal controls. The decrease in available DAT binding sites under treatment with methylphenidate correlates well with the improvement in clinical symptoms. The data of this study help to elucidate the complex dysregulation of the dopaminergic neurotransmitter system in patients suffering from ADHD and the effect of treatment with psychoactive drugs. (orig.)

  5. Methylphenidate for ADHD in children and adolescents: throwing the baby out with the bathwater

    NARCIS (Netherlands)

    Banaschewski, T.; Buitelaar, J.K.; Chui, C.S.; Coghill, D.; Cortese, S.; Simonoff, E.; Wong, I.C.

    2016-01-01

    A recent Cochrane review assessed the efficacy of methylphenidate for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Notwithstanding the moderate-to-large effect sizes for ADHD symptom reduction found in the meta-analysis, the authors concluded that the quality of the

  6. Behavioral and stimulant treatment of hyperactive children: a therapy study with methylphenidate probes in a within-subject design.

    Science.gov (United States)

    Pelham, W E; Schnedler, R W; Bologna, N C; Contreras, J A

    1980-01-01

    Eight hyperactive children were treated with a behavioral intervention focusing on teacher and parent training over a period of 5 months. Three times, before therapy and after 3 weeks and 13 weeks of intervention, children received methylphenidate during 3-week probe periods. Each week in a probe they received either a placebo, .25 mg/kg, or .75 mg/kg methylphenidate. Classroom observation of on-task behavior suggested that effectiveness of the behavioral intervention was between that of the two dosages of medication before therapy. Both dosages resulted in higher levels of on-task behavior when administered after 13 weeks of behavioral intervention than when administered before therapy. Teacher rating data showed equivalent effects of therapy and the low dosage of methylphenidate alone but a stronger effect of the high dose alone; only the high dose resulted in improved behavior after 13 weeks of behavioral intervention. As a group, only when they received the high dose of methylphenidate after 13 weeks of behavioral intervention did children reach the level of appropriate behavior shown by nonhyperactive controls. However, this level was also reached by two children with the low dose and by one child without medication, and it was not reached by one child. The results suggest that the combination of psychostimulant medication and behavior therapy may be more effective in the short-term than either treatment alone for hyperactive children in school settings. In addition, parent ratings and clinic observation of parent-child interactions suggested that children had improved in the home setting, high-lighting the importance of behavioral parent training in the treatment of hyperactivity.

  7. Methylphenidate Transdermal System in Adults with Past Stimulant Misuse: An Open-Label Trial

    Science.gov (United States)

    McRae-Clark, Aimee L.; Brady, Kathleen T.; Hartwell, Karen J.; White, Kathleen; Carter, Rickey E.

    2011-01-01

    Objective: This 8-week, open-label trial assessed the efficacy of methylphenidate transdermal system (MTS) in 14 adult individuals diagnosed with ADHD and with a history of stimulant misuse, abuse, or dependence. Method: The primary efficacy endpoint was the Wender-Reimherr Adult ADHD Scale (WRAADS), and secondary efficacy endpoints included the…

  8. Differential effects of psychomotor stimulants on attentional performance in rats: nicotine, amphetamine, caffeine and methylphenidate.

    Science.gov (United States)

    Bizarro, L; Patel, S; Murtagh, C; Stolerman, I P

    2004-05-01

    Nicotine can improve attentional performance in the rat as assessed by a modified five-choice serial reaction time task (5-CSRTT), but it is not known if the effect is shared with other psychomotor stimulants. This study compared the effects of nicotine, amphetamine, caffeine and methylphenidate on performance in the 5-CSRTT and determined whether presenting stimuli at unpredictable times by using variable inter-trial intervals (ITI) influenced the sensitivity of the task to the drugs. One group of male hooded rats was trained to obtain food reinforcers by nose-poking in response to 1 s light stimuli presented randomly in one of five apertures, with fixed ITI; for a second group of rats, ITI varied randomly (n=12 per group). As observed previously, nicotine (tested in doses of 0.05-0.2 mg/kg) produced dose-related improvements in accuracy, reduced omission errors and response latencies, but increased anticipatory responding. Amphetamine (0.1-0.8 mg/kg) and methylphenidate (2.5-10 mg/kg) increased accuracy and reduced response latency, and decreased anticipatory responding. Caffeine (2.5-20 mg/kg) did not improve performance except at a small dose that decreased omission errors only. Training at different levels of stimulus predictability influenced performance in the undrugged state but had little impact on profiles of responses to the drugs. The findings with methylphenidate support the potential value of the 5-CSRTT for testing drugs that may be useful in the treatment of attention deficit hyperactivity disorder.

  9. Rapid response to methylphenidate as an add-on therapy to mirtazapine in the treatment of major depressive disorder in terminally ill cancer patients: a four-week, randomized, double-blinded, placebo-controlled study.

    Science.gov (United States)

    Ng, Chong Guan; Boks, Marco P M; Roes, Kit C B; Zainal, Nor Zuraida; Sulaiman, Ahmad Hatim; Tan, Seng Beng; de Wit, Niek J

    2014-04-01

    This is a 4 week, randomized, double-blind, placebo-controlled study to examine the effects of methylphenidate as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients. It involved 88 terminally ill cancer patients from University of Malaya Medical Centre, Kuala Lumpur, Malaysia. They were randomized and treated with either methylphenidate or placebo as add on to mirtazapine. The change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 3 was analyzed by linear regression. Changes of MADRS and Clinical Global Impression-Severity Scale (CGI-S) over 28 days were analyzed using mixed model repeated measures (MMRM). Secondary analysis of MADRS response rates, defined as 50% or more reduction from baseline score. A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale (MADRS) score in the methylphenidate group was observed from day 3 (B=4.14; 95% CI=1.83-6.45). Response rate (defined as 50% or more reduction from baseline MADRS score) in the methylphenidate treated group was superior from day 14. Improvement in Clinical Global Impression-Severity Scale (CGI-S) was greater in the methylphenidate treated group from day 3 until day 28. The drop-out rates were 52.3% in the methylphenidate group and 59.1% in the placebo group (relative risk=0.86, 95%CI=0.54-1.37) due to cancer progression. Nervous system adverse events were more common in methylphenidate treated subjects (20.5% vs 9.1%, p=0.13). In conclusions, methylphenidate as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients, although at an increased risk of the nervous system side effects. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  10. Immediate-Release Methylphenidate for ADHD in Children with Comorbid Chronic Multiple Tic Disorder

    Science.gov (United States)

    Gadow, Kenneth D.; Sverd, Jeffrey; Nolan, Edith E.; Sprafkin, Joyce; Schneider, Jayne

    2007-01-01

    Objective: To examine the safety and efficacy of immediate-release methylphenidate (MPH-IR) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (ages 6-12 years) with Tourette's syndrome (96%) or chronic motor tic disorder (4%). Method: Two cohorts of prepubertal children (N = 71) received placebo and three doses of…

  11. Randomized, 6-Week, Placebo-Controlled Study of Treatment for Adult Attention-Deficit/Hyperactivity Disorder: Individualized Dosing of Osmotic-Release Oral System (OROS) Methylphenidate With a Goal of Symptom Remission.

    Science.gov (United States)

    Goodman, David W; Starr, H Lynn; Ma, Yi-Wen; Rostain, Anthony L; Ascher, Steve; Armstrong, Robert B

    2017-01-01

    To evaluate the efficacy and safety of individualized dosing within the approved dose range for osmotic-release oral system (OROS) methylphenidate hydrochloride in adults with attention-deficit/hyperactivity disorder (ADHD). A double-blind, 6-week trial was conducted between July 2009 and February 2010 at 35 US sites. Adults with ADHD (DSM-IV diagnostic criteria) and a screening ADHD Investigator Symptom Rating Scale (AISRS) score > 24 were randomly assigned to OROS methylphenidate 18 mg or matching placebo. Treatment dose could be increased at 18 mg increments, up to 72 mg/d, until an optimal dose was achieved. AISRS score changes from baseline to end point (primary outcome) were analyzed using analysis of covariance. At baseline, the intent-to-treat population of 169 OROS methylphenidate and 172 placebo subjects (mean age = 35.8 years) had mean (standard deviation [SD]) AISRS scores of 37.8 (6.94) and 37.0 (7.51), respectively. OROS methylphenidate-treated subjects exhibited a significantly greater mean (SD) AISRS score improvement than placebo subjects (-17.1 [12.44] vs -11.7 [13.30]; P ADHD. OROS methylphenidate treatment with individualized doses titrated to achieve symptom remission demonstrated greater ADHD symptom reduction than placebo treatment. These data support the overall efficacy of OROS methylphenidate treatment in the management of adults with ADHD and provide new possibilities for additional intervention. ClinicalTrials.gov identifier: NCT00937040. © Copyright 2017 Physicians Postgraduate Press, Inc.

  12. Differential therapeutic effects of 12-week treatment of atomoxetine and methylphenidate on drug-naïve children with attention deficit/hyperactivity disorder: A counting Stroop functional MRI study.

    Science.gov (United States)

    Chou, Tai-Li; Chia, Seng; Shang, Chi-Yung; Gau, Susan Shur-Fen

    2015-12-01

    Methylphenidate and atomoxetine are effective in treating attention-deficit/hyperactivity disorder (ADHD) with underlying distinct pharmacological mechanisms. To relate neural mechanisms to clinical response, we conducted a comparative trial to differentiate the changes in brain activation of drug-naïve children with ADHD when performing neuropsychological tasks after 12 weeks of pharmacotherapy. We randomized 50 drug-naïve children with ADHD, aged 7-17, to treatment with methylphenidate (n=25) or atomoxetine (n=25). These children were scanned twice with functional magnetic resonance imaging (fMRI) during the counting Stroop task before and after treatment. Focused attention and impulsivity were assessed twice by using the Conner's Continuous Performance Test (CCPT). The final sample for fMRI analysis comprised 20 in the methylphenidate group and 22 in the atomoxetine group. Atomoxetine decreased activations in the dorsal anterior cingulate cortex and dorsolateral prefrontal cortex, which correlated with improvement in focused attention assessed by the CCPT. In contrast, methylphenidate increased activations in the inferior frontal gyrus, which correlated with the decreasing severity of impulsivity assessed by the CCPT. The current findings suggest that differential therapeutic effects on neuronal changes induced by 12-week treatment atomoxetine and methylphenidate may contribute to behavioral improvement. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  13. [Methylphenidate and short-term memory in young females with attention deficit hyperactivity disorder. A study using functional magnetic resonance imaging].

    Science.gov (United States)

    Gonzalez-Garrido, A A; Barrios, F A; de la Serna-Tuya, J M; Cocula-León, H; Gómez-Velázquez, F R

    Attention deficit/hyperactivity disorder (ADHD) is a common behavioral disorder found mainly in males, thus current knowledge on its clinical expression in female adults is extremely limited. AIM. To evaluate the behavioral and neural substrates associated with the performance of a short-term memory task in female ADHD adults, with and without methylphenidate exposure, with respect to a control group. Two groups of eight young right-handed, female, university students with ADHD and healthy controls matched by age, gender, handedness and academic level, voluntarily participated. All subjects performed twice an easy auditory short-term memory task (ADHD group without, and 90 minutes post-intake of methylphenidate 0.4 mg/kg in a counterbalanced order). The BOLD-fMRI response was used as a measure of neural activity during task performance. ADHD subjects showed a tendency to improve their performances under medication, showing an increased widespread functional activation, especially relevant over left frontal and cerebellar areas, in comparison with control subjects. Methylphenidate slightly improves short-term memory task performance in adult female ADHD subjects by modifying underlying neural functioning patterns.

  14. Differential Effects of Methylphenidate on Attentional Functions in Children with Attention-Deficit-Hyperactivity Disorder

    Science.gov (United States)

    Konrad, Kerstin; Gunther, Thomas; Hanisch, Charlotte; Herpertz-Dahlmann, Beate

    2004-01-01

    Objective: To examine the effects of methylphenidate on different attentional functions and behavior in children with attention-deficit-hyperactivity disorder (ADHD). Method: A total of 60 ADHD children aged between 8 and 12 years completed a randomized, double-blind, placebo-controlled, within-subject crossover trial with two doses of…

  15. Autonomic correlates at rest and during evoked attention in children with attention-deficit/hyperactivity disorder and effects of methylphenidate.

    Science.gov (United States)

    Negrao, Bianca Lee; Bipath, Priyesh; van der Westhuizen, Deborah; Viljoen, Margaretha

    2011-01-01

    The aim of this study was to assess autonomic nervous system functioning in children with attention-deficit/hyperactivity disorder (ADHD) and to examine the effects of methylphenidate and focussed attention. Children with ADHD (n = 19) were tested while they were stimulant free and during a period in which they were on stimulants. On both occasions, autonomic nervous system functioning was tested at baseline and during focussed attention. Autonomic nervous system functioning of control subjects was also tested at baseline and during focussed attention. Autonomic nervous system activity was determined by means of heart rate variability (HRV) and skin conductivity analyses. Attention was evoked by means of the BioGraph Infiniti biofeedback apparatus. HRV was determined by time domain, frequency domain and Poincaré analysis of RR interval data. Skin conductivity was determined by the BioGraph Infiniti biofeedback apparatus. The main findings of this study were (a) that stimulant-free children with ADHD showed a sympathetic underarousal and parasympathetic overarousal of the sympathovagal balance relative to control subjects; (b) methylphenidate shifted the autonomic balance of children with ADHD towards normal levels; however, a normal autonomic balance was not reached, and (c) stimulant-free children with ADHD exhibited a shift in the sympathovagal balance towards the sympathetic nervous system from baseline to focussed attention; however, methylphenidate appeared to abolish this shift. Stimulant-free children with ADHD have a parasympathetic dominance of the autonomic balance, relative to control subjects. Methylphenidate attempts to restore the normal autonomic balance in children with ADHD, but inhibits the normal autonomic nervous system response to a cognitive challenge. These results indicate that methylphenidate may have a suppressive effect on the normal stress response. Although this may be of benefit to those who interact with children who suffer from ADHD

  16. The association between methylphenidate treatment and the risk for fracture among young ADHD patients: A nationwide population-based study in Taiwan.

    Directory of Open Access Journals (Sweden)

    Vincent Chin-Hung Chen

    Full Text Available Attention-deficit hyperactivity disorder (ADHD is associated with higher risk for fracture. Whether the medical treatment for ADHD would mitigate the risk remains unclear. In this study, we sought to investigate the effect of methylphenidate treatment on risk for fracture, as well the moderational role of treatment duration on the risk of fracture, in a large national sample. Cases less than 18 years old were identified from Taiwan's National Health Insurance Research Database with a new primary diagnosis of ADHD (ICD-9:314 between 1996 and 2013. A total of 6201 cases with ADHD were included as the study cohort. The cases were divided into 3 groups according to the duration of methylphenidate treatment (0, 1-180, and more than 180 days. All groups were followed until the end of 2013 for first diagnoses of fracture (ICD-9 codes 800 to 829. Cox proportional hazards models were applied. Compared to the group without methylphenidate treatment, the risk for fracture was lower among the group treated for more than 180 days. The adjusted hazard ratio was 0.77 (95% Confidence interval: 0.63-0.94. The groups treated for 180 days or fewer had no significant difference in the risk for fracture. In conclusion, methylphenidate treatment was associated with lower risk for fracture among ADHD patients. The association was evident only in the cohort treated for more than 180 days.

  17. The Cochrane Collaboration withdraws a review on methylphenidate for adults with attention deficit hyperactivity disorder

    DEFF Research Database (Denmark)

    Boesen, Kim; Saiz, Luis Carlos; Erviti, Juan

    2017-01-01

    A Cochrane systematic review on immediate-release methylphenidate for adults with attention deficit hyperactivity disorder (ADHD) was withdrawn from the Cochrane Library on 26 May 2016 after substantial criticism of its methods and flawed conclusions. Retraction of scientific papers on this basis...

  18. The effect of methylphenidate on three forms of response inhibition in boys with AD/HD

    NARCIS (Netherlands)

    Scheres, A.; Oosterlaan, J.; Swanson, J.; Morein-Zamir, S.; Meiran, N.; Schut, H.; Vlasveld, L.; Sergeant, J.A.

    2003-01-01

    The current study was aimed at (a) investigating the effect of three doses methylphenidate (MPH) and placebo on inhibition of a prepotent response, inhibition of an ongoing response, and interference control in Attention Deficit/Hyperactivity Disorder (AD/HD), and (b) studying dose-response

  19. Methylphenidate Improves Working Memory and Set-Shifting in AD/HD: Relationships to Baseline Memory Capacity

    Science.gov (United States)

    Mehta, Mitul A.; Goodyer, Ian M.; Sahakian, Barbara J.

    2004-01-01

    Objective: Catecholamine stimulant drugs are highly efficacious treatments for attention deficit/hyperactivity disorders (AD/HD). Catecholamine modulation in humans influences performance of numerous cognitive tasks, including tests of attention and working memory (WM). Clear delineation of the effects of methylphenidate upon such cognitive…

  20. Methylphenidate, modafinil, and caffeine for cognitive enhancement in chess: A double-blind, randomised controlled trial.

    Science.gov (United States)

    Franke, Andreas G; Gränsmark, Patrik; Agricola, Alexandra; Schühle, Kai; Rommel, Thilo; Sebastian, Alexandra; Balló, Harald E; Gorbulev, Stanislav; Gerdes, Christer; Frank, Björn; Ruckes, Christian; Tüscher, Oliver; Lieb, Klaus

    2017-03-01

    Stimulants and caffeine have been proposed for cognitive enhancement by healthy subjects. This study investigated whether performance in chess - a competitive mind game requiring highly complex cognitive skills - can be enhanced by methylphenidate, modafinil or caffeine. In a phase IV, randomized, double-blind, placebo-controlled trial, 39 male chess players received 2×200mg modafinil, 2×20mg methylphenidate, and 2×200mg caffeine or placebo in a 4×4 crossover design. They played twenty 15-minute games during two sessions against a chess program (Fritz 12; adapted to players' strength) and completed several neuropsychological tests. Marked substance effects were observed since all three substances significantly increased average reflection time per game compared to placebo resulting in a significantly increased number of games lost on time with all three treatments. Treatment effects on chess performance were not seen if all games (n=3059) were analysed. Only when controlling for game duration as well as when excluding those games lost on time, both modafinil and methylphenidate enhanced chess performance as demonstrated by significantly higher scores in the remaining 2876 games compared to placebo. In conjunction with results from neuropsychological testing we conclude that modifying effects of stimulants on complex cognitive tasks may in particular result from more reflective decision making processes. When not under time pressure, such effects may result in enhanced performance. Yet, under time constraints more reflective decision making may not improve or even have detrimental effects on complex task performance. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

  1. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder sub-optimally treated with immediate release methylphenidate.

    Directory of Open Access Journals (Sweden)

    Jurjen van der Schans

    Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD is a common psychiatric disorder in children and adolescents. Immediate-release methylphenidate (IR-MPH is the medical treatment of first choice. The necessity to use several IR-MPH tablets per day and associated potential social stigma at school often leads to reduced compliance, sub-optimal treatment, and therefore economic loss. Replacement of IR-MPH with a single-dose extended release (ER-MPH formulation may improve drug response and economic efficiency.To evaluate the cost-effectiveness from a societal perspective of a switch from IR-MPH to ER-MPH in patients who are sub-optimally treated.A daily Markov-cycle model covering a time-span of 10 years was developed including four different health states: (1 optimal response, (2 sub-optimal response, (3 discontinued treatment, and (4 natural remission. ER-MPH options included methylphenidate osmotic release oral system (MPH-OROS and Equasym XL/Medikinet CR. Both direct costs and indirect costs were included in the analysis, and effects were expressed as quality-adjusted life years (QALYs. Univariate, multivariate as well as probabilistic sensitivity analysis were conducted and the main outcomes were incremental cost-effectiveness ratios.Switching sub-optimally treated patients from IR-MPH to MPH-OROS or Equasym XL/Medikinet CR led to per-patient cost-savings of €4200 and €5400, respectively, over a 10-year treatment span. Sensitivity analysis with plausible variations of input parameters resulted in cost-savings in the vast majority of estimations.This study lends economic support to switching patients with ADHD with suboptimal response to short-acting IR-MPH to long-acting ER-MPH regimens.

  2. Evidence on methylphenidate in children and adolescents with ADHD is in fact of ‘very low quality’

    DEFF Research Database (Denmark)

    Storebø, O. J.; Zwi, Morris; Krogh, Helle B

    2016-01-01

    Banaschewski and colleagues from the European Attention Deficit Hyperactivity Disorder (ADHD) guideline group make a number of critical comments regarding our systematic review on methylphenidate for children and adolescents with ADHD. In this article, we present our views, showing that our trial...... selection was not flawed and was undertaken with scientific justification. Similarly, our data collection and interpretation was systematic and correct. We have followed a sound methodology for assessing risk of bias and our conclusions are not misleading. We acknowledge that different researchers might...... such errors and to engage in debate on methodological and ethical issues. In terms of clinical implications, we are advocating that clinicians, patients and their relatives should weight carefully risks and benefits of methylphenidate. Clinical experience seems to suggest that there are people who benefit...

  3. How Oppositionality, Inattention, and Hyperactivity Affect Response to Atomoxetine versus Methylphenidate: A Pooled Meta-Analysis

    Science.gov (United States)

    van Wyk, Gregory W.; Hazell, Philip L.; Kohn, Michael R.; Granger, Renee E.; Walton, Richard J.

    2012-01-01

    Objective: To assess how threshold oppositional defiant disorder (ODD), inattention, and hyperactivity-impulsivity affect the response to atomoxetine versus methylphenidate. Method: Systematic review of randomized controlled trials (RCTs; greater than or equal to 6 weeks follow-up). The primary measure was core symptom response--greater than or…

  4. Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

    OpenAIRE

    Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

    2010-01-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and...

  5. Predicting methylphenidate response in attention deficit hyperactivity disorder: a preliminary study.

    Science.gov (United States)

    Johnston, Blair A; Coghill, David; Matthews, Keith; Steele, J Douglas

    2015-01-01

    Methylphenidate (MPH) is established as the main pharmacological treatment for patients with attention deficit hyperactivity disorder (ADHD). Whilst MPH is generally a highly effective treatment, not all patients respond, and some experience adverse reactions. Currently, there is no reliable method to predict how patients will respond, other than by exposure to a trial of medication. In this preliminary study, we sought to investigate whether an accurate predictor of clinical response to methylphenidate could be developed for individual patients, using sociodemographic, clinical and neuropsychological measures. Of the 43 boys with ADHD included in this proof-of-concept study, 30 were classed as responders and 13 as non-responders to MPH, with no significant differences in age nor verbal intelligence quotient (IQ) between the groups. Here we report the application of a multivariate analysis approach to the prediction of clinical response to MPH, which achieved an accuracy of 77% (p = 0.005). The most important variables to the classifier were performance on a 'go/no go' task and comorbid conduct disorder. This preliminary study suggested that further investigation is merited. Achieving a highly significant accuracy of 77% for the prediction of MPH response is an encouraging step towards finding a reliable and clinically useful method that could minimise the number of children needlessly being exposed to MPH. © The Author(s) 2014.

  6. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [123I]FP-CIT and a dedicated small animal SPECT

    International Nuclear Information System (INIS)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf; Schramm, Nils

    2005-01-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [ 123 I]FP-CIT. [ 123 I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [ 123 I]FP-CIT scans with bone metabolism and perfusion scans obtained with 99m Tc-DPD and 99m Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [ 123 I]FP-CIT scans with images of brain perfusion obtained with 99m Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V '' 3 ) of 0.24±0.26 (mean ± SD) and 1.09±0.42, respectively (ttest, two-tailed, p '' 3 values amounted to 0.05±0.28 (methylphenidate) and 0.3±0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [ 123 I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [ 123 I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and small animal imaging systems. (orig.)

  7. Risperidone Versus Methylphenidate in Treatment of Preschool Children With Attention-Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Arabgol, Fariba; Panaghi, Leily; Nikzad, Vahid

    2015-02-01

    Attention Deficit Hyperactivity Disorder (ADHD) is a common psychiatric diagnosis among preschool children. The aim of this study was to examine the Risperidone treatment compared to Methylphenidate (MPH) in preschool children with ADHD. Thirty three outpatient preschool children, aged 3-6 years, diagnosed with ADHD (The diagnosis of ADHD was established by two child and adolescent psychiatrists according to the DSM-IV-TR criteria), participated in a 6-week, double-blind clinical trial with risperidone (0.5-1.5 mg/d) and methylphenidate (5-20 mg/d), in two divided doses. Treatment outcomes were assessed using the Parent ADHD Rating Scale and Conners Rating Scale. Patients were assessed by a child psychiatrist at baseline, 2, 4 and 6 weeks after the medication started. Side effects were also rated by side effects questionnaire. There were no significant differences between the two protocols on the Parent ADHD Rating Scale scores (P > 0.05) and Parent Conners Rating Scale scores (P > 0.05). Both groups showed a significant improvement in ADHD symptoms over the 6 weeks of treatment for parent ADHD Rating Scale (P benefits and adverse effects in long term use and comorbid conditions.

  8. The impact of methylphenidate and its enantiomers on dopamine synthesis and metabolism in vitro

    DEFF Research Database (Denmark)

    Bartl, Jasmin; Palazzesi, Ferruccio; Parrinello, Michele

    2017-01-01

    Methylphenidate (MPH), a psychostimulant, is an effective first-line treatment for the symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Although most MPH formulations are composed of the racemic 1:1 mixture of the two enantiomers (d- and l-threo), converging lines of evid...... to the stereoselectivity of the investigated enzymes and pharmacological effects of MPH enantiomers....

  9. Treatment outcomes after methylphenidate in adults with attention-deficit/hyperactivity disorder treated with lisdexamfetamine dimesylate or atomoxetine

    Directory of Open Access Journals (Sweden)

    Joseph A

    2016-03-01

    Full Text Available Alain Joseph,1 Martin Cloutier,2 Annie Guérin,2 Roy Nitulescu,2 Vanja Sikirica3 1Global HEOR and Epidemiology, Shire, Zählerweg, Zug, Switzerland; 2Analysis Group, Inc., Montreal, Quebec, Canada; 3Global HEOR and Epidemiology, Shire, Wayne, PA, USA Purpose: To compare treatment adherence, discontinuation, add-on, and daily average consumption (DACON among adults with attention-deficit/hyperactivity disorder receiving second-line lisdexamfetamine dimesylate (LDX or atomoxetine (ATX, following methylphenidate.Patients and methods: A retrospective cohort study using US commercial claims databases (Q2/2009–Q3/2013.Results: At month 12, the LDX cohort (N=2,718 had a higher adherence level (proportion of days covered: 0.48 versus 0.30, P<0.001 and was less likely to discontinue (Kaplan–Meier estimate: 63% versus 85%, P<0.001 than the ATX cohort (N=674. There were no statistical differences in treatment add-on rates between cohorts (Kaplan–Meier estimate: 26% versus 25%, P=0.297. The LDX cohort had a lower DACON (1.10 versus 1.31, P<0.001 and was less likely to have a DACON >1 (adjusted odds ratio: 0.20, 95% confidence interval: 0.15–0.25, P<0.001 than the ATX cohort.Conclusion: Adults with attention-deficit/hyperactivity disorder treated with LDX following methylphenidate had a higher treatment adherence and lower discontinuation and DACON relative to those treated with ATX following methylphenidate. Keywords: ADHD, adult, adherence, lisdexamfetamine dimesylate, atomoxetine

  10. Methylphenidate and Comorbid Anxiety Disorder in Children with both Chronic Multiple Tic Disorder and ADHD

    Science.gov (United States)

    Gadow, Kenneth D.; Nolan, Edith E.

    2011-01-01

    Objective: To determine if comorbid anxiety disorder is associated with differential response to immediate release methylphenidate (MPH-IR) in children with both ADHD and chronic multiple tic disorder (CMTD). Method: Children with (n = 17) and without (n = 37) diagnosed anxiety disorder (ANX) were evaluated in an 8-week, placebo-controlled trial…

  11. Neonatal programming with testosterone propionate reduces dopamine transporter expression in nucleus accumbens and methylphenidate-induced locomotor activity in adult female rats.

    Science.gov (United States)

    Dib, Tatiana; Martínez-Pinto, Jonathan; Reyes-Parada, Miguel; Torres, Gonzalo E; Sotomayor-Zárate, Ramón

    2018-07-02

    Research in programming is focused on the study of stimuli that alters sensitive periods in development, such as prenatal and neonatal stages, that can produce long-term deleterious effects. These effects can occur in various organs or tissues such as the brain, affecting brain circuits and related behaviors. Our laboratory has demonstrated that neonatal programming with sex hormones affects the mesocorticolimbic circuitry, increasing the synthesis and release of dopamine (DA) in striatum and nucleus accumbens (NAcc). However, the behavioral response to psychostimulant drugs such as methylphenidate and the possible mechanism(s) involved have not been studied in adult rats exposed to sex hormones during the first hours of life. Thus, the aim of this study was to examine the locomotor activity induced by methylphenidate (5mg/kg i.p.) and the expression of the DA transporter (DAT) in NAcc of adult rats exposed to a single dose of testosterone propionate (TP: 1mg/50μLs.c.) or estradiol valerate (EV: 0.1mg/50μLs.c.) at postnatal day 1. Our results demonstrated that adult female rats treated with TP have a lower methylphenidate-induced locomotor activity compared to control and EV-treated adult female rats. This reduction in locomotor activity is related with a lower NAcc DAT expression. However, neither methylphenidate-induced locomotor activity nor NAcc DAT expression was affected in EV or TP-treated adult male rats. Our results suggest that early exposure to sex hormones affects long-term dopaminergic brain areas involved in the response to psychostimulants, which could be a vulnerability factor to favor the escalating doses of drugs of abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Long-term oral methylphenidate treatment in adolescent and adult rats: differential effects on brain morphology and function

    NARCIS (Netherlands)

    Marel, K. van der; Klomp, A.; Meerhoff, G.F.; Schipper, P.; Lucassen, P.J.; Homberg, J.R.; Dijkhuizen, R.M.; Reneman, L.

    2014-01-01

    Methylphenidate is a widely prescribed psychostimulant for treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents, which raises questions regarding its potential interference with the developing brain. In the present study, we investigated effects of 3 weeks oral

  13. The effectiveness of methylphenidate in the treatment of encopresis independent from attention-deficit hyperactivity disorder symptoms.

    Science.gov (United States)

    Akça, Ömer Faruk; Yılmaz, Savaş

    2015-01-01

    Several medications are reported to be effective in treatment of encopresis. However, mechanisms of action related to these drugs are not known. We report a patient with ADHD and encopresis whose encopretic signs have disappeared with long acting methylphenidate while they have not changed with atomoxetine.

  14. The Effectiveness of Methylphenidate in the Treatment of Encopresis Independent from Attention-Deficit Hyperactivity Disorder Symptoms

    OpenAIRE

    Ak?a, ?mer Faruk; Y?lmaz, Sava?

    2015-01-01

    Several medications are reported to be effective in treatment of encopresis. However, mechanisms of action related to these drugs are not known. We report a patient with ADHD and encopresis whose encopretic signs have disappeared with long acting methylphenidate while they have not changed with atomoxetine.

  15. Quantitation of dopamine transporter blockade by methylphenidate: first in vivo investigation using [{sup 123}I]FP-CIT and a dedicated small animal SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaus, Susanne; Wirrwar, Andreas; Antke, Christina; Arkian, Shahram; Mueller, Hans-Wilhelm; Larisch, Rolf [Heinrich-Heine University, Clinic of Nuclear Medicine, Duesseldorf (Germany); Schramm, Nils [Research Center Juelich, Central Laboratory for Electronics, Juelich (Germany)

    2005-03-01

    The aim of this study was to investigate the feasibility of assessing dopamine transporter binding after treatment with methylphenidate in the rat using a recently developed high-resolution small animal single-photon emission computed tomograph (TierSPECT) and [{sup 123}I]FP-CIT. [{sup 123}I]FP-CIT was administered intravenously 1 h after intraperitoneal injection of methylphenidate (10 mg/kg) or vehicle. Animals underwent scanning 2 h after radioligand administration. The striatum was identified by superimposition of [{sup 123}I]FP-CIT scans with bone metabolism and perfusion scans obtained with {sup 99m}Tc-DPD and {sup 99m}Tc-tetrofosmin, respectively. As these tracers do not pass the blood-brain barrier, their distribution permits the identification of extracerebral anatomical landmarks such as the orbitae and the harderian glands. The cerebellum was identified by superimposing [{sup 123}I]FP-CIT scans with images of brain perfusion obtained with {sup 99m}Tc-HMPAO. Methylphenidate-treated animals and vehicle-treated animals yielded striatal equilibrium ratios (V''{sub 3}) of 0.24{+-}0.26 (mean {+-} SD) and 1.09{+-}0.42, respectively (ttest, two-tailed, p<0.0001). Cortical V''{sub 3} values amounted to 0.05{+-}0.28 (methylphenidate) and 0.3{+-}0.39 (saline, p=0.176). This first in vivo study of rat dopamine transporter binding after pre-treatment with methylphenidate showed a mean reduction of 78% in striatal [{sup 123}I]FP-CIT accumulation. The results can be interpreted in terms of a pharmacological blockade in the rat striatum and show that in vivo quantitation of dopamine transporter binding is feasible with [{sup 123}I]FP-CIT and the TierSPECT. This may be of future relevance for in vivo investigations on rat models of attention deficit/hyperactivity disorder. Furthermore, our findings suggest that investigations in other animal models, e.g. of Parkinson's and Huntington's disease, may be feasible using SPECT radioligands and

  16. Mass Spectrometry Imaging Shows Cocaine and Methylphenidate Have Opposite Effects on Major Lipids in Drosophila Brain.

    Science.gov (United States)

    Philipsen, Mai H; Phan, Nhu T N; Fletcher, John S; Malmberg, Per; Ewing, Andrew G

    2018-03-20

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to study the effects of cocaine versus methylphenidate administration on both the localization and abundance of lipids in Drosophila melanogaster brain. A J105 ToF-SIMS with a 40 keV gas cluster primary ion source enabled us to probe molecular ions of biomolecules on the fly with a spatial resolution of ∼3 μm, giving us unique insights into the effect of these drugs on molecular lipids in the nervous system. Significant changes in phospholipid composition were observed in the central brain for both. Principal components image analysis revealed that changes occurred mainly for phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols. When the lipid changes caused by cocaine were compared with those induced by methylphenidate, it was shown that these drugs exert opposite effects on the brain lipid structure. We speculate that this might relate to the molecular mechanism of cognition and memory.

  17. Segmental hair testing to disclose chronic exposure to psychoactive drugs.

    Science.gov (United States)

    Marchei, Emilia; Palmi, Ilaria; Pichini, Simona; Pacifici, Roberta; Anton Airaldi, Ileana-Rita; Costa Orvay, Juan Antonio; García Serra, Joan; Bonet Serra, Bartolomé; García-Algar, Óscar

    2016-06-15

    This study presents the case of a 4-year-old healthy child admitted to the paediatric ward for suspected accidental intoxication due to ingestion of narcoleptic drugs (methylphenidate, sertraline and quetiapine), taken on a regular basis by his 8-year-old brother affected by Asperger syndrome.Intoxication can be objectively assessed by measurements of drugs and metabolites in biological matrices with short-term (blood and urine) or long-term (hair) detection windows. At the hospital, the child's blood and urine were analysed by immunoassay (confirmed by liquid chromatography-mass spectrometry), and sertraline and quetiapine and their metabolites were identified. The suspicion that the mother administered drugs chronically prompted the analysis of six, consecutive 2-cm segments of the child's hair, using ultra-high performance liquid chromatography-tandem mass spectrometry, thereby accounting for ingestion over the previous 12 months. Quetiapine was found in the first four segments with a mean concentration of 1.00 ng/mg ± 0.94 ng/mg hair while sertraline and its metabolite, desmethyl-sertraline, were found in all segments with a mean concentration of 2.65 ± 0.94 ng/mg and 1.50 ± 0.94 ng/mg hair, respectively. Hair analyses were negative for methylphenidate and its metabolite (ritalinic acid). Biological matrices testing for psychoactive drugs disclosed both acute and chronic intoxication with quetiapine and sertraline administered by the mother.

  18. Risperidone Versus Methylphenidate in Treatment of Preschool Children With Attention-Deficit Hyperactivity Disorder

    OpenAIRE

    Arabgol, Fariba; Panaghi, Leily; Nikzad, Vahid

    2015-01-01

    Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common psychiatric diagnosis among preschool children. Objectives: The aim of this study was to examine the Risperidone treatment compared to Methylphenidate (MPH) in preschool children with ADHD. Patients and Methods: Thirty three outpatient preschool children, aged 3-6 years, diagnosed with ADHD (The diagnosis of ADHD was established by two child and adolescent psychiatrists according to the DSM-IV-TR criteria), participated i...

  19. Methylphenidate for ADHD in children and adolescents: throwing the baby out with the bathwater.

    Science.gov (United States)

    Banaschewski, Tobias; Buitelaar, Jan; Chui, Celine S L; Coghill, David; Cortese, Samuele; Simonoff, Emily; Wong, Ian C K

    2016-11-01

    A recent Cochrane review assessed the efficacy of methylphenidate for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Notwithstanding the moderate-to-large effect sizes for ADHD symptom reduction found in the meta-analysis, the authors concluded that the quality of the evidence is low and therefore the true magnitude of these effects remains uncertain. We identified a number of major concerns with the review, in the domains of study inclusion, approaches to quality assessment and interpretation of data relating to serious adverse events as well as of the clinical implications of the reported effects. We also found errors in the extraction of data used to estimate the effect size of the primary outcome. Considering all the shortcomings, the conclusion in the Cochrane review that the status of the evidence is uncertain is misplaced. Professionals, parents and patients should refer to previous reviews and existing guidelines, which include methylphenidate as one of the safe and efficacious treatment strategies for ADHD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  20. Quality of life of methylphenidate treatment-responsive adolescents with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Pin-Chen Yang

    2012-05-01

    Full Text Available Quality of life (QOL in methylphenidate treatment-responsive adolescents with attention deficit/hyperactivity disorder (ADHD was assessed. Patients were 12- to 18-year-old adolescents with ADHD (total n = 45 who had been on methylphenidate treatment for at least 3 months and were clinically judged to be improved. The self-completed Taiwanese Quality of Life Questionnaire for Adolescents (TQOLQA was used, and the resulting measures were compared between adolescents with ADHD and: (1 community adolescents (n = 2316; (2 treatment-responsive adolescents with a chronic medical condition (i.e., adolescents with leukemia in its first and complete continuous remission for at least 3 years after chemotherapy (n = 39. Patients’ cognitive profile and their daily executive functioning were also obtained for analysis. The QOL of the treated adolescents with ADHD was reported to be worse than that of both the community healthy adolescents and the adolescent leukemia survivors in the self-reported TQOLQA domain of “psychological well-being”. Treated adolescents with ADHD still had impaired executive skills in natural, everyday environments, and the scores for daily executive abilities could predict the QOL measures. Factors besides pharmacotherapy should be explored to further improve the QOL of medication-treated adolescents with ADHD.

  1. Effect of methylphenidate on ICU and hospital length of stay in patients with severe and moderate traumatic brain injury.

    Science.gov (United States)

    Moein, Houshang; Khalili, Hossein A; Keramatian, Kamyar

    2006-09-01

    Traumatic brain injury is one of the major causes of death and disability among young people. Methylphenidate, a neural stimulant and protective drug, which has been mainly used for childhood attention deficit/hyperactivity disorder, has shown some benefits in late psychosocial problems in patients with traumatic brain injury. Its effect on arousal and consciousness has been also revealed in the sub-acute phase of traumatic brain injury. We studied its effect on the acute phase of moderate and severe traumatic brain injury (TBI) in relation to the length of ICU and hospital admission. Severely and moderately TBI patients (according to inclusion and exclusion criteria) were randomized to treatment and control groups. The treatment group received methylphenidate 0.3mg/kg per dose PO BID by the second day of admission until the time of discharge, and the control group received a placebo. Admission information and daily Glasgow Coma Scale (GCS) were recorded. Medical, surgical, and discharge plans for patients were determined by the attending physician, blinded to the study. Forty patients with severe TBI (GCS = 5-8) and 40 moderately TBI patients (GCS = 9-12) were randomly divided into treatment and control groups on the day of admission. In the severely TBI patients, both hospital and ICU length of stay, on average, were shorter in the treatment group compared with the control group. In the moderately TBI patients while ICU stay was shorter in the treatment group, there was no significant reduction of the period of hospitalization. There were no significant differences between the treatment and control groups in terms of age, sex, post resuscitation GCS, or brain CT scan findings, in either severely or moderately TBI patients. Methylphenidate was associated with reductions in ICU and hospital length of stay by 23% in severely TBI patients (P = 0.06 for ICU and P = 0.029 for hospital stay time). However, in the moderately TBI patients who received methylphenidate

  2. Performance on a strategy set shifting task during adolescence in a genetic model of attention deficit/hyperactivity disorder: Methylphenidate vs. atomoxetine treatments

    Science.gov (United States)

    Harvey, Roxann C; Jordan, Chloe J; Tassin, David H; Moody, Kayla R; Dwoskin, Linda P; Kantak, Kathleen M

    2013-01-01

    Research examining medication effects on set shifting in teens with attention deficit/hyperactivity disorder (ADHD) is lacking. An animal model of ADHD may be useful for exploring this gap. The Spontaneously Hypertensive Rat (SHR) is a commonly used animal model of ADHD. SHR and two comparator strains, Wistar-Kyoto (WKY) and Wistar (WIS), were evaluated during adolescence in a strategy set shifting task under conditions of a 0-sec or 15-sec delay to reinforcer delivery. The task had three phases: initial discrimination, set shift and reversal learning. Under 0-sec delays, SHR performed as well as or better than WKY and WIS. Treatment with 0.3 mg/kg/day atomoxetine had little effect, other than to modestly increase trials to criterion during set shifting in all strains. Under 15-sec delays, SHR had longer lever press reaction times, longer latencies to criterion and more trial omissions than WKY during set shifting and reversal learning. These deficits were not reduced systematically by 1.5 mg/kg/day methylphenidate or 0.3 mg/kg/day atomoxetine. Regarding learning in SHR, methylphenidate improved initial discrimination, whereas atomoxetine improved set shifting but disrupted initial discrimination. During reversal learning, both drugs were ineffective in SHR, and atomoxetine made reaction time and trial omissions greater in WKY. Overall, WIS performance differed from SHR or WKY, depending on phase. Collectively, a genetic model of ADHD in adolescent rats revealed that neither methylphenidate nor atomoxetine mitigated all deficits in SHR during the set shifting task. Thus, methylphenidate or atomoxetine monotherapy may not mitigate all set shift task-related deficits in teens with ADHD. PMID:23376704

  3. Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Lakić Aneta

    2012-01-01

    Full Text Available Introduction. Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD is a clinical entity consisting of a cluster of symptoms including hyperactivity, attention disorder and impulse control disorder group. In the context of ADHD etiology we may say that genetic, clinical and imaging studies point out a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs, which increase extracellular dopamine in the brain. Basically, it is a biological and not psychological disorder, which is important both for the comprehension and therapeutical approach to this problem. Today, the best recommended approach regarding children with ADHD is a combination of two therapeutic modalities: pharmacotherapy and behavioral treatment. The first-choice drugs for this disorder belong to the group of sympathomimetics - psychostimulants and atomoxetine (more recently. As the firstchoice therapy, methylphenydate in sustained release form has numerous advantages. Like all drugs, methylphenidate has its unwanted side effects. Most common are: loss of appetite, weight loss, sleeping disorders, irritability, headache. These side effects are well-known and documented in the literature. By analysing the available literature we have found cases of psychiatric side effects such as: psychosis, mania, visual hallucinations, agitation, suicidal ideas. We have not found examples of ADHD in children who use increased dosage of sustained release of methylphenidate leading to depressive symptomatology. On the other side, methylphenidate may be prescribed for off-label use in treatmentresistant cases of depression. Case report. The case of a 7- year-old boy diagnosed with ADHD was on a minimal dose of sustained release form of methylphenidate. After initial titration of the drug, i.e. after raising the dose to the next level the boy developed clinical signs of depression. The treatment was ceased and depressive

  4. Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

    Directory of Open Access Journals (Sweden)

    Mathilde Holmskov

    Full Text Available To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR with 95% confidence intervals (CI using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23 and weight (RR 3.89, 95% CI 1.43 to 10.59. In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04. We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

  5. Methylphenidate and Atomoxetine Enhance Prefrontal Function through alpha[subscript 2]-Adrenergic and Dopamine D[subscript 1] Receptors

    Science.gov (United States)

    Gamo, Nao J.; Wang, Min; Arnsten, Amy F. T.

    2010-01-01

    Objective: This study examined the effects of the attention-deficit/hyperactivity disorder treatments, methylphenidate (MPH) and atomoxetine (ATM), on prefrontal cortex (PFC) function in monkeys and explored the receptor mechanisms underlying enhancement of PFC function at the behavioral and cellular levels. Method: Monkeys performed a working…

  6. Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Jan K Buitelaar

    2009-08-01

    Full Text Available Jan K Buitelaar1, J Antoni Ramos-Quiroga2, Miguel Casas2, J J Sandra Kooij3, Asko Niemelä4, Eric Konofal5, Joachim Dejonckheere6, Bradford H Challis7, Rossella Medori81Department of Psychiatry, University Medical Center, St. Radboud and Karakter Child and Adolescent Psychiatry University Center, Nijmegen, The Netherlands; 2Department of Psychiatry, Hospital Universitari Vall d’Hebron and Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 3PsyQ, Psycho-Medical Programs, Program Adult ADHD, Den Haag, The Netherlands; 4Oulu University Hospital, Department of Psychiatry, Oulu, Finland; 5Groupe Hospitalier Pitie-Salpetriere, Paris, France; 6SGS Life Sciences, Mechelen, Belgium; 7Johnson & Johnson Pharmaceutical Research and Development, Titusville, NJ, USA; 8Janssen-Cilag EMEA, Neuss, GermanyAbstract: The osmotic release oral system (OROS methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety and tolerability of OROS methylphenidate in a flexible dose regimen (18–90 mg daily for the treatment of adults diagnosed with ADHD (N = 370. Medication was adjusted to optimize efficacy and tolerability for each patient. Adverse events, vital signs, and laboratory parameters were assessed. Most patients (337; 91% completed the seven-week treatment and the final dispensed dose was 18 mg (8%, 36 mg (29%, 54 mg (34%, 72 mg (20%, or 90 mg (9%. Adverse events were reported in 253 (68% patients and most were mild or moderate in severity; most frequently reported included headache (17%, decreased appetite (13%, and insomnia (11%. Adverse events were rarely serious (<1%; 2/370. Small mean increases in systolic and diastolic blood pressure (both 2.4 mmHg and pulse (3.2 bpm were observed. Body weight decreased

  7. Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized, double blind, placebo-controlled trial.

    Science.gov (United States)

    Mohammadpour, Nakisa; Jazayeri, Shima; Tehrani-Doost, Mehdi; Djalali, Mahmoud; Hosseini, Mostafa; Effatpanah, Mohammad; Davari-Ashtiani, Rozita; Karami, Elham

    2018-04-01

    Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD. Sixty-two children aged 5-12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed. Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism. The trial was registered in www.irct.ir is (IRCT201404222394N10).

  8. Changes in plasma Brain-derived neurotrophic factor (BDNF) levels induced by methylphenidate in children with Attention deficit-hyperactivity disorder (ADHD).

    Science.gov (United States)

    Amiri, Ali; Torabi Parizi, Gholamreza; Kousha, Maryam; Saadat, Farshid; Modabbernia, Mohammad-Jafar; Najafi, Kiomars; Atrkar Roushan, Zahra

    2013-12-02

    It has been suggested that BDNF may play a role in the pathogenesis of ADHD. Our aim is to determine whether methylphenidate can induce changes in plasma BDNF levels of children with ADHD. We assessed levels of plasma BDNF in 28 ADHD patients (age range = 3.5-10 years) before and after 6 weeks treatment with effective dosages of methylphenidate. Then we evaluated the correlation of levels of plasma BDNF with clinical variables, especially ADHD Conner's parents rating scale. According to the paired sample T-test, the mean plasma BDNF level in the baseline was 193.06 pg/ml, whereas 271.06 pg/ml in the end point, thus showing significantly higher mean plasma BDNF levels in the post-treatment situation than in the pretreatment (t = -3.393, df = 27, p = 0.002). Pearson's correlation test revealed that there was also significant negative correlation between levels of BDNF in the plasma of ADHD patients before treatment and improvement in hyperactivity symptoms with treatment (Pearson's correlation = -0.395, p = 0.037). The mean plasma BDNF levels increased after 6 weeks of treatment with methylphenidate. Also, we found an improvement in hyperactivity symptoms with decreasing baseline plasma BDNF levels. We recommend that more studies should be conducted in order to assess the possible roles of plasma BDNF levels in treatment response prediction and prognosis. © 2013 Elsevier Inc. All rights reserved.

  9. Methylphenidate, Interstimulus Interval, and Reaction Time Performance of Children with Attention Deficit/Hyperactivity Disorder : A Pilot Study

    NARCIS (Netherlands)

    van der Meere, J. J.; Shalev, R. S.; Borger, N.; Wiersema, J.R

    2009-01-01

    Thirteen children with attention deficit/hyperactivity disorder (ADHD: DSM-IV-TR) participated in the pilot study. They carried out a Go/No-Go test with a short (2 seconds) and long (6 seconds) interstimulus interval (ISI) when on placebo and a therapeutic dose of methylphenidate (MPH). For the

  10. Case Report: Testicular failure possibly associated with chronic use of methylphenidate [v1; ref status: indexed, http://f1000r.es/48z

    Directory of Open Access Journals (Sweden)

    Ranjith Ramasamy

    2014-09-01

    Full Text Available Methylphenidate is a commonly prescribed treatment for attention deficit hyperactivity disorder (ADHD. However, little is known about its adverse effects on the male reproductive system. We report a 20-year-old male patient whose chief complaint was of delayed puberty. He spoke in a high-pitched voice and complained of lack of body hair, impaired libido, inadequate erectile function, chronic fatigue, and low energy. He had been treated with methylphenidate as an infant and had continued treatment for 17 years. On examination, the patient was lean and visibly lacked facial or body hair. He further explained that he had never been able to grow underarm or facial hair and that he was often mistakenly considered a young teenager rather than a 20-year-old. The patient’s genitalia were categorized as Tanner Stage 2. Laboratory studies confirmed low serum follicle-stimulating hormone (FSH, luteinizing hormone (LH, and testosterone levels. The patient was given exogenous testosterone supplementation with pellets and human chorionic gonadotropin to maintain testicular size. After 4 months his symptoms improved and he demonstrated signs of puberty. Our goal is to further elucidate the possible impact of methylphenidate on the male reproductive system.

  11. Methylphenidate treatment of attention deficit hyperactivity disorder in young people with learning disability and difficult-to-treat epilepsy: Evidence of clinical benefit

    Science.gov (United States)

    Fosi, Tangunu; Lax-Pericall, Maria T; Scott, Rod C; Neville, Brian G; Aylett, Sarah E

    2013-01-01

    Purpose To establish the efficacy and safety of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) in a group of children and young people with learning disability and severe epilepsy. Methods This retrospective study systematically reviewed the case notes of all patients treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center between 1998 and 2005. Treatment efficacy was ascertained using clinical global impressions (CGI) scores, and safety was indexed by instances of >25% increase in monthly seizure count within 3 months of starting MPH. Key Findings Eighteen (18) patients were identified with refractory epilepsies (14 generalized, 4 focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was diagnosed at a median age of 11.5 years (range 6–18 years). With use of a combination of a behavioral management program and MPH 0.3–1 mg/kg/day, ADHD symptoms improved in 61% of patients (11/18; type A intraclass correlation coefficient of CGI 0.85, 95% confidence interval [CI] 0.69–0.94). Daily MPH dose, epilepsy variables, and psychiatric comorbidity did not relate to treatment response across the sample. MPH adverse effects led to treatment cessation in three patients (dysphoria in two, anxiety in one). There was no statistical evidence for a deterioration of seizure control in this group with the use of MPH. Significance Methylphenidate with behavioral management was associated with benefit in the management of ADHD in more than half of a group of children with severe epilepsy and additional cognitive impairments. Eighteen percent had significant side effects but no attributable increase in seizures. Methylphenidate is useful in this group and is likely to be under employed. PMID:24304474

  12. Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Buitelaar, J.K.; Ramos-Quiroga, J.A.; Casas, M.; Kooij, J.J.; Niemela, A.; Konofal, E.; Dejonckheere, J.; Challis, B.H.; Medori, R.

    2009-01-01

    The osmotic release oral system (OROS) methylphenidate formulation is a prolonged-release medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. We conducted a seven-week open-label extension of a double-blind study to assess the safety

  13. The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

    Science.gov (United States)

    Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

    2004-01-01

    Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

  14. Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    Bottelier, Marco A.; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G. H.; Bouziane, Cheima; Kooij, J. J. Sandra; de Ruiter, Michiel B.; Reneman, Liesbeth

    2017-01-01

    In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant

  15. OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: A randomized, placebo-controlled cross-over study

    NARCIS (Netherlands)

    Bron, T.I.; Bijlenga, D.; Boonstra, A. M.; Breuk, M.; Pardoen, W.F.H.; Beekman, A.T.F.; Kooij, J.J.S

    2014-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is linked to impaired executive functioning (EF). This is the first study to objectively investigate the effects of a long-acting methylphenidate on neurocognitive test performance of adults with ADHD. Twenty-two adults with ADHD participated in a

  16. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies

    DEFF Research Database (Denmark)

    Storebø, Ole Jakob; Pedersen, Nadia; Ramstad, Erica

    2018-01-01

    Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in childhood. The psychostimulant methylphenidate is the most frequently used medication to treat it. Several studies have investigated the benefits of methylphenidate, showing possible favourable...... of the Diagnostic and Statistical Manual of Mental Disorders or the 9th or 10th edition of theInternational Classification of Diseases, with or without comorbid diagnoses. We required that at least 75% of participants had a normal intellectual capacity (intelligence quotient of more than 70 points) and were aged.......36, 95% confidence interval (CI) 1.17 to 1.57; 2 studies, 72,005 participants); any psychotic disorder (RR 1.36, 95% CI 1.17 to 1.57; 1 study, 71,771 participants); and arrhythmia (RR 1.61, 95% CI 1.48 to 1.74; 1 study, 1224 participants) compared to no intervention. In the non-comparative cohort studies...

  17. Impact of Methylphenidate Delivery Profiles on Driving Performance of Adolescents with Attention-Deficit/hyperactivity Disorder: A Pilot Study

    Science.gov (United States)

    Cox, Daniel J.; Merkel, R. Lawrence; Penberthy, Jennifer Kim; Kovatchev, Boris; Hankin, Cheryl S.

    2004-01-01

    Objective: Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at high risk for driving accidents. One dose of methylphenidate (MPH) improves simulator driving performances of ADHD-diagnosed adolescents at 1.5 hours post-dose. However, little is known about the effects of different MPH delivery profiles on driving performance…

  18. Methylphenidate Ameliorates Depressive Comorbidity in ADHD Children without any Modification on Differences in Serum Melatonin Concentration between ADHD Subtypes

    Directory of Open Access Journals (Sweden)

    Isabel Cubero-Millán

    2014-09-01

    Full Text Available The vast majority of Attention-deficit/hyperactivity disorder (ADHD patients have other associated pathologies, with depressive symptoms as one of the most prevalent. Among the mediators that may participate in ADHD, melatonin is thought to regulate circadian rhythms, neurological function and stress response. To determine (1 the serum baseline daily variations and nocturnal excretion of melatonin in ADHD subtypes and (2 the effect of chronic administration of methylphenidate, as well as the effects on symptomatology, 136 children with ADHD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision: DSM-IV-TR criteria were divided into subgroups using the “Children’s Depression Inventory” (CDI. Blood samples were drawn at 20:00 and 09:00 h, and urine was collected between 21:00 and 09:00 h, at inclusion and after 4.61 ± 2.29 months of treatment. Melatonin and its urine metabolite were measured by radioimmunoassay RIA. Factorial analysis was performed using STATA 12.0. Melatonin was higher predominantly in hyperactive-impulsive/conduct disordered children (PHI/CD of the ADHD subtype, without the influence of comorbid depressive symptoms. Methylphenidate ameliorated this comorbidity without induction of any changes in the serum melatonin profile, but treatment with it was associated with a decrease in 6-s-melatonin excretion in both ADHD subtypes. Conclusions: In untreated children, partial homeostatic restoration of disrupted neuroendocrine equilibrium most likely led to an increased serum melatonin in PHI/CD children. A differential cerebral melatonin metabolization after methylphenidate may underlie some of the clinical benefit.

  19. Effects of Methylphenidate and Bupropion on DHEA-S and Cortisol Plasma Levels in Attention-Deficit Hyperactivity Disorder

    Science.gov (United States)

    Lee, Moon-Soo; Yang, Jae-Won; Ko, Young-Hoon; Han, Changsu; Kim, Seung-Hyun; Lee, Min-Soo; Joe, Sook-Haeng; Jung, In-Kwa

    2008-01-01

    We evaluated plasma levels of DHEA-S and cortisol before and after treating ADHD patients with one of two medications: methylphenidate (n = 12) or bupropion (n = 10). Boys with ADHD (combined type) were evaluated with the Korean ADHD rating scale (K-ARS) and the computerized ADHD diagnostic system (ADS). All assessments were measured at baseline…

  20. Adverse drug reaction labelling for atomoxetine, methylphenidate and modafinil

    DEFF Research Database (Denmark)

    Aagaard, Lise; Hansen, Ebba Holme

    2013-01-01

    Medical product information contains information about efficacy and safety for marketed pharmaceuticals. Three studies have compared safety labelling for different therapeutic categories in different countries and detected large variations in a number of reported adverse drug reactions (ADRs......). The rapid increase in use of medications for treatment of ADHD symptoms has created concern due to lack of information about effects from long-term use. The aim of this study was to compare ADR information in product information (PI)/summary of product characteristics (SPC) for oral formulations...... of atomoxetine, methylphenidate and modafinil marketed by the same pharmaceutical companies in Australia, Denmark and the United States. Discrepancies in listed ADRs were defined as types of ADRs (system organ class) not listed in all countries. For ADRs where discrepancies were detected, we extracted...

  1. Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence

    NARCIS (Netherlands)

    Crunelle, Cleo L.; van den Brink, Wim; Veltman, Dick J.; van Emmerik-van Oortmerssen, Katelijne; Dom, Geert; Schoevers, Robert A.; Booij, Jan

    2013-01-01

    Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the

  2. Response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study

    Directory of Open Access Journals (Sweden)

    Valdizán-Usón JR

    2013-02-01

    Full Text Available JR Valdizán-Usón,1 A Cánovas-Martínez,2 MT De Lucas-Taracena,3 F Díaz-Atienza,4 LS Eddy-Ives,5 A Fernández-Jaén,6 M Fernández-Pérez,7 M García-Giral,8 P García-Magán,9 M Garraus-Oneca,10 MA Idiazábal-Alecha,11 M López-Benito,12 G Lorenzo-Sanz,13 J Martínez-Antón,14 MA Martínez-Granero,15 F Montañés-Rada,16 F Mulas-Delgado,17 G Ochando-Perales,18 E Ortega-García,19 A Pelaz-Antolín,20 JA Ramos-Quiroga,21 FC Ruiz-Sanz,22 J Vaquerizo-Madrid,23 A Yusta-Izquierdo241Unidad Trastornos Neurofuncionales, Clínica Montpellier, Zaragoza, 2Hospital Dr Peset, Valencia, 3Hospital 12 de Octubre, Madrid, 4Hospital Virgen de las Nieves, Granada, 5Centre Mèdic Sant Ramon, Santa Coloma de Gramenet, Barcelona, 6Hospital Universitario Quirón, Madrid, 7Centro de Salud La Felguera, Langreo, Asturias, 8Hospital Clínic, Barcelona, 9Unidad Salud Mental, Talavera de la Reina, 10Clínica Universitaria de Navarra, Pamplona, 11Hospital Ntra. Sra. del Pilar, Barcelona, 12Centro Salud Contrueces, Gijón, 13Hospital Ramón y Cajal, Madrid, 14Complejo Hospitalario Carlos Haya, Málaga, 15Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, 16Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, 17Hospital Universitario La Fe, Valencia, 18Hospital Universitario La Fe, Valencia, 19Complejo Asistencial Universitario de León, 20Centro Salud Mental, Alcalá de Henares, 21Hospital Universitari Vall d'Hebron. CIBERSAM. Department of Psychiatry and Legal Medicine. Universitat Autònoma de Barcelona, 22Hospital General Rio Carrión, Palencia, 23Hospital Materno-Infantil, Badajoz, 24Hospital Universitario, Guadalajara, SpainBackground: The purpose of this multicenter Spanish study was to evaluate the response to immediate-release methylphenidate by children and adults diagnosed with attention-deficit/hyperactivity disorder (ADHD, as well as to obtain information on current therapy patterns and safety characteristics.Methods: This multicenter

  3. Methylphenidate does not influence smoking-reinforced responding or attentional performance in adult smokers with and without attention deficit hyperactivity disorder (ADHD).

    Science.gov (United States)

    Kollins, Scott H; Schoenfelder, Erin; English, Joseph S; McClernon, F Joseph; Dew, Rachel E; Lane, Scott D

    2013-10-01

    Individuals with Attention Deficit Hyperactivity Disorder (ADHD) smoke cigarettes at rates higher than the general population and questions have been raised about how stimulant drugs-the frontline pharmacological treatment for ADHD-influence smoking risk and behavior in those with ADHD. In the present study adult regular smokers with (n = 16) and without (n = 17) ADHD participated in 3 experimental sessions in which they completed a Progressive Ratio (PR) task to measure the relative reinforcing effects of cigarette smoking and money after oral administration of placebo and 2 active doses of methylphenidate (10 mg and 40 mg). We also measured attention and inhibitory control via a Continuous Performance Test (CPT). Methylphenidate had no effect on smoking-reinforced responding, attention, or inhibitory control in either group. Attention and inhibitory control were associated with smoking-reinforced responding, but unsystematically and only in the non-ADHD group. Several design features, such as the value of the monetary response option, the PR schedule, and the potential effects of smoking on attention and inhibitory control, could have contributed to the negative findings and are discussed as such. Although inconsistent with some previous human laboratory studies of stimulant drugs and smoking, results are consistent with recent trials of stimulant drugs as adjuncts for smoking cessation in adult smokers with ADHD. In general, methylphenidate at mild and moderate doses did not influence the relative reinforcing effects of cigarette smoking in adults with and without ADHD. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  4. Atomoxetine could improve intra-individual variability in drug-naïve adults with attention-deficit/hyperactivity disorder comparably with methylphenidate: A head-to-head randomized clinical trial.

    Science.gov (United States)

    Ni, Hsing-Chang; Hwang Gu, Shoou-Lian; Lin, Hsiang-Yuan; Lin, Yu-Ju; Yang, Li-Kuang; Huang, Hui-Chun; Gau, Susan Shur-Fen

    2016-05-01

    Intra-individual variability in reaction time (IIV-RT) is common in individuals with attention-deficit/hyperactivity disorder (ADHD). It can be improved by stimulants. However, the effects of atomoxetine on IIV-RT are inconclusive. We aimed to investigate the effects of atomoxetine on IIV-RT, and directly compared its efficacy with methylphenidate in adults with ADHD. An 8-10 week, open-label, head-to-head, randomized clinical trial was conducted in 52 drug-naïve adults with ADHD, who were randomly assigned to two treatment groups: immediate-release methylphenidate (n=26) thrice daily (10-20 mg per dose) and atomoxetine once daily (n=26) (0.5-1.2 mg/kg/day). IIV-RT, derived from the Conners' continuous performance test (CCPT), was represented by the Gaussian (reaction time standard error, RTSE) and ex-Gaussian models (sigma and tau). Other neuropsychological functions, including response errors and mean of reaction time, were also measured. Participants received CCPT assessments at baseline and week 8-10 (60.4±6.3 days). We found comparable improvements in performances of CCPT between the immediate-release methylphenidate- and atomoxetine-treated groups. Both medications significantly improved IIV-RT in terms of reducing tau values with comparable efficacy. In addition, both medications significantly improved inhibitory control by reducing commission errors. Our results provide evidence to support that atomoxetine could improve IIV-RT and inhibitory control, of comparable efficacy with immediate-release methylphenidate, in drug-naïve adults with ADHD. Shared and unique mechanisms underpinning these medication effects on IIV-RT awaits further investigation. © The Author(s) 2016.

  5. The age-dependent effects of a single-dose methylphenidate challenge on cerebral perfusion in patients with attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Schrantee, A.; Mutsaerts, H.J.M.M.; Bouziane, C.; Tamminga, H.G.H.; Bottelier, M.A.; Reneman, L.

    2017-01-01

    Methylphenidate (MPH) is a stimulant drug and an effective treatment for attention-deficit/hyperactivity disorder (ADHD) in both children and adults. Pre-clinical studies suggest that the response to stimulants is dependent on age, which may reflect the ontogeny of the dopamine (DA) system, which

  6. High sibling correlation on methylphenidate response but no association with DAT1-10R homozygosity in Dutch sibpairs with ADHD

    NARCIS (Netherlands)

    van der Meulen, Emma M; Bakker, Steven C; Pauls, David L; Oteman, Nicole; Kruitwagen, Cas L J J; Pearson, Peter L; Sinke, Richard J; Buitelaar, Jan K

    2005-01-01

    BACKGROUND: A minority of patients with attention-deficit hyperactivity disorder (ADHD) do not respond favorably to methylphenidate. This has been partially associated with homozygosity for the Dopamine transporter (DAT1) 10-repeat allele and the presence of one or two Dopamine D4 receptor (DRD4)

  7. High sibling correlation on methylphenidate response but no association with DAT1-10R homozygosity in Dutch sibpairs with ADHD.

    NARCIS (Netherlands)

    Meulen, E.M. van der; Bakker, S.C.; Pauls, D.L.; Oteman, N.; Kruitwagen, C.L.J.J.; Pearson, P.L.; Sinke, R.J.; Buitelaar, J.K.

    2005-01-01

    BACKGROUND: A minority of patients with attention-deficit hyperactivity disorder (ADHD) do not respond favorably to methylphenidate. This has been partially associated with homozygosity for the Dopamine transporter (DAT1) 10-repeat allele and the presence of one or two Dopamine D4 receptor (DRD4)

  8. Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

    Directory of Open Access Journals (Sweden)

    Huss M

    2017-07-01

    Full Text Available Michael Huss,1 Praveen Duhan,2 Preetam Gandhi,3 Chien-Wei Chen,4 Carsten Spannhuth,3 Vinod Kumar5 1Child and Adolescent Psychiatry, University Medicine, Mainz, Germany; 2Global Medical Affairs, Novartis Healthcare Pvt. Ltd., Hyderabad, India; 3Development Franchise, Established Medicine Neuroscience, Novartis Pharma AG, Basel, Switzerland; 4Biostatistics Cardio-Metabolic & Established Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 5Established Medicines, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH, a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. Keywords: methylphenidate, dose optimization, attention-deficit/hyperactivity disorder, ADHD

  9. Use of partial AUC (PAUC) to evaluate bioequivalence--a case study with complex absorption: methylphenidate.

    Science.gov (United States)

    Fourie Zirkelbach, Jeanne; Jackson, Andre J; Wang, Yaning; Schuirmann, Donald J

    2013-01-01

    Methylphenidate modified-release products produce early and late peak concentrations critical for treatment of morning and afternoon symptoms of attention deficit hyperactivity disorder (ADHD). Standard bioequivalence (BE) criteria cannot be applied to these products. The performance of partial area under the drug concentration-time curve (PAUC), Cmax and AUCINF to assess BE were independently evaluated for two products. A two-stage analysis was performed on plasma data for two methylphenidate modified-release products (Product 1 and 2). Simulations using the fitted parameters determined how changes in fast absorption rate constant (K0Fast) and fraction available (F1) affected curve shape and BE determination using Cmax, AUCINF and PAUC. The sensitivity of the mean PAUC(test)/PAUC(reference) ratios to changes in K0Fast(test) are product dependent. Product 1 mean PAUC(test)/PAUC(reference) ratios for PAUC0-4h are more responsive to both decreases and increases in K0Fast(test) than Product 2. Product 2 showed a greater response in the mean PAUC(test)/PAUC(reference) ratio for PAUC0-4h when the K0Fast(test) is decreased and less response as the value is increased. PAUC estimated curve shape is sensitive to changes in absorption and are product specific, and may require a new PAUC metric for each drug. A non-product specific metric to assess curve shape is warranted.

  10. Effect of Food Intake on the Pharmacokinetics of a Novel Methylphenidate Extended-Release Oral Suspension for Attention Deficit Hyperactivity Disorder.

    Science.gov (United States)

    Sallee, Floyd R; Palumbo, Donna R; Abbas, Richat; Berry, Sally A; Puthli, Shivanand P; Kathala, Kalyan K

    2017-09-01

    We conducted an open-label, single-dose, randomized, crossover study in healthy adults to assess the impact of food on the bioavailability of 60 mg methylphenidate extended-release oral suspension (MEROS; Quillivant XR™)-a long-acting stimulant for the treatment of attention deficit hyperactivity disorder-by comparing the pharmacokinetic parameters under fed and fasting conditions. When MEROS 60 mg was administered under fed conditions compared with fasting conditions, the exposure of methylphenidate (d enantiomer) was higher, with a mean area under the plasma concentration-vs-time curve (AUC) 0-t of 160.2 ng·h/mL vs 140.4 ng·h/mL, and a mean AUC 0-inf of 163.2 ng·h/mL vs 143.7 ng·h/mL, respectively. The ratios of the ln-transformed geometric means for methylphenidate for AUC 0-t and AUC 0-inf were 119.5% (90%CI, 115.7% to 123.5%) and 119.0% (90%CI, 115.2% to 122.8%), respectively, within the standard 80% to 125% bioequivalence acceptance range indicating no food effect on the overall exposure (rate and extent). There was a small increase in the peak plasma concentration (127.6% [90%CI, 119.9% to 135.8%]). However, this effect was small and not likely to be clinically significant. Overall, MEROS 60 mg was safe in both the fed and fasting condition when administered to healthy volunteers in this study. © 2017 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

  11. Association of Carboxylesterase 1 Gene (CES1) Polymorphism with Weight loss in Children with Attention Deficit Hyperactivity Disorder during Methylphenidate Treatment

    DEFF Research Database (Denmark)

    Oxenbøll, Maria; Kaalund-Jørgensen, Kristine; Rasmussen, Simone

    2017-01-01

    Children with Attention Deficit Hyperactivity Disorder (ADHD) show large variations in response to methylphenidate (MPH) treatment, which may result from genetic factors associated with MPH metabolism. We aimed at investigating a possible link between the -75 T>G polymorphism in the 5’ untranslated...

  12. A randomized, placebo-controlled trial of three fixed dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder.

    NARCIS (Netherlands)

    Medori, R.; Ramos-Quiroga, J.A.; Casas, M.; Kooij, J.J.S.; Niemela, A.; Trott, G.E.; Lee, E.; Buitelaar, J.K.

    2008-01-01

    BACKGROUND: There is increasing recognition of attention-deficit/hyperactivity disorder (ADHD) in adults and the need to evaluate efficacy and safety of methylphenidate treatment in these patients. METHODS: In this double-blind trial, 401 adults with ADHD (218 men; 18-63 years) were randomly

  13. The role of the dopaminergic system in mood, motivation and cognition in Parkinson's disease: a double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate.

    Science.gov (United States)

    Drijgers, Rosa L; Verhey, Frans R J; Tissingh, Gerrit; van Domburg, Peter H M F; Aalten, Pauline; Leentjens, Albert F G

    2012-09-15

    In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. The Influence of Methylphenidate on Hyperactivity and Attention Deficits in Children With ADHD. A Virtual Classroom Test

    OpenAIRE

    Mühlberger, Andreas; Jekel, K.; Probst, Thomas; Schecklmann, Martin

    2016-01-01

    Objective: This study compares the performance in a continuous performance test within a virtual reality classroom (CPT-VRC) between medicated children with ADHD, unmedicated children with ADHD, and healthy children. Method: N = 94 children with ADHD (n = 26 of them received methylphenidate and n = 68 were unmedicated) and n = 34 healthy children performed the CPT-VRC. Omission errors, reaction time/variability, commission errors, and body movements were assessed. Furthermore, ADHD...

  15. Resolution of methylphenidate osmotic release oral system-induced hair loss in two siblings after dose escalation.

    Science.gov (United States)

    Ardic, Ulku Akyol; Ercan, Eyup Sabri

    2017-11-01

    This report describes the cases of two siblings who experienced hair loss after treatment with methylphenidate (MPH) osmotic release oral system (OROS). Hair loss was resolved after discontinuation of the drug, but the children re-initiated treatment, after which hair loss again occurred, but they continued the treatment. After dose escalation, the hair loss resolved. This is the first report to describe resolution of OROS-MPH-induced hair loss after dose escalation. © 2017 Japan Pediatric Society.

  16. Age-dependent effects of methylphenidate on the human dopaminergic system in young vs adult patients with attention-deficit/hyperactivity disorder: A randomized clinical trial

    NARCIS (Netherlands)

    Schrantee, A. (Anouk); Tamminga, H.G.H. (Hyke G. H.); C. Bouziane (Cheima); Bottelier, M.A. (Marco A.); E.E. Bron (Esther); H.J.M.M. Mutsaerts (Henri J. M.); A.H. Zwinderman (Ailko); Groote, I.R. (Inge R.); S.A.R.B. Rombouts (Serge); Lindauer, R.J.L. (Ramon J. L.); S. Klein (Stefan); W.J. Niessen (Wiro); B.C. Opmeer (Brent); Boer, F. (Frits); P.J. Lucassen; Andersen, S.L. (Susan L.); H.M. Geurts (Hilde ); L. Reneman (Liesbeth)

    2016-01-01

    textabstractIMPORTANCE Although numerous children receivemethylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system. OBJECTIVES To determine

  17. Effects of methylphenidate on body index and physical fitness in Korean children with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Kang, Kyoung Doo; Yun, Sin Weon; Chung, Unsun; Kim, Tae Ho; Park, Jeong Ha; Park, In Hui; Han, Doug Hyun

    2016-03-01

    The side effects of methylphenidate (MPH) on growth remain a controversial concern. This study aimed to investigate the effect of MPH on clinical symptoms, growth, and physical fitness in Korean children. Fifty male children with attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (MPH-ADHD), 69 MPH-naïve male children with ADHD (Naïve-ADHD), and 60 age-matched and sex-matched healthy control subjects were recruited. Intelligence quotient (IQ), clinical symptoms of ADHD, body index (height, weight, and body mass index [BMI]), and physical fitness (muscular strength, endurance, flexibility, agility, speed, and balance) were assessed. Total IQ and performance IQ scores were significantly different among the three groups, as were mean Korean Attention Deficit Hyperactivity Disorder (K-ARS)-total, K-ARS-inattention, and K-ARS-hyperactivity scores. There was no significant difference in height, weight, or BMI among the three groups. There were significant differences in skill-related fitness scores for balance (healthy controls > MPH-ADHD > Naïve-ADHD) and agility shuttle test time (healthy controls attention, and balance and agility measures of skill-related fitness in Korean children with ADHD. MPH was not associated with growth delays in height, weight, and BMI. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Randomized Controlled Trial of Osmotic-Release Methylphenidate with Cognitive-Behavioral Therapy in Adolescents with Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders

    Science.gov (United States)

    Riggs, Paula D.; Winhusen, Theresa; Davies, Robert D.; Leimberger, Jeffrey D.; Mikulich-Gilbertson, Susan; Klein, Constance; Macdonald, Marilyn; Lohman, Michelle; Bailey, Genie L.; Haynes, Louise; Jaffee, William B.; Haminton, Nancy; Hodgkins, Candace; Whitmore, Elizabeth; Trello-Rishel, Kathlene; Tamm, Leanne; Acosta, Michelle C.; Royer-Malvestuto, Charlotte; Subramaniam, Geetha; Fishman, Marc; Holmes, Beverly W.; Kaye, Mary Elyse; Vargo, Mark A.; Woody, George E.; Nunes, Edward V.; Liu, David

    2011-01-01

    Objective: To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD). Method: This was a…

  19. Effects of 7-day continuous D-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Banks, Matthew L

    2015-10-01

    Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. The effect of methylphenidate on sustained attention among adolescents with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Lufi, Dubi; Bassin-Savion, Shiry; Rubel, Lilach

    2015-01-01

    Twenty-seven adolescents diagnosed as having attention-deficit hyperactivity disorder (ADHD) were tested twice with a computerized MATH-CPT (mathematics continuous performance test). In one administration, the participants took medication (methylphenidate, MPH) 1.5 hr before being tested. In another administration, the MATH-CPT was administered without the medication. Treatment with MPH improved the "overall attention level" and in measures of "reaction time" and "impulsivity." MPH did not improve the performance in the four measures of sustained attention. Knowing that treatment with MPH does not improve sustained attention can be helpful in reaching a decision of whether or not a child should be treated with MPH.

  1. Novelty-seeking trait predicts the effect of methylphenidate on creativity.

    Science.gov (United States)

    Gvirts, Hila Z; Mayseless, Naama; Segev, Aviv; Lewis, D Yael; Feffer, Kfir; Barnea, Yael; Bloch, Yuval; Shamay-Tsoory, Simon G

    2017-05-01

    In recent years the use of psychostimulants for cognitive enhancement in healthy individuals with no psychiatric disorders has been on the rise. However, it is still unclear whether psychostimulants improve certain cognitive functions at the cost of others, and how these psychostimulants interact with individual personality differences. In the current study, we investigated whether the effect of one common stimulant, methylphenidate (MPH), on creativity is associated with novelty seeking. Thirty-six healthy adults, without attention-deficit hyperactivity disorder (ADHD) symptomology, were assigned randomly in a double-blind fashion to receive MPH or placebo. We found that the effect of MPH on creativity was dependent on novelty-seeking (NS) personality characteristics of the participants. MPH increased creativity in individuals with lower NS, while it reduced creativity levels in individuals with high NS. These findings highlight the role of the dopaminergic system in creativity, and indicate that among healthy individuals NS can be seen as a predictor of the effect of MPH on creativity.

  2. An Analysis of Patient Adherence to Treatment during a 1-Year, Open-Label Study of OROS[R] Methylphenidate in Children with ADHD

    Science.gov (United States)

    Faraone, Stephen V.; Biederman, Joseph; Zimmerman, Brenda

    2007-01-01

    Objective: Treatment adherence is an important aspect of ADHD symptom management, but there are many factors that may influence adherence. Method: This analysis assessed adherence to OROS methylphenidate during a 1-year, open-label study in children. Adherence was defined as the number of days medication was taken divided by the number of days in…

  3. Effect of Osmotic-Release Oral System Methylphenidate on Different Domains of Attention and Executive Functioning in Children with Attention-Deficit-Hyperactivity Disorder

    Science.gov (United States)

    Blum, Nathan J.; Jawad, Abbas F.; Clarke, Angela T.; Power, Thomas J.

    2011-01-01

    Aim: This study investigated whether components of attention and executive functioning improve when children with attention-deficit-hyperactivity disorder (ADHD) are treated with osmotic-release oral system (OROS) methylphenidate. Method: Thirty children (24 males, six females; mean age 8y 6mo, SD 1y 11mo; range 6y 5mo-12y 6mo) with ADHD combined…

  4. Effects of Methylphenidate on performance of a practical pistol shooting task: a quantitative electroencephalography (qEEG study

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    Paes Flávia

    2011-02-01

    Full Text Available Abstract Background The present study examined absolute alpha power using quantitative electroencephalogram (qEEG in bilateral temporal and parietal cortices in novice soldiers under the influence of methylphenidate (MPH during the preparatory aiming period in a practical pistol-shooting task. We anticipated higher bi-hemispheric cortical activation in the preparatory period relative to pre-shot baseline in the methylphenidate group when compared with the control group because methylphenidate has been shown to enhance task-related cognitive functions. Methods Twenty healthy, novice soldiers were equally distributed in control (CG; n = 10 and MPH groups 10 mg (MG; n = 10 using a randomized, double blind design. Subjects performed a pistol-shooting task while electroencephalographic activity was acquired. Results We found main effects for group and practice blocks on behavioral measures, and interactions between group and phases on electroencephalographic measures for the electrodes T3, T4, P3 and P4. Regarding the behavioral measures, the MPH group demonstrated significantly poorer in shooting performance when compared with the control and, in addition, significant increases in the scores over practice blocks were found on both groups. In addition, regarding the electroencephalographic data, we observed a significant increase in alpha power over practice blocks, but alpha power was significantly lower for the MPH group when compared with the placebo group. Moreover, we observed a significant decrease in alpha power in electrodes T4 and P4 during PTM. Conclusion Although we found no correlation between behavioral and EEG data, our findings show that MPH did not prevent the learning of the task in healthy subjects. However, during the practice blocks (PBs it also did not favor the performance when compared with control group performance. It seems that the CNS effects of MPH demanded an initial readjustment period of integrated operations relative

  5. Methylphenidate and Atomoxetine-Responsive Prefrontal Cortical Genetic Overlaps in "Impulsive" SHR/NCrl and Wistar Rats.

    Science.gov (United States)

    Dela Peña, Ike; Dela Peña, Irene Joy; de la Peña, June Bryan; Kim, Hee Jin; Shin, Chan Young; Han, Doug Hyun; Kim, Bung-Nyun; Ryu, Jong Hoon; Cheong, Jae Hoon

    2017-09-01

    Impulsivity, the predisposition to act prematurely without foresight, is associated with a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). Identifying genetic underpinnings of impulsive behavior may help decipher the complex etiology and neurobiological factors of disorders marked by impulsivity. To identify potential genetic factors of impulsivity, we examined common differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of adolescent SHR/NCrl and Wistar rats, which showed marked decrease in preference for the large but delayed reward, compared with WKY/NCrl rats, in the delay discounting task. Of these DEGs, we examined drug-responsive transcripts whose mRNA levels were altered following treatment (in SHR/NCrl and Wistar rats) with drugs that alleviate impulsivity, namely, the ADHD medications methylphenidate and atomoxetine. Prefrontal cortical genetic overlaps between SHR/NCrl and Wistar rats in comparison with WKY/NCrl included genes associated with transcription (e.g., Btg2, Fos, Nr4a2), synaptic plasticity (e.g., Arc, Homer2), and neuron apoptosis (Grik2, Nmnat1). Treatment with methylphenidate and/or atomoxetine increased choice of the large, delayed reward in SHR/NCrl and Wistar rats and changed, in varying degrees, mRNA levels of Nr4a2, Btg2, and Homer2, genes with previously described roles in neuropsychiatric disorders characterized by impulsivity. While further studies are required, we dissected potential genetic factors that may influence impulsivity by identifying genetic overlaps in the PFC of "impulsive" SHR/NCrl and Wistar rats. Notably, these are also drug-responsive transcripts which may be studied further as biomarkers to predict response to ADHD drugs, and as potential targets for the development of treatments to improve impulsivity.

  6. Effectiveness of parental training, methylphenidate treatment, and their combination on academic achievements and behavior at school of children with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Golubchik, Pavel; Hamerman, Hagar; Manor, Iris; Peskin, Miriam; Weizman, Abraham

    2018-03-30

    This study aimed to compare the effectiveness of parental training (PT), methylphenidate treatment (MPH), and the combination of PT and MPH treatment (PT/MPH) on school achievements in children with attention-deficit hyperactivity disorder (ADHD). Twenty eight ADHD patients (age: 10.1±1.11 years) were divided into three groups: (a) PT (N=10), (b) PT/MPH (N=8), and (c) MPH alone (N=10). Their grades in academics and conduct, from their school reports before and after treatment (6 months), were coded as achievement scores. No significant differences in baseline academic and conduct scores were found between the groups (F=0.033, d.f.=2, P=0.97 and F=0.024, d.f.=2, P=0.98, respectively). No significant changes before versus after treatment were detected in academic (3.83±0.93 vs. 3.85±0.88, paired t=0.086, d.f.=9, P=0.93, NS) or conduct (3.90±1.10 vs. 4.10±1.00, paired t=1.50, d.f.=9, P=0.17, NS) scores in the PT group. The same was true for the PT/MPH group (academic scores: 3.75±0.98 vs. 4.05±0.83, d.f.=7, t=0.927, P=0.38; conduct scores: 3.85±0.83 vs. 4.12±0.83, d.f.=7, t=0.79, P=0.45). Only the MPH group showed significant improvements in those scores (academic scores: 3/73±0.85 vs. 4/44±0.48, d.f.=9, t=3.33, P=0.0088; conduct scores: 3.80±0.70 vs. 4.60±0.70, d.f.=9, t=3.2, P=0.011). Methylphenidate alone is superior to either parental training or parental training/methylphenidate in improving academics and conduct at school.

  7. Questões atuais no tratamento farmacológico do TDAH em adultos com metilfenidato Actual issues in the pharmacological treatment of ADHD in adults with methylphenidate

    Directory of Open Access Journals (Sweden)

    Mario R. Louzã

    2007-01-01

    Full Text Available O tratamento farmacológico do transtorno do déficit de atenção com hiperatividade (TDAH em adultos inclui o uso de psicoestimulantes, antidepressivos e atomoxetina, sendo o primeiro considerado a indicação de primeira escolha. A eficácia do metilfenidato foi demonstrada em adultos quando se empregavam doses maiores, proporcionalmente similares àquelas usadas em estudos em crianças. O perfil de eventos adversos do metilfenidato, incluindo aqueles relativos ao sistema cardiovascular, parece bastante seguro.Pharmacotherapy of attention-deficit/hyperactivity disorder in adulthood includes psychostimulants, antidepressants and atomoxetine, the first of them being considered the first choice. Methylphenidate efficacy has been demonstrated in adults when higher doses were used, in a proportionate similar way to what has been described in children. Methylphenidate profile of adverse events, including cardiovascular ones, seems to be safe.

  8. Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

    Science.gov (United States)

    Bock, J; Breuer, S; Poeggel, G; Braun, K

    2017-03-01

    In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

  9. Serum brain-derived neurotrophic factor levels in treatment-naïve boys with attention-deficit/hyperactivity disorder treated with methylphenidate: an 8-week, observational pretest-posttest study.

    Science.gov (United States)

    Akay, Aynur Pekcanlar; Resmi, Halil; Güney, Sevay Alsen; Erkuran, Handan Özek; Özyurt, Gonca; Sargin, Enis; Topuzoglu, Ahmet; Tufan, Ali Evren

    2018-01-01

    Brain-derived neurotrophic factor (BDNF) is an important neurotrophin in the brain that modulates dopaminergic neurons. In this study, we aimed to investigate the changes in serum BDNF levels of children with attention-deficit/hyperactivity disorder (ADHD) in response to OROS methylphenidate treatment. We also aimed to determine whether there were any pre-post-differences between ADHD subtypes and comorbid psychiatric disorders in serum BDNF levels. Fifty male children with ADHD and 50 male healthy controls within the age range of 6-12 years were recruited to the study. The psychiatric diagnoses were determined by applying a structured interview with Kiddie schedule for affective disorders and schizophrenia for school-age children-present and lifetime version. The symptom severity of ADHD was measured using the Clinical Global Impression ADHD Severity Scale (CGI-S). Physicians completed Du Paul ADHD questionnaires. The levels of serum BDNF were assessed before and after 8 weeks of treatment with effective dosages of OROS methylphenidate. In the present study, the mean serum BDNF levels of boys with ADHD and of the healthy controls were 2626.33 ± 1528.05 and 2989.11 ± 1420.08 pg/mL, respectively. Although there were no statistically significant difference between the ADHD group and healthy controls at baseline (p = 0.22), the increase of serum BDNF was statistically significant from baseline to endpoint in the ADHD group (p = 0.04). The mean serum BDNF levels at baseline and endpoint of the ADHD group were 2626.33 ± 1528.05 and 3255.80 ± 1908.79 pg/mL, respectively. The serum BDNF levels of ADHD-inattentive subtype were significantly lower at baseline (p = 0.02), whereas BDNF levels post-treatment showed no significant difference. The increase of serum BDNF levels with methylphenidate treatment after 8 weeks was significantly higher in the inattentive group (p = 0.005). The increase of serum BDNF levels with methylphenidate treatment after 8

  10. Association Between 5-HTTLPR Polymorphism and Tics after Treatment with Methylphenidate in Korean Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Park, Seo Yeon; Kim, Eun Joo; Cheon, Keun-Ah

    2015-10-01

    The purpose of this study is to examine the relationship between 5-HTTLPR polymorphism (44-bp insertion/deletion polymorphism of serotonin transporter gene) and methylphenidate (MPH) treatment response, as well as the association between the adverse events of MPH treatment and 5-HTTLPR polymorphism in children with attention-deficit/hyperactivity disorder (ADHD). A total of 114 children with ADHD (mean age 9.08 ± 1.94 years) were recruited from the child psychiatric clinic in a hospital in South Korea. We have extracted the genomic DNA of the subjects from their blood lymphocytes and analyzed 5-HTTLPR polymorphism of the SLC6A4 gene. All children were treated with MPH for 8 weeks, with clinicians monitoring both the improvement of ADHD symptoms and the side effects. We compared the response to MPH treatment and adverse events among those with the genotype of 5-HRRLPR polymorphism. There was no significant association between the 5-HTTLPR genotype and the response to MPH treatment in children with ADHD. Subjects with the S/L+L/L genotype tended to have tics and nail biting (respectively, p tics and nail-biting as an adverse event of methylphenidate. This may aid in our understanding of the genetic contribution and genetic susceptibility of a particular allele in those ADHD patients with tics or nail biting.

  11. Effects of Methylphenidate and Behavior Modification on the Social and Academic Behavior of Children with Disruptive Behavior Disorders: The Moderating Role of Callous/Unemotional Traits

    Science.gov (United States)

    Waschbusch, Daniel A.; Carrey, Normand J.; Willoughby, Michael T.; King, Sara; Andrade, Brendan F.

    2007-01-01

    This study examined whether response to behavior modification with and without methylphenidate differed for children with attention-deficit/hyperactivity disorder (ADHD) and conduct problems (CP) depending on the presence of callous/unemotional (CU) traits. Participants were 37 children ages 7 to 12, including 19 with ADHD/CP-only and 18 with…

  12. Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Park, Subin; Kim, Jae-Won; Yang, Young-Hui; Hong, Soon-Beom; Park, Min-Hyeon; Kim, Boong-Nyun; Shin, Min-Sup; Yoo, Hee-Jeong; Cho, Soo-Churl

    2012-05-16

    Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD. Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2. There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes. Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.

  13. Adverse pregnancy outcomes after exposure to methylphenidate or atomoxetine during pregnancy

    Directory of Open Access Journals (Sweden)

    Bro SP

    2015-01-01

    Full Text Available Søren Pauli Bro,1 Maiken Ina Siegismund Kjaersgaard,2 Erik Thorlund Parner,2 Merete Juul Sørensen,3 Jørn Olsen,4 Bodil Hammer Bech,4 Lars Henning Pedersen,4,5 Jakob Christensen,6,7 Mogens Vestergaard11Research Unit and Section for General Practice, Department of Public Health, 2Section for Biostatistics, Department of Public Health, Aarhus University, 3Regional Center for Child and Adolescent Psychiatry, Aarhus University Hospital, 4Section for Epidemiology, Department of Public Health, 5Department of Clinical Medicine – Obstetrics and Gynecology, Aarhus University, 6Department of Clinical Pharmacology, 7Department of Neurology, Aarhus University Hospital, Aarhus, DenmarkObjective: To determine if prenatal exposure to methylphenidate (MPH or atomoxetine (ATX increases the risk of adverse pregnancy outcomes in women with attention deficit/hyperactivity disorder (ADHD.Materials and methods: This was a population-based cohort study of all pregnancies in Denmark from 1997 to 2008. Information on use of ADHD medication, ADHD diagnosis, and pregnancy outcomes was obtained from nationwide registers.Results: We identified 989,932 pregnancies, in which 186 (0.02% women used MPH/ATX and 275 (0.03% women had been diagnosed with ADHD but who did not take MPH/ATX. Our reference pregnancies had no exposure to MPH/ATX and no ADHD diagnosis. Exposure to MPH/ATX was associated with an increased risk of spontaneous abortion (SA; ie, death of an embryo or fetus in the first 22 weeks of gestation (adjusted relative risk [aRR] 1.55, 95% confidence interval [CI] 1.03–2.36. The risk of SA was also increased in pregnancies where the mother had ADHD but did not use MPH/ATX (aRR 1.56, 95% CI 1.11–2.20. The aRR of Apgar scores <10 was increased among exposed women (aRR 2.06, 95% CI 1.11–3.82 but not among unexposed women with ADHD (aRR 0.99, 95% CI 0.48–2.05.Conclusion: MPH/ATX was associated with a higher risk of SA, but our study indicated that it may at

  14. The Comparison of the Effectiveness of Parents Behavioral Training and Medication with Ritalin on the Rate of the Signs of Attention-Deficit Hyperactivity Disorder (ADHD

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    Mina Shahrbanian

    2013-04-01

    Full Text Available Introduction: The aim of the present research is to determine the effectiveness of parents’ behavioral training in compare to medication on the rate of the signs of attention deficit hyperactivity disorder (ADHD. Materials & Methods: Our population in this research was all boys in the elementary school (third, fourth and fifth grades and finally a sample of 630 subjects were included. We used a questionnaire of children’s morbid signs (CSI-4 which was completed by parents. For determination of acceptable scores in this scale, all subjects who obtained score 6 and more were selected and out of these subjects by use of random method as many as 45 subjects were chosen and 15 subjects were considered as the behavioral experimental group (under special care of a psychiatrist and the other 15 subjects were randomly put as the control group. The parents participated in seven sessions of behavioral training program, while for control group no kinds of training and medication intervention were carried out. Results: The results showed that both parent’s behavioral training program and medication have been effective meaningfully on ADHD (P=0.0005, also considering the averages differences, medication with Ritalin has caused more reduction of the signs of ADHD than parent’s behavioral training. Conclusion: At present, for children afflicted with ADHD, multi interventions are recommended that contains medication and parents training.

  15. Methylphenidate administration determines enduring changes in neuroglial network in rats.

    Science.gov (United States)

    Cavaliere, Carlo; Cirillo, Giovanni; Bianco, Maria Rosaria; Adriani, Walter; De Simone, Antonietta; Leo, Damiana; Perrone-Capano, Carla; Papa, Michele

    2012-01-01

    Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hyperactivity disorder (ADHD), triggers alterations of reward-based behavior paralleled by persistent and plastic synaptic changes of neuronal and glial markers within key areas of the reward circuits. By immunohistochemistry, we observe a marked increase of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expression and a down-regulation of glial glutamate transporter GLAST in dorso-lateral and ventro-medial striatum. Using electron microscopy, we find in the prefrontal cortex a significant reduction of the synaptic active zone length, paralleled by an increase of dendritic spines. We demonstrate that in limbic areas the MPH-induced reactive astrocytosis affects the glial glutamatergic uptake system that in turn could determine glutamate receptor sensitization. These processes could be sustained by NO production and synaptic rearrangement and contribute to MPH neuroglial induced rewiring. Copyright © 2011. Published by Elsevier B.V.

  16. Does switching from oral extended-release methylphenidate to the methylphenidate transdermal system affect health-related quality-of-life and medication satisfaction for children with attention-deficit/hyperactivity disorder?

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    Landgraf Jeanne M

    2009-12-01

    Full Text Available Abstract Background To evaluate health-related quality of life (HRQL and medication satisfaction after switching from a stable dose of oral extended-release methylphenidate (ER-MPH to methylphenidate transdermal system (MTS via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD. Methods In a 4-week, multisite, open-label study, 171 children (164 in the intent-to-treat [ITT] population aged 6-12 years diagnosed with ADHD abruptly switched from a stable dose of oral ER-MPH to MTS nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. Subjects remained on the scheduled dose for the first week, after which the dose was then titrated to an optimal effect. The ADHD Impact Module-Children (AIM-C, a disease-specific validated HRQL survey instrument measuring child and family impact, was used to assess the impact of ADHD symptoms on the lives of children and their families at baseline and study endpoint. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS at study endpoint. Both the AIM-C and MSS were completed by a caregiver (parent/legally authorized representative. Tolerability was monitored by spontaneous adverse event (AE reporting. Results AIM-C child and family HRQL mean scores were above the median possible score at baseline and were further improved at endpoint across all MTS doses. Similar improvements were noted for behavior, missed doses, worry, and economic impact AIM-C item scores. Overall, 93.8% of caregivers indicated a high level of satisfaction with their child's use of the study medication. The majority of treatment-emergent AEs (> 98% were mild to moderate in intensity, and the most commonly reported AEs included headache, decreased appetite, insomnia, and abdominal pain. Seven subjects discontinued the study due to intolerable AEs (n = 3 and application site reactions (n = 4. Conclusion This study demonstrates that MTS, when carefully

  17. Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Park Subin

    2012-05-01

    Full Text Available Abstract Background Dysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD. We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD. Methods Fifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT. After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2. Results There was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006 than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T showed a greater decrease in the mean commission error scores (p = 0.003 than those with the A/A genotypes. Conclusions Our results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.

  18. Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment.

    Science.gov (United States)

    Nora, Gerald J; Harun, Rashed; Fine, David F; Hutchison, Daniel; Grobart, Adam C; Stezoski, Jason P; Munoz, Miranda J; Kochanek, Patrick M; Leak, Rehana K; Drabek, Tomas; Wagner, Amy K

    2017-07-01

    Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days after a 5-min VF-CA when compared to Sham or Naïve. VF-CA increased D-Str-evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (V max ). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after establishing a baseline, pre-drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus Sham and reduced D-Str V max in VF-CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF-CA versus Sham. Our work demonstrates that 5-min VF-CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions. © 2017 International Society for Neurochemistry.

  19. Effect of methylphenidate on the quality of life in children with epilepsy and attention deficit hyperactivity disorder: and open-label study using an osmotic-controlled release oral delivery system.

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    Yoo, Hanik K; Park, Subin; Wang, Hee-Ryung; Lee, Joong Sun; Kim, Kunwoo; Paik, Kyoung-Won; Yum, Mi Sun; Ko, Tae-Sung

    2009-12-01

    This open study explored whether methylphenidate could be tolerated and effective in improving the quality of life (QOL) and attention deficit hyperactivity disorder (ADHD) symptoms of children with epilepsy and ADHD. Twenty-five subjects (aged 10.1 +/- 3.0 years) with ADHD and epilepsy were recruited at an outpatient clinic in Seoul, Korea. We used the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE), ADHD rating scale (ARS) and clinical global impression (CGI) in this study. Osmotic-controlled release oral delivery system (OROS) methylphenidate, 1.0 +/- 0.4 mg/kg/day, was administered for 55.2 +/- 7.5 days. The QOL subscales including physical restriction (p = 0.005), self-esteem (p = 0.002), memory (p < 0.001), language (p = 0.005), other cognition (p < 0.001), social interaction (p = 0.002), behaviour (p < 0.001), general health (p = 0.002) and QOL (p < 0.001) were significantly increased and the ARS (p < 0.001) and CGI-Severity of illness scores (p < 0.001) were significantly reduced after medication. Although 60% of subjects had experienced adverse effects, most were tolerable and only two subjects withdrew from the study owing to unbearable adverse effects (anorexia and insomnia). Two subjects had seizure attacks during the study period without having to discontinue the trial drug. Despite limitations related to the small sample size and the open design of the present pilot study, our results suggest that OROS methylphenidate may be well tolerated and effective in reducing ADHD symptoms and improving QOL in this patient population.

  20. Changes of Heart Rate Variability during Methylphenidate Treatment in Attention-Deficit Hyperactivity Disorder Children: A 12-Week Prospective Study.

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    Kim, Hayeon Jennifer; Yang, Jaewon; Lee, Moon Soo

    2015-09-01

    The aim of this study was to clarify the relationship between the autonomic nervous system and attention deficit hyperactivity disorder (ADHD) rating scales and to evaluate the usefulness of heart rate variability (HRV) as a psychophysiological biomarker for ADHD. Subjects were recruited from outpatients in the Department of Child and Adolescent Psychiatry at the Korea University Medical Center from August 2007 to December 2010. Subjects received methylphenidate. Time- and frequency-domain analyses of HRV, the Korean ADHD rating scale (K-ARS), and computerized ADHD diagnostic system were evaluated before treatment. After a 12-week period of medication administration, we repeated the HRV measurements and K-ARS rating. Eighty-six subjects were initially enrolled and 37 participants completed the 12-week treatment and HRV measurements subsequent to the treatment. Significant correlations were found between the K-ARS inattention score and some HRV parameters. All of the HRV parameters, except the standard deviations of the normal-to-normal interval, very low frequency, and low frequency to high frequency, showed a significant positive correlation between baseline and endpoint measures in completers. High frequency (HF) and the square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), which are related to parasympathetic vagal tone, showed significant decreases from baseline to endpoint. The HRV test was shown to be reproducible. The decrease in HF and RMSSD suggests that parasympathetic dominance in ADHD can be altered by methylphenidate treatment. It also shows the possibility that HRV parameters can be used as psychophysiological markers in the treatment of ADHD.

  1. Additional biological therapies for attention-deficit hyperactivity disorder: repetitive transcranical magnetic stimulation of 1 Hz helps to reduce methylphenidate

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    Helmut Niederhofer

    2011-12-01

    Full Text Available Excessive hyperactivity, impulsiveness and attentional difficulties characterize attentiondeficit hyperactivity disorder (ADHD. The aim of this case report is to signal the possible therapeutic effectiveness of the repetitive transcranial magnetic stimulation (rTMS. Low frequency (1Hz, 1200 stim/die for five days was applied on the impending scalp in the motor additional area of a patient suffering from combined type ADHD who received methylphenidate (MPH. We saw a significant improvement, especially according to criteria associated with hyperactivity. The improvement lasted for at least three weeks and suggested the final reduction in dosage of MPH.to 10 mg.

  2. Distúrbio do déficit de atenção: tratamento com metilfenidato Attention deficit disorder: treatment with methylphenidate

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    Marilisa M. Guerreiro

    1996-03-01

    Full Text Available Os autores apresentam os resultados do tratamento com metilfenidato usado em 24 crianças com diagnóstico de distúrbio do déficit de atenção realizado com base nos critérios expostos no DSM-III. A dose utilizada foi de 5 a 10 mg ao dia, dividida em uma ou duas tomadas. Resposta satisfatória ao tratamento foi encontrada em 79,1% dos pacientes e insatisfatória em 16,6%. Em um caso o resultado não pode ser avaliado pela necessidade de interrupção precoce do tratamento. Efeitos colaterais ocorreram em duas crianças (cefaléia e/ou náusea. Os resultados terapêuticos e os efeitos colaterais indesejáveis são comparados com os da literatura, ressaltando-se a eficácia e a segurança do tratamento com metilfenidato .The authors present the results of the treatment with methylphenidate in 24 children with attention deficit disorder based on DSM-III. The prescribed dose was 5 to 10 mg per day, once or twice a day. The results were good in 79.1% of the patients and poor in 16.6%. The drug was withdrawn in one patient because of side effects and the evaluation of efficacy was not possible. Side effects occurred in 2 children (headache and/or nausea. The therapeutic response and the side effects are compared with the literature. The authors claim attention to the efficacy and safety of the treatment with methylphenidate.

  3. Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder

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    Teuscher NS

    2015-05-01

    Full Text Available Nathan S Teuscher,1 Akwete Adjei,2 Robert L Findling,3,4 Laurence L Greenhill,5 Robert J Kupper,2 Sharon Wigal6 1PK/PD Associates, Trophy Club, TX, 2Rhodes Pharmaceuticals L.P., Coventry, RI, 3Department of Psychiatric Services and Research, Kennedy Krieger Institute, Baltimore, MD, 4Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, 5Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, 6AVIDA Inc., Newport Beach, CA, USA Abstract: A new multilayer-bead formulation of extended-release methylphenidate hydrochloride (MPH-MLR has been evaluated in pharmacokinetic studies in healthy adults and in Phase III efficacy/safety studies in children and adolescents with attention deficit hyperactivity disorder (ADHD. Using available data in healthy adults, a two-input, one-compartment, first-order elimination population pharmacokinetic model was developed using nonlinear mixed-effect modeling. The model was then extended to pediatric subjects, and was found to adequately describe plasma concentration–time data for this population. A pharmacokinetic/pharmacodynamic model was also developed using change from baseline in the ADHD Rating Scale (ADHD-RS-IV total scores from a pediatric Phase III trial and simulated plasma concentration–time data. During simulations for each MPH-MLR dose level (10–80 mg, increased body weight resulted in decreased maximum concentration. Additionally, as maximum concentration increased, ADHD-RS-IV total score improved (decreased. Knowledge of the relationship between dose, body weight, and clinical response following the administration of MPH-MLR in children and adolescents may be useful for clinicians selecting initial dosing of MPH-MLR. Additional study is needed to confirm these results. Keywords: population pharmacokinetics, Aptensio XR™, MPH-MLR, methylphenidate

  4. Transdermal and oral dl-methylphenidate-ethanol interactions in C57BL/6J mice: transesterification to ethylphenidate and elevation of d-methylphenidate concentrations.

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    Bell, Guinevere H; Novak, Andrew J; Griffin, William C; Patrick, Kennerly S

    2011-07-01

    We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl-methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d-MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l-MPH, and (3) will l-MPH enantioselectively interact with ethanol to yield l-ethylphenidate (l-EPH)? Mice were dosed with MTS (¼ of a 12.5 cm(2) patch on shaved skin) or a comparable oral dl-MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic-mass spectrometry monitoring of N-(S)-prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l-MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l-EPH and to an elevation in d-MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route-dependent drug absorption rate differences, MTS was associated with significant MPH-ethanol interactions. Ethanol-mediated increases in circulating concentrations of d-MPH carry toxicological and abuse liability implications should this animal model hold for ethanol-consuming attention-deficit hyperactivity disorder patients or coabusers. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  5. Methylphenidate treatment in children with attention deficit hyperactivity disorder and comorbid social phobia.

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    Golubchik, Pavel; Sever, Jonathan; Weizman, Abraham

    2014-07-01

    The aim of this study was to assess the response of social phobia (SP) symptoms to methylphenidate (MPH) treatment in children with attention deficit hyperactivity disorder (ADHD). Twenty-one ADHD patients with SP, aged between 8 and 18 years, received 12 weeks of MPH treatment. The severity of SP symptoms were assessed by the Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA), and the severity of ADHD symptoms was assessed by the ADHD Rating Scale at baseline and at endpoint. MPH treatment was associated with a significant decrease in the ADHD Rating Scale scores (P<0.0001) and in the total LSAS-CA scores (P=0.013), as well as the school-related items of LSAS-CA (P=0.011). A significant correlation was found between the reductions in ADHD score and total LSAS-CA score (P=0.038), especially in school-related SP. The improvement in ADHD symptoms because of MPH treatment correlates with a parallel improvement in SP. MPH treatment appears to be safe and effective in ADHD/SP children.

  6. Prediction of methylphenidate treatment outcome in adults with attention-deficit/hyperactivity disorder (ADHD).

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    Retz, Wolfgang; Retz-Junginger, Petra

    2014-11-01

    Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent mental disorder of childhood, which often persists in adulthood. Methylphenidate (MPH) is one of the most effective medications to treat ADHD, but also few adult patients show no sufficient response to this drug. In this paper, we give an overview regarding genetic, neuroimaging, clinical and other studies which have tried to reveal the reasons for non-response in adults with ADHD, based on a systematic literature search. Although MPH is a well-established treatment for adults with ADHD, research regarding the prediction of treatment outcome is still limited and has resulted in inconsistent findings. No reliable neurobiological markers of treatment response have been identified so far. Some findings from clinical studies suggest that comorbidity with substance use disorders and personality disorders has an impact on treatment course and outcome. As MPH is widely used in the treatment of adults with ADHD, much more work is needed regarding positive and negative predictors of long-term treatment outcome in order to optimize the pharmacological treatment of adult ADHD patients.

  7. The effects of methylphenidate on cognitive performance of healthy male rats

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    Claire Louise Rostron

    2013-06-01

    Full Text Available We aimed to investigate the effects of methylphenidate (MPH in healthy rats on two distinct radial maze tasks which rely on brain structures and neurotransmitters known to be affected by MPH: the Random Foraging Non-Delay Task (RFNDT and the Delay Spatial Win Shift Task (DSWT. Hooded Lister rats were trained to complete either the RFNDT or the DSWT having received oral treatment of either a vehicle or MPH (3.0 mg/kg and 5.0 mg/kg for RFNDT, 3.0 mg/kg for DSWT. We found no effect of MPH on the RFNDT relative to the control group. However, those treated with 5.0 mg/kg MPH did take significantly longer to reach criterion performance than those treated with the 3.0 mg/kg MPH, suggesting some doses of MPH can have detrimental effects. For the DSWT, if MPH was present in both phases, performance did not differ from when it was absent in both phases. However, when present in only one phase there was an increase in errors made, although this only reached significance for when MPH was present only in the test-phase. These data suggest that MPH may have detrimental effects on task performance and can result in state dependent effects in healthy individuals.

  8. Does Methylphenidate Affect Cystometric Parameters in Spontaneously Hypertensive Rats?

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    Khae Hawn Kim

    2015-06-01

    Full Text Available Purpose: Methylphenidate (MPH is one of the most commonly prescribed psychostimulants for attention deficit hyperactivity disorder (ADHD. However, there is limited research on its effects on lower urinary tract function. This study investigated changes in cystometric parameters after intragastric administration of MPH in conscious spontaneously hypertensive rats (SHRs, an animal model of ADHD. Methods: Fourteen- to 16-week-old male SHRs (n=10, weighing between 280 and 315 g, were used. Three micturition cycles were recorded before administering MPH. One hour after each intragastric MPH injection, three cycles of cystometrogram were obtained in the awake condition. Various cystometric parameters were evaluated, including basal pressure (BP, maximal pressure (MP, threshold pressure (TP, bladder capacity (BC, micturition volume (MV, micturition interval (MI, and residual volume (RV. The data were analyzed using paired Student t-tests. Results: Five SHRs were each administered a dose of 3-mg/kg MPH, and the other five received a dose of 6-mg/kg MPH. BP and MP increased significantly in the rats that received the 3-mg/kg MPH injection, but not in those that received the 6-mg/kg injection. BC, MV, and MI significantly increased in the rats that received the 6-mg/kg MPH injection, but not in those that received the 3-mg/kg injection. There were no significant changes in TP after either injection. Conclusions: Significant increases in BC, MV, and MI after the 6-mg/kg MPH injection suggest that the peripheral and the central nervous systems may play important roles in bladder function in those receiving MPH for ADHD.

  9. Predictors of pharmacological treatment outcomes with atomoxetine or methylphenidate in patients with attention-deficit/hyperactivity disorder from China, Egypt, Lebanon, Russian Federation, Taiwan, and United Arab Emirates.

    Science.gov (United States)

    Treuer, T; Feng, Q; Desaiah, D; Altin, M; Wu, S; El-Shafei, A; Serebryakova, E; Gado, M; Faries, D

    2014-09-01

    The reduced availability of data from non-Western countries limits our ability to understand attention-deficit/hyperactivity disorder (ADHD) treatment outcomes, specifically, adherence and persistence of ADHD in children and adolescents. This analysis assessed predictors of treatment outcomes in a non-Western cohort of patients with ADHD treated with atomoxetine or methylphenidate. Data from a 12-month, prospective, observational study in outpatients aged 6-17 years treated with atomoxetine (N = 234) or methylphenidate (N = 221) were analysed post hoc to determine potential predictors of treatment outcomes. Participating countries included the Russian Federation, China, Taiwan, Egypt, United Arab Emirates and Lebanon. Factors associated with remission were analysed with stepwise multiple logistic regression and classification and regression trees (CART). Cox proportional hazards models with propensity score adjustment assessed differences in atomoxetine persistence among initial-dose cohorts. In patients treated with atomoxetine who had available dosing information (N = 134), Cox proportional hazards revealed lower (atomoxetine-treated patients were associated with age (older), country (United Arab Emirates) and gender (female) (all p atomoxetine) and prior atomoxetine use were associated with greater remission rates. These findings may help clinicians assess factors upon initiation of ADHD treatment to improve course prediction, proper dosing and treatment adherence and persistence. Observational study, therefore no registration. © 2014 John Wiley & Sons Ltd.

  10. Methylphenidate improves motor functions in children diagnosed with Hyperkinetic Disorder

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    Iversen Synnøve

    2009-05-01

    Full Text Available Abstract Background A previous study showed that a high percentage of children diagnosed with Hyperkinetic Disorder (HKD displayed a consistent pattern of motor function problems. The purpose of this study was to investigate the effect of methylphenidate (MPH on such motor performance in children with HKD Methods 25 drug-naïve boys, aged 8–12 yr with a HKD-F90.0 diagnosis, were randomly assigned into two groups within a double blind cross-over design, and tested with a motor assessment instrument, during MPH and placebo conditions. Results The percentage of MFNU scores in the sample indicating 'severe motor problems' ranged from 44–84%, typically over 60%. Highly significant improvements in motor performance were observed with MPH compared to baseline ratings on all the 17 subtests of the MFNU 1–2 hr after administration of MPH. There were no significant placebo effects. The motor improvement was consistent with improvement of clinical symptoms. Conclusion The study confirmed our prior clinical observations showing that children with ADHD typically demonstrate marked improvements of motor functions after a single dose of 10 mg MPH. The most pronounced positive MPH response was seen in subtests measuring either neuromotor inhibition, or heightened muscular tone in the gross movement muscles involved in maintaining the alignment and balance of the body. Introduction of MPH generally led to improved balance and a generally more coordinated and controlled body movement.

  11. Methylphenidate and emotional-motivational processing in attention-deficit/hyperactivity disorder.

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    Conzelmann, Annette; Woidich, Eva; Mucha, Ronald F; Weyers, Peter; Müller, Mathias; Lesch, Klaus-Peter; Jacob, Christian P; Pauli, Paul

    2016-08-01

    In line with the assumption that emotional-motivational deficits are one core dysfunction in ADHD, in one of our previous studies we observed a reduced reactivity towards pleasant pictures in adult ADHD patients as compared to controls. This was indicated by a lack of attenuation of the startle reflex specifically during pleasant pictures in ADHD patients. The first choice medical agents in ADHD, methylphenidate (MPH), is discussed to normalize these dysfunctions. However, experimental evidence in the sense of double-blind placebo-controlled study designs is lacking. Therefore, we investigated 61 adult ADHD patients twice, one time with placebo and one time with MPH with the same experimental design as in our study previously and assessed emotion processing during the presentation of pleasant, neutral and unpleasant pictures. We obtained startle reflex data as well as valence and arousal ratings in association with the pictures. As previously shown, ADHD patients showed a diminished startle attenuation during pleasant pictures while startle potentiation during unpleasant pictures was normal. Valence and arousal ratings unsuspiciously increased with increasing pleasantness and arousal of the pictures, respectively. There were no significant influences of MPH. The study replicates that ADHD patients show a reduced reactivity towards pleasant stimuli. MPH did not normalize this dysfunction. Possibly, MPH only influences emotions during more complex behavioural tasks that involve executive functions in adults with ADHD. Our results emphasize the importance for the use of double-blind placebo-controlled designs in psychopharmacological research.

  12. Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.

    Science.gov (United States)

    Inglis, S K; Carucci, S; Garas, P; Häge, A; Banaschewski, T; Buitelaar, J K; Dittmann, R W; Falissard, B; Hollis, C; Kovshoff, H; Liddle, E; McCarthy, S; Nagy, P; Neubert, A; Rosenthal, E; Sonuga-Barke, E; Wong, I; Zuddas, A; Coghill, D C

    2016-04-26

    Methylphenidate is the most frequently used medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in Europe. Following concerns about its safety, the European Commission called for research into the long-term effects of methylphenidate on children and adolescents with ADHD. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) research programme was designed to address this call. At the heart of this programme is a 2-year longitudinal naturalistic pharmacovigilance study being conducted in 27 European sites. 3 cohorts of children and adolescents (aged 6-17) living in the UK, Germany, Italy and Hungary are being recruited:Group 1 (Medicated ADHD): 800 ADHD medication-naive children and adolescents with a clinical diagnosis of ADHD about to start methylphenidate treatment for the first time.Group 2 (Unmedicated ADHD): 400 children and adolescents with a clinical diagnosis of ADHD who have never been treated with ADHD medication and have no intention of beginning medication.Group 3 (Non-ADHD): 400 children and adolescents without ADHD who are siblings of individuals in either group 1 or 2.All participants will be assessed 5 times during their 2-year follow-up period for growth and development, psychiatric, neurological and cardiovascular health. The primary outcome measure will be the height velocity SD score. Ethical approval for the study has been granted by the East of Scotland Research Ethics Service. Following this approval, patient information leaflets and consent forms were translated as necessary and submissions made by lead sites in each of the other 3 countries to their own ethics committees. Following ethical approval in each country, local ethical permissions at each site were sought and obtained as needed. The study's website (http://www.adhd-adduce.org/page/view/2/Home) provides information for researchers, participants and the general public. NCT01470261. Published by the BMJ Publishing Group Limited

  13. Methylphenidate modulates activity within cognitive neural networks of patients with post-stroke major depression: A placebo-controlled fMRI study

    Directory of Open Access Journals (Sweden)

    Rajamannar Ramasubbu

    2008-10-01

    Full Text Available Rajamannar Ramasubbu1, Bradley G Goodyear21Departments of Psychiatry and Clinical Neurosciences; 2Department of Radiology and Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, Calgary, AB, CanadaBackground: Methylphenidate (MP is a dopamine- and noradrenaline-enhancing agent beneficial for post-stroke depression (PSD and stroke recovery due to its therapeutic effects on cognition, motivation, and mood; however, the neural mechanisms underlying its clinical effects remain unknown. This study used functional magnetic resonance imaging (fMRI to investigate the effect of MP on brain activity in response to cognitive tasks in patients with PSD.Methods: Nine stroke outpatients with DSM IV defined major depression underwent fMRI during two cognitive tasks (2-back and serial subtraction on four occasions, on the first and third day of a three-day treatment of MP and placebo. Nine healthy control (HC subjects matched for age and sex scanned during a single session served as normative data for comparison. The main outcome measure was cognitive task-dependent brain activity.Results: For the 2-back task, left prefrontal, right parietal, posterior cingulate, and temporal and bilateral cerebellar regions exhibited significantly greater activity during the MP condition relative to placebo. Less activity was detected in rostral prefrontal and left parietal regions. For serial subtraction, greater activity was detected in medial prefrontal, biparietal, bitemporal, posterior cingulate, and bilateral cerebellar regions, as well as thalamus, putamen, and insula. Further, underactivation observed during the placebo condition relative to HC improved or reversed during MP treatment. No significant differences in behavioral measures were found between MP and placebo conditions or between patients and HC.Conclusions: Short-term MP treatment may improve and normalize activity in cognitive neuronal networks in patients with PSD

  14. Effects of methylphenidate on acute math performance in children with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Grizenko, Natalie; Cai, Emmy; Jolicoeur, Claude; Ter-Stepanian, Mariam; Joober, Ridha

    2013-11-01

    Examine the short-term (acute) effects of methylphenidate (MPH) on math performance in children with attention-deficit hyperactivity disorder (ADHD) and what factors predict improvement in math performance. One hundred ninety-eight children with ADHD participated in a double-blind, placebo-controlled, randomized crossover MPH trial. Math response to MPH was determined through administration of math problems adjusted to their academic level during the Restricted Academic Situation Scale (RASS). Student t tests were conducted to assess change in math performance with psychostimulants. Correlation between change on the RASS and change on the math performance was also examined. Linear regression was performed to determine predictor variables. Children with ADHD improved significantly in their math with MPH (P math performance on MPH was highly correlated. A child's age at baseline and Wechsler Individual Achievement Test (WIAT)-Numerical Operations standard scores at baseline accounted for 15% of variances for acute math improvement. MPH improves acute math performance in children with ADHD. Younger children with lower math scores (as assessed by the WIAT) improved most on math scores when given psychostimulants. NCT00483106.

  15. Effects of methylphenidate during emotional processing in amphetamine users: preliminary findings.

    Science.gov (United States)

    Bottelier, M A; Schouw, M L J; de Ruiter, M B; Ruhe, H G; Lindauer, R J L; Reneman, L

    2015-12-01

    D-amphetamine (dAMPH) and methylphenidate (MPH) are stimulants used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Preclinical studies have shown that in healthy animals, dAMPH induces dopamine (DA) dysfunction, as evidenced for instance by loss of DA levels and its transporters. It has also been suggested that DA plays an important role in emotional processing, and that altered DA-ergic intervention may modulate amygdala function. To explore the role of the DA system in emotional processing we examined emotional processing using functional magnetic resonance imaging (fMRI) in eight male recreational users of dAMPH and eight male healthy controls. We compared brain activation between both groups during an emotional face-processing task with and without an oral MPH challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1½ hours after receiving an oral dose of 35 mg MPH. A significant Valence*Group interaction (p = .037) indicated amygdala hyperreactivity to fearful facial expressions in dAMPH users that was robust against adjustment for age (p = .015). Furthermore, duration of amphetamine use in years was positively correlated with amygdala reactivity in dAMPH users (r = .76; p = .029). These exploratory findings are in line with previous findings suggesting that DA plays a role in emotional processing.

  16. A prenatal nicotine exposure mouse model of methylphenidate responsive ADHD-associated cognitive phenotypes.

    Science.gov (United States)

    Zhu, Jinmin; Fan, Fangfang; McCarthy, Deirdre M; Zhang, Lin; Cannon, Elisa N; Spencer, Thomas J; Biederman, Joseph; Bhide, Pradeep G

    2017-05-01

    Prenatal exposure to nicotine via cigarette smoke or other forms of tobacco use is a significant environmental risk factor for attention deficit hyperactivity disorder (ADHD). The neurobiological mechanisms underlying the link between prenatal nicotine exposure (PNE) and ADHD are not well understood. Animal models, especially rodent models, are beginning to bridge this gap in knowledge. Although ADHD is characterized by hyperactivity, inattention, impulsivity and working memory deficits, the majority of the animal models are based on only one or two ADHD associated phenotypes, in particular, hyperactivity or inattention. We report a PNE mouse model that displays the full range of ADHD associated behavioral phenotypes including working memory deficit, attention deficit and impulsive-like behavior. All of the ADHD-associated phenotypes respond to a single administration of a therapeutic equivalent dose of methylphenidate. In an earlier study, we showed that PNE produces hyperactivity, frontal cortical hypodopaminergic state and thinning of the cingulate cortex. Collectively, these data suggest that the PNE mouse model recapitulates key features of ADHD and may be a suitable preclinical model for ADHD research. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  17. Methylphenidate-risperidone combination in child psychiatry: A retrospective analysis of 44 cases.

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    Javelot, H; Glay-Ribau, C; Ligier, F; Weiner, L; Didelot, N; Messaoudi, M; Socha, M; Body-Lawson, F; Kabuth, B

    2014-05-01

    Psychotimulant-antipyschotic combinations are frequently used in child psychiatry, but have been rarely described in the literature. We propose here a retrospective study of 44 children who received the combination methylphenidate (MPH)-risperidone (RIS). The sample is composed of children who received either MPH (n=28) or RIS (n=16) as primary treatment. A vast majority of the children had a comorbid attention deficit hyperactivity disorder (ADHD) diagnosis. For over 60% of patients, regardless of their initial monotherapy, bitherapy decreased the symptoms of ADHD and conduct disorder, sleep disorders and anxiety. Concerning the safety of the bitherapy, a compensation effect on weight gain and appetite was respectively observed in 70% and 50% of patients. Even though iatrogenic tachycardia can be encountered with both drugs, it has never been reported when they are associated and we have reported a total of 3 cases in our study. We have also observed a case of dyskinesia resolved with the discontinuation of the treatment. MPH-RIS bitherapy appears to be particularly effective in ADHD with conduct disorder symptoms. Although tolerance may limit its use, the benefit/risk ratio seems favourable for a number of children. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Methylphenidate effects in the young brain: friend or foe?

    Science.gov (United States)

    Loureiro-Vieira, Sara; Costa, Vera Marisa; de Lourdes Bastos, Maria; Carvalho, Félix; Capela, João Paulo

    2017-08-01

    Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH) is a first-line stimulant drug available worldwide for its treatment. Despite the proven therapeutic efficacy, concerns have been raised regarding the possible consequences of chronic MPH exposure during childhood and adolescence. Disturbances in the neurodevelopment at these crucial stages are major concerns given the unknown future life consequences. This review is focused on the long-term adverse effects of MPH to the brain biochemistry. Reports conducted with young and/or adolescent animals and studies with humans are reviewed in the context of long-term consequences after early life-exposure. MPH pharmacokinetics is also reviewed as there are differences among laboratory animals and humans that may be relevant to extrapolate the findings. Studies reveal that exposure to MPH in laboratory animals during young and/or adolescent ages can impact the brain, but the outcomes are dependent on MPH dose, treatment period, and animal's age. Importantly, the female sex is largely overlooked in both animal and human studies. Unfortunately, human reports that evaluate adults following adolescent or child exposure to MPH are very scarce. In general, human data indicates that MPH is generally safe, although it can promote several brain changes in early ages. Even so, there is a lack of long course patient evaluation to clearly establish whether MPH-induced changes are friendly or foe to the brain and more human studies are needed to assess the adult brain changes that arise from early MPH treatment. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

  19. The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder

    International Nuclear Information System (INIS)

    Szobot, Claudia M.; Ketzer, Carla; Kapczinski, Flavio; Cunha, Renato D.; Parente, Maria A.; Langleben, Daniel D.; Acton, Paul D.; Rohde, Luis A.P.

    2003-01-01

    Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer ( 99m Tc-ECD) and single-photon emission tomography (SPET). The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD. (orig.)

  20. The acute effect of methylphenidate on cerebral blood flow in boys with attention-deficit/hyperactivity disorder

    Energy Technology Data Exchange (ETDEWEB)

    Szobot, Claudia M; Ketzer, Carla; Kapczinski, Flavio [Department of Psychiatry, Federal University of Rio Grande do Sul (Brazil); Cunha, Renato D [Service of Nuclear Medicine, Hospital de Clinicas de Porto Alegre (Brazil); Parente, Maria A [Department of Psychology, Federal University of Rio Grande do Sul (Brazil); Langleben, Daniel D [Department of Psychiatry, University of Pennsylvania (United States); Acton, Paul D [Department of Radiology, University of Pennsylvania (United States); Rohde, Luis A.P. [Department of Psychiatry, Federal University of Rio Grande do Sul (Brazil); Servico de Psiquiatria da Infancia e Adolescencia, Hospital de Clinicas de Porto Alegre (HCPA), Rua Ramiro Barcelos 2350, CEP 90035-003, RS Porto Alegre (Brazil)

    2003-03-01

    Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer ({sup 99m}Tc-ECD) and single-photon emission tomography (SPET). The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD. (orig.)

  1. Six months methylphenidate treatment improves emotion dysregulation in adolescents with attention deficit/hyperactivity disorder: a prospective study

    Directory of Open Access Journals (Sweden)

    Suzer Gamli I

    2018-05-01

    Full Text Available Ipek Suzer Gamli,1 Aysegul Yolga Tahiroglu2 1Sanliurfa Education and Research Hospital, Eyyubiye, Sanliurfa, Turkey; 2Child and Adolescent Psychiatry Department, Cukurova University School of Medicine, Saricam, Adana, Turkey Purpose: Individuals with attention deficit/hyperactivity disorder (ADHD may suffer from emotional dysregulation (ED, although this symptom is not listed among the diagnostic criteria. Methylphenidate (MPH is useful in reducing emotional symptoms in ADHD. The aim of the present study was to determine both psychosocial risk factors and presence of ED in adolescents with ADHD before and after MPH treatment. Participants and methods: Eighty-two patients aged 12–18 years with ADHD were included as participants. The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime, the Difficulties in Emotion Regulation Scale (DERS, sociodemographic form, and the Inventory of Statements About Self-Injury were administered. Results were compared before and after 6 months MPH treatment. Results: A significant improvement was detected on DERS for impulsivity (15.9±6.8 initial vs 14.2±6.5 final test, p<0.01 and total score (88.4±23.3 initial vs 82.4±2.7 final test, p<0.05 across all patients taking MPH regardless of subtype and sex. Despite treatment, a significant difference remained for impulsivity, strategies, and total score in patients with comorbid oppositional defiant disorder (ODD compared with those without ODD, but no difference was detected for conduct disorder comorbidity. In patients who self-harm, scores for goals, impulsivity, strategies, clarity, and total score were higher before treatment: furthermore, impulsivity and total score remained high after treatment. In maltreated patients, goals, impulsivity, strategies, and total scores were significantly higher before treatment; however, their symptoms were ameliorated after treatment with MPH. Conclusion: Individuals with

  2. Adolescent Exposure to Methylphenidate Increases Impulsive Choice Later in Life

    Directory of Open Access Journals (Sweden)

    Zarish Abbas

    2017-10-01

    Full Text Available Background: The psychostimulant methylphenidate (MPH is known to temporarily reduce impulsive choice and promote self-control. What is not sufficiently understood is how repeated treatment with MPH affects impulsive choice in the long run, and whether any such effect is contingent on exposure at certain developmental stages.Methods: Using an animal model for impulsive choice, we examined first whether giving MPH through early adolescence alters delay discounting, an operational measure of impulsive choice, later in adulthood. We then tested whether equivalent long-term effects are observed if exposure to the drug occurred during adulthood. Starting on postnatal day 25 or postnatal day 60, male rats received one of a range of doses of MPH for 10 consecutive days. Twenty-six days later, all rats were trained to choose between a lever that produced a small immediate reward and a lever that produced a large reward after a range of delays.Results: Rats showed a long-term decrease in the selection of the delayed larger reward when treated with moderate doses of MPH during early adolescence, but not when treated with the lower or higher doses. In contrast, no differences were observed in the selection of the delayed larger reward in animals that were treated with various doses of MPH during adulthood.Conclusions: Our findings suggest effects of MPH on impulsive choice that are contingent on dosage and on the developmental period of exposure. When administered during adolescence, moderate doses of MPH increase impulsive choice long after the end of treatment, whereas these same doses administered during adulthood were without effect

  3. Ethylphenidate as a selective dopaminergic agonist and methylphenidate-ethanol transesterification biomarker.

    Science.gov (United States)

    Patrick, Kennerly S; Corbin, Timothy R; Murphy, Cristina E

    2014-12-01

    We review the pharmaceutical science of ethylphenidate (EPH) in the contexts of drug discovery, drug interactions, biomarker for dl-methylphenidate (MPH)-ethanol exposure, potentiation of dl-MPH abuse liability, contemporary "designer drug," pertinence to the newer transdermal and chiral switch MPH formulations, as well as problematic internal standard. d-EPH selectively targets the dopamine transporter, whereas d-MPH exhibits equipotent actions at dopamine and norepinephrine transporters. This selectivity carries implications for the advancement of tailored attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in the era of genome-based diagnostics. Abuse of dl-MPH often involves ethanol coabuse. Carboxylesterase 1 enantioselectively transesterifies l-MPH with ethanol to yield l-EPH accompanied by significantly increased early exposure to d-MPH and rapid potentiation of euphoria. The pharmacokinetic component of this drug interaction can largely be avoided using dexmethylphenidate (dexMPH). This notwithstanding, maximal potentiated euphoria occurs following dexMPH-ethanol. C57BL/6 mice model dl-MPH-ethanol interactions: an otherwise depressive dose of ethanol synergistically increases dl-MPH stimulation; a substimulatory dose of dl-MPH potentiates a low, stimulatory dose of ethanol; ethanol elevates blood, brain, and urinary d-MPH concentrations while forming l-EPH. Integration of EPH preclinical neuropharmacology with clinical studies of MPH-ethanol interactions provides a translational approach toward advancement of ADHD personalized medicine and management of comorbid alcohol use disorder. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. Methylphenidate alleviates manganese-induced impulsivity but not distractibility

    Science.gov (United States)

    Beaudin, Stephane A.; Strupp, Barbara J.; Uribe, Walter; Ysais, Lauren; Strawderman, Myla; Smith, Donald R.

    2017-01-01

    Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50 mg Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107 – 115) on an attention task that specifically tapped selective attention and impulse control. Animals were treated with oral MPH (2.5 mg/kg/d) throughout testing on the attention task. Our findings show that lifelong postnatal Mn exposure impaired impulse control and selective attention in young adulthood, and that a therapeutically relevant oral MPH regimen alleviated the Mn-induced dysfunction in impulse control, but not selective attention, and actually impaired focused attention in the Mn group. In addition, the effect of MPH was qualitatively different for the Mn-exposed versus control animals across a range of behavioral measures of inhibitory control and attention, as well as dendritic spine density in the mPFC, suggesting that postnatal Mn exposure alters catecholaminergic systems modulating these behaviors. Collectively these findings suggest that MPH may hold promise for treating the behavioral dysfunction caused by developmental Mn exposure, although further research is needed with multiple MPH doses to determine whether a dose can be identified that

  5. Methylphenidate alleviates manganese-induced impulsivity but not distractibility.

    Science.gov (United States)

    Beaudin, Stephane A; Strupp, Barbara J; Uribe, Walter; Ysais, Lauren; Strawderman, Myla; Smith, Donald R

    2017-05-01

    Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107-115) on an attention task that specifically tapped selective attention and impulse control. Animals were treated with oral MPH (2.5mg/kg/d) throughout testing on the attention task. Our findings show that lifelong postnatal Mn exposure impaired impulse control and selective attention in young adulthood, and that a therapeutically relevant oral MPH regimen alleviated the Mn-induced dysfunction in impulse control, but not selective attention, and actually impaired focused attention in the Mn group. In addition, the effect of MPH was qualitatively different for the Mn-exposed versus control animals across a range of behavioral measures of inhibitory control and attention, as well as dendritic spine density in the mPFC, suggesting that postnatal Mn exposure alters catecholaminergic systems modulating these behaviors. Collectively these findings suggest that MPH may hold promise for treating the behavioral dysfunction caused by developmental Mn exposure, although further research is needed with multiple MPH doses to determine whether a dose can be identified that ameliorates the

  6. Influence of Methylphenidate on the Frequency of Stuttering: A Randomized Controlled Trial.

    Science.gov (United States)

    Rabaeys, Henk; Bijleveld, Henny-Annie; Devroey, Dirk

    2015-10-01

    Recently, a case report described a decrease in frequency of stuttering after intake of methylphenidate (MPH). This study was undertaken to investigate if this effect could again be reproduced in a population of young healthy male adult persons with developmental stuttering. A double-blind randomized crossover trial, with a 2-week washout period, including 15 Dutch-speaking young healthy persons with developmental stuttering, assessed the effects of a single dose of 20 mg MPH compared with placebo on stuttering. Dependent and 1-sample t tests were used to detect significant differences. The end point was the number of stutter moments and self-perceived improvement. MPH yielded a significant decrease in the number of stutter moments when reading and speaking (P = 0.002), which was not the case with placebo (P = 0.090). There was a significant improvement from baseline after intake of MPH as compared with placebo (P = 0.003). Self-perceived improvement with MPH was not significantly better as compared with placebo (P = 0.28). This study showed that the participants had an objective statistically significant decrease in the frequency of stuttering with MPH, and this was not the case with placebo. This was also the case for a reduction in stutter moments when reading out loud and speaking spontaneously. However, this result was not subjectively perceived by the participants. © The Author(s) 2015.

  7. Methylphenidate does not enhance visual working memory but benefits motivation in macaque monkeys.

    Science.gov (United States)

    Oemisch, Mariann; Johnston, Kevin; Paré, Martin

    2016-10-01

    Working memory is a limited-capacity cognitive process that retains relevant information temporarily to guide thoughts and behavior. A large body of work has suggested that catecholamines exert a major modulatory influence on cognition, but there is only equivocal evidence of a direct influence on working memory ability, which would be reflected in a dependence on working memory load. Here we tested the contribution of catecholamines to working memory by administering a wide range of acute oral doses of the dopamine and norepinephrine reuptake inhibitor methylphenidate (MPH, 0.1-9 mg/kg) to three female macaque monkeys (Macaca mulatta), whose working memory ability was measured from their performance in a visual sequential comparison task. This task allows the systematic manipulation of working memory load, and we therefore tested the specific hypothesis that MPH modulates performance in a manner that depends on both dose and memory load. We found no evidence of a dose- or memory load-dependent effect of MPH on performance. In contrast, significant effects on measures of motivation were observed. These findings suggest that an acute increase in catecholamines does not seem to affect the retention of visual information per se. As such, these results help delimit the effects of MPH on cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. The Influence of Methylphenidate on Hyperactivity and Attention Deficits in Children With ADHD: A Virtual Classroom Test.

    Science.gov (United States)

    Mühlberger, A; Jekel, K; Probst, T; Schecklmann, M; Conzelmann, A; Andreatta, M; Rizzo, A A; Pauli, P; Romanos, M

    2016-05-13

    This study compares the performance in a continuous performance test within a virtual reality classroom (CPT-VRC) between medicated children with ADHD, unmedicated children with ADHD, and healthy children. N = 94 children with ADHD (n = 26 of them received methylphenidate and n = 68 were unmedicated) and n = 34 healthy children performed the CPT-VRC. Omission errors, reaction time/variability, commission errors, and body movements were assessed. Furthermore, ADHD questionnaires were administered and compared with the CPT-VRC measures. The unmedicated ADHD group exhibited more omission errors and showed slower reaction times than the healthy group. Reaction time variability was higher in the unmedicated ADHD group compared with both the healthy and the medicated ADHD group. Omission errors and reaction time variability were associated with inattentiveness ratings of experimenters. Head movements were correlated with hyperactivity ratings of parents and experimenters. Virtual reality is a promising technology to assess ADHD symptoms in an ecologically valid environment. © The Author(s) 2016.

  9. Methylphenidate disintegration from oral formulations for intravenous use by experienced substance users.

    Science.gov (United States)

    Bjarnadottir, G D; Johannsson, M; Magnusson, A; Rafnar, B O; Sigurdsson, E; Steingrimsson, S; Asgrimsson, V; Snorradottir, I; Bragadottir, H; Haraldsson, H M

    2017-09-01

    Methylphenidate (MPH) is a prescription stimulant used to treat attention-deficit hyperactivity disorder. MPH is currently the preferred substance among most intravenous (i.v.) substance users in Iceland. Four types of MPH preparations were available in Iceland at the time of study: Immediate-release (IR), sustained-release (SR), osmotic controlled-release oral delivery (OROS) tablet and osmotic-controlled release (OCR). MPH OROS has previously been rated the least desirable by i.v. users and we hypothesized that this was associated with difficulty of disintegrating MPH from OROS formulation. The aim of the study was to measure the amount of MPH and the viscosity of the disintegrated solutions that were made from the four MPH formulations by four i.v.-users and non-users. A convenience sample of four i.v. substance users and 12 non-users. Non-users imitated the methods applied by experienced i.v. substance users for disintegrated MPH formulations. Both groups managed to disintegrate over 50% of MPH from IR and SR formulations but only 20% from OROS (pusers and non-users. To our knowledge, this is the first investigation of viscosity and the amount of disintegrated MPH from prescription drugs for i.v. use. The results indicate that the ease of disintegration, amount of MPH and viscosity may explain the difference in popularity for i.v. use between different MPH formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Prospective, naturalistic study of open-label OROS methylphenidate treatment in Chinese school-aged children with attention-deficit/hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yi; GONG Mei-en; YIN Qing-yun; MAI Jian-ning; JING Jin; LUO Xiang-yang; MA Hong-wei; LI Hai-bo; XIE Ling; LI Yan; Kuang Gui-fang; WANG Yu-feng; YI Ming-ji; WANG Feng; ZHU Xiao-hua; YAO Yah-bin; QIN Jiong; WANG Li-wen; ZOU Li-ping; JIN Xing-ming; XU Tong; WANG Yi; QI Yuan-li

    2011-01-01

    Background Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood,characterized by the core symptoms of hyperactivity,impulsivity and inattention and puts great burden on children themselves,their families and the society.Osmotic release oral system methylphenidate (OROS-MPH) is a once-daily controlled-release formulation developed to overcome some of the limitations associated with immediate-release methylphenidate (IR-MPH).It has been marketed in China since 2005 but still lacks data from large-sample clinical trials on efficacy and safety profiles.The aim of this study was to evaluate the effectiveness and safety of OROS-MPH in children aged 6 to 16 years with ADHD under naturalistic clinical setting.Methods This 6-week,multi-center,prospective,open-label study enrolled 1447 ADHD children to once-daily OROS-MPH (18 mg,36 mg or 54 mg) treatment.The effectiveness measures were parent-rated Inattention and Overactivity With Aggression (IOWA) Conners I/O and O/D subscales,physician-rated CGI-I and parent-rated global efficacy assessment scale.Blood pressure,pulse rate measurement,adverse events (AEs) and concomitant medications and treatment review were conducted by the investigator and were served as safety measures.Results A total of 1447 children with ADHD (mean age (9.52±2.36) years) were enrolled in this trial.Totally 96.8%children received an OROS-MPH modal dose of 18 mg,3.1% with 36 mg and 0.1% with 54 mg at the endpoint of study.The parent IOWA Conners I/O score at the end of week 2 showed statistically significant (P <0.001) improvement with OROS-MPH (mean:6.95±2.71) versus the score at baseline (10.45±2.72).The change in the parent IOWA Conners O/D subscale,CGI-I and parent-rated global efficacy assessment scale also supported the superior efficacy for OROS-MPH treatment.Fewer than half of 1447 patients (511 (35.3%)) reported AEs,and the majority of the events reported were mild (68.2

  11. Prior methylphenidate self-administration alters the subsequent reinforcing effects of methamphetamine in rats.

    Science.gov (United States)

    Baladi, Michelle G; Nielsen, Shannon M; Umpierre, Anthony; Hanson, Glen R; Fleckenstein, Annette E

    2014-12-01

    Methylphenidate (MPD) is clinically effective in treating the symptoms of attention-deficit hyperactivity disorder; however, its relatively widespread availability has raised public health concerns on nonmedical use of MPD among certain adult populations. Most preclinical studies investigate whether presumed therapeutically relevant doses of MPD alter sensitivity to the reinforcing effects of other drugs, but it remains unclear whether doses of MPD likely exceeding therapeutic relevance impact the subsequent reinforcing effects of drugs. To begin to address this question, the effect of prior MPD self-administration (0.56 mg/kg/infusion) on the subsequent reinforcing effects of methamphetamine (METH, 0.032 or 0.1 mg/kg/infusion) was investigated in male Sprague-Dawley rats. For comparison, it was also determined whether prior experimenter-administered MPD, injected daily at a presumed therapeutically relevant dose (2 mg/kg), altered the subsequent reinforcing effects of METH. Results indicated that, under the current conditions, only a history of MPD self-administration increased sensitivity to the subsequent reinforcing effects of METH. Furthermore, MPD did not impact food-maintained responding, suggesting that the effect of MPD might be specific to drug reinforcers. These data suggest that short-term, nonmedical use of MPD might alter the positive reinforcing effects of METH in a manner relevant to vulnerability to drug use in humans.

  12. The effect of methylphenidate on very low frequency electroencephalography oscillations in adult ADHD.

    Science.gov (United States)

    Cooper, Ruth E; Skirrow, Caroline; Tye, Charlotte; McLoughlin, Grainne; Rijsdijk, Fruhling; Banaschweski, Tobias; Brandeis, Daniel; Kuntsi, Jonna; Asherson, Philip

    2014-04-01

    Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02-0.2Hz) during a cued continuous performance task. 41 untreated adults with ADHD and 47 controls were assessed, and 21 cases followed up after MPH treatment, with a similar follow-up for 38 controls (mean follow-up=9.4months). Cases had enhanced frontal and parietal VLF-EEG and increased omission errors. In the whole sample, increased parietal VLF-EEG correlated with increased omission errors. After controlling for subthreshold comorbid symptoms, VLF-EEG case-control differences and treatment effects remained. Post-treatment, a time by group interaction emerged; VLF-EEG and omission errors reduced to the same level as controls, with decreased inattentive symptoms in cases. Reduced VLF-EEG following MPH treatment provides preliminary evidence that changes in VLF-EEG may relate to MPH treatment effects on ADHD symptoms; and that VLF-EEG may be an intermediate phenotype of ADHD. Further studies of the treatment effect of MPH in larger controlled studies are required to formally evaluate any causal link between MPH, VLF-EEG and ADHD symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    International Nuclear Information System (INIS)

    Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, D.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-01-01

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  14. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

    Energy Technology Data Exchange (ETDEWEB)

    Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.; Maloney, T.; Tomasi, D.; Alia-Klein, N.; Shan, J.; Honorario, J.; Samaras, d.; Wang, R.; Telang, F.; Wang, G.-J.; Volkow, N.D.

    2010-09-21

    Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

  15. Remission in children and adolescents diagnosed with attention-deficit/hyperactivity disorder via an effective and tolerable titration scheme for osmotic release oral system methylphenidate.

    Science.gov (United States)

    Chou, Wen-Jiun; Chen, Shin-Jaw; Chen, Ying-Sheue; Liang, Hsin-Yi; Lin, Chih-Chien; Tang, Ching-Shu; Huang, Yu-Shu; Yeh, Chin-Bin; Chou, Miao-Chun; Lin, Dai-Yueh; Hou, Po-Hsun; Wu, Yu-Yu; Liu, Hung-Jen; Huang, Ya-Fen; Hwang, Kai-Ling; Chan, Chin-Hong; Pan, Chia-Ho; Chang, Hsueh-Ling; Huang, Chi-Fen; Hsu, Ju-Wei

    2012-06-01

    The purpose of this study was to identify the optimal dose of osmotic release oral system methylphenidate (OROS-MPH) using a dosage forced-titration scheme to achieve symptomatic remission in children with attention- deficit/hyperactivity disorder (ADHD). We also evaluated the efficacy and safety of, and patient and parent satisfaction with, the change in therapy from immediate-release methylphenidate (IR-MPH) to OROS-MPH over 10 weeks. We recruited 521 children and adolescents aged 6-18 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of ADHD, who had received IR-MPH treatments (titration phase of OROS-MPH to achieve symptomatic remission (defined as a score of 0 or 1 for each of the first 18 ADHD items in the Chinese version of the Swanson, Nolan, and Pelham, Version IV [SNAP-IV]), followed by a 4-week maintenance phase. The global ADHD severity and drug side effects of the participants were evaluated. Parents completed the ratings scales for the ADHD-related symptoms. Patient and parent satisfaction for the OROS-MPH treatment was also assessed. Among the 439 participants with ADHD who completed the trial, 290 participants (66.1%) achieved symptomatic remission. The mean dose of OROS-MPH among participants in remission was 36.7 mg (1.08 mg/kg) per day. Increased efficacy, superior satisfaction, and safety equivalent to that of IR-MPH were demonstrated in intra-individual comparisons from the baseline to the end of study. Determinants for remission included less severe ADHD symptoms (SNAP-IV score history of ADHD, and an appropriate dosage of medication according to the patient's weight. The findings suggest remission as a treatment goal for ADHD therapy by providing an optimal dosage of medication for children and adolescents with ADHD through using an effective and tolerable forced-titration scheme.

  16. Methylphenidate enhances cognitive performance in adults with poor baseline capacities regardless of attention-deficit/hyperactivity disorder diagnosis.

    Science.gov (United States)

    Agay, Nirit; Yechiam, Eldad; Carmel, Ziv; Levkovitz, Yechiel

    2014-04-01

    We compare the view that the effect of methylphenidate (MPH) is selective to individuals with attention-deficit/hyperactivity disorder (ADHD) with an alternative approach suggesting that its effect is more prominent for individuals with weak baseline capacities in relevant cognitive tasks. To evaluate theses 2 approaches, we administered sustained attention, working memory, and decision-making tasks to 20 ADHD adults and 19 control subjects, using a within-subject placebo-controlled design. The results demonstrated no main effects of MPH in the decision-making tasks. In the sustained attention and working-memory tasks, MPH enhanced performance of both ADHD and non-ADHD adults to a similar extent compared with placebo. Hence, the effect of MPH was not selective to ADHD adults. In addition, those benefitting most from MPH in all 3 task domains tended to be individuals with poor task performance. However, in most tasks, individuals whose performance was impaired by MPH were not necessarily better (or worse) performers. The findings suggest that the administration of MPH to adults with ADHD should consider not only clinical diagnosis but also their functional (performance-based) profile.

  17. Gender Differences in the Behavioral Symptoms and Neuropsychological Performance of Patients with Attention-Deficit/Hyperactivity Disorder Treated with Methylphenidate: A Two-Year Follow-up Study.

    Science.gov (United States)

    Wang, Liang-Jen; Chen, Chih-Ken; Huang, Yu-Shu

    2015-08-01

    This study investigated the gender differences in behavioral symptoms, as rated by various informants, and in neuropsychological performance, among patients with attention-deficit/hyperactivity disorder (ADHD) treated with methylphenidate during 24 months in a clinical setting. Study participants comprised 128 boys (mean age: 13.2±2.4 years) and 26 girls (mean age: 12.8±1.0 years) with ADHD. All patients were prescribed short-acting oral methylphenidate, taken two or three times daily; each dose ranged between 0.3 and 1.0 mg/kg. At the baseline and 6, 12, 18, and 24 months later, behavioral symptoms were evaluated using the parent and teacher forms of the Swanson, Nolan, and Pelham Version IV (SNAP-IV) scale for ADHD and the ADHD Rating Scale (completed by a child psychiatrist). In addition, neuropsychological function was assessed using the Test of Variables of Attention (TOVA) at each interval. Although both the boys and girls exhibited a significant decrease in the ADHD symptoms observed by parents and clinicians, the girls improved more than the boys did. Based on the teacher reports, neither the boys nor the girls exhibited significant decreases in ADHD symptoms. The symptoms rated by teachers were more severe in the boys than in the girls throughout the first 12 months; however, the gender difference lessened after 12 months. Based on the TOVA assessment, a composite score (containing response time, response time variability, and ADHD score obtained using the TOVA) did not indicate differences between genders. However, another composite score (containing omission errors, commission errors, and response sensitivity) suggested significant improvement only in the boys. The results suggested that according to a longitudinal follow-up, behavioral and neuropsychological changes among patients with ADHD might differ between genders. Gathering multidimensional information from patients with ADHD is essential in determining how gender modifies the functional

  18. Combined ω3 and ω6 supplementation in children with attention-deficit hyperactivity disorder (ADHD) refractory to methylphenidate treatment: a double-blind, placebo-controlled study.

    Science.gov (United States)

    Perera, Hemamali; Jeewandara, Kamal Chandima; Seneviratne, Sudarshi; Guruge, Chandima

    2012-06-01

    Children (6-12 years) with attention-deficit hyperactivity disorder (ADHD) being treated with methylphenidate and standard behavior therapy for more than 6 months, whose parents reported no improvement in behavior and academic learning, were randomly assigned to receive supplementation with a combined ω3 and ω6 preparation or a placebo. Outcome was measured at 3 and 6 months after treatment using a self-assessment checklist completed by the parents. Statistically significant improvement was found in the treatment group compared with the placebo group (P parents and teachers. Distractibility failed to show improvement. Effect sizes ranged from 0.3 to 1.1 at 3 months and 0.2 to 1.4 at 6 months for individual symptom variables.

  19. Reinforcement Enhances Vigilance Among Children With ADHD: Comparisons to Typically Developing Children and to the Effects of Methylphenidate

    Science.gov (United States)

    Bubnik, Michelle G.; Hawk, Larry W.; Pelham, William E.; Waxmonsky, James G.; Rosch, Keri S.

    2014-01-01

    Sustained attention and reinforcement are posited as causal mechanisms in Attention-Deficit/Hyperactivity Disorder (ADHD), but their interaction has received little empirical study. In two studies, we examined the impact of performance-based reinforcement on sustained attention over time, or vigilance, among 9- to 12-year-old children. Study 1 demonstrated the expected vigilance deficit among children with ADHD (n=25; 12% female) compared to typically developing (TD) controls (n=33; 22% female) on a standard continuous performance task (CPT). During a subsequent visit, reinforcement improved attention more among children with ADHD than controls. Study 2 examined the separate and combined effects of reinforcement and acute methylphenidate (MPH) on CPT performance in children with ADHD (n=19; 21% female). Both reinforcement and MPH enhanced overall target detection and attenuated the vigilance decrement that occurred in no-reinforcement, placebo condition. Cross-study comparisons suggested that the combination of MPH and reinforcement eliminated the vigilance deficit in children with ADHD, normalizing sustained attention. This work highlights the clinically and theoretically interesting intersection of reinforcement and sustained attention. PMID:24931776

  20. 盐酸哌甲酯控释剂治疗儿童ADHD临床疗效影响因素分析%Factors influencing efficacy of methylphenidate hydrochloride controlled release agent on children with attention deficit hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    王四美; 龚群; 陈津津; 张凤玲; 何琳

    2017-01-01

    Objective To observe the influencing factors of clinical effect of methylphenidate hydrochloride controlled release agent as central nervous system stimulant on attention deficit hyperactivity disorder (ADHD) in children.Methods Method of self-control was used to select 711 children diagnosed as ADHD and needing therapy in Shanghai Children ' s Hospital during the period of January 2014 to December 2015.After treatment with methylphenidate hydrochloride controlled release agent , therapeutic efficacy was evaluated before and after treatment with Swanson Nolan and Pelham Version IV (SNAP-Ⅳ) and Combined Raven's Test (CRT) at 6 week and 6 month. Results Methylphenidate hydrochloride controlled release agent was more effective to inattentive type and ADHD combined type than to hyperactive-impulsive type (χ2 =73.109,P<0.01).It was better to ADHD children with good cognitive function than to children with cognition dysfunction (χ2 =100.225, P <0.01).Conclusion Methylphenidate hydrochloride controlled release agent is effective to different types of ADHD children , and the therapeutic efficacy is influenced by ADHD subtypes , children ' s intelligence and dosage .%目的 观察中枢神经兴奋剂盐酸哌甲酯控释剂治疗注意缺陷多动障碍(ADHD)患儿临床疗效的影响因素.方法采取自身对照研究方法,选取2014年1月至2015年12月在上海市儿童医院儿保门诊就诊被诊断为ADHD并需要进行治疗的患儿711例;经过盐酸哌甲酯控释剂治疗后,分别于6周、6个月后采用斯诺佩评估量表(SNAP-Ⅳ)的家长使用量表、联合型瑞文测验(CRT)等相关测试,进行治疗前后疗效评估.结果盐酸哌甲酯控释剂对注意力缺陷型和混合型的ADHD患儿治疗效果明显优于多动型/冲动型(χ2=73.109,P<0.01);对认知功能好的ADHD患儿疗效优于合并认知障碍者(χ2=100.225,P<0.01).结论盐酸哌甲酯控释剂治疗儿童不同类型ADHD疗效肯定;疗效受到ADHD类型、患儿智力、药物剂量等的影响.

  1. Ginkgo biloba as an adjunct to methylphenidate in the treatment of attention deficit hyperactivity disorder in children: review of articles

    Directory of Open Access Journals (Sweden)

    Paria Hebrani

    2015-01-01

    Full Text Available Attention-deficit/hyperactivity disorder is one of the most common psychiatric disorders in childhood. The medications which inhibit the reuptake of noradrenline and dopamine including psychostimulants such as methylphenidate and dextroamphetamine and non-stimulating pre-frontal cortex noradrenaline reuptake inhibitor such as atomoxetine, are the standard treatment of ADHD. Adverse effects of stimulants have been reported in thirty percent of patients with attention-deficit/hyperactivity disorder. More than fifty percent of the parents of these children have tried one or more complementary or alternative medicines including vitamins in their children. Ginkgo biloba has been described to be effective for various neuropsychiatric symptoms. It was assumed that ginkgo biloba might improve some symptoms of attention deficit disorder as well. Nevertheless, no systematic study reported a possible efficacy of ginkgo biloba in attention deficit disorder. This review article evaluates the available evidence on the efficacy of ginkgo biloba medication in Attention-deficit/hyperactivity disorder children to present an appropriate guidance for this common child disorder.

  2. Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder and Substance Use Disorders.

    Science.gov (United States)

    Simon, Nicolas; Rolland, Benjamin; Karila, Laurent

    2015-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopment disorder occurring during childhood. However, ADHD persists into adulthood in 45.7% of cases. The global prevalence of adult ADHD is estimated to 5.3%, with no difference between Europe and North America. ADHD is often comorbid with substance use disorder (SUD), with Odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients without SUD. Methylphenidate (MPH) alleviates ADHD symptoms and, as such, is currently considered as a first choice medication. MPH blocks the dopamine and norepinephrine transporters leading to an increase in extracellular dopamine. It should be noted that its subjective effects are highly dependent on the pharmacokinetic and especially on the rate of input, which highlights the importance of choosing a sustained-release formulation. Meanwhile, prescribing MPH to patients with comorbid SUD has always been challenging for clinicians. The aim of this review is to address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on each of the following types of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH treatment should be evaluated individually in adults with comorbid ADHD and SUD. The choice of the formulation should favor sustained- release MPH over immediate release MPH. Cardiovascular parameters also have to be monitored during long-term use.

  3. Association of the GRIN2B rs2284411 polymorphism with methylphenidate response in attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Kim, Johanna I; Kim, Jae-Won; Park, Jong-Eun; Park, Subin; Hong, Soon-Beom; Han, Doug Hyun; Cheong, Jae Hoon; Choi, Jae-Won; Lee, Sumin; Kim, Bung-Nyun

    2017-08-01

    We investigated the possible association between two NMDA subunit gene polymorphisms (GRIN2B rs2284411 and GRIN2A rs2229193) and treatment response to methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). A total of 75 ADHD patients aged 6-17 years underwent 6 months of MPH administration. Treatment response was defined by changes in scores of the ADHD-IV Rating Scale (ADHD-RS), clinician-rated Clinical Global Impression-Improvement (CGI-I), and Continuous Performance Test (CPT). The association of the GRIN2B and GRIN2A polymorphisms with treatment response was analyzed using logistic regression analyses. The GRIN2B rs2284411 C/C genotype showed significantly better treatment response as assessed by ADHD-RS inattention ( p=0.009) and CGI-I scores ( p=0.009), and there was a nominally significant association in regard to ADHD-RS hyperactivity-impulsivity ( p=0.028) and total ( p=0.023) scores, after adjusting for age, sex, IQ, baseline Clinical Global Impression-Severity (CGI-S) score, baseline ADHD-RS total score, and final MPH dose. The GRIN2B C/C genotype also showed greater improvement at the CPT response time variability ( pADHD.

  4. Effect of methylphenidate on enhancement of spatial learning by novel alternated dual task.

    Science.gov (United States)

    Veetil, Praveen Kottath; Mukkadan, Joseph Kurian

    2011-01-01

    The novel alternated dual task (ADT) arranged rats to learn T-maze spontaneous alternation task and radial arm maze (RAM) task alternatively, and by doing ADT, rats could acquire the tasks more easily than non alternated dual task (NADT) group. Also retention capacity of ADT group was significantly more and ADT help to learn a complex task faster than learning it in isolation from other tasks. In the present study effect of methylphenidate (MPD), a mood elevator, known to enhance learning and memory, on ADT procedure is assessed. Also effect of ADT procedure and MPD on spatial learning and memory are compared. Different groups were assigned by administering MPD (intraperitoneal injection at a dose of 3 mg/kg body weight) during different phases of behavioural experiments, and control groups received saline injection. MPD administration increased both acquisition and retention capacities. The amelioration attained for retention of complex task by ADT procedure, could be achieved by NADT rats only by administration of MPD. The influence of ADT procedure on acquisition and retention of TM and RAM tasks were similar to the effects of MPD, especially for the RAM task. MPD at low dose is found to enhance the learning and memory capacity in rats, than deteriorating it, supporting the use of MPD as a drug to treat attention deficit hyperactive disorder. The recent reports suggesting the effect of MPD only on retention and not on acquisition could not be confirmed, as enhancement for both acquisition and retention was found in this study.

  5. Determinants of adherence to methylphenidate and the impact of poor adherence on maternal and family measures.

    Science.gov (United States)

    Gau, Susan S F; Shen, Hsin-Yi; Chou, Miao-Churn; Tang, Ching-Shu; Chiu, Yen-Nan; Gau, Churn-Shiouh

    2006-06-01

    The aim of this study was to examine the association between adherence to immediate-release methylphenidate (IR MPH) and maternal psychological distress, parenting style, parent- child relationship, and perceived family support. The sample consisted of 307 children with attention-deficit hyperactivity disorder (ADHD) (271 boys and 36 girls), 6-17 years of age, who had been treated with IR MPH for the past 6 months. The measures included the Chinese Health Questionnaire, Parental Bonding Instrument, Family APGAR, and Home Behaviors of the Social Adjustment Inventory for Children and Adolescents. Reasons for poor adherence (n = 79; 25.7%) included forgetting medication (72.7%), the medication having no effect (20.0%), and refusing medication (12.7%). Increased age and three-times-daily administration were the major predictors for poor adherence to IR MPH. Poor adherence was associated with increased degree of maternal psychological distress, indifferent parenting, maternal overprotection/control, poor family support, decreased interaction with parents, and increased problems at home. Findings indicate that multiple daily dosing of MPH increases the likelihood of poor adherence, particularly in adolescents, and that poor adherence is associated with impaired maternal/family process. Once-daily administration of MPH is necessary to improve adherence and to decrease the possible exacerbation of tense parent-child relationships caused by poor drug adherence.

  6. Effectiveness of atomoxetine and methylphenidate for problematic online gaming in adolescents with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Park, Jeong Ha; Lee, Young Sik; Sohn, Ji Hyun; Han, Doug Hyun

    2016-11-01

    There is a high prevalence of problematic online gaming in adolescents with attention deficit hyperactivity disorder (ADHD). In the current study, we compared the effectiveness of atomoxetine (ATM) and methylphenidate (MPH) on problematic online gaming in adolescents with ADHD. We recruited 86 adolescents diagnosed with ADHD together with Internet gaming disorder. These participants were divided into two treatment groups: 44 participants were treated with MPH for 12 weeks, and 42 participants were treated with ATM for 12 weeks. During the 3-month study period, the MPH group showed greater improvement in Korean ADHD rating scale scores than the ATM group. The ATM group showed greater improvement in Child Depression Inventory scores than the MPH group. However, Young Internet Addiction Scale and Behavioral Inhibition & Activation Scales score changes did not differ significantly between the MPH and ATM groups. In both groups, changes in Young Internet Addiction Scale scores were positively correlated with the changes in Behavioral Inhibition & Activation Scales scores. Both MPH and ATM reduced the severity of Internet gaming disorder symptoms, and this reduction was correlated with impulsivity reduction, which also resulted from both ADHD medications. These findings suggest impulsivity plays a critical role in the development of problematic online gaming. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Mediators of methylphenidate effects on math performance in children with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Froehlich, Tanya E; Antonini, Tanya N; Brinkman, William B; Langberg, Joshua M; Simon, John O; Adams, Ryan; Fredstrom, Bridget; Narad, Megan E; Kingery, Kathleen M; Altaye, Mekibib; Matheson, Heather; Tamm, Leanne; Epstein, Jeffery N

    2014-01-01

    Stimulant medications, such as methylphenidate (MPH), improve the academic performance of children with attention-deficit hyperactivity disorder (ADHD). However, the mechanism by which MPH exerts an effect on academic performance is unclear. We examined MPH effects on math performance and investigated possible mediation of MPH effects by changes in time on-task, inhibitory control, selective attention, and reaction time variability. Children with ADHD aged 7 to 11 years (N = 93) completed a timed math worksheet (with problems tailored to each individual's level of proficiency) and 2 neuropsychological tasks (Go/No-Go and Child Attention Network Test) at baseline, then participated in a 4-week, randomized, controlled, titration trial of MPH. Children were then randomly assigned to their optimal MPH dose or placebo for 1 week (administered double-blind) and repeated the math and neuropsychological tasks (posttest). Baseline and posttest videorecordings of children performing the math task were coded to assess time on-task. Children taking MPH completed 23 more math problems at posttest compared to baseline, whereas the placebo group completed 24 fewer problems on posttest versus baseline, but the effects on math accuracy (percent correct) did not differ. Path analyses revealed that only change in time on-task was a significant mediator of MPH's improvements in math productivity. MPH-derived math productivity improvements may be explained in part by increased time spent on-task, rather than improvements in neurocognitive parameters, such as inhibitory control, selective attention, or reaction time variability.

  8. Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial.

    Science.gov (United States)

    Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle

    2018-01-01

    Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Methylphenidate increases glucose uptake in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

    2015-10-01

    Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

    2016-08-01

    To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

  11. Extinction memory is facilitated by methylphenidate and regulated by dopamine and noradrenaline receptors.

    Science.gov (United States)

    Furini, Cristiane R G; Behling, Jonny A K; Zinn, Carolina G; Zanini, Mara Lise; Assis Brasil, Eduardo; Pereira, Luiza Doro; Izquierdo, Ivan; de Carvalho Myskiw, Jociane

    2017-05-30

    Extinction is defined as the learned inhibition of retrieval and is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear disorders. The psychostimulant, methylphenidate (MPH) is known to increase extracellular levels of noradrenaline and dopamine by blocking their reuptake and studies have demonstrated that MPH can modulate hippocampal physiology and/or functions including long-term potentiation (LTP), learning and memory. However, the influence of MPH on fear extinction memory has been insufficiently studied. Here we investigate the effect of MPH infused into the CA1 region of the hippocampus on extinction memory in animals normally incapable of showing contextual fear conditioning (CFC) extinction because of weak training, and the possible mechanisms through which it acts during this process. For this, male Wistar rats with infusion cannulae stereotaxically implanted in the CA1 region were submitted to a weak extinction protocol in a CFC apparatus. Animals that received intra-CA1 infusion of MPH (12.5μg/side) 20min before the extinction training (Ext Tr) expressed less freezing behavior than Veh-treated animals during both Ext Tr and extinction retention Test (Ext Test). Additionally, the administration of MPH+Timolol (1μg/side) or MPH+SCH23390 (1.5μg/side) intra-CA1 20min before the Ext Tr blocked the enhancing effect of the MPH on extinction learning. These results suggest that MPH in the CA1 region of the hippocampus is able to induce the consolidation of extinction memory and this process occurs through both β-adrenergic and D1/D5 dopaminergic receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Sex differences in attentional performance and their modulation by methylphenidate in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Günther, Thomas; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2010-06-01

    Still little is known about neuropsychological differences between boys and girls with attention-deficit/hyperactivity disorder (ADHD) and whether there are sex-specific differences in the modulation of attentional performance by methylphenidate (MPH). In this study, 27 males and 27 females between 8-12 years old and with ADHD were investigated in a double-blind, placebo-controlled trial on five computerized attention tests (0.25 vs. 0.5 mg/kg MPH as a single dose, versus placebo). Boys and girls with ADHD did not differ with respect to age, intelligence quotient (IQ), symptom severity, co-morbidity patterns, and ADHD subtype. However, ADHD boys were more impulsive on a sustained attention task, whereas girls with ADHD had more deficits on tasks measuring selective attention. Attentional performance increased differentially as a function of MPH dose, with some tasks showing linear improvement with higher dosage whereas more complex tasks in particular showed inverse U-shaped patterns of MPH effects. However, these effects were comparable between girls and boys. Our data suggest that there are some gender differences in attentional performance in subjects with ADHD in a clinical sample, even if symptom severity and co-morbidity are controlled; however, modulation of attention by MPH does not seem to differ between sexes.

  13. Methylphenidate use and poly-substance use among undergraduate students attending a South African university

    Directory of Open Access Journals (Sweden)

    Francois Steyn

    2016-03-01

    Full Text Available Background: Methylphenidate hydrochloride (MPH is used in the treatment of attention deficit hyperactivity disorder (ADHD. The non-medical use of MPH by learners and students has been reported by numerous studies from abroad. The practice stems from beliefs about the benefits of MPH in achieving academic success. Little is known about the use of MPH in South African student populations. Objectives: The study set out to determine (1 the extent and dynamics associated with MPH use and (2 poly-substance use among undergraduate students attending a South African university. Methods: 818 students took part in a written, group-administered survey. Data analysis resulted in descriptive results regarding MPH use and tests of association identified differences in MPH and poly-substance use among respondents. Results: One in six respondents (17.2% has used MPH in the past, although only 2.9% have been diagnosed with ADHD. Nearly a third (31.7% of users obtained MPH products illegally. The majority (69.1% used MPH only during periods of academic stress. A significant association ( p < 0.001 was found between MPH use and the frequency of using alcohol, tobacco, cannabis, hard drugs (e.g. cocaine and prescription medication. Conclusion: MPH use among students appears similar to experiences abroad, especially in the absence of clinical diagnosis for ADHD. Institutions of higher education should inform parents and students about the health risks associated with the illicit use of MPH. Prescribers and dispensers of MPH products should pay close attention to practices of stockpiling medication and poly-substance use among students who use MPH.

  14. Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning.

    Science.gov (United States)

    Zubedat, Salman; Aga-Mizrachi, Shlomit; Cymerblit-Sabba, Adi; Ritter, Ami; Nachmani, Maayan; Avital, Avi

    2015-01-01

    Either pre- or post-natal environmental factors seem to play a key role in brain and behavioral development and to exert long-term effects. Increasing evidence suggests that exposure to prenatal stress (PS) leads to motor and learning deficits and elevated anxiety, while enriched environment (EE) shows protective effects. The dopaminergic system is also sensitive to environmental life circumstances and affects attention functioning, which serves as the preliminary gate to cognitive processes. However, the effects of methylphenidate (MPH) on the dopaminergic system and attentional functioning, in the context of these life experiences, remain unclear. Therefore, we aimed to examine the effects of EE or PS on distinct types of attention, along with possible effects of MPH exposure. We found that PS impaired selective attention as well as partial sustained attention, while EE had beneficial effects. Both EE and MPH ameliorated the deleterious effects of PS on attention functioning. Considering the possible psychostimulant effect of MPH, we examined both anxiety-like behavior as well as motor learning. We found that PS had a clear anxiogenic effect, whereas EE had an anxiolytic effect. Nevertheless, the treatment with both MPH and/or EE recovered the deleterious effects of PS. In the motor-learning task, the PS group showed superior performance while MPH led to impaired motor learning. Performance decrements were prevented in both the PS + MPH and EE + MPH groups. This study provides evidence that peripubertal exposure to EE (by providing enhanced sensory, motor, and social opportunities) or MPH treatments might be an optional therapeutic intervention in preventing the PS long-term adverse consequences.

  15. Adding methylphenidate to prism-adaptation improves outcome in neglect patients. A randomized clinical trial.

    Science.gov (United States)

    Luauté, Jacques; Villeneuve, Laurent; Roux, Adeline; Nash, Stuart; Bar, Jean-Yves; Chabanat, Eric; Cotton, François; Ciancia, Sophie; Sancho, Pierre-Olivier; Hovantruc, Patrick; Quelard, François; Sarraf, Thierry; Cojan, Yann; Hadj-Bouziane, Fadila; Farné, Alessandro; Janoly-Dumenil, Audrey; Boisson, Dominique; Jacquin-Courtois, Sophie; Rode, Gilles; Rossetti, Yves

    2018-04-04

    Spatial neglect is one of the main predictors of poor functional recovery after stroke. Many therapeutic interventions have been developed to alleviate this condition, but to date the evidence of their effectiveness is still scarce. The purpose of this study was to test whether combining prism adaptation (PA) and methylphenidate (MP) could enhance the recovery of neglect patients at a functional level. RITAPRISM is a multicentre, randomized, double-blind, placebo-controlled study comparing PA plus placebo (control) versus PA plus MP. 24 patients were prospectively enrolled (10 in the placebo group and 14 in the MP group). The main result is a long-term functional improvement (on the functional independence measure (FIM) and on Bergego's scale) induced by MP combined with PA. No serious adverse event occurred. The long-term benefit on activities of daily living (ADL) obtained in this randomized controlled trial set this intervention apart from previous attempts and supports with a high level of evidence the value of combining PA and MP in order to improve the autonomy of neglect patients. Further studies will be needed to clarify the mechanism of this improvement. Although not specifically assessed at this stage, a part of the improvement in ADL might be related to the collateral effect of MP on mood, executive functions or fatigue, and/or the combined effect of PA and MP on motor intentional bias of neglect patients. This study provides Class I evidence that adding MP to PA improves the functional outcome of neglect patients. EUCTR2008-000325-20-FR. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Cognitive and emotional behavioural changes associated with methylphenidate treatment: a review of preclinical studies.

    Science.gov (United States)

    Britton, Gabrielle B

    2012-02-01

    There is evidence from animal studies that repeated exposure to methylphenidate (MPH), a widely used psychostimulant for the treatment of attention deficit hyperactivity disorder (ADHD), produces behavioural, structural and neurochemical changes that persist long after drug administration has ended. However, the translational utility of much of this work is compromised by the use of drug doses and routes of administration that produce plasma and brain MPH levels that fall outside the clinical range, i.e. experimental parameters more relevant to drug abuse than ADHD. We used PubMed to identify pre-clinical studies that employed repeated MPH administration at low doses in young rodents and examined long-term effects on cognition, emotion, and brain structure and function. A review of this work suggests that repeated MPH treatment during early development can modify a number of cognitive, behavioural and brain processes, but these are reduced when low therapeutic doses are employed. Moreover, MPH sites of action extend beyond those implicated in ADHD. Studies that combined neurobiological and behavioural approaches provide important insights into the mechanisms underlying MPH-produced effects on cognitive and behavioural processes, which may be relevant to MPH therapeutic efficacy. There is an emerging consensus that pharmacological treatment of childhood psychiatric disorders produces persistent neuroadaptations, highlighting the need for studies that assess long-term effects of early developmental pharmacotherapy. In this regard, studies that mimic clinical therapy with rodents are useful experimental approaches for defining the behavioural and neural plasticity associated with stimulant therapy in paediatric populations.

  17. Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Cao, Ai-hua; Yu, Lin; Wang, Yu-wei; Wang, Jun-mei; Yang, Le-jin; Lei, Ge-Fei

    2012-02-28

    Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.

  18. Methylphenidate and comorbid anxiety disorder in children with both chronic multiple tic disorder and ADHD.

    Science.gov (United States)

    Gadow, Kenneth D; Nolan, Edith E

    2011-04-01

    To determine if comorbid anxiety disorder is associated with differential response to immediate release methylphenidate (MPH-IR) in children with both ADHD and chronic multiple tic disorder (CMTD). Children with (n = 17) and without (n = 37) diagnosed anxiety disorder (ANX) were evaluated in an 8-week, placebo-controlled trial with rating scales and laboratory measures. The +ANX group obtained more severe parent, teacher, and child ratings of anxiety and more severe parent ratings of depression, tics, oppositional defiant disorder (ODD), and peer aggression than the -ANX group. Treatment with short-term MPH-IR was associated with improvement in ADHD, ODD, and peer aggression in the +ANX group. When controlling for ODD severity, there were no apparent group differences in therapeutic response to MPH-IR in children ±ANX. There was little evidence that MPH-IR contributed to improvement in anxiety or depression symptoms in the +ANX group. There was some indication that children with comorbid anxiety may differentially experience greater increase in systolic blood pressure (0.5 mg/kg of MPH-IR > placebo). Findings suggest that the co-occurrence of diagnosed CMTD+ADHD+ANX represents a particularly troublesome clinical phenotype, at least in the home setting. Comorbid anxiety disorder was not associated with a less favorable response to MPH-IR in children with ADHD+CMTD, but replication with larger samples is warranted before firm conclusions can be drawn about potential group differences.

  19. Are psychiatric comorbidities and associated cognitive functions related to treatment response to methylphenidate in boys with attention-deficit/hyperactivity disorder?

    Directory of Open Access Journals (Sweden)

    Chan MH

    2017-04-01

    Full Text Available Mandy H Chan,1 Patrick WL Leung,2 Ting-pong Ho,3 Se-fong Hung,4 Chi-chiu Lee,5 Chun-pan Tang,5 Ka-chai Cheung,2 Fung-yee Ching,2 Fefe HK Chan,6 Lu-hua Chen,2 Merce Garcia-Barcelo,7 Pak-chung Sham3 1Department of Clinical Psychology, Kowloon Hospital, Hospital Authority, 2Department of Psychology, The Chinese University of Hong Kong, 3Department of Psychiatry, University of Hong Kong, 4Department of Psychiatry, The Chinese University of Hong Kong, 5Department of Psychiatry, Kwai Chung Hospital, Hospital Authority, 6Department of Clinical Psychology, Alice Ho Mui Ling Nethersole Hospital, Hospital Authority, 7Department of Surgery, University of Hong Kong, Hong Kong, People’s Republic of China Background: Methylphenidate (MPH has been found to be an effective medication for attention-deficit/hyperactivity disorder (ADHD. However, there are neither consistent nor sufficient findings on whether psychiatric comorbidities and associated cognitive functions of ADHD are related to treatment response to MPH in ADHD children.Objectives: This study investigated whether psychiatric comorbidities, IQ, and neurocognitive deficits are related to treatment response to MPH in ADHD children. In some ways, it is preferable to have a drug that the effectiveness of which to a disorder is not affected by its associated cognitive functions and psychiatric comorbidities. On the other hand, it is likely that the baseline symptom severity of ADHD is associated with the effectiveness of MPH treatment on the symptoms post treatment.Methods: A total of 149 Chinese boys (aged 6–12 years with ADHD, combined type, and normal IQ participated in this study. Assessment of ADHD symptom severity was conducted pre and post MPH treatment, while assessment of psychiatric comorbidities, IQ, and neurocognitive deficits was performed in a non-medicated condition. Treatment response was defined as the ADHD symptom severity post MPH treatment.Results: Results indicated that MPH

  20. Effect of OROS methylphenidate on encopresis in children with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Yılmaz, Savaş; Bilgiç, Ayhan; Hergüner, Sabri

    2014-04-01

    Although encopresis shows a high rate of comorbidity in patients with attention-deficit/hyperactivity disorder (ADHD), the etiologic origin of this relationship and the effect of ADHD drugs on encopresis are unclear. In this chart review, we explored the effect of OROS long-acting methylphenidate (MPH) treatment on encopresis in children with ADHD. We also evaluated the relationship between the clinical variables of ADHD and encopresis. The sample consisted of 21 children and adolescents (20 boys and 1 girl) with encopresis and coexisting ADHD 7-15 years of age. Their clinical characteristics and baseline (visit 1) and end of the second months' (visit 2) Conners' Parent Rating Scale (CPRS) subscores were recorded. Retrospective clinician determinations were made using the Clinical Global Impressions-Severity subscale (CGI-S) for encopresis severity and the Clinical Global Impressions-Improvement subscale (CGI-I) for encopresis response. According to the CGI-I, 14 subjects (71.4 %) showed much or very much improvement in their encopresis at the second visit. All of the CPRS scores showed a significant reduction during the second visit. No association was found between the CGI-I score and the changes in any of the CPRS scores. Baseline oppositional defiant disorder (ODD) and conduct disorder (CD) scores were correlated with the CGI-S score; however, no association was found between core ADHD symptom severity and the CGI-S score. With regard to the encopresis outcome, the baseline CD score was negatively correlated with the CGI-I score, and the baseline ODD score was prone to show a negative correlation with the CGI-I score. These results suggest that coexisting behavioral problems may be a vulnerability factor based on the severity of encopresis, and that MPH treatment may have a positive effect on encopresis in children and adolescents with ADHD.

  1. Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate.

    Science.gov (United States)

    Bruxel, E M; Salatino-Oliveira, A; Genro, J P; Zeni, C P; Polanczyk, G V; Chazan, R; Rohde, L A; Hutz, M H

    2013-10-01

    Carboxylesterase 1 is the enzyme involved in methylphenidate (MPH) metabolism. The aim of this study was to evaluate the association between a -75 T>G polymorphism and appetite reduction in children with attention-deficit/hyperactivity disorder (ADHD). A sample of 213 children with ADHD was investigated. The primary outcome was appetite reduction measured by the Barkley Stimulant Side Effect Rating Scale applied at baseline, at 1 and 3 months of treatment. MPH doses were augmented until no further clinical improvement or significant adverse events occurred. The G allele presented a trend for association with appetite reduction scores (P=0.05). A significant interaction between the G allele and treatment over time for appetite reduction scores was also observed (P=0.03). The G allele carriers presented a higher risk for appetite reduction worsening when compared with T allele homozygotes (odds ratio=3.47, P=0.01). The present results suggest an influence of carboxylesterase 1 -75 T>G polymorphism on the worsening of appetite reduction with MPH treatment in youths with ADHD.

  2. Attention deficit/hyperactivity disorder and interictal epileptiform discharges: it is safe to use methylphenidate?

    Science.gov (United States)

    Socanski, Dobrinko; Aurlien, Dag; Herigstad, Anita; Thomsen, Per Hove; Larsen, Tor Ketil

    2015-02-01

    This study investigated whether interictal epileptiform discharges (IED) on a baseline routine EEG in children with ADHD was associated with the occurrence of epileptic seizures (Sz) or influenced the use of methylphenidate (MPH) during 2 years follow-up. A retrospective chart-review of 517 ADHD children with EEG revealed IED in 39 cases. These patients (IED group) were matched on age and gender with 39 patients without IED (non-IED group). We measured at baseline, 1 year and 2 years Sz occurrence, the use of MPH and antiepileptic drug (AED). At baseline, 12 patients in the IED group had active epilepsy and three of them had Sz during the last year. 36 (92.3%) patients were treated with MPH. Initial positive response to MPH was achieved in 83.3% compared with 89.2% in the non-IED group. At 1 and 2 years follow-up, three patients who also had Sz at baseline and difficult to treat epilepsy, had Sz, without changes in seizure frequency. We found no statistically significant differences between the groups with respect to MPH use at 1 year and at 2 years. Ten patients from IED group, who did not have confirmed epilepsy diagnosis, temporarily used AEDs during the first year of follow-up. Despite the occurrence of IED, the use of MPH was safe during 2 years follow-up. IED predict the Sz occurrence in children with previous epilepsy, but does not necessarily suggest an increased seizure risk. A caution is warranted in order not to overestimate the significance of temporarily occurrence of IED. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  3. The impact of methylphenidate and its enantiomers on dopamine synthesis and metabolism in vitro.

    Science.gov (United States)

    Bartl, Jasmin; Palazzesi, Ferruccio; Parrinello, Michele; Hommers, Leif; Riederer, Peter; Walitza, Susanne; Grünblatt, Edna

    2017-10-03

    Methylphenidate (MPH), a psychostimulant, is an effective first-line treatment for the symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Although most MPH formulations are composed of the racemic 1:1 mixture of the two enantiomers (d- and l-threo), converging lines of evidence indicate that d-threo MPH seems to be superior to the l-isomer. We aimed to investigate whether MPH racemic mixture or pure enantiomers influence the enzyme activity of tyrosine hydroxylase (TH), monoamine oxidase B (MAO-B), catechol-O-methyltransferase (COMT), and aldehyde dehydrogenase (ALDH) in vitro in homogenates of rat PC12 cells incubated with racemic, d- and l-threo MPH (1nM up to 100μM), or a vehicle for control. We could observe dose dependent enhancement of TH activity with d-threo MPH, probably due to its higher affinity to the enzyme, which we could confirm for d-threo versus l-threo MPH via docking and molecular dynamic simulations analysis. MAO-B enzyme activity was found to be enhanced when incubated with both d- and l-isomers but not with the racemic mixture. This conflicting result was hypothesized to be due to possible aggregation of the two enantiomers or other molecular conformations. Such a possible interaction was observed indirectly, when TH was incubated with constant d-threo MPH while increasing l-isomer (increasing total MPH concentrations). Hence, TH activity was slightly decreased with increased l-isomer. In conclusion, the current in vitro investigation points to the stereoselectivity of the investigated enzymes and pharmacological effects of MPH enantiomers. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Methylphenidate-induced improvements of various measures of attention in adults with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Tucha, O; Mecklinger, L; Laufkötter, R; Klein, H E; Walitza, S; Lange, K W

    2006-10-01

    The present study examined the effect of the stimulant medication methylphenidate (MPH) on attentional functioning of adults with ADHD. Sixteen adults with a diagnosed ADHD without comorbidity were assessed twice, at baseline off MPH and following MPH treatment. The assessment battery consisted of reaction time tasks of low complexity, including measures of alertness--subdivided into tonic and phasic alertness, vigilance, divided attention, flexibility and such aspects of selective attention as including focused attention, inhibition and integration of sensory information. In addition, 16 healthy participants who were matched to adults with ADHD according to sex, age, education level and intellectual functions were also assessed twice using the same test battery. The results of the present study suggest that adults with ADHD off stimulant medication are seriously impaired in various components of attention including vigilance, divided attention, selective attention and flexibility. These impairments of attention were observed primarily in regard to reaction time and its variability. Treatment of adults with ADHD using individually tailored doses of MPH has a positive effect on measures of alertness, vigilance, selective attention, divided attention and flexibility. However, even on MPH adults with ADHD displayed considerable deficits in vigilance and integration of sensory information. The present findings indicate that adults with ADHD are not differentially impaired in attentional processes but may suffer from a more global deficit of attention. Although MPH treatment has been found to be effective in the treatment of the attention deficit of adults with ADHD, additional treatment appears to be necessary.

  5. [11C]d-threo-methylphenidate PET in patients with Parkinson's disease and essential tremor

    International Nuclear Information System (INIS)

    Breit, S.; Reimold, M.; Reischl, G.; Klockgether, T.; Wuellner, U.

    2006-01-01

    Twenty Parkinson's disease (PD) patients, 6 patients with essential tremor and 10 healthy controls were studied with the dopamine transporter ligand [ 11 C]d-threo-methylphenidate ([ 11 C]dMP) and positron emission tomography (PET) to assess dopamine terminal loss in relation to disease duration and motor disability. Dopamine transporter availability was expressed as [11C]dMP binding potential (BP dMP ) in percentage of the mean of healthy controls. In PD patients (age at onset 57.7 ± 8.9 ys; disease duration 5.2 ± 3.3 ys; UPDRS motor score 24.2 ± 9.8; Hoehn and Yahr 2.1 ± 0.8; mean ± SD) BP dMP was reduced to 30 % (range: 11 - 55 %) in the putamen and 52 % (range: 14 - 96 %) in the caudate nucleus. BPdMP in the putamen closely correlated with the UPDRS motor score (r = -0.79, p dMP . Interestingly, when plotted over disease duration, PD patients with severe asymmetry of symptoms showed significantly lower BP dMP in the contralateral putamen (exponential fit: 34 % at onset) than the other PD patients (41 % at onset), indicating a different symptomatic threshold of these subgroups and an even closer correlation with the hypothetical 'true' disease duration. The exponential fit across all patients indicated a mean symptomatic threshold of 37 % contra- and 62 % ipsilateral, corresponding with an observed mean BP dMP of 51 % (average contra- and ipsilateral) in those patients with disease duration less than one year. No differences in BP dMP were observed between patients with essential tremor and healthy controls. [ 11 C]dMP appears to be a useful and sensitive marker of dopaminergic dysfunction in PD and can be used to assess and monitor disease severity. (author)

  6. Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

    Science.gov (United States)

    Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

    2010-02-01

    Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

  7. The effect of methylphenidate on decision making in patients with borderline personality disorder and attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Gvirts, Hila Z; Lewis, Yael D; Dvora, Shira; Feffer, Kfir; Nitzan, Uriel; Carmel, Ziv; Levkovitz, Yechiel; Maoz, Hagai

    2018-07-01

    Impaired decision making in patients with borderline personality disorder (BPD) has been reported in several studies. Although methylphenidate (MPH) is known to ameliorate impaired decision making in patients with attention-deficit/hyperactivity disorder (ADHD), it has not yet been examined in patients with BPD. We therefore assessed the efficacy of a single dose of MPH on cognitive functions and decision making in patients with BPD. Twenty-two patients diagnosed with BPD participated in the study. The study was a randomized, double-blind placebo-controlled, random block order cross-over trial. Patients participated in two sessions and performed the Test of Variables of Attention, a digit-span test, and the computerized Iowa Gambling Task, after they had been administered either the MPH or a placebo. ADHD symptoms were assessed using the Adult ADHD Self-Report Scale-18. Lower scores on the inattention symptoms scale were associated with a greater improvement in decision making following the administration of MPH when compared with improvements in patients with higher ADHD scores [F(1,17)=5.63, P=0.030]. We conclude that MPH may improve decision making in patients with BPD, although this effect is mediated by the level of ADHD symptoms. Further studies are needed to assess whether a prolonged beneficial effect of MPH on decision making in patients with BPD might also be present in 'real life'.

  8. The effect of methylphenidate on postural stability under single and dual task conditions in children with attention deficit hyperactivity disorder - a double blind randomized control trial.

    Science.gov (United States)

    Jacobi-Polishook, Talia; Shorer, Zamir; Melzer, Itshak

    2009-05-15

    To investigate the effects of Methylphenidate (MPH) on postural stability in attention deficit hyperactivity disorder (ADHD) children in single and dual task conditions. A randomized controlled double-blind study analyzing postural stability in 24 ADHD children before and after MPH vs. placebo treatments, in three task conditions: (1) Single task, standing still; (2) dual task, standing still performing a memory-attention demanding task; (3) standing still listening to music. MPH resulted in a significant improvement in postural stability during the dual task condition and while listening to music, with no equivalent improvement in placebo controls. MPH improves postural stability in ADHD, especially when an additional task is performed. This is probably due to enhanced attention abilities, thus contributing to improved balance control during performance of tasks that require attention. MPH remains to be studied as a potential drug treatment to improve balance control and physical functioning in other clinical populations.

  9. Quantification of Methylphenidate, Dexamphetamine, and Atomoxetine in Human Serum and Oral Fluid by HPLC With Fluorescence Detection.

    Science.gov (United States)

    Stegmann, Benedikt; Dörfelt, Anett; Haen, Ekkehard

    2016-02-01

    For psychostimulants, a marked individual variability in the dose-response relationship and large differences in plasma concentrations after similar doses are known. Therefore, optimizing the efficacy of these drugs is at present the most promising way to exploit their full pharmacological potential. Moreover, it seems important to examine oral fluid as less invasive biological matrix for its benefit in therapeutic drug monitoring for patients with hyperkinetic disorder. A high-performance liquid chromatography method for quantification of methylphenidate (MPH), dexamphetamine (DXA), and atomoxetine in serum and oral fluid has been developed and validated. The analytical procedure involves liquid-liquid extraction, derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride as a label and chromatographic separation on a Phenomenex Gemini-NX C18 analytical column using gradient elution with water-acetonitrile. The derivatized analytes were detected at 330 nm (excitation wavelength) and 440 nm (emission wavelength). To examine the oral fluid/serum ratios, oral fluid samples were collected simultaneously to blood samples from patients with hyperkinetic disorder. The method allows quantification of all analytes in serum and oral fluid within 16 minutes under the same or similar conditions. Oral fluid/serum ratios for MPH and DXA were highly variable and showed an accumulation of these drugs in oral fluid. The developed method covers the determination of MPH, DXA, and atomoxetine concentrations in serum and oral fluid after the intake of therapeutic doses. Oral fluid samples are useful for the qualitative detection of MPH and DXA.

  10. Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Cao Ai-hua

    2012-02-01

    Full Text Available Abstract Background Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD, it is rarely examined in animal models. Methods This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD and Wistar-Kyoto (WKY and Sprague-Dawley (SD rats (normoactive control strains, on attentional set-shifting task (ASST performance. Furthermore, the dose-effects of methylphenidate (MPH on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose, MPH-H (higher dose, and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. Results The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21 = 639.636, p p p p p Conclusions The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.

  11. Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    McDonald, Brenna C; Flashman, Laura A; Arciniegas, David B; Ferguson, Robert J; Xing, Li; Harezlak, Jaroslaw; Sprehn, Gwen C; Hammond, Flora M; Maerlender, Arthur C; Kruck, Carrie L; Gillock, Karen L; Frey, Kim; Wall, Rachel N; Saykin, Andrew J; McAllister, Thomas W

    2017-08-01

    The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (PABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI.

  12. Methylphenidate effect in children with ADHD can be measured by an ecologically valid continuous performance test embedded in virtual reality.

    Science.gov (United States)

    Pollak, Yehuda; Shomaly, Hanan Barhoum; Weiss, Patrice L; Rizzo, Albert A; Gross-Tsur, Varda

    2010-02-01

    Continuous performance tasks (CPTs) embedded in a virtual reality (VR) classroom environment have been shown to be a sensitive and user-friendly assessment tool to detect cognitive deficits related to attention-deficit/hyperactivity disorder (ADHD). The aim of the current study was to compare the performance of children with ADHD on a VR-CPT while on and off treatment with methylphenidate (MPH) and to compare the VR-CPT to a currently used CPT, Test of Variables of Attention (TOVA). Twenty-seven children with ADHD underwent the VR-CPT, the same CPT without VR (no VR-CPT), and the TOVA, 1 hour after the ingestion of either placebo or 0.3 mg/kg MPH, in a double-blind, placebo-controlled, crossover design. Immediately following CPT, subjects described their subjective experiences on the Short Feedback Questionnaire. MPH reduced omission errors to a greater extent on the VR-CPT compared to the no VR-CPT and the TOVA, and decreased other CPT measures on all types of CPT to a similar degree. Children rated the VR-CPT as more enjoyable compared to the other types of CPT. It is concluded that the VR-CPT is a sensitive and user-friendly assessment tool in measuring the response to MPH in children with ADHD.

  13. Factors Associated With Adherence to Methylphenidate Treatment in Adult Patients With Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders.

    Science.gov (United States)

    Skoglund, Charlotte; Brandt, Lena; Almqvist, Catarina; DʼOnofrio, Brian M; Konstenius, Maija; Franck, Johan; Larsson, Henrik

    2016-06-01

    Adherence to treatment is one of the most consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associated with treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcome measure was days in active MPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P attention-deficit/hyperactivity disorder and SUD.

  14. Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder.

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    Bottelier, Marco A; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G H; Bouziane, Cheima; Kooij, J J Sandra; de Ruiter, Michiel B; Reneman, Liesbeth

    2017-11-30

    In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90min after an acute oral challenge with MPH (0.5mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. The Possible Effect of Methylphenidate Treatment on Empathy in Children Diagnosed with Attention-Deficit/Hyperactivity Disorder, Both With and Without Comorbid Oppositional Defiant Disorder.

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    Golubchik, Pavel; Weizman, Abraham

    2017-06-01

    To assess the Empathizing Quotient (EQ) of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD) only or comorbid with oppositional defiant disorder (ODD) and compare the two groups' responses to methylphenidate (MPH) treatment. Fifty-two children (8-18 years) diagnosed with ADHD, 26 of whom were also diagnosed with comorbid ODD (ADHD/ODD), were treated with MPH for 12 weeks. The level of EQ was assessed with the Children's version of the Empathizing Quotient (EQ-C) and the severity of ADHD symptoms with the ADHD Rating Scale (ADHD-RS). Assessments were done at baseline and at end point. A significant increase in EQ scores was obtained in both groups following MPH treatment (p = 0.003 for ADHD/ODD; p = 0.002 for ADHD). Significant correlation was found in the ADHD group between the changes in ADHD-RS and those in EQ, following MPH treatment (p = 0.015), but not in the ADHD/ODD group (p = 0.48). A correlation exists between MPH-related improvement in ADHD symptoms and between more empathy in children with ADHD not comorbid with ODD.

  16. Effect of Methylphenidate on Emotional Dysregulation in Children With Attention-Deficit/Hyperactivity Disorder + Oppositional Defiant Disorder/Conduct Disorder.

    Science.gov (United States)

    Kutlu, Ayse; Akyol Ardic, Ulku; Ercan, Eyup Sabri

    2017-04-01

    Emotional dysregulation (ED) is a frequent feature of attention-deficit/hyperactivity disorder (ADHD). It can be observed as a dysregulation profile or a deficient emotional self-regulation (DESR) profile. Oppositional defiant disorder/conduct disorder (ODD/CD) comorbidity is prevalent in ADHD and known to be related with ED. The first-line treatment of ADHD includes psychostimulants, but their effects on ED are not well studied. This study aimed to evaluate the outcomes of methylphenidate (MPH) treatment on ED in ADHD + ODD/CD cases. A total of 118 ADHD + ODD/CD patients with a mean age of 9.0 ± 1.9 years were treated with MPH for 1 year. Also, parents of cases were recruited for a parent-training program, which initiated after first month of MPH treatment. Symptom severity was assessed at baseline and 12th month by Turgay Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Based Child and Adolescent Behavior Disorders Screening and Rating Scale-Parent Form, Children Depression Inventory, Child Behavior Checklist 4-18 years, and Parental Acceptance and Rejection Questionnaire-Mother Form. Emotional dysregulation (DESR + DP) was present in 85.6% of cases. Conduct disorder was significantly higher in patients with DP, whereas ODD was significantly higher in the DESR and non-ED groups (P disorders as ODD and CD, which are comorbid with ADHD. The MPH treatment is effective on ED independently from other clinical determinants.

  17. Motor deficits, impaired response inhibition, and blunted response to methylphenidate following neonatal exposure to decabromodiphenyl ether.

    Science.gov (United States)

    Markowski, Vincent P; Miller-Rhodes, Patrick; Cheung, Randy; Goeke, Calla; Pecoraro, Vincent; Cohen, Gideon; Small, Deena J

    2017-09-01

    Decabromodiphenyl ether (decaBDE) is an applied brominated flame retardant that is widely-used in electronic equipment. After decades of use, decaBDE and other members of its polybrominated diphenyl ether class have become globally-distributed environmental contaminants that can be measured in the atmosphere, water bodies, wildlife, food staples and human breastmilk. Although it has been banned in Europe and voluntarily withdrawn from the U.S. market, it is still used in Asian countries. Evidence from epidemiological and animal studies indicate that decaBDE exposure targets brain development and produces behavioral impairments. The current study examined an array of motor and learning behaviors in a C57BL6/J mouse model to determine the breadth of the developmental neurotoxicity produced by decaBDE. Mouse pups were given a single daily oral dose of 0 or 20mg/kg decaBDE from postnatal day 1 to 21 and were tested in adulthood. Exposed male mice had impaired forelimb grip strength, altered motor output in a circadian wheel-running procedure, increased response errors during an operant differential reinforcement of low rates (DRL) procedure and a blunted response to an acute methylphenidate challenge administered before DRL testing. With the exception of altered wheel-running output, exposed females were not affected. Neither sex had altered somatic growth, motor coordination impairments on the Rotarod, gross learning deficits during operant lever-press acquisition, or impaired food motivation. The overall pattern of effects suggests that males are more sensitive to developmental decaBDE exposure, especially when performing behaviors that require effortful motor output or when learning tasks that require sufficient response inhibition for their successful completion. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Auditory Processing Assessment in Children with Attention Deficit Hyperactivity Disorder: An Open Study Examining Methylphenidate Effects.

    Science.gov (United States)

    Lanzetta-Valdo, Bianca Pinheiro; Oliveira, Giselle Alves de; Ferreira, Jane Tagarro Correa; Palacios, Ester Miyuki Nakamura

    2017-01-01

    Introduction  Children with Attention Deficit Hyperactivity Disorder can present Auditory Processing (AP) Disorder. Objective  The study examined the AP in ADHD children compared with non-ADHD children, and before and after 3 and 6 months of methylphenidate (MPH) treatment in ADHD children. Methods  Drug-naive children diagnosed with ADHD combined subtype aging between 7 and 11 years, coming from public and private outpatient service or public and private school, and age-gender-matched non-ADHD children, participated in an open, non-randomized study from February 2013 to December 2013. They were submitted to a behavioral battery of AP tests comprising Speech with white Noise, Dichotic Digits (DD), and Pitch Pattern Sequence (PPS) and were compared with non-ADHD children. They were followed for 3 and 6 months of MPH treatment (0.5 mg/kg/day). Results  ADHD children presented larger number of errors in DD ( p  < 0.01), and less correct responses in the PPS ( p  < 0.0001) and in the SN ( p  < 0.05) tests when compared with non-ADHD children. The treatment with MPH, especially along 6 months, significantly decreased the mean errors in the DD ( p  < 0.01) and increased the correct response in the PPS ( p  < 0.001) and SN ( p  < 0.01) tests when compared with the performance before MPH treatment. Conclusions  ADHD children show inefficient AP in selected behavioral auditory battery suggesting impaired in auditory closure, binaural integration, and temporal ordering. Treatment with MPH gradually improved these deficiencies and completely reversed them by reaching a performance similar to non-ADHD children at 6 months of treatment.

  19. Possible association of norepinephrine transporter -3081(A/T polymorphism with methylphenidate response in attention deficit hyperactivity disorder

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    Shin Min-Sup

    2010-10-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a heritable disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Methylphenidate (MPH has been shown to block the norepinephrine transporter (NET, and genetic investigations have demonstrated that the norepinephrine transporter gene (SLC6A2 is associated with ADHD. The aims of this study were to examine the association of the SLC6A2 -3081(A/T and G1287A polymorphisms with MPH response in ADHD. Methods This study enrolled 112 children and adolescents with ADHD. A response criterion was defined based on the Clinical Global Impression-Improvement (CGI-I score, and the ADHD Rating Scale-IV (ARS score was also assessed at baseline and 8 weeks after MPH treatment. Results We found that the subjects who had the T allele as one of the alleles (A/T or T/T genotypes at the -3081(A/T polymorphism showed a better response to MPH treatment than those with the A/A genotype as measured by the CGI-I. We also found a trend towards a difference in the change of the total ARS scores and hyperactivity/impulsivity subscores between subjects with and without the T allele. No significant association was found between the genotypes of the SLC6A2 G1287A polymorphism and response to ADHD treatment. Conclusion Our findings provide evidence for the involvement of the -3081(A/T polymorphism of SLC6A2 in the modulation of the effectiveness of MPH treatment in ADHD.

  20. Uso não Prescrito de Metilfenidato entre Estudantes de uma Faculdade de Medicina do Sul de Minas Gerais / Non-Medical use of Methylphenidate among Students of a Medical School in the Southern of Minas Gerais State

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    Ana Clara Mauad Coli

    2016-09-01

    Full Text Available Objetivo: Identificar dentre acadêmicos de uma Faculdade de Medicina no Sul de Minas Gerais, usuários do metilfenidato, os principais motivos de utilização deste fármaco, as formas de aquisição e os possíveis efeitos colaterais. Materiais e Métodos: O estudo é descritivo e transversal e para a coleta de dados foi utilizado um questionário fechado, de caráter anônimo e de autopreenchimento, aplicado entre os meses de agosto e dezembro de 2015. Foram incluídos ao acaso 120 alunos dos 6 anos do curso médico. Resultados: Entre os participantes, 70 (58,33% eram do sexo feminino e 50 (41,67% eram do sexo masculino e a média de idade foi de 22,27 anos. Foi encontrada uma prevalência de 25% para o uso não prescrito de metilfenidato, com maior proporção de uso no sexo masculino. O aumento da concentração em época de provas foi citado como propósito de uso por 76,67% do total de pessoas que fazem uso indiscriminado. Além disso, 66,67% afirmaram ter tido o primeiro contato com a substância na faculdade e 60% obtiveram a droga por meio de doação de amigos. Os principais efeitos colaterais citados foram: ansiedade, insônia, euforia, taquicardia, redução de apetite, irritabilidade, cefaleia e tremores. Conclusão: O presente estudo evidencia uma elevada prevalência do uso não prescrito de metilfenidato, por acadêmicos de Medicina. Objective: Identify among the academic students, users of methylphenidate in a medical school in the southern Minas Gerais, the main reasons for the use, the access and the possible side effects. Materials and Methods: The study is a cross-sectional, quantitative and descriptive study among 120 students of six series of the medical school. The instrument used for gathering data was an anonymous self-filling questionnaire, applied between August and December 2015. Results: Among the participants, 70 (58.33% were female and 50 (41.67% were male and the average age was 22, 27 years. A prevalence of 25

  1. Do Stimulants Reduce the Risk for Alcohol and Substance Use in Youth With ADHD? A Secondary Analysis of a Prospective, 24-Month Open-Label Study of Osmotic-Release Methylphenidate.

    Science.gov (United States)

    Hammerness, Paul; Petty, Carter; Faraone, Stephen V; Biederman, Joseph

    2017-01-01

    The purpose of this study was to examine the impact of stimulant treatment on risk for alcohol and illicit drug use in adolescents with ADHD. Analysis of data derived from a prospective open-label treatment study of adolescent ADHD ( n = 115, 76% male), and a historical, naturalistic sample of ADHD ( n = 44, 68% male) and non-ADHD youth ( n = 52, 73% male) of similar age and sex. Treatment consisted of extended-release methylphenidate in the clinical trial or naturalistic stimulant treatment. Self-report of alcohol and drug use was derived from a modified version of the Drug Use Screening Inventory. Rates of alcohol and drug use in the past year were significantly lower in the clinical trial compared with untreated and treated naturalistic ADHD comparators, and similar to rates in non-ADHD comparators. Well-monitored stimulant treatment may reduce the risk for alcohol and substance use in adolescent ADHD.

  2. Methylphenidate does not improve interference control during a working memory task in young patients with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Prehn-Kristensen, Alexander; Krauel, Kerstin; Hinrichs, Hermann; Fischer, Jochen; Malecki, Ulrike; Schuetze, Hartmut; Wolff, Stephan; Jansen, Olav; Duezel, Emrah; Baving, Lioba

    2011-05-04

    Patients with attention-deficit/hyperactivity disorder (ADHD) show deficits in working memory (WM) which may be related to prefrontal dysfunction. Methylphenidate (MPH) can restore WM deficits in ADHD by enhancing prefrontal activity. At the same time, changes in striatal activation could cause ADHD patients to be more interference-sensitive during working memory tasks. However, it is unclear whether MPH reduces WM distractibility in ADHD. In this fMRI study, 12 ADHD patients and 12 healthy controls participated on two separate days in a delayed-match-to-sample test. During the delay interval, a distractor stimulus was presented in half of the trials. Children and adolescents with ADHD received MPH only on one of the two sessions. Behavioral data analyses revealed that MPH normalized WM in ADHD. However, MPH did not improve WM performance when a distractor was presented during the delay interval. Functional images showed that MPH enhanced prefrontal activity during the delay in ADHD patients when no distractor was present. If the delay was interrupted by a distractor, only healthy controls showed activation of the caudate. In patients with ADHD, however, in line with behavioral data, MPH did not enhance caudate activity. In healthy youth, caudate activity is involved in interference control allowing the successful maintenance of information in working memory even in the presence of distraction. Our findings suggest that interference control, linked to caudate activity, is not adequately enhanced by MPH in ADHD. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Differential impact of methylphenidate and atomoxetine on sustained attention in youth with attention-deficit/hyperactivity disorder.

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    Bédard, Anne-Claude V; Stein, Mark A; Halperin, Jeffrey M; Krone, Beth; Rajwan, Estrella; Newcorn, Jeffrey H

    2015-01-01

    This study examined the effects of atomoxetine (ATX) and OROS methylphenidate (MPH) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder (ADHD). It was hypothesized that performance would be improved by both treatments, but response profiles would differ because the medications work via different mechanisms. One hundred and two youth (77 male; mean age = 10.5 ± 2.7 years) with ADHD received ATX (1.4 ± 0.5 mg/kg) and MPH (52.4 ± 16.6 mg) in a randomized, double-blind, crossover design. Medication was titrated in 4-6-week blocks separated by a 2-week placebo washout. Inhibitory control and attention measures were obtained at baseline, following washout, and at the end of each treatment using Conners' Continuous Performance Test II (CPT-II), which provided age-adjusted T-scores for reaction time (RT), reaction time variability (RT variability), and errors. Repeated-measures analyses of variance were performed, with Time (premedication, postmedication) and Treatment type (ATX, MPH) entered as within-subject factors. Data from the two treatment blocks were checked for order effects and combined if order effects were not present. Clinicaltrials.gov: NCT00183391. Main effects for Time on RT (p = .03), RTSD (p = .001), and omission errors (p = .01) were significant. A significant Drug × Time interaction indicated that MPH improved RT, RTSD, and omission errors more than ATX (p attention in youth with ADHD. However, the dissociation of cognitive and behavioral change with treatment indicates that CPT measures cannot be considered proxies for symptomatic improvement. Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

  4. Diacylglycerol kinase β knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity.

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    Mitsue Ishisaka

    Full Text Available BACKGROUND: Diacylglycerol kinase (DGK is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKβ is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKβ knockout (KO mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density, hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKβ KO mice in order to investigate the function of DGKβ in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD. METHODOLOGY/PRINCIPAL FINDINGS: DGKβ KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.. In the open field test, DGKβ KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p., but showed a similar response to an N-methyl-d-aspartate (NMDA receptor antagonist, MK-801 (0.3 mg/kg, i.p., when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK, which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKβ KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKβ KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKβ KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKβ has a pivotal involvement in ERK regulation in the striatum.

  5. The role of the polymorphic efflux transporter P-glycoprotein on the brain accumulation of d-methylphenidate and d-amphetamine.

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    Zhu, Hao-Jie; Wang, Jun-Sheng; DeVane, C Lindsay; Williard, Robin L; Donovan, Jennifer L; Middaugh, Lawrence D; Gibson, Brian B; Patrick, Kennerly S; Markowitz, John S

    2006-07-01

    The psychostimulant medications methylphenidate (MPH) and amphetamine (AMP), available in various ratios or enantiopure formulations of their respective active dextrorotary isomers, constitute the majority of agents used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Substantial interindividual variability occurs in their pharmacokinetics and tolerability. Little is known regarding the potential role of drug transporters such as P-glycoprotein (P-gp) in psychostimulant pharmacokinetics and response. Therefore, experiments were carried out in P-gp knockout (KO) mice versus wild-type (WT) mice after intraperitoneal dosing (2.5 mg/kg) of d-MPH or (3.0 mg/kg) of d-AMP. After the administration of each psychostimulant, locomotor activity was assessed at 30-min intervals for 2 h. Total brain-to-plasma drug concentration ratios were determined at 10-, 30-, and 80-min postdosing time-points. The results showed no statistically supported genotypic difference in d-AMP-induced locomotor activity stimulation or in brain-to-plasma ratio of d-AMP. As for d-MPH, the P-gp KO mice had 33% higher brain concentrations (p brain-to-plasma ratios (p brain concentrations, d-MPH-induced locomotor activity increase was attenuated for P-gp compared with that for WT mice. These data indicate that P-gp has no apparent effect on the pharmacokinetics and pharmacodynamics of d-AMP. In addition, d-MPH is a relatively weak P-gp substrate, and its entry into the brain may be limited by P-gp. Furthermore, the mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO mice remains to be elucidated.

  6. Countering the Attention Deficit Hyperactivity Disorder Epidemic: A Question of Ethics?

    Science.gov (United States)

    Graham, Linda J.

    2007-01-01

    Recently in Australia, another media skirmish erupted over the problem currently called "Attention Deficit Hyperactivity Disorder". This particular event was precipitated by the comments of a respected District Court judge. His claim that doctors are creating a generation of violent juvenile offenders by prescribing Ritalin to young…

  7. Effects of two doses of methylphenidate on simulator driving performance in adults with attention deficit hyperactivity disorder.

    Science.gov (United States)

    Barkley, Russell A; Murphy, Kevin R; O'Connell, Trisha; Connor, Daniel F

    2005-01-01

    Numerous studies have documented an increased frequency of vehicular crashes, traffic citations, driving performance deficits, and driving-related cognitive impairments in teens and adults with attention deficit hyperactivity disorder. The present study evaluated the effects of two single, acute doses of methylphenidate (10 and 20 mg) and a placebo on the driving performance of 53 adults with ADHD (mean age=37 years, range=18-65) using a virtual reality driving simulator, examiner and self-ratings of simulator performance, and a continuous performance test (CPT) to evaluate attention and inhibition. A double-blind, drug-placebo, within-subjects crossover design was used in which all participants were tested at baseline and then experienced all three drug conditions. A significant beneficial effect for the high dose of medication was observed on impulsiveness on CPT, variability of steering in the standard driving course, and driving speed during the obstacle course. A beneficial effect of the low dose of medication also was evident on turn signal use during the standard driving course. An apparent practice effect was noted on some of the simulator measures between the baseline and subsequent testing sessions that may have interacted with and thereby obscured drug effects on those measures. The results, when placed in the context of prior studies of stimulants on driving performance, continue to recommend their clinical use as one means of reducing the driving risks in ADHD teens and adults. Given the significantly higher risk of adverse driving outcomes associated with ADHD, industry needs to better screen for ADHD among employees who drive as part of employment so as to improve safety and reduce costs. Use of stimulants to treat the adult ADHD driver may reduce safety risks.

  8. Evaluation of sleep organization in patients with attention deficit hyperactivity disorder (ADHD) and ADHD as a comorbidity of epilepsy.

    Science.gov (United States)

    Kalil Neto, Felipe; Nunes, Magda L

    2017-05-01

    Epilepsy or attention deficit hyperactivity disorder (ADHD) can influence sleep organization in different ways. The aim of this study was to evaluate sleep organization in children and adolescents with ADHD and epilepsy, and to analyze the influence of methylphenidate. This was an observational, cross-sectional study of children and adolescents with epilepsy, who were seizure free for at least three months, and were also diagnosed with ADHD. They were selected from the epilepsy and child neurology outpatient clinic of a university hospital in Brazil. After sample size calculation, patients were consecutively included into four different groups, with 21 patients each: epilepsy + ADHD using methylphenidate, epilepsy + ADHD not using methylphenidate, only ADHD, and a healthy control group. All participants were evaluated with the Sleep Disturbance Scale for Children (SDSC) and monitored with actigraphy for five nights/days. Actigraphic analysis showed a higher number of night awakenings in the epilepsy + ADHD groups; they were most prominent in the group without methylphenidate (p = 0.001). Parental reports demonstrated a higher risk for sleep disturbances in the epilepsy + ADHD without methylphenidate and the ADHD groups (p ADHD as a comorbidity of epilepsy impairs sleep organization in children, and the use of short-acting methylphenidate seems to improve it. Both objective (actigraphic) and subjective (SDSC) measures showed significant sleep alterations between primary ADHD and ADHD as a comorbidity of epilepsy; this was most prominent in the group without methylphenidate. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Methylphenidate and the response to growth hormone treatment in short children born small for gestational age.

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    Renes, Judith S; de Ridder, Maria A J; Breukhoven, Petra E; Lem, Annemieke J; Hokken-Koelega, Anita C S

    2012-01-01

    Growth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD). Treatment of ADHD with methylphenidate (MP) has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory. To explore the effects of MP treatment on growth in GH-treated short SGA children Anthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr), 39 of whom were also treated with MP (SGA-GH/MP). The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis. The SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (± 0.1 SD) lower in the SGA-GH/MP group (P = 0.17). Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (-1.9 SDS and -1.9 SDS respectively, P = 0.46). Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups. MP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected.

  10. Methylphenidate and the response to growth hormone treatment in short children born small for gestational age.

    Directory of Open Access Journals (Sweden)

    Judith S Renes

    Full Text Available BACKGROUND: Growth hormone (GH treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA. Children born SGA have a higher risk of developing attention deficit hyperactivity disorder (ADHD. Treatment of ADHD with methylphenidate (MP has greatly increased in recent years, therefore more children are being treated with GH and MP simultaneously. Some studies have found an association between MP treatment and growth deceleration, but data are contradictory. OBJECTIVE: To explore the effects of MP treatment on growth in GH-treated short SGA children METHODS: Anthropometric measurements were performed in 78 GH-treated short SGA children (mean age 10.6 yr, 39 of whom were also treated with MP (SGA-GH/MP. The SGA-GH/MP group was compared to 39 SGA-GH treated subjects. They were matched for sex, age and height at start of GH, height SDS at start of MP treatment and target height SDS. Serum insulin-like growth factor-I (IGF-I and IGF binding protein-3 (IGFBP-3 levels were yearly determined. Growth, serum IGF-I and IGFBP-3 levels during the first three years of treatment were analyzed using repeated measures regression analysis. RESULTS: The SGA-GH/MP group had a lower height gain during the first 3 years than the SGA-GH subjects, only significant between 6 and 12 months of MP treatment. After 3 years of MP treatment, the height gain was 0.2 SDS (± 0.1 SD lower in the SGA-GH/MP group (P = 0.17. Adult height was not significantly different between the SGA-GH/MP and SGA-GH group (-1.9 SDS and -1.9 SDS respectively, P = 0.46. Moreover, during the first 3 years of MP treatment IGF-I and IGFBP-3 measurements were similar in both groups. CONCLUSION: MP has some negative effect on growth during the first years in short SGA children treated with GH, but adult height is not affected.

  11. Types of adult attention-deficit hyperactivity disorder (ADHD): baseline characteristics, initial response, and long-term response to treatment with methylphenidate.

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    Reimherr, Fred W; Marchant, Barrie K; Gift, Thomas E; Steans, Tammy A; Wender, Paul H

    2015-06-01

    Much recent research describes the importance of emotional symptoms in ADHD. While there is no accepted system for including emotionality in diagnosing ADHD, the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) provides a tool to facilitate this. It assesses a range of adult ADHD symptoms which load on two factors: inattentive and emotional dysregulation. The consistently high inattentive factor was used to define significant elevation on the more variable emotional dysregulation factor (which contains four WRAADDS domains: hyperactivity/restlessness, temper, affective lability, and emotional over-reactivity) allowing the definition of two ADHD diagnostic types. We compared these two types on a broad range of adult subject characteristics, including response to methylphenidate (MPH) treatment assessed during two clinical trials. Marked impairment in three of the four emotional domains reflected a symptom severity level equivalent to that of the inattentive factor. 59 % met this threshold, defining them as ADHD emotion dysregulation presentation, as opposed to 41 % with ADHD inattentive presentation. Cluster analysis validated these groups by generating similar clusters with 85 % agreement regarding membership. ADHD emotional dysregulation presentation subjects showed more childhood ADHD symptoms, adult symptoms of oppositional defiant disorder, and evidence of personality disorder. Both types showed similar improvement during the double-blind MPH arm of the trials and during a 6-month open-label phase. Based on the presence of symptoms of emotional dysregulation, ADHD in adults can be conceptualized as two types. Impairment and comorbidity in adults with ADHD are largely concentrated in ADHD emotional dysregulation presentation patients.

  12. "Smart Pills" Promising, Problematic

    Science.gov (United States)

    Sparks, Sarah D.

    2012-01-01

    An explosion in the variety and availability of cognitive-enhancing drugs, from prescriptions like Ritalin to commercial drinks like NeuroFuel, raises concerns for scientists and educators alike--not just over the potential for abuse, but also over what educators and researchers consider, and how they approach, normal achievement. Evidence is…

  13. SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A systematic review and meta-analysis.

    Science.gov (United States)

    Soleimani, Robabeh; Salehi, Zivar; Soltanipour, Soheil; Hasandokht, Tolou; Jalali, Mir Mohammad

    2018-04-01

    Methylphenidate (MPH) is the most commonly used treatment for attention-deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in all patients. This meta-analysis investigated the potential role of SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or naturalistic studies were selected from electronic databases. A meta-analysis was conducted using a random-effects model. Cohen's d effect size and 95% confidence intervals (CIs) were determined. Sensitivity analysis and meta-regression were performed. Q-statistic and Egger's tests were conducted to evaluate heterogeneity and publication bias, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Sixteen studies with follow-up periods of 1-28 weeks were eligible. The mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials, the meta-analysis of naturalistic studies indicated that children without 10/10 repeat carriers had better response to MPH (Cohen's d: -0.09 and 0.44, respectively). The 9/9 repeat polymorphism had no effect on the response rate (Cohen's d: -0.43). In the meta-regression, a significant association was observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD in some genetic models. Sensitivity analysis indicated the robustness of our findings. No publication bias was observed in our meta-analysis. The GRADE evaluations revealed very low levels of confidence for each outcome of response to MPH. The results of clinical trials and naturalistic studies regarding the effect size between different polymorphisms of SLC6A3 were contradictory. Therefore, further research is recommended. © 2017 Wiley Periodicals, Inc.

  14. Suicide risk reduction in youths with attention-deficit/hyperactivity disorder prescribed methylphenidate: A Taiwan nationwide population-based cohort study.

    Science.gov (United States)

    Liang, Sophie Hsin-Yi; Yang, Yao-Hsu; Kuo, Ting-Yu; Liao, Yin-To; Lin, Tzu-Chin; Lee, Yena; McIntyre, Roger S; Kelsen, Brent A; Wang, Tsu-Nai; Chen, Vincent Chin-Hung

    2018-01-01

    Attention-deficit/hyperactivity disorder (ADHD) youths have increased suicide risk. Nevertheless, the beneficial effects of methylphenidate (MPH) on suicide attempt have received relatively little attention. To investigate the MPH usage and the risk of suicide attempt among ADHD youths. We identified 84,898 youths less than 18 years old with ADHD diagnosis between 1997 and 2013 from National Health Insurance, and examined whether MPH use affected suicide attempt risk using Cox proportional-hazards models. Among ADHD youths, reduction of suicide risk was found in patients prescribed 90-180days of MPH after adjusting for confounding factors (hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.19-0.90) and a greater reduction in those prescribed more than 180days of MPH (HR: 0.28, 95% CI: 0.17-0.48). We observed a 59% suicide attempt risk reduction among ADHD youths prescribed between 90 and 180days and a 72% risk reduction in those prescribed more than 180days of MPH. The protective benefit observed by the group prescribed MPH for longer duration underscores the importance of psychoeducation and compliance enhancement as part of ADHD management. Indication bias is identified as a limitation of this study, and future self-case control study to investigate the association between suicide attempt and ADHD medication is suggested. This nationwide population-based cohort study showed that among ADHD youths, reduction of suicide risk was observed in patients prescribed MPH for duration 90days and longer, underscoring the importance of appropriate ADHD pharmacotherapy and enhancing drug compliance. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. The influence of methylphenidate on the power spectrum of ADHD children – an MEG study

    Directory of Open Access Journals (Sweden)

    Bauer Susanne

    2005-07-01

    Full Text Available Abstract Background The present study was dedicated to investigate the influence of Methylphenidate (MPH on cortical processing of children who were diagnosed with different subtypes of Attention Deficit Hyperactivity Disorder (ADHD. As all of the previous studies investigating power differences in different frequency bands have been using EEG, mostly with a relatively small number of electrodes our aim was to obtain new aspects using high density magnetoencephalography (MEG. Methods 35 children (6 female, 29 male participated in this study. Mean age was 11.7 years (± 1.92 years. 17 children were diagnosed of having an Attention-Deficit/Hyperactivity Disorder of the combined type (ADHDcom, DSM IV code 314.01; the other 18 were diagnosed for ADHD of the predominantly inattentive type (ADHDin, DSM IV code 314.0. We measured the MEG during a 5 minute resting period with a 148-channel magnetometer system (MAGNES™ 2500 WH, 4D Neuroimaging, San Diego, USA. Power values were averaged for 5 bands: Delta (D, 1.5–3.5 Hz, Theta (T, 3.5–7.5 Hz, Alpha (A, 7.5–12.5 Hz, Beta (B, 12.5–25 Hz and Global (GL, 1.5–25 Hz.. Additionally, attention was measured behaviourally using the D2 test of attention with and without medication. Results The global power of the frequency band from 1.5 to 25 Hz increased with MPH. Relative Theta was found to be higher in the left hemisphere after administration of MPH than before. A positive correlation was found between D2 test improvement and MPH-induced power changes in the Theta band over the left frontal region. A linear regression was computed and confirmed that the larger the improvement in D2 test performance, the larger the increase in Theta after MPH application. Conclusion Main effects induced by medication were found in frontal regions. Theta band activity increased over the left hemisphere after MPH application. This finding contradicts EEG results of several groups who found lower levels of Theta power

  16. An update on the safety of psychostimulants for the treatment of attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Groenman, Annabeth P.; Schweren, Lizanne J. S.; Dietrich, Andrea; Hoekstra, Pieter J.

    Introduction: Methylphenidate is the first-line pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD). Although methylphenidate has a well-established evidence base for treating ADHD, its long-term benefits are unclear.Areas covered: Physical adverse effects, psychiatric

  17. Effect of methylphenidate on neurocognitive test battery: an evaluation according to the diagnostic and statistical manual of mental disorders, fourth edition, subtypes.

    Science.gov (United States)

    Durak, Sibel; Ercan, Eyup Sabri; Ardic, Ulku Akyol; Yuce, Deniz; Ercan, Elif; Ipci, Melis

    2014-08-01

    The aims of this study were to evaluate the neuropsychological characteristics of the restrictive (R) subtype according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and the attention-deficit/hyperactivity disorder (ADHD) combined (CB) type and predominantly inattentive (PI) type subtypes and to evaluate whether methylphenidate (MPH) affects neurocognitive test battery scores according to these subtypes. This study included 360 children and adolescents (277 boys, 83 girls) between 7 and 15 years of age who had been diagnosed with ADHD and compared the neuropsychological characteristics and MPH treatment responses of patients with the R subtype-which has been suggested for inclusion among the ADHD subtypes in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-with those of patients with the PI and CB subtypes. They did not differ from the control subjects in the complex attention domain, which includes Continuous Performance Test, Stroop test, and Shifting Attention Test, which suggests that the R subtype displayed a lower level of deterioration in these domains compared with the PI and CB subtypes. The patients with the CB and PI subtypes did not differ from the control subjects in the Continuous Performance Test correct response domain, whereas those with the R subtype presented a poorer performance than the control subjects. The R subtype requires a more detailed evaluation because it presented similar results in the remaining neuropsychological evaluations and MPH responses.

  18. Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence.

    Science.gov (United States)

    Crunelle, Cleo L; van den Brink, Wim; Veltman, Dick J; van Emmerik-van Oortmerssen, Katelijne; Dom, Geert; Schoevers, Robert A; Booij, Jan

    2013-12-01

    Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [(123)I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients. This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  19. Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder--a single photon emission computed tomography with [Tc(99m)]TRODAT-1 study.

    Science.gov (United States)

    Szobot, Claudia M; Shih, Ming Chi; Schaefer, Thais; Júnior, Neivo; Hoexter, Marcelo Q; Fu, Ying Kai; Pechansky, Flávio; Bressan, Rodrigo A; Rohde, Luis A P

    2008-04-15

    Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc(99m)]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (pADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.

  20. Time course and predictors of health-related quality of life improvement and medication satisfaction in children diagnosed with attention-deficit/hyperactivity disorder treated with the methylphenidate transdermal system.

    Science.gov (United States)

    Frazier, Thomas W; Weiss, Margaret; Hodgkins, Paul; Manos, Michael J; Landgraf, Jeanne M; Gibbins, Christopher

    2010-10-01

    The aim of this study was to evaluate the time course and predictors of improvement in health-related quality of life (HRQL) and medication satisfaction in children diagnosed with attention-deficit/hyperactivity disorder (ADHD) and treated with the methylphenidate transdermal system (MTS). Temporal relationships between ADHD symptoms, medication satisfaction, and HRQL measures were examined via latent growth curve, structural path, and growth mixture models. Higher levels of medication satisfaction at the end of titration predicted greater increases in family HRQL (p=0.004) and, to a lesser extent, child HRQL (p=0.068) throughout the study. At 4 of 6 (pchild HRQL. At 2 of 6 (pchild or family HRQL improvements at subsequent time points. A uniform pattern of change for child HRQL was noted, with most HRQL change following the pattern of symptom change during titration. Three distinct patterns of change were noted for family HRQL. In most cases, medication satisfaction, ADHD symptoms, and HRQL improved simultaneously, suggesting that HRQL was not a delayed response to improvement in symptoms. Children showed a uniform pattern of improvement in HRQL that followed symptom change; three distinct patterns of change were found for improvement in family HRQL.

  1. Drug holiday utilisation in ADHD-diagnosed children and ...

    African Journals Online (AJOL)

    Objective: Attention deficit hyperactivity disorder (ADHD) is a prevalent disorder affecting people in all age groups. Pharmacological treatment with psychostimulants, specifically methylphenidate, is first line management. The ideal dosing regimen of methylphenidate is debatable with daily use being considered harmful by ...

  2. Análise da eficácia do metilfenidato usando a versão abreviada do questionário de conners em transtorno de déficit de atenção/hiperatividade Analysis of the methylphenidate's efficacy using the abbreviated version Conners' questionnaire in attention deficit hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Ênio Roberto de Andrade

    2004-03-01

    Full Text Available O transtorno de déficit de atenção/hiperatividade (TDAH é quadro diagnóstico bastante complexo, de início precoce, com evolução crônica que repercute em diversos contextos. Três a 5% das crianças em idade escolar apresentam esse transtorno. O questionário de Conners vem sendo utilizado como instrumento de levantamento epidemiológico para o TDAH. OBJETIVO: Este estudo visa a utilização deste instrumento para a análise da eficácia do tratamento com metilfenidato em crianças com TDAH. MÉTODO: Foram selecionadas 21 crianças do gênero masculino, com TDAH do tipo combinado, idade cronológica entre sete anos completos a 10 anos e 11 meses e todos foram tratados com metilfenidato. A versão abreviada do questionário de Conners para pais e professores foi aplicada em dois momentos: um antes da medicação e outro entre seis a oito meses após o seu início. RESULTADOS: Obteve-se redução na pontuação no questionário de Conners em todas as crianças com TDAH concomitante à melhora clínica. CONCLUSÃO: Observou-se que o questionário de Conners mostrou-se útil não só como auxílio diagnóstico, mas também como um instrumento de avaliação da eficácia do tratamento do TDAH.The attention deficit/hyperactivity disorder (ADHD is a complex diagnosis. Its installation is precocious, with chronic evolution that impacts on the subject's performance in several contexts. Three to 5% of the school aged children present this disorder. The Conners' questionnaire has been used as an instrument of epidemiological survey for ADHD children. OBJECTIVE: This study aimed to investigate if this instrument could be an useful tool for the analysis of the methylphenidate's treatment efficacy in ADHD's children. METHOD: Twenty-one male children were selected, with ADHD combined type, chronological ages ranging from seven to 10 years and 11 months and all were treated with methylphenidate. The Conners' questionnaire abbreviated version for parents

  3. Dopaminergic dysfunction in abstinent dexamphetamine users: results from a pharmacological fMRI study using a reward anticipation task and a methylphenidate challenge.

    Science.gov (United States)

    Schouw, M L J; De Ruiter, M B; Kaag, A M; van den Brink, W; Lindauer, R J L; Reneman, L

    2013-06-01

    Dopamine (DA) is involved in systems governing motor actions, motivational processes and cognitive functions. Preclinical studies have shown that even relatively low doses of d-amphetamine (dAMPH) (equivalent to doses used in clinical Practice) can lead to DA neurotoxicity in rodents and non-human primates (Ricaurte et al., 2005). Therefore, we investigated the DAergic function in eight male recreational users of dAMPH and eight male healthy controls using functional magnetic resonance imaging (fMRI). We compared brain activation between both groups during a monetary incentive delay task (Knutson et al., 2001) with and without an oral methylphenidate (MPH) challenge. All subjects were abstinent for at least 2 weeks during the baseline scan. The second scan was performed on the same day 1.5 h after receiving an oral dose of 35 mg MPH (approximately 0.5 mg/kg) when peak MPH binding was assumed. When anticipating reward, dAMPH users showed lower striatal activation in comparison to control subjects. In addition, MPH induced a reduction in the striatal activation during reward anticipation in healthy controls, whereas no such effect was observed in dAMPH users. The combination of these findings provides further evidence for frontostriatal DAergic dysfunction in recreational dAMPH users and is consistent with preclinical data suggesting neurotoxic effects of chronic dAMPH use. The findings of this explorative study could have important implications for humans in need for treatment with dAMPH, such as patients suffering from ADHD and therefore this study needs replication in a larger sample. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  4. A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder

    Directory of Open Access Journals (Sweden)

    C.M. Szobot

    2008-03-01

    Full Text Available Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS on attention-deficit/hyperactivity disorder (ADHD symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD. Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo or group B (reverse order. The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV and the Clinical Global Impression Scale (CGI. We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100% and cocaine users (N = 7; 43.8%. Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001. MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

  5. Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2017-04-01

    Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α 2 -adrenergic receptors. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  6. Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Kim, Bung-Nyun; Kim, Jae-Won; Cummins, Tarrant D R; Bellgrove, Mark A; Hawi, Ziarih; Hong, Soon-Beom; Yang, Young-Hui; Kim, Hyo-Jin; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

    2013-06-01

    Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time

  7. Methylphenidate

    Science.gov (United States)

    ... class of medications called central nervous system (CNS) stimulants. It works by changing the amounts of certain ... a day in the morning with or without food. The long-acting suspension (Quillivant XR) will begin ...

  8. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    International Nuclear Information System (INIS)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi, F.

    2012-01-01

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [ 11 C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([ 11 C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [ 11 C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  9. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    Energy Technology Data Exchange (ETDEWEB)

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  10. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  11. Family-based association study of DRD4 gene in methylphenidate-responded Attention Deficit/Hyperactivity Disorder.

    Directory of Open Access Journals (Sweden)

    Patrick Wing-Leung Leung

    Full Text Available The 48-basepair (48-bp variable number tandem repeat (VNTR polymorphism in exon 3 of the dopamine receptor D4 gene (DRD4 is implicated in the etiology of attention-deficit/ hyperactivity disorder (ADHD. In particular, ADHD in European-ancestry population is associated with an increased prevalence of the 7-repeat (7R allele of the exon 3 VNTR. However, it is intriguing to note that the 7R allele has been found to be of very low prevalence in the Chinese general population. In a previous case-control study, our research team had found that the 7R allele was similarly absent in Chinese ADHD children in Hong Kong. Instead, there was an increased prevalence of the 2R allele in Chinese ADHD children. Interestingly, in Asian samples, the 2R allele had been found to be an evolutionary derivative of the 7R allele with equivalent biochemical functionality. So, the finding of an association between ADHD and 2R allele in Chinese population does not exactly contradict the original 7R allele finding in European-ancestry population. However, given the potential pitfall of population stratification in the previous case-control design, this current study tested the 2R allele and ADHD association using a methodologically more rigorous family-based approach on 33 Chinese ADHD probands who had favorable clinical responses to stimulant medication (methylphenidate. Haplotype Relative Risk (HRR analysis and Transmission Disequilibrium Test (TDT both showed a significant preferential transmission of the 2R allele from the biological parents to ADHD probands (pone-tailed = 0.038, OR = 2.04; pone-tailed = 0.048, OR = 2.29, respectively. A second hypothesis speculates that it is the deviation, including 7R and 2R alleles, from the conserved ancestral 4R allele which confers risk to ADHD. Thus, a preferential transmission of non-4R alleles, against the 4R allele, from biological parents to their ADHD probands is predicted. Both HRR analysis and TDT confirmed such

  12. A Phase III, Double-Blind, Placebo-Controlled Prospective Randomized Clinical Trial of d-Threo-Methylphenidate HCl in Brain Tumor Patients Receiving Radiation Therapy

    International Nuclear Information System (INIS)

    Butler, Jerome M.; Case, L. Douglas; Atkins, James; Frizzell, Bart; Sanders, George; Griffin, Patricia; Lesser, Glenn; McMullen, Kevin; McQuellon, Richard; Naughton, Michelle; Rapp, Stephen; Stieber, Volker; Shaw, Edward G.

    2007-01-01

    Purpose: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT. Methods and Materials: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam. Results: The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms. Conclusions: Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL

  13. Before Ritalin : children and neurasthenia in the Netherlands

    NARCIS (Netherlands)

    Bakker, Nelleke

    2010-01-01

    This article is concerned with the history of the neurological disorder that preceded ADHD: 'neurasthenia' or nervousness, conceived of as a functional disease of the nervous system. Around 1900 it appeared on the scene of children's disorders and it disappeared at the time of the pharmacological

  14. Before Ritalin: Children and Neurasthenia in the Netherlands

    Science.gov (United States)

    Bakker, Nelleke

    2010-01-01

    This article is concerned with the history of the neurological disorder that preceded ADHD: "neurasthenia" or nervousness, conceived of as a functional disease of the nervous system. Around 1900 it appeared on the scene of children's disorders and it disappeared at the time of the pharmacological turn in psychiatry by the late 1960s. In…

  15. Subjective effects, misuse, and adverse effects of osmotic-release methylphenidate treatment in adolescent substance abusers with attention-deficit/hyperactivity disorder.

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    Winhusen, Theresa M; Lewis, Daniel F; Riggs, Paula D; Davies, Robert D; Adler, Lenard A; Sonne, Susan; Somoza, Eugene C

    2011-10-01

    Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non-substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13-18) with at least one non-nicotine SUD and one with 255 adult smokers (18-55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. With good monitoring, and in the context of substance abuse treatment, OROS-MPH can

  16. A modelled economic evaluation comparing atomoxetine with methylphenidate in the treatment of children with attention-deficit/hyperactivity disorder in Spain

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    Dilla Tatiana

    2009-04-01

    Full Text Available Abstract Background Attention Deficit/Hyperactivity Disorder (ADHD is a neurobehavioural disorder, affecting 3–6% of school age children and adolescents in Spain. Methylphenidate (MPH, a mild stimulant, had long been the only approved medication available for ADHD children in Spain. Atomoxetine is a non-stimulant alternative in the treatment of ADHD with once-a-day oral dosing. This study aims to estimate the cost-effectiveness of atomoxetine compared to MPH. In addition, atomoxetine is compared to 'no medication' for patient populations who are ineligible for MPH (i.e. having stimulant-failure experience or co-morbidities precluding stimulant medication. Methods An economic model with Markov processes was developed to estimate the costs and benefits of atomoxetine versus either MPH or 'no medication'. The incremental cost per quality-adjusted life-year (QALY was calculated for atomoxetine relative to the comparators. The Markov process incorporated 14 health states, representing a range of outcomes associated with treatment options. Utility values were obtained from the utility valuation survey of 83 parents of children with ADHD. The clinical data were based on a thorough review of controlled clinical trials and other clinical literature, and validated by international experts. Costs and outcomes were estimated using Monte Carlo simulation over a 1-year duration, with costs estimated from the perspective of the National Health Service in Spain. Results For stimulant-naïve patients without contra-indications to stimulants, the incremental costs per QALY gained for atomoxetine were € 34 308 (compared to an immediate-release MPH and € 24 310 (compared to an extended-release MPH. For those patients who have stimulant-failure experience or contra-indications to stimulants, the incremental costs per QALY gained of atomoxetine compared to 'no medication' were € 23 820 and € 23 323, respectively. Conclusion The economic evaluation showed

  17. Comparative efficacy and safety of methylphenidate and atomoxetine for attention-deficit hyperactivity disorder in children and adolescents: Meta-analysis based on head-to-head trials.

    Science.gov (United States)

    Liu, Qiang; Zhang, Hong; Fang, Qingqing; Qin, Lili

    2017-11-01

    Comparative efficacy and safety are important issues for appropriate drug selection for attention-deficit hyperactivity disorder (ADHD) treatment. Therefore we conducted a meta-analysis, where we compared atomoxetine (ATX) and methylphenidate (MPH) for ADHD treatment in children and adolescents. Literature retrieval was conducted in relevant databases from their inception to April 2016 to select head-to-head trials that compared ATX and MPH in children and adolescents. Outcomes like response rate, ADHD Rating Scale (ADHD-RS) score, and adverse events were compared between ATX and MPH treatments. The standardized mean difference (SMD) and risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were used as the effect size for continuous data or dichotomous data, respectively. Eleven eligible randomized-controlled trials were included, and two of them were double-blind, while the remaining were open-label. Compared to ATX, MPH showed a higher response rate (RR = 1.14, 95% CI [1. 09, 1.20]), decreased inattention (SMD = -0.13, 95% CI [-0.25, -0.01]) and lower risk of adverse events (drowsiness: RR = 0.17, 95% CI [0.11, 0.26; nausea: RR = 0.49; 95% CI [0.29, 0.85; vomiting: RR = 0.41, 95% CI [0.27, 0.63]). However, MPH presented a higher risk of insomnia than ATX (RR = 2.27, 95% CI [1.63, 3.15], p < .01). Results of the meta-analysis add additional evidence of the effectiveness of both ATX and MPH and suggest that MPH should be a first treatment option in most patients with ADHD.

  18. Drug use prevalence among students of universities of medical sciences in Tehran

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    Farhad Taremian

    2014-02-01

    Full Text Available Objective: This study was aimed to determine the prevalence of drug use among students of universities of Medical Sciences in Tehran. Method: Four thousands of medical students (both sexes in academic year 1388-89 in different level of education, B.A., M.Sc. and Ph.D. were selected by random stratified sampling method. These students were selected from Iran, Tehran and Shahid Beheshti Universities of Medical Sciences considering their sex and level of education. We used drug use prevalence questionnaire. Findings: The most prevalent drug of abuse in life time period was qalyan (classical pipe, followed by cigarette, and alcohol. The least frequent drug of abuse was Shisheh, followed by heroine krack. As we expected, drugs morphine, ritalin and tramadol were placed in forth, fifth and sixth of prevalent drugs. Use of different substances was significantly more prevalent in male students. Conclusion: Using soft drugs (qalyan, cigarette and alcohol was more prevalent than hard drugs (hashish, taryak, heroine kerack among Universities Medical Sciences of Tehran. Similar to drug use pattern in society, use of all of drugs were more prevalent in male students. We should pay special attention to use of drugs such as tramadol, ritalin, petedin and morphine.

  19. Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice.

    Science.gov (United States)

    Griffin, William C; McGovern, Robin W; Bell, Guinevere H; Randall, Patrick K; Middaugh, Lawrence D; Patrick, Kennerly S

    2013-02-01

    Prior research indicates methylphenidate (MPH) and alcohol (ethanol, EtOH) interact to significantly affect responses humans and mice. The present studies tested the hypothesis that MPH and EtOH interact to potentiate ethanol-related behaviors in mice. We used several behavioral tasks including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas chromatographic methods to measure brain tissue levels of EtOH and the D- and L-isomers of MPH and the metabolite, ethylphenidate (EPH). In discrimination, EtOH (1 g/kg) produced a significant leftward shift in the MPH generalization curve (1-2 mg/kg) for MPH-trained mice, but no effects of MPH (0.625-1.25 mg/kg) on EtOH discrimination in EtOH-trained mice (0-2.5 g/kg) were observed. In CPP, the MPH (1.25 mg/kg) and EtOH (1.75 g/kg) combination significantly increased time on the drug paired side compared to vehicle (30.7 %), but this was similar to MPH (28.8 %) and EtOH (33.6 %). Footslip errors measured in a parallel rod apparatus indicated that the drug combination was very ataxic, with footslips increasing 29.5 % compared to EtOH. Finally, brain EtOH concentrations were not altered by 1.75 g/kg EtOH combined with 1.25 mg/kg MPH. However, EtOH significantly increased D-MPH and L-EPH without changing L-MPH brain concentrations. The enhanced behavioral effects when EtOH is combined with MPH are likely due to the selective increase in brain D-MPH concentrations. These studies are consistent with observations in humans of increased interoceptive awareness of the drug combination and provide new clinical perspectives regarding enhanced ataxic effects of this drug combination.

  20. Processing speed can monitor stimulant-medication effects in adults with attention deficit disorder with hyperactivity.

    Science.gov (United States)

    Nielsen, Niels Peter; Wiig, Elisabeth H; Bäck, Svante; Gustafsson, Jan

    2017-05-01

    Treatment responses to methylphenidate by adults with ADHD are generally monitored against DSM-IV/DSM-V symptomatology, rating scales or interviews during reviews. To evaluate the use of single- and dual-dimension processing-speed and efficiency measures to monitor the effects of pharmacological treatment with methylphenidate after a short period off medication. A Quick Test of Cognitive Speed (AQT) monitored the effects of immediate-release methylphenidate in 40 previously diagnosed and medicated adults with ADHD. Processing speed was evaluated with prior prescription medication, without medication after a 2-day period off ADHD medication, and with low-dose (10/20 mg) and high-dose (20/40 mg) methylphenidate hydrochloride (Medikinet IR). Thirty-three participants responded to the experimental treatments. One-way ANOVA with post-hoc analysis (Scheffe) indicated significant main effects for single dimension colour and form and dual-dimension colour-form naming. Post-hoc analysis indicated statistical differences between the no- and high-dose medication conditions for colour and form, measures of perceptual speed. For colour-form naming, a measure of cognitive speed, there was a significant difference between no- and low-dose medication and between no- and high-dose medications, but not between low- and high-dose medications. Results indicated that the AQT tests effectively monitored incremental effects of the methylphenidate dose on processing speed after a 2-day period off medication. Thus, perceptual (colour and form) and cognitive speed (two-dimensional colour-form naming) and processing efficiency (lowered shift costs) increased measurably with high-dose medication. These preliminary findings warrant validation with added measures of associated behavioural and cognitive changes.

  1. A Naturalistic Comparison of Methylphenidate and Risperidone Monotherapy in Drug-Naive Youth With Attention-Deficit/Hyperactivity Disorder Comorbid With Oppositional Defiant Disorder and Aggression.

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    Masi, Gabriele; Manfredi, Azzurra; Nieri, Giulia; Muratori, Pietro; Pfanner, Chiara; Milone, Annarita

    2017-10-01

    Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are frequently co-occurring in youth, but data about the pharmacological management of this comorbidity are scarce, especially when impulsive aggression is prominent. Although stimulants are the first-line medication for ADHD, second-generation antipsychotics, namely, risperidone, are frequently used. We aimed to assess effectiveness and safety of monotherapy with the stimulant methylphenidate (MPH) and risperidone in a consecutive sample of 40 drug-naive male youths diagnosed as having ADHD-combined presentation, comorbid with ODD and aggression, without psychiatric comorbidities, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). Twenty males treated with MPH (mean age, 8.95 ± 1.67 years) and 20 males treated with risperidone (mean age, 9.35 ± 2.72 years), followed up to 6 months, were assessed according to efficacy measures (Child Behavior Checklist [CBCL], Clinical Global Impression-Severity [CGI-S] and Improvement [CGI-I], Children Global Assessment Scale), and safety measures. At the end of the follow-up, both medications were similarly effective based on CBCL subscales of aggression and rule-breaking behaviors, on Diagnostic and Statistical Manual of Mental Disorders-oriented oppositional defiant problems and conduct problems, and on CGI-S, CGI-I, and Children Global Assessment Scale, but only MPH was effective on CBCL attention problems and attention-deficit/hyperactivity problems. Risperidone was associated with weight gain and elevated prolactin levels. Although the nonrandomized, nonblind design limits the conclusions of our exploratory study, our findings suggest that when ADHD is comorbid with ODD and aggression MPH and risperidone are both effective on aggressive behavior, but

  2. A systematic review of the safety information contained within the Summaries of Product Characteristics of medications licensed in the United Kingdom for Attention Deficit Hyperactivity Disorder. how does the safety prescribing advice compare with national guidance?

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    Savill Nicola

    2012-01-01

    Full Text Available Abstract Background The safety of paediatric medications is paramount and contraindications provide clear pragmatic advice. Further advice may be accessed through Summaries of Product Characteristics (SPCs and relevant national guidelines. The SPC can be considered the ultimate independent guideline and is regularly updated. In 2008, the authors undertook a systematic review of the SPC contraindications of medications licensed in the United Kingdom (UK for the treatment of Attention Deficit Hyperactivity Disorder (ADHD. At that time, there were fewer contraindications reported in the SPC for atomoxetine than methylphenidate and the specific contraindications varied considerably amongst methylphenidate formulations. In 2009, the European Medicines Agency (EMA mandated harmonisation of methylphenidate SPCs. Between September and November 2011, there were three changes to the atomoxetine SPC that resulted in revised prescribing information. In addition, Clinical Guidance has also been produced by the National Institute for Health and Clinical Excellence (NICE (2008, the Scottish Intercollegiate Guidelines Network (SIGN (2009 and the British National Formulary for Children (BNFC. Methods An updated systematic review of the Contraindications sections of the SPCs of all medications currently licensed for treatment of ADHD in the UK was undertaken and independent statements regarding contraindications and relevant warnings and precautions were then compared with UK national guidance with the aim of assessing any disparity and potential areas of confusion for prescribers. Results As of November 2011, there were seven medications available in the UK for the treatment of ADHD. There are 15 contraindications for most formulations of methylphenidate, 14 for dexamfetamine and 5 for atomoxetine. Significant differences exist between the SPCs and national guidance part due to the ongoing reactive process of amending the former as new information becomes known

  3. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  4. An Investigation of Stimulant Effects on the EEG of Children With Attention-Deficit/Hyperactivity Disorder.

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    Clarke, Adam R; Barry, Robert J; Baker, Iris E; McCarthy, Rory; Selikowitz, Mark

    2017-07-01

    Stimulant medications are the most commonly prescribed treatment for Attention-Deficit/Hyperactivity Disorder (AD/HD). These medications result in a normalization of the EEG. However, past research has found that complete normalization of the EEG is not always achieved. One reason for this may be that studies have used different medications interchangeably, or groups of subjects on different stimulants. This study investigated whether methylphenidate and dexamphetamine produce different levels of normalization of the EEG in children with AD/HD. Three groups of 20 boys participated in this study. There were 2 groups with a diagnosis of AD/HD; one group, good responders to methylphenidate, and the second, good responders to dexamphetamine. The third group was a normal control group. Baseline EEGs were recorded using an eyes-closed resting condition, and analyzed for total power and relative delta, theta, alpha, and beta. Subjects were placed on a 6-month trial of methylphenidate or dexamphetamine, after which a second EEG was recorded. At baseline, the children with AD/HD had elevated relative theta, less relative alpha and beta compared with controls. Baseline differences were found between the two medication groups, with the dexamphetamine group having greater EEG abnormalities than the methylphenidate group. The results indicate that good responders to methylphenidate and dexamphetamine have different EEG profiles when assessed before medication, and these differences may represent different underlying central nervous system deficits. The 2 medications were found to result in substantial normalization of the EEG, with no significant differences in EEG changes occurring between the 2 medications. This indicates that the degree of pretreatment EEG abnormality was the major factor contributing to the degree of normalization of the EEG. As good responders to the 2 medications appear to have different central nervous system abnormalities, it is recommended that

  5. Behavioral Effects of Neurofeedback Compared to Stimulants and Physical Activity in Attention-Deficit/Hyperactivity Disorder: A Randomized Controlled Trial.

    Science.gov (United States)

    Geladé, Katleen; Janssen, Tieme W P; Bink, Marleen; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

    2016-10-01

    The efficacy of neurofeedback as a treatment for attention-deficit/hyperactivity disorder (ADHD), and whether neurofeedback is a viable alternative for stimulant medication, is still an intensely debated subject. The current randomized controlled trial compared neurofeedback to (1) optimally titrated methylphenidate and (2) a semi-active control intervention, physical activity, to account for nonspecific effects. A multicenter 3-way parallel-group study with balanced randomization was conducted. Children with a DSM-IV-TR diagnosis of ADHD, aged 7-13 years, were randomly allocated to receive neurofeedback (n = 39), methylphenidate (n = 36), or physical activity (n = 37) over a period of 10-12 weeks. Neurofeedback comprised theta/beta training on the vertex (Cz). Physical activity consisted of moderate to vigorous intensity exercises. Neurofeedback and physical activity were balanced in terms of number (~30) and duration of sessions. A double-blind pseudorandomized placebo-controlled crossover titration procedure was used to determine an optimal dose in the methylphenidate intervention. Parent and teacher ratings on the Strengths and Difficulties Questionnaire (SDQ) and Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) were used to assess intervention outcomes. Data collection took place between September 2010 and March 2014. Intention-to-treat analyses revealed an improvement in parent-reported behavior on the SDQ and the SWAN Hyperactivity/Impulsivity scale, irrespective of received intervention (ηp² = 0.21-0.22, P ≤ .001), whereas the SWAN Inattention scale revealed more improvement in children who received methylphenidate than neurofeedback and physical activity (ηp² = 0.13, P ≤ .001). Teachers reported a decrease of ADHD symptoms on all measures for methylphenidate, but not for neurofeedback or physical activity (range of ηp² = 0.14-0.29, P ADHD symptoms in children with ADHD. ClinicalTrials.gov identifier: NCT01363544. © Copyright

  6. An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults.

    Science.gov (United States)

    Kollins, Scott H; Schoenfelder, Erin N; English, Joseph S; Holdaway, Alex; Van Voorhees, Elizabeth; O'Brien, Benjamin R; Dew, Rachel; Chrisman, Allan K

    2015-01-01

    Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of delta-9-tetrahydocannibinol (THC); and 0mg, 10mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10mg THC+0mg, 10mg, and 40 mg MPH=89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of "Feel Drug," "Good Effects," and "Take Drug Again." THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Efficacy of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder previously treated with methylphenidate: a post hoc analysis

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    Jain Rakesh

    2011-11-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18 on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population. Methods In this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R, and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD. Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint. Results Of 290 randomized participants enrolled, 28

  8. On Ritalin, Adderall, and Cognitive Enhancement: Metaethics, Bioethics, Neuroethics

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    Nythamar de Oliveira

    2016-09-01

    Full Text Available http://dx.doi.org/10.5007/1677-2954.2016v15n3p343 In this article, I argue that the neuroethics of cognitive enhancement can help us bridge the explanatory gap between metaethics and bioethics (qua normative, applied ethics and throw light on the classic gap between moral beliefs and neural correlates of brain processes. Insofar as it unveils the irreducibility of first-person propositional attitudes (esp. moral beliefs and judgments, neuroethics allows for justifying cosmetic, pharmacological interventions so as to bring about human enhancement, regardless of descriptive accounts of its neural correlates and independently of the cognitivist, noncognitivist or hybrid inputs of metanormative theories. Precisely because it cannot provide the ultimate grounds for any conservative, libertarian or liberal attitudes towards cognitive enhancement, neuroethics is better conceived in terms of a Rawlsian-like wide reflective equilibrium, procedurally and without any specific substantive commitment to any moral or comprehensive doctrine of sorts.

  9. Comparative treatment patterns, healthcare resource utilization and costs of atomoxetine and long-acting methylphenidate among children and adolescents with attention-deficit/hyperactivity disorder in Germany.

    Science.gov (United States)

    Greven, Peter; Sikirica, Vanja; Chen, Yaozhu J; Curtice, Tammy G; Makin, Charles

    2017-09-01

    Attention-deficit/hyperactivity disorder (ADHD) imposes a substantial burden on patients and their families. A retrospective, propensity score-matched cohort study compared treatment patterns, healthcare resource utilization (HRU) and costs among children/adolescents with ADHD aged 6-17 years at treatment initiation (index) in Germany who received atomoxetine (ATX) or long-acting methylphenidate (LA-MPH) monotherapy. Patients received at least one prescription for their index medication (ATX/LA-MPH) during 2006-2010; the first prescription marked the index date. ATX- and LA-MPH-indexed cohorts were matched 1:1 (n = 737); a patient subset was identified that had not received ADHD-indicated medications in 12 months prior to index (novel initiators: ATX, n = 486; LA-MPH, n = 488). Treatment patterns were evaluated among novel initiators, and HRU and costs among the matched cohorts in the 12 months after index. No significant differences in baseline characteristics were found between the novel initiator patient subsets. ATX-indexed novel initiators had significantly longer persistence to index medication [mean (standard deviation; SD) days: 222.0 (133.9) vs 203.2 (135.0), P = 0.029) but higher switching rates (8.8 vs 5.5 %, P = 0.045) than LA-MPH-indexed novel initiators. The total ATX-indexed cohort required more prescriptions [any medication; mean (SD): 20.9 (11.5) vs 15.7 (9.0), P < 0.001] and outpatient visits [mean (SD): 10.1 (6.3) vs 8.3 (5.3), P < 0.001], and incurred significantly higher total median healthcare costs (€1144 vs €541, P < 0.001) versus matched LA-MPH patients. These real-world data indicate that, among children/adolescents with ADHD in Germany, ATX-indexed patients may require more prescriptions and physician visits, and incur higher total healthcare costs, than matched LA-MPH patients.

  10. A review of medications used in the treatment of attention deficit hyperactivity disorder

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    Matej Štuhec

    2013-04-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is one of the most common developmental disorders in children and adolescents with core symptoms of hyperactivity, impulsivity andinattention. Atomoxetine, immediate-release methylphenidate and extended release methylphenidate are approved for use in patients with ADHD in Slovenia. In addition, ADHD is also treated off-label with bupropion, tricyclic antidepressants and some other drugs. According to the recently adopted American and European guidelines, pharmacotherapy includes the initial, maintenance and terminal phase. Consideration of pharmacokinetic parameters of the selected drugs and potential drug-drug interactions, if the patient is taking other medications, helps to reduce symptoms of ADHD, and improves the selection of drug and appropriate dosing regimen. Clinical outcomes should be measured by standardised questionnaires. The drug of choice is methylphenidate. Guidelines for the treatment of ADHD should also include recommendations on psychosocial treatments and destigmatization of patients with this disorder. In this paper, pharmacotherapy guidelines for patients with ADHD are highlighted.

  11. Guanfacine extended release for children and adolescents with attention-deficit/hyperactivity disorder: efficacy following prior methylphenidate treatment

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    Huss M

    2016-05-01

    Full Text Available Michael Huss,1 Vanja Sikirica,2 Amaia Hervas,3,4 Jeffrey H Newcorn,5 Valerie Harpin,6 Brigitte Robertson71Child and Adolescent Psychiatry, Johannes Gutenberg University Mainz, Mainz, Germany; 2Global Health Economics, Outcomes Research and Epidemiology, Shire, Wayne, PA, USA; 3Child and Adolescent Mental Health Unit, University Hospital Mútua de Terressa, Barcelona, Spain; 4Developmental Disorders Unit (UETD, Hospital San Juan de Dios, Barcelona, Spain; 5Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 6Ryegate Children’s Centre, Sheffield Children’s NHS Foundation Trust, Sheffield, UK; 7Global Clinical Development, Shire, Wayne, PA, USAAbstract: Guanfacine extended release (GXR and atomoxetine (ATX are nonstimulant treatments for attention-deficit/hyperactivity disorder (ADHD. As nonstimulant treatments are often used after stimulants in ADHD, GXR was assessed relative to prior stimulant treatment in a randomized controlled trial (RCT, in which ATX was included as a reference arm, and in the open-label phase of a randomized-withdrawal study (RWS. Participants were 6–17 years old with ADHD Rating Scale version IV (ADHD-RS-IV scores ≥32 and Clinical Global Impressions – Severity scores ≥4. RCT participants received dose-optimized GXR (1–7 mg/day, ATX (10–100 mg/day, or placebo for 10–13 weeks. RWS participants received dose-optimized GXR (1–7 mg/day for 13 weeks. Participants’ last stimulant medication prior to enrolment, and reasons for stopping this medication, were collected at baseline. Change from baseline ADHD-RS-IV score and the proportion of responders were assessed by prior stimulant exposure. Of 163 RCT and 296 RWS participants who had previously received stimulant treatment, 142 and 224, respectively, had received methylphenidate (MPH; due to the low number of participants and the heterogeneity of non-MPH treatments, we only report data for prior MPH treatment. The most

  12. Functional outcomes from a head-to-head, randomized, double-blind trial of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder and an inadequate response to methylphenidate.

    Science.gov (United States)

    Nagy, Peter; Häge, Alexander; Coghill, David R; Caballero, Beatriz; Adeyi, Ben; Anderson, Colleen S; Sikirica, Vanja; Cardo, Esther

    2016-02-01

    Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score.

  13. Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders.

    Science.gov (United States)

    Pringsheim, Tamara; Steeves, Thomas

    2011-04-13

    Attention Deficit Hyperactivity Disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include the stimulants methylphenidate and amphetamine; nonstimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics.  To assess the effects of pharmacological treatments for ADHD on ADHD symptoms and tic severity in children with ADHD and comorbid tic disorders.  We searched CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to July 2009), EMBASE (1980 to July 2009), CINAHL (1982 to July 2009), PsycINFO (1806 to July Week 4 2009) and BIOSIS Previews (1985 to July 2009). Dissertation Abstracts (searched via Dissertaation Express), and the metaRegister of Controlled Trials were searched (30 July 2009). We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel group and cross-over study designs. Two authors independently extracted data using standardized forms. We included a total of eight randomized controlled studies in the review but were unable to combine any of these in meta-analysis. Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. All treatments, with the exception of deprenyl, were efficacious in treating symptoms of ADHD. Tic symptoms improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and the combination of methylphenidate and clonidine. Fear of worsening tics

  14. Study Drugs

    OpenAIRE

    Lam, Stephanie Phuong; Roosta, Natalie; Nielsen, Mikkel Fuhr; Meyer, Maria Holmgaard; Friis, Katrine Birk

    2016-01-01

    In recent years, students around the world, started to use preparations as Ritalin and Modafinil,also known as study drugs, to improve their cognitive abilities1. It is a common use among thestudents in United States of America, but it is a new tendency in Denmark. Our main focus is tolocate whether study drugs needs to be legalized in Denmark or not. To investigate this ourstarting point is to understand central ethical arguments in the debate. We have chosen twoarguments from Nick Bostrom a...

  15. Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Schulz, Kurt P; Fan, Jin; Bédard, Anne-Claude V; Clerkin, Suzanne M; Ivanov, Iliyan; Tang, Cheuk Y; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2012-09-01

    CONTEXT Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and impairing psychiatric disorder that affects both children and adults. There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD; however, little is known about the mechanisms by which these different treatments exert their therapeutic effects. OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylphenidate hydrochloride vs the nonstimulant atomoxetine hydrochloride. DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylphenidate (n = 18) or atomoxetine (n = 18) using a parallel-groups design. SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine, New York, New York. PARTICIPANTS Thirty-six youth with ADHD (mean [SD] age, 11.2 [2.7] years; 27 boys) recruited from randomized clinical trials. MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version. RESULTS Treatment with methylphenidate vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean (SD) improvements in ratings of ADHD symptoms (55% [30%] vs 57% [25%]). Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments. Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylphenidate in the right inferior frontal gyrus, left anterior cingulate/supplementary motor area, and bilateral posterior cingulate cortex. These findings were not attributable to baseline differences in activation. CONCLUSIONS Treatment with methylphenidate and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic

  16. Brain 1H MRS study in children suffering from attention-deficit/hyperactivity disorder

    International Nuclear Information System (INIS)

    Jin Zhen; Zhang Lei; Zeng Yawei; Wang Yan; Zang Yufeng; Wang Yufeng

    2002-01-01

    Objective: To determine whether the children suffering from Attention -deficit/hyperactivity disorder (ADHD) had neurochemical abnormalities in basis ganglia and if the state could be affected by methylphenidate. Methods: Proton magnetic resonance spectroscopy scans were performed on bilateral globus pallidum of 12 ADHD body before and after one dose of methylphenidate 10 mg. Spectral peaks of N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), glutamate plus glutamine (α-Glx) and creatine (Cr) were measured and their ratios were compared with 12 age-, handedness-, and IQ-matched healthy boys. Results: In children having ADHD, NAA/Cr ratio decrease significantly in bilateral globus pallidum (left side t = 7.01, P 0.05; right side t = -1.04, P > 0.05). The post-drug NAA/Cr ratios in ADHD children remained significantly different from those in healthy children (left side t = 3.68, P 0.05). Conclusion: In children suffering from ADHD, neuronal loss-dysfunction exists in bilateral striatum. One does of methylphenidate could not affect the state significantly. Further investigations are needed to confirm whether the cholinergic system is involved in ADHD

  17. Effectiveness and safety of atomoxetine for ADHD in population between 6 and 19 years: a systematic review

    Directory of Open Access Journals (Sweden)

    José Calleja

    2012-09-01

    Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD is generally treated with pharmacological interventions such as psychostimulants. The most used widely used one is methylphenidate followed by atomoxetine. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of atomoxetine in ADHD treatment in the 6-19 year-old population. Methods: A systematic review of intervention studies that evaluated effectiveness of atomoxetine compared with placebo and methylphenidate was conducted. Outcomes assessed were educational functioning, psychosocial functioning, quality of life and adverse effects. The search was done up to February 2012 in English and Spanish in the following databases: PubMed/MEDLINE, LILACS, Cochrane, DARE and National Guideline Clearinghouse. The articles were independently evaluated by two investigators. Results: Of the 108 studies found initially, 11 were included, among which five systematic reviews, one primary article and 5 clinical guidelines. Conclusions: Atomoxetine is recommended as a second option in ADHD and was found to be superior to placebo. Its use is recommended when methylphenidate fails or comorbidities are present.

  18. A hidden Markov model to assess drug-induced sleep fragmentation in the telemetered rat.

    Science.gov (United States)

    Diack, C; Ackaert, O; Ploeger, B A; van der Graaf, P H; Gurrell, R; Ivarsson, M; Fairman, D

    2011-12-01

    Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across species. The EEG shows frequent transitions between specific sleep states leading to multiple correlated sojourns in these states. We have developed a Markov model to consider the high correlation in the data and quantitatively compared sleep disturbance in telemetered rats induced by methylphenidate, which is known to disturb sleep, and of a new chemical entity (NCE). It was assumed that these drugs could either accelerate or decelerate the transitions between the sleep states. The difference in sleep disturbance of methylphenidate and the NCE were quantitated and different mechanisms of action on rebound sleep were identified. The estimated effect showed that both compounds induce sleep fragmentation with methylphenidate being fivefold more potent compared to the NCE.

  19. Prescriptions, Nonmedical Use, and Emergency Department Visits Involving Prescription Stimulants

    Science.gov (United States)

    Chen, Lian-Yu; Crum, Rosa M.; Strain, Eric C.; CalebAlexander, G.; Kaufmann, Christopher; Mojtabai, Ramin

    2018-01-01

    Objective Little is known regarding the temporal trends in prescription, nonmedical use and emergency department (ED) visits involving prescription stimulants in the United States. We aimed to examine the three national trends involving dextroamphetamine-amphetamin (Adderall) and methylphenidate in adults and adolescents. Method Three national surveys conducted between 2006-2011 were used: National Disease and Therapeutic Index (NDTI), a survey of office-based practices, National Survey on Drug Use and Health (NSDUH), a population survey of substance use, and Drug Abuse Warning Network (DAWN), a survey of ED visits. Ordinary least square regression was used to examine temporal changes over time and the associations between these three trends. Results In adolescents, treatment visits involving dextroamphetamine-amphetamine and methylphenidate decreased over time; nonmedical dextroamphetamine-amphetamine use remained stable while nonmedical methylphenidate use declined by 54.4% in 6 years. ED visits involving either medication remained stable. In adults, treatment visits involving dextroamphetamine-amphetamine remained unchanged while nonmedical use went up by 67% and ED visits went up by 156%. These three trends involving methylphenidate remained unchanged. The major source for both medications was a friend or relative across age groups; two-thirds of these friends/relatives had obtained the medication from a physician. Conclusions Trends of prescriptions for stimulants do not correspond to trends in reports of nonmedical use and ED visits. Increased nonmedical stimulant use may not be simply attributed to increased prescribing trends. Future studies should focus on deeper understanding of the proportion, risk factors and motivations for drug diversions. PMID:26890573

  20. The impact of synapsin III gene on the neurometabolite level alterations after single-dose methylphenidate in attention-deficit hyperactivity disorder patients

    Directory of Open Access Journals (Sweden)

    Başay Ö

    2016-05-01

    Full Text Available Ömer Başay,1 Burge Kabukcu Basay,1 Huseyin Alacam,2 Onder Ozturk,1 Ahmet Buber,1 Senay Gorucu Yilmaz,3 Yılmaz Kıroğlu,4 Mehmet Emin Erdal,5 Hasan Herken2 1Department of Child and Adolescent Psychiatry, Faculty of Medicine, Pamukkale University, Denizli, 2Department of Psychiatry, Faculty of Medicine, Pamukkale University, Denizli, 3Department of Nutrition and Dietetics, Faculty of Health Sciences, Gaziantep University, Gaziantep, 4Department of Radiology, School of Medicine, Pamukkale University, Denizli, 5Department of Medical Biology and Genetics, Faculty of Medicine, Mersin University, Mersin, Turkey Objective: To investigate the neurometabolite level changes according to synapsin III gene rs133945G>A and rs133946C>G polymorphisms by using magnetic resonance spectroscopy (MRS in patients with attention-deficit hyperactivity disorder (ADHD.Methods: Fifty-seven adults diagnosed with ADHD were recruited for the study. The participants were examined by single-voxel 1H MRS when medication naïve and 30 minutes after oral administration of 10 mg methylphenidate (Mph. Those who had been on a stimulant discontinued the medication 48 hours before MRS imaging. Spectra were taken from the anterior cingulate cortex, dorsolateral prefrontal cortex, striatum, and cerebellum, and N-acetylaspartate (NAA, choline, and creatine levels were examined. For genotyping of the synapsin III gene polymorphisms, DNA was isolated from peripheral blood leukocytes. The effects of age, sex, and ADHD subtypes were controlled in the analyses.Results: After a single dose of Mph, choline levels increased significantly in the striatum of rs133945G>A polymorphism-GG genotypes (P=0.020 and NAA levels rose in the anterior cingulate cortex of rs133946C>G polymorphism-CG genotypes (P=0.014. Both rs133945G>A and rs133946C>G polymorphisms were found to statistically significantly affect the alteration of NAA levels in response to Mph in dorsolateral prefrontal cortex with

  1. High on Crime Fiction and Detection

    DEFF Research Database (Denmark)

    Grodal, Torben Kragh

    2010-01-01

    how crime fiction activates strong salience (in some respects similar to the effect of dopamine-drugs like cocaine, Ritalin, and amphetamine) and discusses the role of social intelligence in crime fiction. It further contrasts the unempathic classical detector fictions with two subtypes of crime...... fiction that blend seeking with other emotions: the hardboiled crime fiction that blends detection with action and hot emotions like anger and bonding, and the moral crime fiction that strongly evokes moral disgust and contempt, often in conjunction with detectors that perform hard to fake signals...

  2. Methylphenidate Transdermal Patch

    Science.gov (United States)

    ... for ADHD, which may include counseling and special education. Make sure to follow all of your doctor's ... that was covered by the patch seizures motion tics or verbal tics believing things that are not ...

  3. The Impact of Methylphenidate on Motor Performance in Children with both Attention Deficit Hyperactivity Disorder and Developmental Coordination Disorder: A Randomized Double-Blind Crossover Clinical Trial

    Directory of Open Access Journals (Sweden)

    Robabeh Soleimani

    2017-07-01

    Full Text Available Background: Children with attention deficit hyperactivity disorder/developmental coordination disorder (ADHD/DCD suffer from problems associated with gross and fine motor skills. There is no effective pharmacological therapy for such patients. We aimed to assess the impact of methylphenidate (MPH on motor performance of children with ADHD/DCD. Methods: In this double-blind placebo-controlled, 17 children (12 boys with ADHD/DCD with a mean age of 7 years 6 months were recruited in Shafa Hospital, Rasht, Iran. The response was defined as ≥25% reduction in the total score of ADHD rating scale-IV from the baseline. Sixteen boys entered phase 2 of the study in which the impact of MPH on motor function was determined through a crossover randomized clinical trial. Eligible individuals were scheduled for baseline and two assessment visits after a one-week period of intervention. We used the short form of Bruininks-Oseretsky test (BOT-2 to identify the disability of motor function. Children were randomly assigned to receive MPH or inert ingredients (placebo. In the second period, medication (MPH/placebo was crossed over. The effects of MPH were analyzed using χ2 test for related samples to compare the performance during baseline, placebo, and MPH trials. The results were analyzed using the SPSS software version 16.0. Results: The mean minimal effective dose of MPH per day was 17.3 mg (0.85 mg/kg. Children with higher ADHD rating scale had a significantly lower standard score in BOT-2 (P=0.03. Following MPH intake, 26.6% of the children showed clinically significant improvement in motor function. However, the improvement was not statistically different between the MPH and placebo. Conclusion: Although MPH improved ADHD symptoms, problems with motor performance still remained. Further work is required to determine the probable effects of MPH in a higher dosage or in different subtypes of ADHD. Trial Registration Number: IRCT201107071483N2

  4. [The effects of psychostimulants on the cognitive results and behaviour of children with the combined subtype of attention deficit with hyperactivity].

    Science.gov (United States)

    Mulas, F; Roselló, B; Morant, A; Hernández, S; Pitarch, I

    Many studies have shown the efficacy of methylphenidate in treating children with attention deficit and hyperactivity to reduce the main symptoms of the disorder and problems of behaviour: behaviour which is disruptive, antisocial, negative and aggressive. 1. Analyze the therapeutic effects of methylphenidate on the cognitive function of children with TDAH, combined subtype, evaluated by means of neuropsychological tests of attention and inhibitory control. 2. Determine the efficacy of methylphenidate in improving the basic symptoms of TDAH C according to the DSM 1V for parents and teachers, and their behaviour, evaluated by their teachers, in the combined subtype. The sample was made up of 48 children with TDAH C. 24 of these had been referred by paediatricians and received drug treatment with methylphenidate, 0.5 mg/kg once in the morning and once after lunch (TDAH C/CTF). The other group of 24 children with TDAH C were referred from their teachers to a school psychologist so that they followed the usual guidelines for orientation but not a systematically developed treatment (TDAH C/C or control group). RESULTS. In relation to the first objective the results were good for the TDAH C/CTF compared with the TDAH C/C group regarding the proportion of children who improved their results on neuropsychological testing of planning inhibitory control and attention. The differences between the two groups were statistically significant in the latent period of the reflexive impulsive test (MFF), arithmetic, cancellation of rhomboids and cancellation of numbers. Regarding the second objective, the improvement in the TDAH C/CTF group according to the teachers opinions were statistically significant with respect to attention, hyperactivity and impulsiveness, as compared with the control group. However, according to the parents assessment, although improvement was greater in both dimensions, the differences between the two groups did not reach statistical significance. Finally

  5. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders.

    Science.gov (United States)

    Bloch, Michael H; Panza, Kaitlyn E; Landeros-Weisenberger, Angeli; Leckman, James F

    2009-09-01

    The Food and Drug Administration currently requires the package inserts of most psychostimulant medications to list the presence of a tic disorder as a contraindication to their use. Approximately half of children with Tourette's syndrome experience comorbid attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of different medications in treating ADHD and tic symptoms in children with both Tourette's syndrome and ADHD. We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of medications in the treatment of ADHD in the children with comorbid tics. We used a random effects meta-analysis with standardized mean difference as our primary outcome to estimate the effect size of pharmaceutical agents in the treatment of ADHD symptoms and tics. Our meta-analysis included nine studies involving 477 subjects. We assessed the efficacy of six medications-dextroamphetamine, methylphenidate, alpha-2 agonists (clonidine and guanfacine), desipramine, atomoxetine, and deprenyl. Methylphenidate, alpha-2 agonists, desipramine, and atomoxetine demonstrated efficacy in improving ADHD symptoms in children with comorbid tics. Alpha-2 agonists and atomoxetine significantly improved comorbid tic symptoms. Although there was evidence that supratherapeutic doses of dextroamphetamine worsens tics, there was no evidence that methylphenidate worsened tic severity in the short term. Methylphenidate seems to offer the greatest and most immediate improvement of ADHD symptoms and does not seem to worsen tic symptoms. Alpha-2 agonists offer the best combined improvement in both tic and ADHD symptoms. Atomoxetine and desipramine offer additional evidence-based treatments of ADHD in children with comorbid tics. Supratherapeutic doses of dextroamphetamine should be avoided.

  6. Brain {sup 1}H MRS study in children suffering from attention-deficit/hyperactivity disorder

    Energy Technology Data Exchange (ETDEWEB)

    Zhen, Jin; Lei, Zhang; Yawei, Zeng; Yan, Wang [306 Hospital, Beijing (China). Center for fMRI and Dept. of Radiology; Yufeng, Zang; Yufeng, Wang [Beijing Univ., Beijing (China). Inst. of Mental Health

    2002-06-01

    Objective: To determine whether the children suffering from Attention -deficit/hyperactivity disorder (ADHD) had neurochemical abnormalities in basis ganglia and if the state could be affected by methylphenidate. Methods: Proton magnetic resonance spectroscopy scans were performed on bilateral globus pallidum of 12 ADHD body before and after one dose of methylphenidate 10 mg. Spectral peaks of N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), glutamate plus glutamine ({alpha}-Glx) and creatine (Cr) were measured and their ratios were compared with 12 age-, handedness-, and IQ-matched healthy boys. Results: In children having ADHD, NAA/Cr ratio decrease significantly in bilateral globus pallidum (left side t = 7.01, P < 0.01; right side t = 4.95, P < 0.01), while only the right globus pallidum shows significant Cho/Cr ratio rise (t = 2.33, P < 0.05). The abnormalities could be improved by one dose of methylphenidate. However, the post-drug NAA/Cr ratios were not significantly different from the pre-drug ratios (left side t = -1.34, P > 0.05; right side t = -1.04, P > 0.05). The post-drug NAA/Cr ratios in ADHD children remained significantly different from those in healthy children (left side t = 3.68, P < 0.01; right side t = 2.50, P < 0.05). The post-drug Cho/Cr ratio was no more significantly differ from controls (t = 0.87, P > 0.05). Conclusion: In children suffering from ADHD, neuronal loss-dysfunction exists in bilateral striatum. One does of methylphenidate could not affect the state significantly. Further investigations are needed to confirm whether the cholinergic system is involved in ADHD.

  7. Attention Patterns in Children with Attention Deficit Disorder with or without Hyperactivity

    Directory of Open Access Journals (Sweden)

    Gil Zalsman

    2003-01-01

    Full Text Available The objective of this study was to differentiate the attention patterns associated with attention deficit disorder with or without hyperactivity using continuous performance test (CPT. The diagnoses were based on the DSM-III, III-R, and IV criteria and of the 39 children who participated in the study, 14 had attention deficit disorder with hyperactivity (ADDH and 11 had attention deficit disorder without hyperactivity (ADDWO, while 14 normal children served as a control group. Attention patterns were examined according to the performance of subjects on the CPT and parental scores on the ADHD Rating Scale, the Child Attention Profile, and the Conners Rating Scale. CPT performances were assessed before and after administration of 10 mg methylphenidate. We found as hypothesized that the CPT differentiated between the ADDH and ADDWO groups. However, contrary to our expectations, the ADDH children made more omission errors than the ADDWO children; they also showed more hyperactivity and impulsivity. The performance of both groups improved to an equal degree after the administration of methylphenidate. It is conluded that different subtypes of the attention deficit disorders are characterized by different attention profiles and that methylphenidate improves scores on test of continuous performance.

  8. Improving the Dictation in Attention Deficit Hyperactivity Disorder by Using Computer Based Interventions: A Clinical Trial

    Directory of Open Access Journals (Sweden)

    Mahdi Tehranidoost

    2006-07-01

    Full Text Available Objective: The aim of the current study was to assess the impact of computer games and computer-assisted type instruction on dictation scores of elementary school children with attention deficit – hyperactivity disorder (ADHD. Method: In this single-blind clinical trial, 37 elementary school children with ADHD, selected by convenience sampling and divided into group I (n=17 and group II (n=20, underwent eight one-hour sessions (3 sessions per week of intervention by computer games versus computer-assisted type instruction, respectively. 12 school dictation scores were considered: 4 scores preintervention, 4 scores during interventions, and 4 scores post-intervention. Dictation test was taken during each session. Data was analyzed using repeated measure ANOVA. Results: Two groups were matched for age, gender, school grade, medication, IQ, parent’s and teacher’s Conners’ scale scores, having computer at home, history of working with computer, and mean dictation scores. There was no significant difference in dictation scores before and after interventions and also between the study groups. The improvement in school dictation scores had no significant correlation with age, gender, Ritalin use, owning a computer at home and past history of computer work, baseline dictation scores, Ritalin dose, educational status, IQ, and the total score of parent’s and teacher’s Conners’ rating scale. Conclusion: Absence of significant improvement in dictation scores in study groups may be due to the confounding effect of other variables with known impact on dictation scores. Further studies in this field should also assess the change of attention and memory.

  9. PET IMAGING STUDIES IN DRUG ABUSE RESEARCH.

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Volkow, N.D.; Ding, Y.S.; Logan, J.; Wang, G.J.

    2001-01-29

    . This will be followed by highlights of PET studies of the acute effects of the psychostimulant drugs cocaine and methylphenidate (ritalin) and studies of the chronic effects of cocaine and of tobacco smoke on the human brain. This chapter concludes with the description of a study which uses brain imaging coupled with a specific pharmacological challenge to address the age-old question of why some people who experiment with drugs become addicted while others do not.

  10. Dissociation between spontaneously hypertensive (SHR) andWistar–Kyoto (WKY) rats in baseline performance and methylphenidate response on measures of attention, impulsivity and hyperactivity in a Visual Stimulus Position Discrimination Task

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.

    2009-10-08

    The spontaneously hypertensive rat (SHR) is a widely accepted rodent model of Attention Deficit/Hyperactivity Disorder (ADHD), and methylphenidate (MP) is a central nervous systemstimulant that has been shown to have a dose-related positive effect on attention task performance in humans with ADHD. The current study was undertaken to compare SHR to its typical control strain, Wistar-Kyoto(WKY) rats, on the performance of a Visual Stimulus Position Discrimination Task (VSPDT) as well as of the responsiveness of the two rat strains to MP treatment. The rats were initially trained on the VSPDT, in which a light cue was presented randomly at three different cue-light intervals (1 s, 300 ms and 100 ms) over one of two levers, and presses on the lever corresponding to the light cue were reinforced with a food pellet. Once rats reached stable performance, the treatment phase of the study began, during which they received daily intraperitoneal (IP) injections of saline, 2 mg/kg, 5 mg/kg, and 10 mg/kg of MP in a randomized order immediately prior to being tested on the VSPDT. Baseline performance accuracy on the VSPDT did not differ between the groups. Furthermore, a striking strain dissociation was evident in the response of the two strains to treatment; VSPDT performance was substantially disrupted by the 5 and 10 mg/kg dose in the WKY rats but only mildly in the SHR rats. Response omissions were also increased only in WKY rats. Finally, both strains had increased locomotor activity in the operant chamber following MP treatment. These findings point to an important difference in response tendency toMP in the two strains that supports a view that a critical difference between these strains may suggest neurochemical and neuroadaptive differences associated with the behavioral impairments of ADHD.

  11. Chronic treatment with extended release methylphenidate does not alter dopamine systems or increase vulnerability for cocaine self-administration: a study in nonhuman primates.

    Science.gov (United States)

    Gill, Kathryn E; Pierre, Peter J; Daunais, James; Bennett, Allyson J; Martelle, Susan; Gage, H Donald; Swanson, James M; Nader, Michael A; Porrino, Linda J

    2012-11-01

    Despite the widespread use of stimulant medications for the treatment of attention deficit hyperactivity disorder, few studies have addressed their long-term effects on the developing brain or susceptibility to drug use in adolescence. Here, we determined the effects of chronic methylphenidate (MPH) treatment on brain dopamine (DA) systems, developmental milestones, and later vulnerability to substance abuse in juvenile nonhuman primates. Male rhesus monkeys (approximately 30 months old) were treated daily with either a sustained release formulation of MPH or placebo (N=8 per group). Doses were titrated to achieve initial drug blood serum levels within the therapeutic range in children and adjusted throughout the study to maintain target levels. Growth, including measures of crown-rump length and weight, was assessed before and after 1 year of treatment and after 3-5 months washout. In addition, positron emission tomography scans were performed to quantify binding availability of D2/D3 receptors and dopamine transporters (DATs). Distribution volume ratios were calculated to quantify binding of [¹⁸F]fluoroclebopride (DA D2/D3) and [¹⁸F]-(+)-N-(4-fluorobenzyl)-2β-propanoyl-3β-(4-chlorophenyl)tropane (DAT). Chronic MPH did not differentially alter the course of weight gain or other measures of growth, nor did it influence DAT or D2/D3 receptor availability after 1 year of treatment. However, after washout, the D2/D3 receptor availability of MPH-treated animals did not continue to decline at the same rate as control animals. Acquisition of intravenous cocaine self-administration was examined by first substituting saline for food reinforcement and then cocaine doses (0.001-0.1 mg/kg per injection) in ascending order. Each dose was available for at least five consecutive sessions. The lowest dose of cocaine that maintained response rates significantly higher than saline-contingent rates was operationally defined as acquisition of cocaine reinforcement. There

  12. Dopamine transporter density of the basal ganglia in children with attention deficit hyperactivity disorder assessed with I-123 IPT SPECT

    International Nuclear Information System (INIS)

    Ryu, Won Gee; Kim, Tae Hoon; Ryu, Young Hoon; Yun, Mi Jin; Lee, Jong Doo; Cheon, Keun Ah; Chi, Dae Yoon; Kim, Jong Ho; Choi, Tae Hyun

    2003-01-01

    Attention deficit hyperactivity disorder (ADHD) has been known as psychiatric disorder in childhood associated with dopamine dysregulation. In present study, we investigated changes in dopamine transporter (DAT) density of the basal ganglias using I-123 N-(3-iodopropen-2-yl) -2-carbomethoxy-3beta-(4-chlorphenyl) tropane (I-123 IPT) SPECT in children with ADHD before and after methylphenidate treatment. Nine drug-naive children with ADHD and seven normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of I-123 IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of specific/nonspecific DAT binding ratios in the basal ganglia. All children with ADHD reperformed (123I)IPT SPECT after treatment with methylphenidate (0.7mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methyphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/nonspecific DAT binding ratio of basal ganglia. Children with ADHD had a significantly greater specific/nonspecific DAT binding ratio of the basal ganglia comparing to normal children (Right : z = 2.057, p = 0.041 ; Left : z = 2.096, p = 0.032). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both ganglia decreased significantly greater than before treatment with methylphenidate (Right : t = 3.239, p = 0.018 ; Left : t = 3.133, p 0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. These findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD

  13. Dopamine transporter density of the basal ganglia in children with attention deficit hyperactivity disorder assessed with I-123 IPT SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Won Gee; Kim, Tae Hoon; Ryu, Young Hoon; Yun, Mi Jin; Lee, Jong Doo; Cheon, Keun Ah [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of); Chi, Dae Yoon [College of Medicine, Inha Univ., Incheon (Korea, Republic of); Kim, Jong Ho; Choi, Tae Hyun [School of Medicine, Gachon Univ., Gachon (Korea, Republic of)

    2003-08-01

    Attention deficit hyperactivity disorder (ADHD) has been known as psychiatric disorder in childhood associated with dopamine dysregulation. In present study, we investigated changes in dopamine transporter (DAT) density of the basal ganglias using I-123 N-(3-iodopropen-2-yl) -2-carbomethoxy-3beta-(4-chlorphenyl) tropane (I-123 IPT) SPECT in children with ADHD before and after methylphenidate treatment. Nine drug-naive children with ADHD and seven normal children were included in the study. We performed brain SPECT two hours after the intravenous administration of I-123 IPT and made both quantitative and qualitative analyses using the obtained SPECT data, which were reconstructed for the assessment of specific/nonspecific DAT binding ratios in the basal ganglia. All children with ADHD reperformed (123I)IPT SPECT after treatment with methylphenidate (0.7mg/kg/d) during about 8 weeks. SPECT data reconstructed for the assessment of specific/nonspecific DAT binding ratio of the basal ganglia were compared between before and after treatment methyphenidate. We investigated correlation between the change of ADHD symptom severity assessed with ADHD rating scale-IV and specific/nonspecific DAT binding ratio of basal ganglia. Children with ADHD had a significantly greater specific/nonspecific DAT binding ratio of the basal ganglia comparing to normal children (Right : z = 2.057, p = 0.041 ; Left : z = 2.096, p = 0.032). Under treatment with methylphenidate in all children with ADHD, specific/nonspecific DAT binding ratio of both ganglia decreased significantly greater than before treatment with methylphenidate (Right : t = 3.239, p = 0.018 ; Left : t = 3.133, p 0.020). However, no significant correlation between the change of ADHD symptom severity scores and specific/nonspecific DAT binding ratio of the basal ganglia were found. These findings support the complex dysregulation of the dopaminergic neurotransmitter system in children with ADHD.

  14. Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty?

    Science.gov (United States)

    Biehl, Stefanie C; Merz, Christian J; Dresler, Thomas; Heupel, Julia; Reichert, Susanne; Jacob, Christian P; Deckert, Jürgen; Herrmann, Martin J

    2016-05-27

    Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes. © The Author 2016. Published by Oxford University Press on behalf

  15. Trastorno por Déficit de Atención e Hiperactividad (TDAH: controversias terapéuticas

    Directory of Open Access Journals (Sweden)

    Emilia Alonso

    2015-11-01

    A critical analysis of literature published in PubMed was done, which was supplemented by interviews with qualified professionals. We found that the benfits of psychostimulants, especially methylphenidate, are: symptom control, improved neurocognitive performance and quality of life. The most common side effects are mild and transient. Cardiovascular toxicity and decreased growth are serious but rare side effects. Parent training significantly reduces symptoms and cognitive training also improves cognitive abilities. For which we conclude that psychostimulants, especially methylphenidate, are symptomatic first-line treatment. In the long term it is necessary to monitor the growth and cardiovascular risk. It is recommended to combine with non-pharmacological therapy (parent and cognitive training to enhance benefits and reduce risks.

  16. Topiramate via NMDA, AMPA/kainate, GABAA and Alpha2 receptors and by modulation of CREB/BDNF and Akt/GSK3 signaling pathway exerts neuroprotective effects against methylphenidate-induced neurotoxicity in rats.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Beiranvand, Tabassom; Mozaffari, Shiva

    2017-11-01

    Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABA A receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α 2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D 2 receptor antagonist. Open field test (OFT) was used to investigate the disturbances in motor activity. Hippocampal neurodegenerative parameters were evaluated. Protein expressions of CREB/BDNF and Akt/GSK3 signaling pathways were also evaluated. Cresyl violet staining was performed to show and confirm the changes in the shape of the cells. TPM (70 and 100 mg/kg) reduced MPH-induced rise in lipid peroxidation, oxidized form of glutathione (GSSG), IL-1β and TNF-α levels, Bax expression and motor activity disturbances. In addition, TPM treatment increased Bcl-2 expression, the level of reduced form of glutathione (GSH) and the levels and activities of superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes. TPM also inhibited MPH-induced hippocampal degeneration. Pretreatment of animals with DOM, BIC, KET and YOH inhibited TPM-induced neuroprotection and increased oxidative stress, neuroinflammation, neuroapoptosis and neurodegeneration while reducing CREB, BDNF and Akt protein expressions. Also pretreatment with DOM, BIC, KET and YOH inhibited TPM-induced decreases in GSK3. It can be concluded that the mentioned receptors by modulation of CREB/BDNF and Akt/GSK3 pathways, are involved in neuroprotection of TPM against MPH-induced neurodegeneration.

  17. [123I]Iodobenzamide binding to the rat dopamine D2 receptor in competition with haloperidol and endogenous dopamine - an in vivo imaging study with a dedicated small animal SPECT

    International Nuclear Information System (INIS)

    Nikolaus, Susanne; Larisch, Rolf; Wirrwar, Andreas; Jamdjeu-Noune, Marlyse; Antke, Christina; Beu, Markus; Mueller, Hans-Wilhelm; Schramm, Nils

    2005-01-01

    This study assessed [ 123 I]iodobenzamide binding to the rat dopamine D 2 receptor in competition with haloperidol and endogenous dopamine using a high-resolution small animal SPECT. Subsequent to baseline quantifications of D 2 receptor binding, imaging studies were performed on the same animals after pre-treatment with haloperidol and methylphenidate, which block D 2 receptors and dopamine transporters, respectively. Striatal baseline equilibrium ratios (V 3 '' ) of [ 123 I]iodobenzamide binding were 1.42±0.31 (mean±SD). After pre-treatment with haloperidol and methylphenidate, V 3 '' values decreased to 0.54±0.46 (p 123 I]iodobenzamide binding induced by pre-treatment with haloperidol reflects D 2 receptor blockade, whereas the decrease in receptor binding induced by pre-treatment with methylphenidate can be interpreted in terms of competition between [ 123 I]IBZM and endogenous dopamine. Findings show that multiple in vivo measurements of [ 123 I]iodobenzamide binding to D 2 receptors in competition with exogenous and endogenous ligands are feasible in the same animal. This may be of future relevance for the in vivo evaluation of novel radioligands as well as for studying the interrelations between pre- and/or postsynaptic radioligand binding and different levels of endogenous dopamine. (orig.)

  18. Síndrome de Gilles de la Tourette associada ao transtorno de déficit de atenção com hiperatividade: resposta clínica satisfatória a inibidor seletivo da recaptura de serotonina e metilfenidato Tourette syndrome associated with attention-deficit hyperactivity disorder: satisfactory clinical response to selective serotonin reuptake inhibitor and methylphenidate

    Directory of Open Access Journals (Sweden)

    Roberta Benitez Freitas Passos

    2010-01-01

    Full Text Available A Síndrome de Gilles de la Tourette (SGT, caracterizada pela presença de tiques motores e vocais, apresenta elevada associação com transtorno obsessivo-compulsivo (TOC e transtorno de déficit de atenção com hiperatividade (TDAH. Essas condições frequentemente causam mais prejuízo aos pacientes do que os tiques, propriamente. Relata-se o caso clínico de um paciente com SGT e comorbidade com TDAH e TOC. O tratamento com inibidor seletivo de recaptura de serotonina (ISRS e metilfenidato promoveu melhora significativa dos sintomas de TDAH, sintomas compulsivos e tiques.Tourette Syndrome (TS, characterized by motor and vocal tics, is often associated with obsessive compulsive disorder (OCD and attention-deficit hyperactivity disorder (ADHD. These associated conditions frequently cause more impairment in patients than tics themselves. We report the case of TS with comorbid ADHD and OCD. Treatment with selective serotonin reuptake inhibitor and methylphenidate, led to significantly improvement of ADHD symptoms, compulsive symptoms and tics.

  19. Dgroup: DG01970 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ylphenidate (USAN/INN) ... D01296 ... Methylphenidate hydrochloride (JAN/USP) ... DG00970 ... Atomoxetine... ... D07473 ... Atomoxetine (USP/INN) ... D02574 ... Atomoxetine hydrochloride (JAN/USP) ... DG00972 ... De

  20. Conocimiento, política y mercado: acerca del desarrollo de las Ciencias Sociales en Chile (1970-2000 = Knowledge, politics and market: about the development of Social Sciences in Chile (1970-2000

    Directory of Open Access Journals (Sweden)

    Oyanedel, Juan Carlos

    2012-01-01

    Full Text Available O artigo tenta mostrar uma perspectiva geral sobre as mudanças experimentadas pelas Ciências Sociais no Chile entre 1970 e 2000. A análise mostra a relação entre as Ciências Sociais e as mudanças na estrutura política, econômica e social, em nível nacional e internacional, para esse período. A principal hipótese defende que houve uma modificação nas abordagens interpretativas que mostram as Ciências Sociais no Chile devido a uma alteração na sua posição na tríade: Economia – Estado – Sociedade Civil. Tais mudanças, por sua vez, são o resultado das alterações feitas durante a Ditadura Militar (1973-1989 e consolidadas pelos governos da Concertação de Partidos pela Democracia (1990-2006

  1. Fast and Highly Selective LC-MS/MS Screening for THC and 16 Other Abused Drugs and Metabolites in Human Hair to Monitor Patients for Drug Abuse

    NARCIS (Netherlands)

    Koster, Remco A.; Alffenaar, Jan-Willem C.; Greijdanus, Ben; VanDerNagel, Joanneke E. L.; Uges, Donald R. A.

    Background:To facilitate the monitoring of drug abuse by patients, a method was developed and validated for the analysis of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine, benzoylecgonine, morphine,

  2. Application of Sweat Patch Screening for 16 Drugs and Metabolites Using a Fast and Highly Selective LC-MS/MS Method

    NARCIS (Netherlands)

    Koster, Remco A.; Alffenaar, Jan-Willem C.; Greijdanus, Ben; VanDerNagel, Joanneke E. L.; Uges, Donald R. A.

    Background: To facilitate the monitoring of drug abuse by patients, a method was developed and validated for fast and highly selective screening for amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine,

  3. Neurochemical enhancement of conscious error awareness.

    Science.gov (United States)

    Hester, Robert; Nandam, L Sanjay; O'Connell, Redmond G; Wagner, Joe; Strudwick, Mark; Nathan, Pradeep J; Mattingley, Jason B; Bellgrove, Mark A

    2012-02-22

    How the brain monitors ongoing behavior for performance errors is a central question of cognitive neuroscience. Diminished awareness of performance errors limits the extent to which humans engage in corrective behavior and has been linked to loss of insight in a number of psychiatric syndromes (e.g., attention deficit hyperactivity disorder, drug addiction). These conditions share alterations in monoamine signaling that may influence the neural mechanisms underlying error processing, but our understanding of the neurochemical drivers of these processes is limited. We conducted a randomized, double-blind, placebo-controlled, cross-over design of the influence of methylphenidate, atomoxetine, and citalopram on error awareness in 27 healthy participants. The error awareness task, a go/no-go response inhibition paradigm, was administered to assess the influence of monoaminergic agents on performance errors during fMRI data acquisition. A single dose of methylphenidate, but not atomoxetine or citalopram, significantly improved the ability of healthy volunteers to consciously detect performance errors. Furthermore, this behavioral effect was associated with a strengthening of activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe during the methylphenidate condition for errors made with versus without awareness. Our results have implications for the understanding of the neurochemical underpinnings of performance monitoring and for the pharmacological treatment of a range of disparate clinical conditions that are marked by poor awareness of errors.

  4. [The course of behaviour changes in children with attention deficit and hyperactivity after drug treatment].

    Science.gov (United States)

    Roselló, B; Pitarch, I; Abad, L

    2002-02-01

    Several studies have reported differences in behaviour in patients with various subtypes of attention deficit with hyperactivity and the benefits of psychostimulant medication in the treatment of behaviour problems of patients with the attention deficit hyperactivity syndrome (TDAH). 1. To determine possible differences in behaviour between patients with subtypes of the attention deficit hyperactivity disorder; 2. To analyze the efficacy of methylphenidate on behaviour in three subtypes of TDAH, evaluated on the opinions of patients and teachers. A total of 90 children were studied: 39 children with TDAH-C; 36 with TDAH-1 and 15 with TDAH-H/I. All patients were given 0.5 mg/kg of methylphenidate for a period of three months, once in the morning and once in the afternoon. The results show that the children with the three subtypes of TDAH have significant differences in all the behaviour variables studied except for the variable timidity anxiety, in which no differences were observed between the subtypes of TDAH. Statistical analysis also showed that children with all three subtypes of TDAH improved significantly with regard to most of the aspects of behaviour studied after psychostimulant medication, in the opinions of parents and teachers. Our findings are similar to those of other studies and give fresh data on the behaviour and advantages of methylphenidate in the new subtype included in the DSM-1V, the predominantly hyperactive impulsive type.

  5. Combined pharmacotherapy-multimodal psychotherapy in children with Disruptive Behavior Disorders.

    Science.gov (United States)

    Masi, Gabriele; Milone, Annarita; Manfredi, Azzurra; Brovedani, Paola; Pisano, Simone; Muratori, Pietro

    2016-04-30

    Although multi-component psychotherapeutic interventions are first-line treatments for Disruptive Behavior Disorders (DBD), pharmacotherapy is often associated for more severe patients. Our aim was to explore effectiveness of an associated pharmacotherapy in referred children with DBD receiving a one-year psychotherapeutic intervention. Aggression, callous unemotional (CU) traits and emotional dysregulation were outcome measures. The sample included 144 children, aged 8-12 years, 41 (29%) with an ADHD comorbidity. Fifty-five (38%) patients received an additional pharmacotherapy with one medication, methylphenidate, a second generation antipsychotic, or a mood stabilizer. Data were collected before and after the one-year treatment. According to the Child Behavior Checklist (CBCL), aggressive behaviors, rule-breaking behaviors and emotional dysregulation improved in the whole group, as well as parent- and child-reported CU traits. The hierarchical regression model showed that additional pharmacotherapy significantly predicted lower scores at the CBCL aggressive behaviors and emotional dysregulation, but not CU traits at the end of the treatment. The interaction between methylphenidate and ADHD comorbidity predicted lower aggressive behaviors after the treatment. In summary, this naturalistic investigation suggest that an additional pharmacotherapy significantly improved aggression and emotional dysregulation, but not CU traits. When ADHD was comorbid, methylphenidate was more effective than antipsychotics or mood stabilizers in reducing aggression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Neurofeedback for the treatment of children and adolescents with ADHD: a randomized and controlled clinical trial using parental reports

    Directory of Open Access Journals (Sweden)

    Duric Nezla S

    2012-08-01

    Full Text Available Abstract Background A randomized and controlled clinical study was performed to evaluate the use of neurofeedback (NF to treat attention-deficit/hyperactivity disorder (ADHD in children and adolescents. Methods The ADHD population was selected from an outpatient clinic for Child and Adolescent Mental Health in Norway. Ninety-one of the 275 children and adolescents ranging in age from 6 to 18 years (10.5 years participated in 30 sessions of an intensive NF program. The reinforcement contingency was based on the subjects’ production of cortical beta1 activity (15–18 Hz. The ADHD participants were randomized into three groups, with 30 in the NF group, 31 controls in a group that was given methylphenidate, and 30 in a group that received NF and methylphenidate. ADHD core symptoms were reported by parents using the parent form of the Clinician’s Manual for Assessment by Russell A. Barkley. Results Ninety-one children and adolescents were effectively randomized by age, sex, intelligence and distribution of ADHD core symptoms. The parents reported significant effects of the treatments, but no significant differences between the treatment groups were observed. Conclusions NF was as effective as methylphenidate at treating the attentional and hyperactivity symptoms of ADHD, based on parental reports. Trial registration Current Controlled Trials NCT01252446

  7. Impact of psychostimulants and atomoxetine on the expression of 8-hydroxyguanine glycosylase 1 in human cells.

    Science.gov (United States)

    Schmidt, Andreas Johannes; Clement, Hans-Willi; Gebhardt, Stefan; Hemmeter, Ulrich Michael; Schulz, Eberhard; Krieg, Jürgen-Christian; Kircher, Tilo; Heiser, Philip

    2010-06-01

    Oxidative DNA damage as one sign of reactive oxygen species induced oxidative stress is an important factor in the pathogenesis of various psychiatric disorders. Altered levels of DNA base damage products as well as the expression of the main repair enzyme 8-hydroxyguanine glycosylase 1 have been described. The aim of the present study was to examine the effects of drugs (amphetamine, methylphenidate and atomoxetine) used in the treatment of attention deficit-hyperactivity disorder on the expression of this enzyme via reverse transcriptase-polymerase chain reaction in human neuroblastoma SH-SY5Y and human monocytic U-937 cells at concentrations of 50, 500 and 5,000 ng/ml. We observed decreased expression of this enzyme for all applied substances. In U-937 cells, the significance level was reached after treatment with 5,000 ng/ml amphetamine as well as after treatment with 50, 500 and 5,000 ng/ml atomoxetine. Incubation of SH-SY5Y cells with 50 and 5,000 ng/ml amphetamine and 5,000 ng/ml methylphenidate led to significant decreases of 8-hydroxyguanine glycosylase 1. As a positive correlation between the expression of 8-hydroxyguanine glycosylase 1 and the level of oxidative DNA damage products has been described, we accordingly consider these substances (amphetamine, methylphenidate and atomoxetine) to possibly play a protective role in this process.

  8. Concertação social, negociações coletivas e flexibilidade: o caso italiano (1992-2002

    Directory of Open Access Journals (Sweden)

    Tapia Jorge R. B.

    2003-01-01

    Full Text Available The main objective of this article is to examine the characteristic dynamics of second-generation social concertations and their results, based on the Italian case. From the analytical point of view, we seek to demonstrate that: a the social concertation process emerged from the combination of a specific conjuncture marked by the imperatives of the European construct, an acute national political and economic crisis, and strategic choices by social actors; b tripartite negotiation gave rise to a collective bargaining structure at two levels, capable of simultaneously guaranteeing wage moderation, maintenance of wage purchasing power, corporate profit margins, and companies' needs for flexibility, with the exception of flexibility in lay-offs.

  9. Mastering your Fellowship

    African Journals Online (AJOL)

    ), due to HIV-related complications; Sue's 18-month old daughter (Kerry) ... her antiretroviral therapy. ... methylphenidate is indicated, including the differential diagnosis ..... Is not costly to perform. ... providing services to patients with NCDs. (2).

  10. Central nervous system stimulants and drugs that suppress appetite

    DEFF Research Database (Denmark)

    Aagaard, Lise

    2014-01-01

    of the January 2012 to June 2013 publications on central nervous system stimulants and drugs that suppress appetite covers amphetamines (including metamfetamine, paramethoxyamfetamine and paramethoxymetamfetamine), fenfluramine and benfluorex, atomoxetine, methylphenidate, modafinil and armodafinil...

  11. Cognitive enhancement: a brief overview

    African Journals Online (AJOL)

    agonists are able to improve attention, learning and memory.3. Increasingly ... processing, flexible thinking and decision-making under time pressure, and .... Methylphenidate,in short-acting, intermediate-release and long- acting forms, is the ...

  12. Amphetamine-type medicines: a review of pharmacokinetics, pharmacodynamics, and toxicological aspects.

    Science.gov (United States)

    Mariotti, Kristianee C; Rossato, Luciana G; Fröehlich, Pedro E; Limberger, Renata P

    2013-11-01

    Amphetamine-like drugs are sympathomimetic agents with marked central and peripheral stimulant properties. Despite the street illegal drugs such as amphetamine and ecstasy, some amphetamine-like compounds are also legally marketed under medical prescription in the treatment of attention deficit-hyperactivity disorder (methylphenidate) and obesity/overweight (fenproporex and diethylpropione). However, similar with what happens with their illicit analogues, therapeutic amphetamine-like drugs also share important toxicological risks. Although methylphenidate is considered the first choice in the treatment of attention deficit-hyperactivity disorder, its high popularity among teenagers and children is raising concern in the medical community. Regarding weight-loss purposes, the use of amphetamine-like compounds are very controversial, though. Thus, the present review will address pharmacokinetic, pharmacodynamic, and toxicological aspects of amphetamine-like compounds used with therapeutic aims.

  13. Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

    Directory of Open Access Journals (Sweden)

    Swann Alan C

    2006-01-01

    Full Text Available Abstract Background Methylphenidate (MPD is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA, nucleus accumbens (NAc, and prefrontal cortex (PFC. Methods The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39 rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p. on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10. Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min. Results Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% ± 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% ± 5.9% after 2.5 mg/kg MPD, and 56.5% ± 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of

  14. Error and feedback processing in children with ADHD and children with Autistic Spectrum Disorder : An EEG event-related potential study

    NARCIS (Netherlands)

    Groen, Yvonne; Wijers, Albertus A.; Mulder, Lambertus J. M.; Waggeveld, Brenda; Minderaa, Ruud B.; Althaus, Monika

    2008-01-01

    Objective: Performance monitoring was investigated in typically developing (TD) children, children with Autistic Spectrum Disorder (ASD), and Methylphenidate (Mph)-treated and medication-free children with Attention Deficit Hyperactivity Disorder (ADHD). Methods: Subjects performed a feedback-based

  15. Enhancement stimulants: perceived motivational and cognitive advantages

    Directory of Open Access Journals (Sweden)

    Irena P. Ilieva

    2013-10-01

    Full Text Available Psychostimulants like Adderall and Ritalin are widely used for cognitive enhancement by people without ADHD, although the empirical literature has shown little conclusive evidence for effectiveness in this population. This paper explores one potential explanation of this discrepancy: the possibility that the benefit from enhancement stimulants is at least in part motivational, rather than purely cognitive. We review relevant laboratory, survey and interview research and present the results of a new survey of enhancement users with the goal of comparing perceived cognitive and motivational effects. These users perceived stimulant effects on motivationally-related factors, especially energy and motivation, and reported motivational effects to be at least as pronounced as cognitive effects, including effects on "attention."

  16. Attention Deficit Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    ... those with ADHD. Findings from the Preschoolers with ADHD Treatment Study (PATS) indicate that using low dose methylphenidate ( ... abuse, and disability. Also, while many adults with ADHD receive treatment for other mental disorders or substance abuse, a ...

  17. The SPECT tracer [123I]ADAM binds selectively to serotonin transporters: a double-blind, placebo-controlled study in healthy young men

    International Nuclear Information System (INIS)

    Giessen, Elsmarieke van de; Booij, Jan

    2010-01-01

    The tracer 123 I-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine ([ 123 I]ADAM) has been developed to image serotonin transporters (SERTs) with SPECT. Preclinical studies have shown that [ 123 I]ADAM binds selectively to SERTs. Moreover, initial human studies have shown that [ 123 I]ADAM binding could be blocked by selective serotonin reuptake inhibitors (SSRIs). However, in humans it has not been proven that [ 123 I]ADAM binds selectively to SERTs. We examined the in vivo availability of SERTs in 12 healthy young volunteers 5 h after bolus injection of [ 123 I]ADAM. To evaluate the selectivity of binding, four participants were pretreated (double-blinded design) with placebo, four with paroxetine (20 mg) and four with the dopamine/norepinephrine blocker methylphenidate (20 mg). SPECT studies were performed on a brain-dedicated system (Neurofocus), and the SPECT images were coregistered with individual MR scans of the brain. ADAM binding in SERT-rich brain areas and cerebellar cortex (representing non-specific binding) was assessed by drawing regions of interest (ROIs) on the individual MR images. Specific to non-specific ratios were used as the outcome measure. We found that specific to non-specific ratios were statistically significantly lower in paroxetine-pretreated participants than in placebo- or methylphenidate-pretreated participants. No such difference was found between groups pretreated with placebo or methylphenidate. Our preliminary findings suggest that [ 123 I]ADAM binds selectively to SERTs in human brain. (orig.)

  18. [Substance use disorders and ADHD: an overview of recent Dutch research].

    Science.gov (United States)

    van Emmerik-van Oortmerssen, K; Crunelle, C L; Carpentier, P J

    2013-01-01

    ADHD is an important risk factor for the development of substance use disorders (SUD). To provide an overview of recent Dutch research into the prevalence of ADHD in SUD populations and the neurobiological substrate of the reduced effect of pharmacological treatment of this patient group. We describe three studies: a meta-analysis and meta-regression analysis of the prevalence of ADHD in 6689 SUD patients; a cross-sectional study of the prevalence of ADHD and several other psychiatric disorders in 193 methadon maintenance patients, and finally a study in which the availability and occupation of dopamine transporters before and after methylphenidate treatment were measured using SPECT scans in 24 ADHD patients with and without cocaine addiction. The prevalence of ADHD in SUD patients is estimated to be 23.1% (95% confidence interval 19.4-27.2). This prevalence is influenced by the diagnostic instrument for ADHD and by the substance of abuse: cocaine is associated with a lower ADHD prevalence than other substances. The prevalence found among methadone maintenance patients was similar, namely 24.9%; additional comorbid psychiatric disorders were also frequently present. In the imaging study, lower availability of dopamine transporters and lower occupation by methylphenidate were found in cocaine-dependent ADHD patients than in ADHD patients without SUD. These studies confirm the high prevalence of ADHD in SUD patients, and provide a possible explanation for the reduced efficacy of methylphenidate in this patient population.

  19. 75 FR 79404 - Controlled Substances: Established Initial Aggregate Production Quotas for 2011

    Science.gov (United States)

    2010-12-20

    ...), dihydromorphine, fentanyl, gamma hydroxybutyric acid, heroin, hydrocodone, hydromorphone, marihuana, meperidine..., gamma hydroxybutyric acid, heroin, hydrocodone, hydromorphone, marihuana, meperidine, methylphenidate... Hydromorphinol 2 g Hydroxypethidine 2 g Ibogaine 5 g Lysergic acid diethylamide (LSD).... 16 g Marihuana 21,000 g...

  20. Reduced striatal brain volumes in non-medicated adult ADHD patients with comorbid cocaine dependence

    NARCIS (Netherlands)

    van Wingen, G.A.; van den Brink, W.; Veltman, D.J.; Schmaal, L.; Dom, G.; Booij, J.; Crunelle, C.L.

    2013-01-01

    Background: Adult attention deficit/hyperactivity disorder (ADHD) is highly comorbid with other psychiatric disorders, including substance use disorders (SUD). Patients with ADHD and SUD comorbidity respond less well to pharmacological treatment (e.g., methylphenidate), have more severe ADHD

  1. Osmotic Release Oral System Methylphenidate Versus Atomoxetine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Chinese Youth: 8-Week Comparative Efficacy and 1-Year Follow-Up.

    Science.gov (United States)

    Su, Yi; Yang, Li; Stein, Mark A; Cao, Qingjiu; Wang, Yufeng

    2016-05-01

    The purpose of this study was to compare the short-term efficacy, tolerability, and 1-year adherence in Chinese children and adolescents with attention-deficit/hyperactivity disorder (ADHD) treated with either osmotic release oral system methylphenidate (OROS MPH) or atomoxetine (ATX). Children and adolescents meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for ADHD were randomly assigned to receive either OROS MPH (n = 119) or ATX (n = 118). Participants underwent a 1-4 week dose titration period to determine optimal dose, and then were maintained on that dose for 4 weeks (maintenance period). Assessment for efficacy was conducted every week over the titration period and at the end of the maintenance period. The primary efficacy measure was the investigator-rated total ADHD Rating Scale-IV (ADHD-RS-IV) score. Response was further classified as remission (ADHD-RS-IV [18 or 9 items] average score ≤1), robust improvement (ADHD-RS-IV ≥40% decrease in total score), or improvement (≥ 25% decrease in total score) at the end of maintenance period. Medication adherence (taking medication at least 5 days in 1 week) and reasons for nonadherence were evaluated every week over the titration period, at the end of maintenance period, and then at 3, 6, and 12 months. At the end of maintenance period, both OROS MPH and ATX were associated with significant and similar reductions from baseline in ADHD symptoms. Percentages achieving remission, robust improvement, and improvement were comparable for OROS MPH and ATX treatment (35.3% vs. 37.1%, 45.4% vs. 44.8%, 65.5% vs. 66.4%). Medication use decreased over time for both treatments; however, at end of maintenance period, 3 month, 6 month, and 1 year follow-ups, subjects in the OROS MPH group were more likely to be compliant with treatment (74.8%, 50.4%, 38.7%, and 21.8% for OROS MPH vs. 52.5%, 33.9%, 12.7%, and 3.4% for ATX) ( p < 0.05). The most common reasons for

  2. Mathematical model of dopamine autoreceptors and uptake inhibitors and their influence on tonic and phasic dopamine signaling

    DEFF Research Database (Denmark)

    Dreyer, Jakob Kristoffer Kisbye; Hounsgaard, Jørn Dybkjær

    2013-01-01

    autoreceptors influence the behavioral effect of cocaine and methylphenidate and may be the target of antipsychotic medications such as haloperidol. DA autoreceptors are active at two levels: Somatodendritic autoreceptors mainly influence firing rate of DA neurons, and presynaptic autoreceptors control release...

  3. Reduced striatal brain volumes in non-medicated adult ADHD patients with comorbid cocaine dependence

    NARCIS (Netherlands)

    van Wingen, Guido A.; van den Brink, Wim; Veltman, Dick J.; Schmaal, Lianne; Dom, Geert; Booij, Jan; Crunelle, Cleo L.

    2013-01-01

    Adult attention deficit/hyperactivity disorder (ADHD) is highly comorbid with other psychiatric disorders, including substance use disorders (SUD). Patients with ADHD and SUD comorbidity respond less well to pharmacological treatment (e.g., methylphenidate), have more severe ADHD symptoms, and are

  4. Meta-Analysis: Treatment of Attention-Deficit/Hyperactivity Disorder in Children with Comorbod Tic Disorders

    Science.gov (United States)

    Bloch, Michael H.; Panza, Kaitlyn E.; Landeros-Weisenberger, Angeli; Leckman, James F.

    2009-01-01

    Methylphenidate appears to provide the greatest and most immediate improvement of the symptoms of attention deficit hyperactivity disorder and does not appear to worsen tic symptoms based on a meta-analysis study. The meta-analysis included nine studies with 477 subjects.

  5. Prepotent response inhibition predicts treatment outcome in attention deficit/hyperactivity disorder

    NARCIS (Netherlands)

    van der Oord, S.; Geurts, H.M.; Prins, P.J.M.; Emmelkamp, P.M.G.; Oosterlaan, J.

    2012-01-01

    Objective: Inhibition deficits, including deficits in prepotent response inhibition and interference control, are core deficits in ADHD. The predictive value of prepotent response inhibition and interference control was assessed for outcome in a 10-week treatment trial with methylphenidate. Methods:

  6. Chronic exposure to MDMA (Ecstasy elicits behavioral sensitization in rats but fails to induce cross-sensitization to other psychostimulants

    Directory of Open Access Journals (Sweden)

    Swann Alan C

    2006-01-01

    Full Text Available Abstract Background The recreational use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy among adolescents and young adults has become increasingly prevalent in recent years. While evidence suggests that the long-term consequences of MDMA use include neurodegeneration to serotonergic and, possibly, dopaminergic pathways, little is known about susceptibility, such as behavioral sensitization, to MDMA. Methods The objectives of this study were to examine the dose-response characteristics of acute and chronic MDMA administration in rats and to determine whether MDMA elicits behavioral sensitization and whether it cross-sensitizes with amphetamine and methylphenidate. Adult male Sprague-Dawley rats were randomly divided into three MDMA dosage groups (2.5 mg/kg, 5.0 mg/kg, and 10.0 mg/kg and a saline control group (N = 9/group. All three MDMA groups were treated for six consecutive days, followed by a 5-day washout, and subsequently re-challenged with their respective doses of MDMA (day 13. Rats were then given an additional 25-day washout period, and re-challenged (day 38 with similar MDMA doses as before followed by either 0.6 mg/kg amphetamine or 2.5 mg/kg methylphenidate on the next day (day 39. Open-field locomotor activity was recorded using a computerized automated activity monitoring system. Results Acute injection of 2.5 mg/kg MDMA showed no significant difference in locomotor activity from rats given saline (control group, while animals receiving acute 5.0 mg/kg or 10.0 mg/kg MDMA showed significant increases in locomotor activity. Rats treated chronically with 5.0 mg/kg and 10.0 mg/kg MDMA doses exhibited an augmented response, i.e., behavioral sensitization, on experimental day 13 in at least one locomotor index. On experimental day 38, all three MDMA groups demonstrated sensitization to MDMA in at least one locomotor index. Amphetamine and methylphenidate administration to MDMA-sensitized animals did not elicit any significant change

  7. Reports of Perceived Adverse Events of Stimulant Medication on Cognition, Motivation, and Mood: Qualitative Investigation and the Generation of Items for the Medication and Cognition Rating Scale

    NARCIS (Netherlands)

    Kovshoff, H.; Banaschewski, T.; Buitelaar, J.K.; Carucci, S.; Coghill, D.; Danckaerts, M.; Dittmann, R.W.; Falissard, B.; Grimshaw, D.G.; Hollis, C.; Inglis, S.; Konrad, K.; Liddle, E.; McCarthy, S.; Nagy, P.; Thompson, M.; Wong, I.C.; Zuddas, A.; Sonuga-Barke, E.J.

    2016-01-01

    OBJECTIVE: There is no questionnaire to specifically monitor perceived adverse events of methylphenidate (MPH) on cognition, motivation, and mood. The current study therefore had two goals. First, to harvest accounts of such putative events from transcripts of interviews in samples enriched for such

  8. Striatal dysfunction in attention deficit and hyperkinetic disorder

    International Nuclear Information System (INIS)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD

  9. FACTORS INFLUENCING THE MANAGEMENT OF ADHD

    Directory of Open Access Journals (Sweden)

    S ARMAN

    2003-03-01

    Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHDis the most common psychiatric disorder among school age children. It consists of hyperactivity, inattention and impulsive behavior. The onset of the disorder is before the age of 7 years and it happens at least in two situations. It causes significant impairment in social and academic functioning. A determination of factors that influences the therapeutic response in ADHD is the aim of this study. Methods: This study is designed as an analytic descriptive on hyperactive children. The tools that were used was the interview with parents and it provided CSI-4 checklist. Results: Methylphenidate was completely effective in ADHD and oppositional defiant disorder and was effective in majority sign of conduct disorder. There wasn't any relation between therapeutic response and demographic characteristics. Discussion: Methylphenidate is effective not only in ADHD but also in mixed ADHD and disruptive behavior.

  10. Striatal dysfunction in attention deficit and hyperkinetic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

  11. Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder.

    Science.gov (United States)

    Wang, Gene-Jack; Volkow, Nora D; Wigal, Timothy; Kollins, Scott H; Newcorn, Jeffrey H; Telang, Frank; Logan, Jean; Jayne, Millard; Wong, Christopher T; Han, Hao; Fowler, Joanna S; Zhu, Wei; Swanson, James M

    2013-01-01

    Brain dopamine dysfunction in attention deficit/hyperactivity disorder (ADHD) could explain why stimulant medications, which increase dopamine signaling, are therapeutically beneficial. However while the acute increases in dopamine induced by stimulant medications have been associated with symptom improvement in ADHD the chronic effects have not been investigated. We used positron emission tomography and [(11)C]cocaine (dopamine transporter radioligand) to measure dopamine transporter availability in the brains of 18 never-medicated adult ADHD subjects prior to and after 12 months of treatment with methylphenidate and in 11 controls who were also scanned twice at 12 months interval but without stimulant medication. Dopamine transporter availability was quantified as non-displaceable binding potential using a kinetic model for reversible ligands. Twelve months of methylphenidate treatment increased striatal dopamine transporter availability in ADHD (caudate, putamen and ventral striatum: +24%, p<0.01); whereas there were no changes in control subjects retested at 12-month interval. Comparisons between controls and ADHD participants revealed no significant difference in dopamine transporter availability prior to treatment but showed higher dopamine transporter availability in ADHD participants than control after long-term treatment (caudate: p<0.007; putamen: p<0.005). Upregulation of dopamine transporter availability during long-term treatment with methylphenidate may decrease treatment efficacy and exacerbate symptoms while not under the effects of the medication. Our findings also suggest that the discrepancies in the literature regarding dopamine transporter availability in ADHD participants (some studies reporting increases, other no changes and other decreases) may reflect, in part, differences in treatment histories.

  12. Prescribing patterns for attention deficit hyperactivity disorder medications among children and adolescents in Korea, 2007-2011

    Directory of Open Access Journals (Sweden)

    Inmyung Song

    2016-10-01

    Full Text Available OBJECTIVES This study analyzed the prevalence of attention deficit hyperactivity disorder (ADHD medication use among children and adolescents in Korea between January 1, 2007 and December 31, 2011. METHODS Using the Korea National Health Insurance claims database, we identified patients between one and 17 years of age who had at least one medical claim for the diagnosis of ADHD (International Classification of Diseases, 10th revision: F90.0. The annual prevalence of ADHD diagnoses was calculated, using national census data from Statistics Korea on the population aged between one and 17 years as the denominator. The prevalence was age-standardized using the 2010 population as the standard population. The number of patients who were treated with methylphenidate and/or atomoxetine and the prevalence of total patients with ADHD that were treated with either drug were also calculated for each year. All analyses were stratified according to gender and age group (1-5 years, 6-12 years, and 13-17 years. RESULTS The number of patients diagnosed with ADHD increased from 72,704 persons (0.71% in 2007 to 85,468 persons (0.93% in 2011. The annual age-standardized prevalence of ADHD diagnoses increased from 0.67% in 2007 to 0.94% in 2011. The prevalence of methylphenidate use among children and adolescents with ADHD decreased from 73.91% in 2007 to 70.33% in 2011, whereas that of atomoxetine use increased from 5.77% in 2009 to 13.09% in 2011. CONCLUSIONS While methylphenidate remains the most commonly prescribed ADHD drug, the use of atomoxetine has increased.

  13. Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats

    Science.gov (United States)

    Bradshaw, Sarah E.; Agster, Kara L.; Waterhouse, Barry D.; McGaughy, Jill A.

    2016-01-01

    Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct subregions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. PMID:26774596

  14. Priapism associated with the use of stimulant medications and atomoxetine for attention-deficit/hyperactivity disorder in children.

    Science.gov (United States)

    Eiland, Lea S; Bell, Edward A; Erramouspe, John

    2014-10-01

    To review the association of priapism with stimulant medications and atomoxetine commonly used in the treatment of attention-deficit/hyperactivity disorder (ADHD). A comprehensive literature search was conducted through PubMed (1966-May 15, 2014) using the search terms priapism, methylphenidate, amphetamine, atomoxetine, attention-deficit disorder with hyperactivity, and pediatrics. Google Scholar, Scopus, and the Food and Drug Administration (FDA) Web site were also searched. References from identified literature were also reviewed. All identified literature focused on ADHD treatment. Literature regarding priapism caused by methylphenidate, amphetamines, and atomoxetine were included. Stimulant medications and atomoxetine have been linked to the occurrence of priapism in children. Specifically, methylphenidate has been implicated in a recent FDA safety announcement warning as a result of 15 case reports (mean age = 12.5 years), and thus, the drug label and medication guides have been updated to reflect this concern. Prolonged erections and priapism occurred with immediate- and long-acting products, dose increases, and drug withdrawal periods. Priapism has also occurred in 4 patients taking amphetamines and one 11-year-old patient taking atomoxetine for ADHD. Priapism has been associated with stimulants, amphetamines, and atomoxetine use for ADHD in children. Providers and health care practitioners should educate male patients prescribed these ADHD medications as well as caregivers regarding the signs, symptoms, and complications with priapism. Discontinuation and evaluation of the medication is warranted if this adverse drug reaction occurs. Depending on the priapism subtype, other products may be initiated or medications not associated with priapism may be utilized. © The Author(s) 2014.

  15. Psychotic Symptoms Associated with the use of Dopaminergic Drugs, in Patients with Cocaine Dependence or Abuse.

    Science.gov (United States)

    Roncero, Carlos; Abad, Alfonso C; Padilla-Mata, Antonio; Ros-Cucurull, Elena; Barral, Carmen; Casas, Miquel; Grau-López, Lara

    2017-01-01

    In the field of dual diagnosis, physicians are frequently presented with pharmacological questions. Questions about the risk of developing psychotic symptoms in cocaine users who need treatment with dopaminergic drugs could lead to an undertreatment. Review the presence of psychotic symptoms in patients with cocaine abuse/dependence, in treatment with dopaminergic drugs. Systematic PubMed searches were conducted including December 2014, using the keywords: "cocaine", dopaminergic drug ("disulfuram-methylphenidate-bupropion-bromocriptine-sibutramineapomorphine- caffeine") and ("psychosis-psychotic symptoms-delusional-paranoia"). Articles in English, Spanish, Portuguese, French, and Italian were included. Articles in which there was no history of cocaine abuse/dependence, absence of psychotic symptoms, systematic reviews, and animal studies, were excluded. 313 papers were reviewed. 7 articles fulfilled the inclusion-exclusion criteria. There is a clinical trial including 8 cocaine-dependent patients using disulfiram in which 3 of them presented psychotic symptoms and 6 case-reports: disulfuram (1), methylphenidate (1), disulfiram with methylphenidate (2), and bupropion (2), reporting psychotic symptoms, especially delusions of reference and persecutory ideation. Few cases have been described, which suggests that the appearance of these symptoms is infrequent. The synergy of dopaminergic effects or the dopaminergic sensitization in chronic consumption are the explanatory theories proposed by the authors. In these cases, a relationship was found between taking these drugs and the appearance of psychotic symptoms. Given the low number of studies found, further research is required. The risk of psychotic symptoms seems to be acceptable if we compare it with the benefits for the patients but a closer monitoring seems to be advisable.

  16. The SPECT tracer [{sup 123}I]ADAM binds selectively to serotonin transporters: a double-blind, placebo-controlled study in healthy young men

    Energy Technology Data Exchange (ETDEWEB)

    Giessen, Elsmarieke van de [University of Amsterdam, Academic Medical Center, Graduate School Neurosciences Amsterdam, Department of Nuclear Medicine, Amsterdam (Netherlands); Booij, Jan [University of Amsterdam, Academic Medical Center, Graduate School Neurosciences Amsterdam, Department of Nuclear Medicine, Amsterdam (Netherlands); University of Amsterdam, Academic Medical Center, Department of Nuclear Medicine, F2-236, Amsterdam (Netherlands)

    2010-08-15

    The tracer {sup 123}I-2-([2-({l_brace}dimethylamino{r_brace}methyl)phenyl]thio)-5-iodophenylamine ([{sup 123}I]ADAM) has been developed to image serotonin transporters (SERTs) with SPECT. Preclinical studies have shown that [{sup 123}I]ADAM binds selectively to SERTs. Moreover, initial human studies have shown that [{sup 123}I]ADAM binding could be blocked by selective serotonin reuptake inhibitors (SSRIs). However, in humans it has not been proven that [{sup 123}I]ADAM binds selectively to SERTs. We examined the in vivo availability of SERTs in 12 healthy young volunteers 5 h after bolus injection of [{sup 123}I]ADAM. To evaluate the selectivity of binding, four participants were pretreated (double-blinded design) with placebo, four with paroxetine (20 mg) and four with the dopamine/norepinephrine blocker methylphenidate (20 mg). SPECT studies were performed on a brain-dedicated system (Neurofocus), and the SPECT images were coregistered with individual MR scans of the brain. ADAM binding in SERT-rich brain areas and cerebellar cortex (representing non-specific binding) was assessed by drawing regions of interest (ROIs) on the individual MR images. Specific to non-specific ratios were used as the outcome measure. We found that specific to non-specific ratios were statistically significantly lower in paroxetine-pretreated participants than in placebo- or methylphenidate-pretreated participants. No such difference was found between groups pretreated with placebo or methylphenidate. Our preliminary findings suggest that [{sup 123}I]ADAM binds selectively to SERTs in human brain. (orig.)

  17. Premature responding is associated with approach to a food cue in male and female heterogeneous stock rats.

    Science.gov (United States)

    King, Christopher P; Palmer, Abraham A; Woods, Leah C Solberg; Hawk, Larry W; Richards, Jerry B; Meyer, Paul J

    2016-07-01

    Disorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues. To determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed. In the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pretreated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as "sign-trackers" and "goal-trackers" using an index based on these measures. Sign-trackers made more premature responses than goal-trackers but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration. These results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors.

  18. Methylphenidatinduceret ST-elevations-myokardieinfarkt

    DEFF Research Database (Denmark)

    Ruwald, Martin Huth; Ruwald, Anne-Christine Huth; Tønder, Niels

    2012-01-01

    Adult attention deficit and hyperkinetic disorder (ADHD) is increasingly diagnosed and treated with methylphenidate. We present the case of an 20 year-old man, who was diagnosed with ADHD and suffered a ST elevation acute myocardial infarction due to coronary vasospasm related to an overdose...

  19. 76 FR 77257 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-12-12

    ...), this is notice that on September 15, 2011, Johnson Matthey Pharma Services, 70 Flagship Drive, North... Schedule Amphetamine (1100) II Methylphenidate (1724) II Hydrocodone (9193) II The company plans to utilize... conduct analytical testing in support of the company's primary manufacturing facility in West Deptford...

  20. 76 FR 25376 - Manufacturer of Controlled Substances; Notice of Application

    Science.gov (United States)

    2011-05-04

    ...), this is notice that on January 5, 2011, Johnson Matthey Pharma Services, 70 Flagship Drive, North... Schedule Amphetamine (1100) II Methylphenidate (1724) II Hydrocodone (9193) II The company plans to utilize... conduct analytical testing in support of the company's primary manufacturing facility in West Deptford...