Second-generation long-acting injectable antipsychotics in schizophrenia: patient functioning and quality of life

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Montemagni C

2016-04-01

Full Text Available Cristiana Montemagni,1,2 Tiziana Frieri,1,2 Paola Rocca1,2 1Department of Neuroscience, Unit of Psychiatry, University of Turin, 2Department of Mental Health, Azienda Sanitaria Locale (ASL Torino 1 (TO1, Azienda Ospedaliero-Universitaria (AOU Città della Salute e della Scienza di Torino, Turin, Italy Abstract: Long-acting injectable antipsychotics (LAIs were developed to make treatment easier, improve adherence, and/or signal the clinician when nonadherence occurs. Second-generation antipsychotic LAIs (SGA-LAIs combine the advantages of SGA with a long-acting formulation. The purpose of this review is to evaluate the available literature concerning the impact of SGA-LAIs on patient functioning and quality of life (QOL. Although several studies regarding schizophrenia patients’ functioning and QOL have been performed, the quantity of available data still varies greatly depending on the SGA-LAI under investigation. After reviewing the literature, it seems that SGA-LAIs are effective in ameliorating patient functioning and/or QOL of patients with schizophrenia, as compared with placebo. However, while methodological design controversy exists regarding the superiority of risperidone LAI versus oral antipsychotics, the significant amount of evidence in recently published research demonstrates the beneficial influence of risperidone LAI on patient functioning and QOL in stable patients and no benefit over oral treatment in unstable patients. However, the status of the research on SGA-LAIs is lacking in several aspects that may help physicians in choosing the correct drug therapy. Meaningful differences have been observed between SGA-LAIs in the onset of their clinical efficacy and in the relationships between symptoms and functioning scores. Moreover, head-to-head studies comparing the effects of SGA-LAIs on classical measures of psychopathology and functioning are available mainly on risperidone LAI, while those comparing olanzapine LAI with other

Use of second-generation antipsychotics in the acute inpatient management of schizophrenia in the Middle East

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Alkhadhari S

2015-04-01

Full Text Available Sulaiman Alkhadhari,1 Nasser Al Zain,2 Tarek Darwish,3 Suhail Khan,4 Tarek Okasha,5 Hisham Ramy,5 Talaat Matar Tadros6 1Kuwait Center for Mental Health, Safat, Kuwait; 2Al Amal Complex for Mental Health Hospital, Dammam, Saudi Arabia; 3Behavioural Science Pavilion, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 4Jeddah Psychiatric Hospital, Jeddah, Saudi Arabia; 5Institute of Psychiatry, Ain Shams University, Cairo, Egypt; 6Ibrahim Bin Hamad Obaidallah and Seif Bin Ghubash Hospitals, Ras Alkhaimah, United Arab Emirates Background: Management of acute psychotic episodes in schizophrenic patients remains a significant challenge for clinicians. Despite treatment guidelines recommending that second-generation antipsychotics (SGAs should be used as monotherapy, first-generation antipsychotics, polypharmacy, and lower than recommended doses are frequently administered in clinical practice. Minimal data exist regarding the use of SGAs in the Middle East. The objective of this study was to examine the discrepancies between current clinical practice and guideline recommendations in the region. Methods: RECONNECT-S Beta was a multicenter, noninterventional study conducted in Egypt, Kuwait, Saudi Arabia, and the United Arab Emirates to observe the management of schizophrenic patients who were hospitalized due to an acute psychotic episode. Patients underwent one visit on the day of discharge. Demographic and medical history, together with data on antipsychotic treatment and concomitant medication during the hospitalization period and medication recommendations at discharge were recorded. Results: Of the 1,057 patients, 180 (17.0% and 692 (65.5% received SGAs as monotherapy and in combination therapy, respectively. Overall, the most frequently administered medications were given orally, and included risperidone (40.3%, olanzapine (32.5%, and quetiapine (24.6%; the doses administered varied between countries and deviated from the recommended

Movement side effects of antipsychotic drugs in adults with and without intellectual disability: UK population-based cohort study.

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Sheehan, Rory; Horsfall, Laura; Strydom, André; Osborn, David; Walters, Kate; Hassiotis, Angela

2017-08-03

To measure the incidence of movement side effects of antipsychotic drugs in adults with intellectual disability and compare rates with adults without intellectual disability. Cohort study using data from The Health Improvement Network. UK primary care. Adults with intellectual disability prescribed antipsychotic drugs matched to a control group of adults without intellectual disability prescribed antipsychotic drugs. New records of movement side effect including acute dystonias, akathisia, parkinsonism, tardive dyskinaesia and neuroleptic malignant syndrome. 9013 adults with intellectual disability and a control cohort of 34 242 adults without intellectual disability together contributed 148 709 person-years data. The overall incidence of recorded movement side effects was 275 per 10 000 person-years (95% CI 256 to 296) in the intellectual disability group and 248 per 10 000 person-years (95% CI 237 to 260) in the control group. The incidence of any recorded movement side effect was significantly greater in people with intellectual disability compared with those without (incidence rate ratio 1.30, 95% CI 1.18 to 1.42, pmovement side effects between the groups were not due to differences in the proportions prescribed first and second-generation antipsychotic drugs. This study provides evidence to substantiate the long-held assumption that people with intellectual disability are more susceptible to movement side effects of antipsychotic drugs. Assessment for movement side effects should be integral to antipsychotic drug monitoring in people with intellectual disability. Regular medication review is essential to ensure optimal prescribing in this group. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Interaction between anti-Alzheimer and antipsychotic drugs in modulating extrapyramidal motor disorders in mice

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Saki Shimizu

2015-04-01

Full Text Available Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat the behavioral and psychological symptoms of dementia (BPSD. Here, we examined the effects of cholinesterase inhibitors (ChEIs, donepezil and galantamine, on antipsychotic-induced extrapyramidal side effects (EPS in mice. The effects of serotonergic agents on the EPS drug interaction were also evaluated. Donepezil (0.3–3 mg/kg did not induce EPS signs by itself; however, it significantly potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg in dose-dependent and synergistic manners. Galantamine (0.3–3 mg/kg elicited mild bradykinesia at a high dose and dose-dependently augmented haloperidol-induced bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl (a muscarinic antagonist, but not by mecamylamine (a nicotinic antagonist. In addition, the bradykinesia potentiation by galantamine was significantly reduced by (±-8-hydroxy-2-(di-n-propylamino-tetralin (a 5-HT1A agonist, ritanserin (a 5-HT2 antagonist, and SB-258585 (a 5-HT6 antagonist. The present results give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in the treatment of BPSD. In addition, second generation antipsychotics, which can stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be favorable as an adjunctive therapy for BPSD.

Pharmacokinetic-pharmacodynamic modelling of antipsychotic drugs in patients with schizophrenia : Part II: The use of subscales of the PANSS score

NARCIS (Netherlands)

Reddy, Venkatesh Pilla; Kozielska, Magdalena; Suleiman, Ahmed Abbas; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

Background and objectives: The superiority of atypical antipsychotics (also known as second-generation antipsychotics (SGAs)) over typical antipsychotics (first generation antipsychotics (FGAs)) for negative symptom control in schizophrenic patients is widely debated. The objective of this study was

Hypothermia following antipsychotic drug use

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Marum, R.J. van; Wegewijs, M.A.; Loonen, A.J.M.; Beers, E.

2007-01-01

Objective: Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Method: Case reports of hypothermia in APD-users found

Effect of second-generation antipsychotics on employment and productivity in individuals with schizophrenia: an economic perspective.

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Percudani, Mauro; Barbui, Corrado; Tansella, Michele

2004-01-01

Schizophrenia is a serious mental illness that imposes a considerable burden not only on those who are ill, but also on their families, neighbours and the wider society. Costs associated with treating people with schizophrenia are those derived from the use of a wide range of services provided by public psychiatric facilities and/or by voluntary and private agencies. In addition, a large part of the economic impact of schizophrenia is related to the difficulties that patients encounter in finding and keeping paid employment. The introduction of second-generation antipsychotics (SGAs), also defined as atypicals, has increased the therapeutic options available for individuals with schizophrenia. Potential benefits of these agents include a more favourable profile in terms of positive and negative symptoms, less adverse effects and better cognitive functioning than first-generation antipsychotics (FGAs). As a consequence, SGAs might favourably affect the capacity, seriously impaired in schizophrenia, of finding and keeping paid employment. To date, only 13 published studies have investigated the effect of SGA agents on employment and work productivity. Clozapine was studied in eight studies, while both olanzapine and risperidone were studied in three. Clozapine emerged as the SGA with at least some effect on work status. However, all but one clozapine study enrolled only a few individuals and did not adopt an experimental design, making it very difficult to judge the validity and generalisability of findings. Taken together, studies found little benefit, in terms of employment and work productivity, for the use of SGAs compared with FGAs. The evidence available suggests that until data demonstrate a robust effect of newer agents on employment, it remains mandatory for mental health professionals to use the most effective drug treatment together with non-pharmacological interventions, such as vocational rehabilitative programmes nested into models of community

Hypothermia following antipsychotic drug use

NARCIS (Netherlands)

van Marum, Rob J.; Wegewijs, Michelle A.; Loonen, Anton J. M.; Beers, Erna

Objective Hypothermia is an adverse drug reaction (ADR) of antipsychotic drug (APD) use. Risk factors for hypothermia in ADP users are unknown. We studied which risk factors for hypothermia can be identified based on case reports. Methods Case reports of hypothermia in APD-users found in PUBMED or

Second-generation antipsychotic use in children and adolescents: a six-month prospective cohort study in drug-naïve patients.

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Arango, Celso; Giráldez, Miriam; Merchán-Naranjo, Jessica; Baeza, Inmaculada; Castro-Fornieles, Josefina; Alda, Jose-Angel; Martínez-Cantarero, Carmen; Moreno, Carmen; de Andrés, Pilar; Cuerda, Cristina; de la Serna, Elena; Correll, Christoph U; Fraguas, David; Parellada, Mara

2014-11-01

To assess weight and metabolic effects of 6 months of treatment with second-generation antipsychotics in naïve/quasi-naïve youths. This study looked at a nonrandomized, naturalistic, multicenter, inception cohort study of 279 patients aged 4 to 17 years (mean = 14.6 ± 2.9 years). Of those, 248 (88.8%) received a single antipsychotic (risperidone, olanzapine, or quetiapine) and completed 2 visits, and 178 (63.8%) completed the 6-month follow-up. Patients had schizophrenia-spectrum disorders (44.5%), mood-spectrum disorders (23.2%), disruptive behavioral disorders (17.3%), or other disorders (15.1%). Fifteen age- and gender-matched, healthy, nonmedicated individuals served as a comparison group. From baseline to 1 month, 3 months, and 6 months, all anthropometric measures increased significantly with each antipsychotic, that is, 6-month changes with risperidone (n = 157; 7.1 kg and 0.66 body mass index [BMI] z score), olanzapine (n = 44; 11.5 kg and 1.08 BMI z score), and quetiapine (n = 47; 6.3 kg and 0.54 BMI z score), but not in healthy control participants (-0.11 kg and 0.006 BMI z score). Fasting metabolic parameters increased significantly with risperidone (glucose [3.8] mg/dL, insulin [4.9] mU/L, homeostasis model assessment of insulin resistance [HOMA-IR: 1.2], triglycerides [15.6] mg/dL), and olanzapine (glucose [5.0] mg/dL, total cholesterol [21.2] mg/dL, and low-density lipoprotein cholesterol [44.6] mg/dL), but not with quetiapine or in healthy control participants. The percentage of research participants considered to be "at risk of adverse health outcome" increased during the 6 months from 8.9% to 29.2% for risperidone (p < .0001), 6.8% to 38.1% for olanzapine (p < .0001), and 6.3% to 4.0% for quetiapine (p = .91). Olanzapine, quetiapine, and risperidone increase body weight but have different cardiometabolic side effect profiles and different temporal side effect patterns. Copyright © 2014 American Academy of Child and Adolescent

Novel versus conventional antipsychotic drugs.

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Love, R C

1996-01-01

Novel antipsychotic agents differ from conventional ones in several key characteristics, including effectiveness, adverse reactions, and receptor-binding profile. Most of the newer agents have an affinity for the serotonin 5HT2 receptor that is at least 10 times greater than that for the dopamine D2 receptor. This increased affinity for the serotonin receptor may be responsible for another distinguishing characteristic of novel antipsychotic agents--decreased frequency of extrapyramidal side effects. These side effects, which include pseudoparkinsonism, acute dystonias, and akathisia, frequently are the reason for noncompliance with conventional drug therapy. The newer drugs are often effective in patients resistant to treatment with conventional agents. They also appear to reduce the negative symptoms of schizophrenia in many patients.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

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Solmi M

2017-06-01

Full Text Available Marco Solmi,1,2 Andrea Murru,3 Isabella Pacchiarotti,3 Juan Undurraga,4,5 Nicola Veronese,2,6 Michele Fornaro,7,8 Brendon Stubbs,2,9–11 Francesco Monaco,2 Eduard Vieta,3 Mary V Seeman,12 Christoph U Correll,13,14 André F Carvalho2,15 1Neuroscience Department, University of Padua, 2Institute for Clinical Research and Education in Medicine, Padua, Italy; 3Bipolar Disorders Unit, Institute of Neuroscience, Hospital Clínic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; 4Department of Psychiatry, Faculty of Medicine, Clínica Alemana Universidad del Desarrollo, 5Early Intervention Program, J. Horwitz Psychiatric Institute, Santiago, Chile; 6National Research Council, Ageing Section, Padua, 7Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, School of Medicine, University “Federico II”, Naples, Italy; 8New York State Psychiatric Institute, Columbia University, New York, NY, USA; 9Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 10Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, 11Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, UK; 12Institute of Medical Science, Toronto, ON, Canada; 13Department of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, Glen Oaks, 14Department of Psychiatry and Molecular Medicine Hempstead, Hofstra Northwell School of Medicine, Hempstead, NY, USA; 15Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil Abstract: Since the discovery of chlorpromazine (CPZ in 1952, first-generation antipsychotics (FGAs have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI to be treated in the community. Second-generation

Treatment patterns in Medicaid patients with schizophrenia initiated on a first- or second-generation long-acting injectable versus oral antipsychotic

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Pilon D

2017-03-01

Full Text Available Dominic Pilon,1 Kruti Joshi,2 Neeta Tandon,2 Marie-Hélène Lafeuille,1 Rhiannon L Kamstra,1 Bruno Emond,1 Patrick Lefebvre2 1Groupe d’analyse, Ltée, Montréal, QC, Canada; 2Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: Poor antipsychotic (AP adherence is a key issue in patients with schizophrenia. First-generation antipsychotic (FGA and second-generation antipsychotic (SGA long-acting injectable therapies (LAI may improve adherence compared to oral antipsychotics (OAP. The objective of the study was to compare treatment adherence and persistence in Medicaid patients with schizophrenia initiated on first-generation long-acting injectable therapies (FGA-LAI or second-generation long-acting injectable therapies (SGA-LAI versus OAP.Methods: Adults with schizophrenia initiated on FGA-LAI, SGA-LAI, or OAP on or after January 2010 were identified using a six-state Medicaid database (January 2009– March 2015. Outcomes were assessed during the 12 months following treatment initiation. Index medication adherence was assessed using the proportion of days covered ≥80%, while persistence was assessed as no gap of ≥30, ≥60, or ≥90 days between days of supply. Outcomes were compared between FGA/SGA-LAI and OAP cohorts using chi-squared tests and adjusted odds ratios (OR.Results: During follow-up, AP polypharmacy was more common in FGA-LAI patients (N=1,089; 36%; P=0.029 and less common in SGA-LAI patients (N=2,209; 27%; P<0.001 versus OAP patients (N=20,478; 33%. After adjustment, SGA-LAI patients had 24% higher odds of adherence at 12 months (OR: 1.24; P<0.001, in contrast to FGA-LAI patients who had 48% lower odds of adherence (OR: 0.52; P<0.001 relative to OAP patients. SGA-LAI patients were more likely to be persistent (no gap ≥60 days at 12 months than OAP patients (37% vs 30%; P<0.001, but not FGA-LAI patients (31% vs 30%; P=0.776. In comparison to OAP patients, SGA-LAI patients had 46% higher adjusted odds of

Weight gain with add-on second-generation antipsychotics in bipolar disorder: a naturalistic study.

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Najar, H; Joas, E; Kardell, M; Pålsson, E; Landén, M

2017-06-01

Our aim was to investigate the prevalence and magnitude of weight gain in-patients with bipolar disorder when treated with a second-generation antipsychotic as an add-on treatment to a mood stabilizer in routine clinical practice. Data were derived from the quality register for bipolar disorder in Sweden (BipoläR). Patients with bipolar disorder who started add-on treatment with a SGA (n = 575) were compared at next yearly follow-up with age and sex matched patients who were only treated with a mood stabilizer (n = 566). The primary outcome measure was change in body weight and body mass index (BMI). We also assessed the prevalence of clinically significant weight gain defined as ≥7% gain in body weight. The group that received add-on treatment with antipsychotics neither gained more weight nor were at higher risk for a clinically significant weight gain than the reference group. Instead, factors associated with clinically significant weight gain were female sex, young age, low-baseline BMI, and occurrence of manic/hypomanic episodes. We found no evidence of an overall increased risk of weight gain for patients with bipolar disorder after receiving add-on SGA to a mood stabilizer in a routine clinical setting. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A critical assessment of antipsychotic drug monitoring.

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Waraska, J; Nagle, J D

1987-06-01

Analytic problems associated with monitoring antipsychotic drug levels have largely been resolved. Despite the establishment of target values for some drugs, the clinical utility of such levels remains to be determined.

Antipsychotic drug treatment for patients with schizophrenia: theoretical background, clinical considerations and patients preferences

DEFF Research Database (Denmark)

Nielsen, René Ernst; Nielsen, Jimmi

2009-01-01

  The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side......-effects have arisen as the new challenge. The basis of successful pharmacological treatment is a fundamental understanding of the mechanisms of action, the desired effects and side-effects of antipsychotic drugs, a good relationship with the patient and a thorough monitoring of the patient before and during...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ...

Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

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Pompili, Maurizio; Baldessarini, Ross J.; Forte, Alberto; Erbuto, Denise; Serafini, Gianluca; Fiorillo, Andrea; Amore, Mario; Girardi, Paolo

2016-01-01

Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior. PMID:27727180

Do Atypical Antipsychotics Have Antisuicidal Effects? A Hypothesis-Generating Overview

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Maurizio Pompili

2016-10-01

Full Text Available Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia. We carried out a systematic, computerized search for reports of studies involving antipsychotic drug treatment and suicidal behaviors. A total of 19 reports provide data with preliminary support for potential suicide risk-reducing effects of olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in addition to clozapine, and provide some support for antipsychotic drug treatment in general. These preliminary findings encourage further testing of antipsychotics for effects on suicidal behavior, making use of explicit, pre-planned assessments of suicidal behavior.

Determination of antipsychotic drug in human serum by radioreceptor assay

International Nuclear Information System (INIS)

Wu Jinchang; Jiang Yimin

1989-01-01

Serum antipsychotic drug in 50 psychosis cases were measured by radioreceptor assay (RRA) and the values were compared in parallel with that by radioimmunoassay (RIA). The results showed that the RRA values were lower than the RIA values, but both assays gave significant correlation between the serum drug level and antipsychotic dose

Antipsychotic drugs a last resort for these 5 conditions (ADHD, Anxiety, Depression, Insomnia and PTSD)

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... more about antipsychotic drugs, see these additional Best Buy Drugs reports. ■ Use of Antipsychotic Drugs in Children ■ Antipsychotic ... depression with antidepressant medication, see our FREE Best Buy Drugs report here . For more about augmentation therapy with ...

Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug

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Zuardi A.W.

2006-01-01

Full Text Available A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis component, induces anxiety and psychotic-like symptoms in healthy volunteers. These effects of delta9-tetrahydrocannabinol are significantly reduced by cannabidiol (CBD, a cannabis constituent which is devoid of the typical effects of the plant. This observation led us to suspect that CBD could have anxiolytic and/or antipsychotic actions. Studies in animal models and in healthy volunteers clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like properties of CBD have been investigated in animal models using behavioral and neurochemical techniques which suggested that CBD has a pharmacological profile similar to that of atypical antipsychotic drugs. The results of two studies on healthy volunteers using perception of binocular depth inversion and ketamine-induced psychotic symptoms supported the proposal of the antipsychotic-like properties of CBD. In addition, open case reports of schizophrenic patients treated with CBD and a preliminary report of a controlled clinical trial comparing CBD with an atypical antipsychotic drug have confirmed that this cannabinoid can be a safe and well-tolerated alternative treatment for schizophrenia. Future studies of CBD in other psychotic conditions such as bipolar disorder and comparative studies of its antipsychotic effects with those produced by clozapine in schizophrenic patients are clearly indicated.

Mental disorder diagnoses among children and adolescents who use antipsychotic drugs.

Science.gov (United States)

Nesvåg, Ragnar; Hartz, Ingeborg; Bramness, Jørgen G; Hjellvik, Vidar; Handal, Marte; Skurtveit, Svetlana

2016-09-01

Antipsychotic drugs are used increasingly by children and adolescents and there is concern about off-label use. We aimed to study which substances, and for which mental disorder diagnoses, antipsychotic drugs were prescribed to 0-18-year-old boys and girls in Norway. Linked data from the national health registry for prescription drugs in 2010 and mental disorder diagnoses in 2008-2012 were used to study the prevalence of antipsychotic drug use, the type of antipsychotic drug substances used, mental disorder diagnoses in users and distribution of drugs per diagnostic category across gender. In total, 0.18% of Norwegian children and adolescents were prescribed antipsychotic drugs during 2010, of which there were more boys (0.23%) than girls (0.13%). Risperidone was the most frequently used substance among boys (57.4%) and girls (32.3%), followed by aripiprazole (19.4%) in boys and quetiapine (27.4%) in girls. The most common mental disorder diagnoses among male users were hyperkinetic (49.9%) and autism spectrum disorder (27.1%), while anxiety disorders (41.5%) and depressive illness (33.6%) were most common among female users. A schizophrenia-like psychosis diagnosis was given to 11.1% of the male and 18.2% of the female users. A hyperkinetic disorder was diagnosed among 56.9% and 52.4% of the male risperidone and aripiprazole users, respectively. Among female quetiapine users, 57.1% were diagnosed with anxiety disorders and 52.4% with depressive illness. These results demonstrate that children and adolescents who use antipsychotic drugs are predominantly diagnosed with non-psychotic mental disorders such as hyperkinetic disorder among boys and anxiety disorder or depressive illness among girls. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents : A systematic review of randomized, placebo controlled trials and guidelines for clinical practice

NARCIS (Netherlands)

De Hert, M.; Dobbelaere, M.; Sheridan, E. M.; Cohen, D.; Correll, C. U.

Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still

Geographical Variation in Antipsychotic Drug Use in Elderly Patients with Dementia

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Zakarias, Johanne Købstrup; Jensen-Dahm, Christina; Nørgaard, Ane

2016-01-01

BACKGROUND: Use of antipsychotics in elderly patients with dementia has decreased in the past decade due to safety regulations; however use is still high. Geographical variation may indicate discrepancies in clinical practice and lack of adherence to evidence-based guidelines for the management...... of behavioral symptoms. OBJECTIVE: To investigate potential geographical variances in use of antipsychotic drugs in dementia care. METHODS: A registry-based cross-sectional study in the entire elderly population of Denmark (≥65 years) conducted in 2012. Data included place of residence, prescriptions filled......, and hospital discharge diagnoses. Antipsychotic drug use among elderly with (n = 34,536) and without (n = 931,203) a dementia diagnosis was compared across the five regions and 98 municipalities in Denmark, adjusted for age and sex. RESULTS: In 2012, the national prevalence of antipsychotic drug use was 20...

Association between P-glycoprotein polymorphisms and antipsychotic drug-induced hyperprolactinemia

NARCIS (Netherlands)

Geers, Lisanne; Pozhidaev, Ivan V; Ivanova, Svetlana A.; Freidin, Maxim B.; Cohen, Dan; Boiko, Anastasia S; Osmanova, Diana Z; Fedorenko, Olga Yu; Touw, Daniël; Semke, Arkadiy V.; Wilffert, Berend; Bokhan, Nikolay A.; Loonen, Antonius

2017-01-01

Background: Regular therapy for schizophrenia includes maintenance antipsychotic treatment. Unfortunately, antipsychotics also have a spectrum of side effects, including metabolic, endocrine, cardiovascular, and movement disorders. One of the common side effects of these drugs is hyperprolactinemia

Aripiprazole versus other atypical antipsychotics for schizophrenia

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Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; El-Sayeh, Hany George G; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of other second generation antipsychotics. Objectives To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. Selection criteria We included all randomised trials comparing oral aripiprazole with oral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results The review currently includes four trials with 1404 participants on two out of eight possible comparisons - aripiprazole versus olanzapine and aripiprazole versus risperidone. The overall number of participants leaving the studies early was considerable (38.5%), limiting the validity of the findings, but with no significant differences between groups. Aripiprazole was less efficacious than olanzapine in terms of the general mental state (PANSS total score: n=794, 2 RCTs, MD 4.96 CI 1.85 to 8.06), but it was associated with fewer side

Time Trends in Antipsychotic Drug Use in Patients with Dementia

DEFF Research Database (Denmark)

Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane

2015-01-01

: To investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses......, and somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012...

Adverse drug reactions due to antipsychotics and sedative-hypnotics in the elderly

Directory of Open Access Journals (Sweden)

Natasha S Kate

2015-01-01

Full Text Available Psychotropic drugs are commonly used to manage mental and behavioral problems in geriatric patients. This is, however, accompanied by the risk of developing adverse drug reactions (ADRs, impacting the safety with which the drug can be used. In this article, we provide an overview of the factors associated with the ADRs due to psychotropic medication in the elderly, and the ADRs associated with the use of antipsychotics and sedative-hypnotics in the geriatric population. For this, literature searches were conducted through MEDLINE, PubMed, and Google Scholar using keyword terms: Geriatric, elderly, safety, adverse events, ADRs, antipsychotic, names of individual antipsychotics, benzodiazepine, sedative, hypnotic, zolpidem, zaleplon, zopiclone. Research data indicate that antipsychotics are associated with an increased risk of metabolic syndrome, thromboembolism, cerebrovascular and cardiac events, pneumonia, fractures, and increased mortality. Among antipsychotics, aripiprazole seems to have fewer ADRs while other antipsychotics (typical and atypicals have reports of troublesome side effect profiles. Sedative-hypnotics are associated with a risk of falls, fractures, cognitive impairment, and may increase the risk of developing dementia with long-term use. The risk of these complications is present with both benzodiazepines and medications such as zolpidem and zopiclone.

Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic.

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Citrome, L

2011-02-01

To describe the efficacy and safety of lurasidone for the treatment of schizophrenia. The pivotal registration trials were accessed by querying the literature databases PubMed, EMBASE, ISI Web of Knowledge, as well as http://www.fda.gov and http://www.clinicaltrials.gov for the search term 'lurasidone'. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports, abstracts and posters. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Lurasidone is a second-generation antipsychotic approved for the treatment of schizophrenia at a recommended starting dose of 40 mg/day administered once daily with food (≥350 calories). The maximum recommended dose is 80 mg/day. Regulatory approval was based primarily on a clinical trial programme that included four 6-week randomised clinical trials demonstrating efficacy vs. placebo in acute patients with schizophrenia. One additional Phase II clinical trial was considered a failed study because neither lurasidone nor the active control, haloperidol, separated from placebo on the primary outcome measure. One additional Phase III study was completed after the new drug application was submitted to the US Food and Drug Administration. Efficacy outcomes appear consistently in favour of lurasidone 80 mg/day vs. placebo on multiple measures of psychopathology, however, at least two studies also demonstrated efficacy for the doses of 40 and 120 mg/day. NNT vs. placebo was 3-6 for response as defined by ≥20% reduction in psychopathological rating scale total scores from baseline, depending on the study and the dose. Response as defined by a ≥30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were

Antipsychotic agents: efficacy and safety in schizophrenia

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de Araújo AN

2012-11-01

Full Text Available Arão Nogueira de Araújo,1 Eduardo Pondé de Sena,1,2 Irismar Reis de Oliveira,1,3 Mario F Juruena41Postgraduation Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Neurosciences and Mental Health, School of Medicine, Federal University of Bahia, Salvador, Brazil; 4Stress and Affective Disorders Program, Department of Neuroscience and Behavior, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, BrazilAbstract: Antipsychotics have provided a great improvement in the management of people with schizophrenia. The first generation antipsychotics could establish the possibility of managing many psychotic subjects in an outpatient setting. With the advent of the second (SGA and third generation antipsychotics (TGA, other psychiatric disorders such as bipolar depression, bipolar mania, autism, and major depressive disorder have now been approved for the use of these drugs for their treatment. Also, the administration of more specific assessment tools has allowed for better delineation of the repercussions of these drugs on symptoms and the quality of life of patients who use antipsychotic agents. In general, the SGA share similar mechanisms of action to achieve these results: dopamine-2 receptor antagonism plus serotonin-2A receptor antagonism. The TGA (eg, aripiprazole have partial agonist activity at the dopamine-2 receptor site, and are also called dopaminergic stabilizers. The pharmacological profile of SGA and TGA may provide better efficacy against negative symptoms, and are less likely to produce extrapyramidal symptoms; however, the SGA and TGA are associated with many other adverse events. The clinician has to balance the risks and benefits of these medications when choosing an antipsychotic for an individual patient.Keywords: antipsychotic agents, schizophrenia, pharmacology, safety

Pharmacotherapy of schizophrenic patients: preponderance of off-label drug use.

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David Pickar

Full Text Available Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively, mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. "Real world" pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs.

Metabolic effects of second-generation antipsychotics in bipolar youth: comparison with other psychotic and nonpsychotic diagnoses.

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Moreno, Carmen; Merchán-Naranjo, Jessica; Alvarez, Mar; Baeza, Inmaculada; Alda, Jose A; Martínez-Cantarero, Carmen; Parellada, Mara; Sánchez, Bernardo; de la Serna, Elena; Giráldez, Marisa; Arango, Celso

2010-03-01

Despite known metabolic effects of second-generation antipsychotics (SGAs) on children and adolescents, comparative effects in youth with different diagnoses remain underreported. We compared differences in metabolic changes three months after starting treatment with SGAs in youth with bipolar disorder and with other psychotic and nonpsychotic disorders. Weight and metabolic differences among diagnostic groups before and three months after starting treatment with SGAs were compared in a naturalistic cohort of children and adolescents (14.9 +/- 3.0 years) diagnosed with bipolar disorder (n = 31), other psychotic disorders (n = 29), and other nonpsychotic disorders (n = 30), with no (35.6%) or very little (6.6 +/- 9.0 days) previous exposure to antipsychotics. Composite measurements of significant weight gain [weight increase > or = 5% at three months or increase > or = 0.5 in body mass index (BMI) z-score] and 'risk for adverse health outcome' (> or = 95(th) BMI percentile, or > or = 85(th) BMI percentile plus presence of one other obesity-related complication) were included. SGAs (risperidone, olanzapine, and quetiapine) were prescribed in comparable proportion among groups. Baseline weight and metabolic indices were not significantly different among diagnoses. Three months after starting treatment with SGAs, more than 70% patients had significant weight gain, BMI z-score increased in all diagnostic groups (p or = 1 obesity-related complication at follow-up. There are early weight gain and metabolic changes across diagnoses in youth treated with SGAs.

Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

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Izchak Kohen

2010-03-01

Full Text Available Izchak Kohen1, Paula E Lester2, Sum Lam31Division of Geriatric Psychiatry, Zucker-Hillside Hospital, Glen Oaks, NY, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, NY, USA; 3Division of Pharmacy and Geriatrics, St. John’s University College of Pharmacy and Allied Health Professions, Queens, NY, USAAbstract: Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient’s previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence.Keywords: aripiprazole, antipsychotics, elderly, adverse drug reaction

Prevalence of concurrent use of antipsychotic drugs and herbal ...

African Journals Online (AJOL)

The use of herbal medicines with conventional medicines is on the rise. Therefore, drug-herb interactions have become an important issue in drug safety and efficacy in clinical practice. A cross-sectional prospective study using a structured questionnaire was carried out on patients using antipsychotic drugs attending the ...

Direct and Indirect Drug Design Approaches for the Development of Novel Tricyclic Antipsychotics: Potential 5-HT2A Antagonist

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Mahantesh Namdev Jadhav

2013-01-01

Full Text Available Schizophrenia is a mental disorder manifested largely by disintegration of thought processes and emotional responsiveness. Given the therapeutic and toxic limitations of clinically available drugs, it is clear that there is still a need for the development of new generation antipsychotic agents with an improved clinical profile. Development of novel hybrid atypical tricyclic antipsychotic pharmacophore was achieved using direct (by measuring docking score of designed molecules on modelled 5- receptor and indirect (current, clinically available therapeutic agents’ data drug design approaches.

A new generation of antipsychotics: pharmacology and clinical utility of cariprazine in schizophrenia

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Caccia S

2013-08-01

Full Text Available Silvio Caccia, Roberto William Invernizzi, Alessandro Nobili, Luca Pasina IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy Abstract: Cariprazine is a potential antipsychotic awaiting approval from the US Food and Drug Administration. It is a dopamine D2- and D3-receptor partial agonist, with higher affinity for D3 receptors, as opposed to the D2 antagonism of most older antipsychotic agents. Like most lipophilic antipsychotics, it undergoes extensive hepatic metabolism by cytochrome P450 (CYP, mainly the highly variable 3A4, with the formation of active metabolites. However, the parent compound – particularly its active didesmethyl derivative – is cleared very slowly, with elimination half-lives in schizophrenic patients ranging from 2–5 days for cariprazine to 2–3 weeks for didesmethyl-cariprazine. Exposure to the latter was several times that for cariprazine, although didesmethyl-cariprazine did not reach steady state within the 3 weeks of 12.5 mg/day dosing. Preliminary information on its therapeutic role comes from press releases and a few abstracts presented at scientific meetings. In short-term controlled trials, it was more effective than placebo in reducing positive and negative symptoms of schizophrenia, with an effective dose range of 1.5–12 mg/day. Although cariprazine was associated with a higher incidence of akathisia and extrapyramidal side effects than placebo, it did not cause weight gain, metabolic abnormalities, prolactin increase, or corrected QT prolongation. Similarly, cariprazine's efficacy and tolerability for the treatment of bipolar disorder (manic/mixed and depressive episodes was established in the dose range of 3–12 mg/day, although again no long-term data are available. Well-designed clinical trials, mainly direct "head-to-head" comparisons with other second-generation antipsychotic agents, are needed to define the therapeutic role and safety profile of cariprazine in schizophrenia and

Sex differences in the subjective tolerability of antipsychotic drugs

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Barbui, Corrado; Nosè, Michela; Bindman, Jonathan; Schene, Aart; Becker, Thomas; Mazzi, Maria A.; Kikkert, Martijn; Camara, Jayne; Born, Anja; Tansella, Michele

2005-01-01

In recent years, research efforts have been directed to better characterize the Subjective experience of taking psychotropic drugs. This Study investigated the sex difference in the subjective tolerability of antipsychotic drugs. Participants were recruited from patients under the care of

Haloperidol versus second-generation antipsychotics in the long-term treatment of schizophrenia.

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Buoli, Massimiliano; Kahn, René S; Serati, Marta; Altamura, A Carlo; Cahn, Wiepke

2016-07-01

The purpose of the study was to compare antipsychotic monotherapies in terms of time to discontinuation in a sample of schizophrenia patients followed-up for 36 months. Two hundred and twenty schizophrenia patients, treated with antipsychotic monotherapy and followed-up in psychiatric outpatient clinics of Universities of Milan and Utrecht were included in the study. A survival analysis (Kaplan-Meier) of the 36-month follow-up period was performed to compare the single treatment groups. End-point was considered as discontinuation of treatment for recurrence, side effects or non-compliance. Patients treated with haloperidol discontinued more than the other groups (Breslow: risperidone p haloperidol group than in the olanzapine group (p haloperidol group than with olanzapine (p haloperidol. In addition, atypical antipsychotics seem to be more protective against recurrences than haloperidol. However, these results should be cautiously interpreted in the light of potential confounder factors such as duration of illness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Toward an understanding of antipsychotic drug induced weight gain - use of a rodent model

OpenAIRE

Stefanidis, Aneta

2017-01-01

Antipsychotic drug therapy is a fundamental tool in the treatment of schizophrenia and other psychoses. Recent years have seen the development of new antipsychotic compounds with an improved acute adverse effect profile; however these are often associated with weight gain and increased risk of metabolic disturbances. Olanzapine, despite its considerable adverse impact on weight gain and associated pathologies, has been recognized as the most efficacious antipsychotic drug in the treatment of ...

A randomized controlled trial undertaken to test a nurse-led weight management and exercise intervention designed for people with serious mental illness who take second generation antipsychotics.

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Usher, Kim; Park, Tanya; Foster, Kim; Buettner, Petra

2013-07-01

To test the effect of a nurse-led intervention on weight gain in people with serious mental illness prescribed and taking second generation antipsychotic medication. Weight gain and obesity has reached epidemic proportions in the general population with the prevalence of Metabolic Syndrome reaching 20-25% of the global population. People with serious mental illness are at even higher risk, particularly those taking second generation antipsychotic medication. An experimental randomized controlled trial was undertaken. The control group received a 12-week healthy lifestyle booklet. In addition to the booklet, the intervention group received weekly nutrition and exercise education, exercise sessions, and nurse support. Participants (n = 101) were assessed at baseline and 12 weeks. Data were collected between March 2008-December 2010. Seven outcome measures were used: body measurements included girth (cm), weight (kg), height (cm), and body mass index (kg/m(2) ); questionnaires included the medication compliance questionnaire, the Drug Attitude Inventory, the Liverpool University Neuroleptic Side Effect Rating Scale, and the Medical Outcomes Study Short Form 36. Differences in primary outcome measures between baseline and 12 weeks follow-up were compared between intervention and control groups using standard bi-variate statistical tests. The study was conducted between 2008-2010. The analysis of outcome measures for the control group (n = 50) and intervention group (n = 51) was not statistically significant. There was a mean weight change of -0·74 kg at 12 weeks for the intervention group (n = 51), while the control group (n = 50) had a mean weight change of -0·17 kg at 12 weeks. The results were not statistically significant. © 2012 Blackwell Publishing Ltd.

A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice

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Bodén R

2013-03-01

Full Text Available Robert Bodén,1,2 Gunnar Edman,3,4 Johan Reutfors,2 Claes-Göran Östenson,3 Urban Ösby3,4 1Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden; 2Department of Medicine Solna, Centre for Pharmacoepidemiology, Karolinska Institutet, Stockholm, Sweden; 3Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; 4Department of Psychiatry, Tiohundra AB, Norrtälje, Sweden Abstract: It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08–3.04, reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01–2.97; and OR = 2.03, 95% CI 1.32–3.13, hypertension with perphenazine (OR = 2.00, 95% CI 1.21–3.59, and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05–0.89 and positively with haloperidol (OR = 2.02, 95% CI 1.18–3.48. There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In

Temporal and spatial transcriptional fingerprints by antipsychotic or propsychotic drugs in mouse brain.

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Kensuke Sakuma

Full Text Available Various types of antipsychotics have been developed for the treatment of schizophrenia since the accidental discovery of the antipsychotic activity of chlorpromazine. Although all clinically effective antipsychotic agents have common properties to interact with the dopamine D2 receptor (D2R activation, their precise mechanisms of action remain elusive. Antipsychotics are well known to induce transcriptional changes of immediate early genes (IEGs, raising the possibility that gene expressions play an essential role to improve psychiatric symptoms. Here, we report that while different classes of antipsychotics have complex pharmacological profiles against D2R, they share common transcriptome fingerprint (TFP profile of IEGs in the murine brain in vivo by quantitative real-time PCR (qPCR. Our data showed that various types of antipsychotics with a profound interaction of D2R including haloperidol (antagonist, olanzapine (antagonist, and aripiprazole (partial agonist all share common spatial TFPs closely homologous to those of D2R antagonist sulpiride, and elicited greater transcriptional responses in the striatum than in the nucleus accumbens. Meanwhile, D2R agonist quinpirole and propsychotic NMDA antagonists such as MK-801 and phencyclidine (PCP exhibited the contrasting TFP profiles. Clozapine and propsychotic drug methamphetamine (MAP displayed peculiar TFPs that reflect their unique pharmacological property. Our results suggest that transcriptional responses are conserved across various types of antipsychotics clinically effective in positive symptoms of schizophrenia and also show that temporal and spatial TFPs may reflect the pharmacological features of the drugs. Thus, we propose that a TFP approach is beneficial to evaluate novel drug candidates for antipsychotic development.

Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges

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Salem, Haitham; Nagpal, Caesa; Pigott, Teresa; Teixeira, Antonio Lucio

2017-01-01

Background: Akathisia continues to be a significant challenge in current neurological and psychiatric practice. Prompt and accurate detection is often difficult and there is a lack of consensus concerning the neurobiological basis of akathisia. No definitive treatment has been established for akathisia despite numerous preclinical and clinical studies. Method: We reviewed antipsychotic-induced akathisia including its clinical presentation, proposed underlying pathophysiology, current and under investigation therapeutic strategies. Conclusion: Despite the initial promise that second generation antipsychotics would be devoid of akathisia effects, this has not been confirmed. Currently, there are limited therapeutic options for the clinical practice and the evidence supporting the most widely used treatments (beta blockers, anticholinergic drugs) is still absent or inconsistent. PMID:27928948

Second generation antipsychotics in Asperger's Disorder and high functioning autism: a systematic review of the literature and effectiveness of meta-analysis.

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Sochocky, Natalie; Milin, Robert

2013-11-01

Second generation antipsychotics (SGA) have gained increased evidence for the treatment of irritability and aggression in children and adolescents with lower functioning autistic disorder. Individuals with Asperger's Disorder (AD) and High Functioning Autism (HFA) experience significant emotional and behavioral problems and psychiatric comorbidity. There is a need to review the published literature on SGA treatment efficacy in the AD and HFA populations to provide more effective treatment choices for these subgroups. We conducted a systematic review and meta-analysis of the recent English literature on SGA use in children and adolescents (ages 0-24 years) with AD and HFA using the Medline/PubMed and PsychINFO computerized databases. Key search words were 'Asperger', 'high functioning autism', 'autism spectrum disorders (ASD)', and 'pervasive developmental disorder (PDD)' in combination with 'second generation antipsychotics', 'aripiprazole; 'olanzapine', 'quetiapine', 'risperidone', or 'ziprasidone'. Our search yielded 214 citations, however only open-label or randomized-controlled trials (RCT) with ≥25% of their subjects having an IQ≥71 were included in our review. Eleven original studies met our inclusion parameters for review; eight studies for the meta-analysis. These studies, although limited in methodological rigor, and the meta-analytic results suggest that SGAs provide improvement in behavioral symptoms associated with AD and HFA. The majority of the studies reported weight gain as a potentially concerning adverse effect. There is a lack of robustly conducted trials on the use of SGAs in the management of AD and HFA. More research in pharmacological and psychosocial treatments is warranted. Clinicians are cautioned to approach pharmacological treatment prudently balancing benefit with potential cardiometabolic risk.

Paliperidone extended-release: does it have a place in antipsychotic therapy?

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Carlos Schönfeldt-Lecuona

2011-03-01

Full Text Available Maximilian Gahr1,*, Markus A Kölle1,*, Carlos Schönfeldt-Lecuona1, Peter Lepping2, Roland W Freudenmann11Department of Psychiatry and Psychotherapy, University of Ulm, Ulm, Germany; 2Department of Psychiatry, Glyndwr University, Wales, UK *Both authors contributed equally and their order was determined by coin toss.Abstract: Paliperidone (9-hydroxy-risperidone, the active metabolite of risperidone, was approved for treating schizophrenia worldwide in 2006 as paliperidone extended-release (PER, and became the first second-generation antipsychotic specifically licensed for treating schizoaffective disorder in 2009. However, at the same time, its comparatively high cost gave rise to concerns about the cost-effectiveness of PER as compared with its precursor, risperidone. This paper reviews the existing knowledge of the pharmacology, kinetics, efficacy, tolerability, and fields of application of PER, and compares PER with risperidone in order to determine whether it has a place in antipsychotic therapy. An independent assessment of all relevant publications on PER published until July 2010 was undertaken. PER has a unique pharmacological profile, including single dosing, predominantly renal excretion, low drug–drug interaction risk, and differs from risperidone in terms of mode of action and pharmacokinetics. High-level evidence suggests that PER is efficacious and safe in schizophrenia, schizoaffective disorder, and acute manic episodes. There is a striking lack of published head-to-head comparisons between PER and risperidone, irrespective of indication. Low-level evidence shows a lower risk for hyperprolactinemia and higher patient satisfaction with PER than with risperidone. PER adds to the still limited arsenal of second-generation antipsychotics. In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of PER which would justify its substantially

Pharmacogenetics and outcome with antipsychotic drugs.

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Pouget, Jennie G; Shams, Tahireh A; Tiwari, Arun K; Müller, Daniel J

2014-12-01

Antipsychotic medications are the gold-standard treatment for schizophrenia, and are often prescribed for other mental conditions. However, the efficacy and side-effect profiles of these drugs are heterogeneous, with large interindividual variability. As a result, treatment selection remains a largely trial-and-error process, with many failed treatment regimens endured before finding a tolerable balance between symptom management and side effects. Much of the interindividual variability in response and side effects is due to genetic factors (heritability, h(2)~ 0.60-0.80). Pharmacogenetics is an emerging field that holds the potential to facilitate the selection of the best medication for a particular patient, based on his or her genetic information. In this review we discuss the most promising genetic markers of antipsychotic treatment outcomes, and present current translational research efforts that aim to bring these pharmacogenetic findings to the clinic in the near future.

Endogenous and Antipsychotic-Related Risks for Diabetes Mellitus in Young People With Schizophrenia: A Danish Population-Based Cohort Study.

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Rajkumar, Anto P; Horsdal, Henriette Thisted; Wimberley, Theresa; Cohen, Dan; Mors, Ole; Børglum, Anders D; Gasse, Christiane

2017-07-01

Diabetes mellitus contributes to excessive cardiovascular deaths and reduced life expectancy in schizophrenia. This population-based cohort study investigated the endogenous risk for diabetes in antipsychotic-naive schizophrenia and evaluated the risks added by starting antipsychotic treatment in people with schizophrenia. The study followed all people born in Denmark on or after Jan. 1, 1977, until Jan. 1, 2013 (N=2,736,510). The Danish Psychiatric Central Research Register ascertained schizophrenia diagnoses. The Danish National Prescription Registry provided data on prescriptions of antipsychotics. Diabetes was ascertained from the Danish National Patient Register and Danish National Prescription Registry. The authors estimated the endogenous and antipsychotic-related risks for diabetes by using Cox proportional hazards regression models, while accounting for potential confounders. Of the cohort members, 14,118 (0.52%) developed diabetes, and 8,945 (0.33%) developed schizophrenia during follow-up (49,582,279 person-years). The adjusted hazard ratio for diabetes was 3.07 (95% confidence interval [CI], 1.71-5.41) in antipsychotic-naive schizophrenia compared with the general population. The risk for diabetes after starting antipsychotic treatment was significantly higher (adjusted hazard ratio, 3.64; 95% CI, 1.95-6.82) than the risk in antipsychotic-naive schizophrenia, after adjustment for family history of diabetes and other potential confounders. First-line treatment with either first-generation antipsychotics (adjusted hazard ratio, 3.06; 95% CI, 1.32-7.05) or second-generation antipsychotics (adjusted hazard ratio, 3.44; 95% CI, 1.73-6.83) increased the risk for diabetes without a statistically significant difference. Appropriate sensitivity analyses limited to type 2 diabetes corroborated these results. Schizophrenia confers a high endogenous risk for diabetes, and the risk is further increased by both first-generation and second-generation antipsychotics

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro.

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Sárvári, Anitta K; Veréb, Zoltán; Uray, Iván P; Fésüs, László; Balajthy, Zoltán

2014-08-08

Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin and adiponectin, suggesting that both glucose and fat metabolism may be affected by these drugs. These data further suggest that antipsychotic treatments in patients alter the gene expression patterns in adipocytes in a coordinated fashion and priming them for a low-level inflammatory state. Copyright © 2014 Elsevier Inc. All rights reserved.

Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments.

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Das, Chandan; Mendez, Guillermo; Jagasia, Sonal; Labbate, Lawrence A

2012-08-01

Weight gain in schizophrenia, particularly secondary to second-generation antipsychotic (SGA) use, is a common adverse effect and often is associated with significant physical and psychological morbidity. We performed a critical literature review of all controlled clinical trials for pharmacologic and/or behavioral management of SGA-induced weight gain in schizophrenia patients by searching PubMed and Google Scholar. A meta-analysis was performed to estimate and compare weight changes for various medications and behavioral interventions. Sample sizes generally were small. Clinical trials were 6 weeks to 1 year, and weight loss was modest with any treatment. Although several adjunctive pharmacologic treatments showed no weight loss, sibutramine, metformin, and topiramate showed some benefit. Amantadine and orlistat were somewhat less effective and had lower rates of tolerability. Among the behavioral therapies, nutritional counseling combined with exercise showed the most benefit. Behavioral therapies, although modest, showed the most consistent benefits compared with controls. Scheduled pharmacologic treatment to prevent weight gain or promote weight loss in schizophrenia patients on SGA therapy is limited based on current studies. Switching antipsychotic agents has not been established as a long-term solution. Additional long-term studies are required to influence clinical practice.

Maintenance therapy with second generation antipsychotics for bipolar disorder - A systematic review and meta-analysis.

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Lindström, Leif; Lindström, Eva; Nilsson, Mikael; Höistad, Malin

2017-04-15

Second generations antipsychotics (SGA) are frequently used for maintenance treatment in bipolar disorder. We systematically reviewed the efficacy and long-term effects of treatment with SGA, regardless of treatment strategy (SGA administered either as monotherapy or as adjunctive therapy), in comparison to placebo, lithium or valproate. Primary outcomes were relapses (mood episode recurrence) and discontinuation. Clinical studies were identified through database searching in PubMed, Embase, PsychInfo and Cochrane Library and critically appraised based on the Cochrane Handbook. Full data extraction of raw data was performed and analyzed with meta-analyses, and level of evidence graded using GRADE. Only randomized controlled studies (RCT) and observational studies were included, with a minimum follow-up of 6 months. Comparators used were restricted to placebo, lithium, valproate or other anti-epileptic drugs. We identified 15 RCTs on SGA in bipolar disorder with follow-up-time of 6 months up to 2 years, and one observational study reporting long-term effects of up to 4 years. A total of 6142 patients were included in the randomized trials. No long-term RCTs beyond 2 years follow-up was identified. All RCTs except for one included patients with bipolar disorder type I only. All RCTs except for two included patients pre-stabilized on the drug under investigation prior to randomization (enrichment design). For SGA as adjunctive therapy to lithium or valproate, meta-analyses showed that treatment with either aripiprazole (RR: 0.65, 95% CI 0.50-0.85), quetiapine (RR: 0.38, 95% CI 0.32-0.46) or ziprasidone (RR: 0.62, 95% CI 0.40-0.96) reduced the overall risk of relapses in patients that had responded during the stabilization phase. Adjunctive therapy with quetiapine was the only drug that reduced both manic and depressive episodes. For SGA as monotherapy, only quetiapine was shown to be better than lithium/ valproate for both manic and depressive relapses, but only for

Antipsychotic interventions in prodromal psychosis: safety issues.

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Liu, Chen-Chung; Demjaha, Arsime

2013-03-01

In recent years, psychopharmacological intervention in prodromal psychosis, also known as the ultra-high risk (UHR) mental state for psychosis, has attracted much attention. Whilst it has been shown that antipsychotic use in UHR individuals may be effective in potentially delaying or even averting progression to frank psychosis, their use in subjects that do not necessarily convert to psychosis has raised considerable ethical concerns because of their adverse effects. Recent treatment guidelines for patients at UHR for psychosis recommend the use of antipsychotics only in exceptional conditions and with great precautions. To date only a few studies have investigated the use of antipsychotic medications in UHR patients and the potential benefits and risks related to their use in prodromal psychosis remain unclear. We review here all published studies that included UHR patients treated with antipsychotics, regardless of study design. These studies were all of second-generation antipsychotics, given that first-generation antipsychotics cannot be recommended because of their adverse drug reactions. We specifically examine the available descriptions of adverse reactions of the individual antipsychotic medication in each study and discuss the potential effects of various demographic and clinical factors that may impact on safety issues of pharmacological interventions in UHR patients. Clinical trials to date investigating potential benefits of antipsychotic treatments in preventing transition to psychosis were of relatively short duration and have involved a small number of patients. Whilst it appears that pharmacological intervention at this stage may be effective in both reducing the psychopathology and decreasing transition rates, and is potentially safe, in the absence of sufficient evidence-based knowledge to guide treatment, definitive clinical recommendations and guidelines cannot be derived. Certain adverse events take time to develop, such as metabolic syndrome

Assessment of anti-arrhythmic activity of antipsychotic drugs in an animal model

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Mow, Tomas; Frederiksen, Kristen; Thomsen, Morten B.

2015-01-01

limited experimental information exists about the effects of α1-adrenergic receptor activity of antipsychotic drugs in pro-arrhythmic models, we have decided to investigate this. In this study we show that four antipsychotic drugs all have high affinity for α1-adrenergic receptor (sertindole>risperidone>haloperidol......>olanzapine) and all block IKr (sertindole>haloperidol>risperidone>olanzapine). In canine Purkinje fibres, α1-adrenergic stimulation prolonged action potential duration; however, the stimulation does not cause afterdepolarizations, even in the presence of dofetilide-induced delayed repolarization. We showed...

Sertindole versus other atypical antipsychotics for schizophrenia

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Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schwarz, Sandra; Schmid, Franziska; Lewis, Ruth; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second generation (atypical) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether and, if so, how much the effects of the various second generation antipsychotics differ is a matter of debate. Objectives To evaluate the effects of sertindole compared with other second generation antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) and ClinicalTrials.gov (February 2009). Selection criteria We included all randomised trials comparing oral sertindole with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes two short-term low-quality randomised trials (total n=508) both comparing sertindole with risperidone. One third of participants left the studies early (2 RCTs, n=504, RR 1.23 CI 0.94 to 1.60). There was no difference in efficacy (2 RCTs, n=493, WMD PANSS total change from baseline 1.98 CI −8.24 to 12.20). Compared with relatively high doses of risperidone (between 4 and 12 mg/day), sertindole produced significantly less akathisia and parkinsonism (1 RCT, n=321, RR 0.24 CI 0.09 to 0.69, NNT 14, CI 8 to 100). Sertindole produced more cardiac effects (2 RCTs, n=508, RR QTc prolongation 4.86 CI 1.94 to 12.18), weight change (2 RCTs, n=328, WMD 0.99 CI 0.12 to 1.86) and male sexual dysfunction (2 RCTs, n=437, RR 2.90 CI 1.32 to 6.35, NNH 13 CI 8 to 33

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

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Sárvári, Anitta K., E-mail: anittasarvari@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: jzvereb@gmail.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: ipuray@mdanderson.org [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: fesus@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); MTA DE Apoptosis, Genomics and Stem Cell Research Group of the Hungarian Academy of Sciences (Hungary); Balajthy, Zoltán, E-mail: balajthy@med.unideb.hu [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

2014-08-08

Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

Atypical antipsychotics induce both proinflammatory and adipogenic gene expression in human adipocytes in vitro

International Nuclear Information System (INIS)

Sárvári, Anitta K.; Veréb, Zoltán; Uray, Iván P.; Fésüs, László; Balajthy, Zoltán

2014-01-01

Highlights: • Antipsychotics modulate the expression of adipogenic genes in human adipocytes. • Secretion of proinflammatory cytokine IL8 and MCP-1 is induced by antipsychotics. • Adipocyte-dependent inflammatory abnormality could develop during chronic treatment. • Infiltrated macrophages would further enhance proinflammatory cytokine production. - Abstract: Schizophrenia requires lifelong treatment, potentially causing systemic changes in metabolic homeostasis. In the clinical setting, antipsychotic treatment may differentially lead to weight gain among individual patients, although the molecular determinants of such adverse effects are currently unknown. In this study, we investigated changes in the expression levels of critical regulatory genes of adipogenesis, lipid metabolism and proinflammatory genes during the differentiation of primary human adipose-derived stem cells (ADSCs). These cells were isolated from patients with body mass indices <25 and treated with the second-generation antipsychotics olanzapine, ziprasidone, clozapine, quetiapine, aripiprazole and risperidone and the first-generation antipsychotic haloperidol. We found that antipsychotics exhibited a marked effect on key genes involved in the regulation of cell cycle, signal transduction, transcription factors, nuclear receptors, differentiation markers and metabolic enzymes. In particular, we observed an induction of the transcription factor NF-KB1 and NF-KB1 target genes in adipocytes in response to these drugs, including the proinflammatory cytokines TNF-α, IL-1β, IL-8 and MCP-1. In addition, enhanced secretion of both IL8 and MCP-1 was observed in the supernatant of these cell cultures. In addition to their remarkable stimulatory effects on proinflammatory gene transcription, three of the most frequently prescribed antipsychotic drugs, clozapine, quetiapine and aripiprazole, also induced the expression of essential adipocyte differentiation genes and the adipocyte hormones leptin

Amisulpride versus other atypical antipsychotics for schizophrenia

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Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; da Mota Neto, Joaquim I Silveira; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. Objectives To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We updated this search in July 2012 and added 47 new trials to the awaiting classification section. Selection criteria We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50

Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs

International Nuclear Information System (INIS)

Farde, L.; Wiesel, F.A.; Halldin, C.; Sedvall, G.

1988-01-01

Using positron emission tomography and the carbon 11-labeled ligand raclopride, central D2-dopamine receptor occupancy in the putamen was determined in psychiatric patients treated with clinical doses of psychoactive drugs. Receptor occupancy in drug-treated patients was defined as the percent reduction of specific carbon 11-raclopride binding in relation to the expected binding in the absence of drug treatment. Clinical treatment of schizophrenic patients with 11 chemically distinct antipsychotic drugs (including both classic and atypical neuroleptics such as clozapine) resulted in a 65% to 85% occupancy of D2-dopamine receptors. In a depressed patient treated with the tricyclic antidepressant nortriptyline, no occupancy was found. The time course for receptor occupancy and drug levels was followed after withdrawal of sulpiride or haloperidol. D2-dopamine receptor occupancy remained above 65% for many hours despite a substantial reduction of serum drug concentrations. In a sulpiride-treated patient, the dosage was reduced in four steps over a nine-week period and a curvilinear relationship was demonstrated between central D2-dopamine receptor occupancy and serum drug concentrations. The results demonstrate that clinical doses of all the currently used classes of antipsychotic drugs cause a substantial blockade of central D2-dopamine receptors in humans. This effect appears to be selective for the antipsychotics, since it was not induced by the antidepressant nortriptyline

Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications.

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Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique

2016-01-01

The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system.

Prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital, Assam

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Pinaki Chakravarty

2016-01-01

Full Text Available Objective: To study the prescribing pattern of antipsychotic drugs in the outpatient department of psychiatry in Silchar Medical College and Hospital (SMCH of Assam. Methods: It is a prospective cross-sectional study which was carried out for three months from August to November 2015 in the outpatient department of psychiatry. All patients irrespective of their ages and sexes were included in this study. Inpatients, referred patients, patients not willing to give consent, patients of epilepsy as well as those cases where diagnoses were not certain were excluded from the study. The prescription patterns of antipsychotic drugs and the occurrences of various psychiatric diseases on both the sexes were studied after taking permission from the Institutional Ethical Committee (SMCH. Results: A total of 112 prescriptions were analysed. The most common disease was found to be schizophrenia. Total drugs prescribed were 265 and average number of drugs per prescription was 2.36. It was seen that out of the 112 prescriptions, monotherapy was practiced in 19.64% (22 compared to polytherapy in 80.35% (90. Out of 265 prescribed drugs atypical antipsychotics were 112 (42.26%, typical antipsychotics 12 (4.52%, antiepileptics 57 (21.50%, antidepressants 29 (10.94%, antiparkinsonian 29 (10.94%, and others 26 (9.81%. Antipsychotics given orally were 122 of which olanzapine was 54 (44.26%, risperidone 40 (32.78%, chlorpromazine ten (8.19%, quetiapine eight (6.55%, aripiprazole five (4.09%, amisulpiride five (4.09% were seen. Injectable antipsychotics were two, of which only haloperidol two (100%. Antipsychotics in combination prescription with same groups were 14 (12.5%, with antidepressants, antipileptics, antiparkinsonian were 88 (78.57% and other agents were ten (8.92%, which included pantoprazole, multivitamins, and benfotiamine. Conclusion: This study shows that atypical antipsychotics are the most common drugs prescribed in patients with psychotic illness and

Prototypical antipsychotic drugs protect hippocampal neuronal cultures against cell death induced by growth medium deprivation

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Williams Sylvain

2006-03-01

Full Text Available Abstract Background Several clinical studies suggested that antipsychotic-based medications could ameliorate cognitive functions impaired in certain schizophrenic patients. Accordingly, we investigated the effects of various dopaminergic receptor antagonists – including atypical antipsychotics that are prescribed for the treatment of schizophrenia – in a model of toxicity using cultured hippocampal neurons, the hippocampus being a region of particular relevance to cognition. Results Hippocampal cell death induced by deprivation of growth medium constituents was strongly blocked by drugs including antipsychotics (10-10-10-6 M that display nM affinities for D2 and/or D4 receptors (clozapine, haloperidol, (±-sulpiride, domperidone, clozapine, risperidone, chlorpromazine, (+-butaclamol and L-741,742. These effects were shared by some caspases inhibitors and were not accompanied by inhibition of reactive oxygen species. In contrast, (--raclopride and remoxipride, two drugs that preferentially bind D2 over D4 receptors were ineffective, as well as the selective D3 receptor antagonist U 99194. Interestingly, (--raclopride (10-6 M was able to block the neuroprotective effect of the atypical antipsychotic clozapine (10-6 M. Conclusion Taken together, these data suggest that D2-like receptors, particularly the D4 subtype, mediate the neuroprotective effects of antipsychotic drugs possibly through a ROS-independent, caspase-dependent mechanism.

Effects of the Antipsychotic Drug, Haloperidol, on Reproduction in the Fathead Minnow

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Haloperidol is a butyrophenone antipsychotic drug used for the treatment of human hyperactive and manic disorders, agitation, and schizophrenia. The drug is thought to act through antagonism of dopaminergic receptors. We have studied a variety of endocrine-disrupting chemicals wi...

Drug-induced activation of SREBP-controlled lipogenic gene expression in CNS-related cell lines: Marked differences between various antipsychotic drugs

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Vik-Mo Audun O

2006-10-01

Full Text Available Abstract Background The etiology of schizophrenia is unknown, but neurodevelopmental disturbances, myelin- and oligodendrocyte abnormalities and synaptic dysfunction have been suggested as pathophysiological factors in this severe psychiatric disorder. Cholesterol is an essential component of myelin and has proved important for synapse formation. Recently, we demonstrated that the antipsychotic drugs clozapine and haloperidol stimulate lipogenic gene expression in cultured glioma cells through activation of the sterol regulatory element-binding protein (SREBP transcription factors. We here compare the action of chlorpromazine, haloperidol, clozapine, olanzapine, risperidone and ziprasidone on SREBP activation and SREBP-controlled gene expression (ACAT2, HMGCR, HMGCS1, FDPS, SC5DL, DHCR7, LDLR, FASN and SCD1 in four CNS-relevant human cell lines. Results There were marked differences in the ability of the antipsychotic drugs to activate the expression of SREBP target genes, with clozapine and chlorpromazine as the most potent stimulators in a context of therapeutically relevant concentrations. Glial-like cells (GaMg glioma and CCF-STTG1 astrocytoma cell lines displayed more pronounced drug-induced SREBP activation compared to the response in HCN2 human cortical neurons and SH-SY5Y neuroblastoma cells, indicating that antipsychotic-induced activation of lipogenesis is most prominent in glial cells. Conclusion Our present data show a marked variation in the ability of different antipsychotics to induce SREBP-controlled transcriptional activation of lipogenesis in cultured human CNS-relevant cells. We propose that this effect could be relevant for the therapeutic efficacy of some antipsychotic drugs.

Use of antipsychotic drugs in individuals with intellectual disability (ID) in the Netherlands : prevalence and reasons for prescription

NARCIS (Netherlands)

de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

Background We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods A cross-sectional study of medical and pharmaceutical

[Treatment of Adult Schizophrenic Patients With Depot Antipsychotics].

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Jaramillo González, Luis Eduardo; Gómez Restrepo, Carlos; García Valencia, Jenny; de la Hoz Bradford, Ana María; Ávila-Guerra, Mauricio; Bohórquez Peñaranda, Adriana

2014-01-01

To determine the indications of long-acting antipsychotic injection and what its effectiveness and safety in adult patients with schizophrenia during the treatment maintenance phase. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The literature review shows that the evidence has moderate to low quality. 8 articles were used. The risk of relapse was lower with depot risperidone and paliperidone palmitate when compared with placebo. For the risk of hospitalizations comparing depot antipsychotics (APD) versus oral AP, the result is inconclusive. Globally the second-generation APD had a lower risk of discontinuation when compared with placebo. The second generation AP had higher risk of extrapyramidal syndromes than placebo, as in the use of antiparkinsonian. The comparison of second-generation AP injections versus placebo showed an increased risk of early weight gain. The use of depot antipsychotics in the maintenance phase of adult patients diagnosed with schizophrenia is recommended if there is no adherence to oral antipsychotics as the patient's preference. It is not recommended depot antipsychotics in the acute phase of schizophrenia in adults. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

The influence of atypical antipsychotic drugs on sexual function

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Just MJ

2015-07-01

Full Text Available Marek J Just Department of General and Endocrine Surgery, Piekary Medical Centre, Piekary Slaskie, Poland Abstract: Human sexuality is contingent upon many biological and psychological factors. Such factors include sexual drive (libido, physiological arousal (lubrication/erection, orgasm, and ejaculation, as well as maintaining normal menstrual cycle. The assessment of sexual dysfunction can be difficult due to the intimate nature of the problem and patients’ unwillingness to discuss it. Also, the problem of dysfunction is often overlooked by doctors. Atypical antipsychotic treatment is a key component of mental disorders’ treatment algorithms recommended by the National Institute of Health and Clinical Excellence, the American Psychiatric Association, and the British Society for Psychopharmacology. The relationship between atypical antipsychotic drugs and sexual dysfunction is mediated in part by antipsychotic blockade of pituitary dopamine D2 receptors increasing prolactin secretion, although direct correlations have not been established between raised prolactin levels and clinical symptoms. Variety of mechanisms are likely to contribute to antipsychotic-related sexual dysfunction, including hyperprolactinemia, sedation, and antagonism of a number of neurotransmitter receptors (α-adrenergic, dopaminergic, histaminic, and muscarinic. Maintaining normal sexual function in people treated for mental disorders can affect their quality of life, mood, self-esteem, attitude toward taking medication, and compliance during therapy. Keywords: schizophrenia, galactorrhea, hyperprolactinemia, mood disorders, anorgasmia

Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

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Nielsen, R E; Lolk, A; Valentin, J B

2016-01-01

OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality. METHOD: We utilized a nationwide, population-based, retrospective cohort...... study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia. RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased...... or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs...

The effects of antipsychotic drugs on depression level in patients with schizophrenia: clozapine vs. other atypical antipsychotics

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Hülya Ertekin

2016-08-01

Full Text Available Introduction: Depressive symptoms may occur in all stages of schizophrenia disorder. Clozapine is the only antipsychotic that has been demonstrated superior efficacy in schizophrenia and suicidal ideation. The aim of this study is to evaluate depressive symptoms in patients with schizophrenia treated with clozapine and to compare with treated with other atypical antipsychotics.Methods: A cross-sectional descriptive study was carried out on patients with schizophrenia according to DSM-IV-TR between December 2012 and May 2013. All participants were evaluated for demographic characteristics and points of Brief Psychiatric Rating Scale, Positive, Negative Syndrome Scale, and Calgary Depression Scale for Schizophrenia.Results: A total 23.6% (n = 13 patients treated with clozapine, while 76.4% (n = 42 patients were treated with other antipsychotic drugs. 23.1% (n = 3 of patients taking clozapine were women, 76.9% (n = 10 were male. The mean age of patients treated with clozapine was 43.0 ± 11.2. The level of depression of patients treated with clozapine was 15.4% (n = 2. No statistically significant difference was found between patients between treated with clozapine and other antipsychotics regarding age, sex, marital status, education years, work history, age at onset of disease, depression and history of suicide attemptConclusion: As a result of this study it is found that clozapine did not effect on the level of depression in patients with schizophrenia, and depression level of patients with schizophrenia treated with clozapine had no difference from  patients treated  with other antipsychotics.

Antipsychotics and amotivation.

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Fervaha, Gagan; Takeuchi, Hiroyoshi; Lee, Jimmy; Foussias, George; Fletcher, Paul J; Agid, Ofer; Remington, Gary

2015-05-01

Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.

Use of Antipsychotic Drugs in Individuals with Intellectual Disability (ID) in the Netherlands: Prevalence and Reasons for Prescription

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de Kuijper, G.; Hoekstra, P.; Visser, F.; Scholte, F. A.; Penning, C.; Evenhuis, H.

2010-01-01

Background: We investigated antipsychotic drug prescription practice of Dutch ID physicians, studying prevalence of antipsychotic drug use, reasons for prescription and the relationship between these reasons and patient characteristics. Methods: A cross-sectional study of medical and pharmaceutical records in a population living in residential…

The use of antipsychotic medication in child and adolescent psychiatric treatment in Denmark. A cross-sectional survey

DEFF Research Database (Denmark)

Deurell, Maria; Weischer, Merete; Pagsberg, Anne Katrine

2008-01-01

for patients in antipsychotic treatment were: schizophrenia, schizotypal disorder, autism spectrum disorders and personality disorders. Monotherapy was used in 87% of cases. Sixty-four per cent of patients treated with antipsychotics, received a second-generation antipsychotic as the main treatment. All 244......The number of children and adolescents with psychiatric disorders being treated with antipsychotic medication is increasing significantly; however, only a limited evidence-base is available on this topic, especially when children are concerned. This study reports and discusses the use...... patients received one or more additional treatment modalities other than medication. Antipsychotic medication has a definite role in the treatment of children and adolescents with psychiatric disorders. Second-generation antipsychotics used as monotherapy prevail....

Glucoregulation in normal weight schizophrenia patients treated by first generation antipsychotics

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Marić Nađa

2008-01-01

Full Text Available Introduction Schizophrenia patients are at greater risk of obesity, diabetes mellitus (DM, lipid abnormalities and cardiovascular disorders. The metabolic complications in patients are associated with several risk factors: family history of DM, lifestyle, smoking, dietary habits, physical inactivity, but also with antipsychotic medication. In literature, most publications have been focused on the effects of the second generation antipsychotics (SGA on glucose metabolism. However, less attention has been paid to abnormality in glucoregulation, patients with schizophrenia treated with the first generation antipsychotics (FGA. Objective The present study evaluated glucose metabolism in normal weight schizophrenia patients treated with FGA. METHOD The cross-sectional study included 18 patients (FGA treated and 20 healthy controls with neither group differences in sex distribution, age, nor in BMI. Inclusion criteria were normal BMI (20-25 kg/m2. The glucose levels, insulin levels and growth hormone levels during oral glucose tolerance test (OGTT were measured. Results Fasting glucose and insulin levels did not differ significantly between groups. Groups differed in OGTT glucose and insulin peak and area under curve (AUC, level of significance p<0.05 (patients vs. controls: glucose peak 8.3±0.4 vs.6.9±0.5 mmol/l, glucose AUC 758±28 vs. 640±36 mU/l/120 min; insulin peak in patients 92.7±15.6 mU/l; insulin AUC 6060±1016 mU/l/120 min, insulin peak in controls 47.9±6.5 mU/l; insulin AUC 2597±256 mU/l/120 min. Conclusion Patients with schizophrenia, although with normal body mass index, are at high risk of abnormal glucose regulation. Not only SGA increase the risk of impaired glucoregulation and metabolic syndrome, but this may also be due to FGA or schizophrenia per se. .

Use-Dependent Inhibition of Synaptic Transmission by the Secretion of Intravesicularly Accumulated Antipsychotic Drugs

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Tischbirek, Carsten H.; Wenzel, Eva M.; Zheng, Fang

2012-01-01

Tischbirek et al. find that weak-base antipsychotic drugs are accumulated in synaptic vesicles and are secreted upon exocytosis, leading to increased extracellular drug concentrations following neuronal activity. The secretion of the drugs in turn inhibits synaptic transmission in a use-dependent...

[Maintenance Treatment With Antipsychotics for Adult Patients Diagnosed With Schizophrenia].

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Gómez-Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; de la Hoz Bradford, Ana María; Tamayo Martínez, Nathalie; García Valencia, Jenny; Jaramillo González, Luis Eduardo

2014-01-01

To determine the effectiveness and security of the antipsychotics available for the management of adult patients with schizophrenia in the maintenance phase. To develop recommendations of treatment for the maintenance phase of the disease. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. The evidence of NICE guide 82 was adopted and updated. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. 18 studies were included to evaluate the effectiveness and / or safety of different antipsychotic drugs first and second generation. Overall, antipsychotics (AP) showed superiority over placebo in relapse rate over 12 months (RR 0.59 95% CI 0.42, 0.82) and hospitalization rate over 24 months of follow-up (RR 0.38 95% 0.27, 0.55); its use is associated with increased risk of treatment dropout (RR 0.53 95% CI 0.46, 0.61) and adverse events such as weight gain, dystonia, extrapyramidal symptoms and sedation. There was no difference in the outcome of re hospitalizations, comparisons on quality of life, negative symptoms or weight gain between AP first and second generation. Continuous or standard dose regimens appear to be superior to intermittent or low doses in reducing the risk of abandonment of treatment regimes. Adult patients diagnosed with schizophrenia should receive maintenance treatment with antipsychotics. The medication of choice will depend on the management of the acute phase, the patient's tolerance to it and the presentation of adverse events. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Antipsychotic drug prescription rates among Dutch nursing homes : the influence of patient characteristics and the dementia special care unit

NARCIS (Netherlands)

van der Putten, M. J. G.; Wetzels, R. B.; Bor, H.; Zuidema, S. U.; Koopmans, R. T. C. M.

2014-01-01

Objectives: To assess the differences in antipsychotic drug prescription rates in residents with dementia in dementia special care units (SCUs) of Dutch nursing homes, considering the differences in patient characteristics. Method: As part of the Waalbed-II study, the data on antipsychotic drug use

Antipsychotics and associated risk of out-of-hospital cardiac arrest.

Science.gov (United States)

Weeke, P; Jensen, A; Folke, F; Gislason, G H; Olesen, J B; Fosbøl, E L; Wissenberg, M; Lippert, F K; Christensen, E F; Nielsen, S L; Holm, E; Kanters, J K; Poulsen, H E; Køber, L; Torp-Pedersen, C

2014-10-01

Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCAs in Denmark (2001-2010). The risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of the event. Overall, treatment with any antipsychotic drug was associated with OHCA (odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.23-1.89), as was use with typical antipsychotics (OR = 1.66, CI: 1.27-2.17). By contrast, overall, atypical antipsychotic drug use was not (OR = 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs, haloperidol (OR = 2.43, CI: 1.20-4.93) and levomepromazine (OR = 2.05, CI: 1.18-3.56), were associated with OHCA, as was one atypical antipsychotic drug, quetiapine (OR = 3.64, CI: 1.59-8.30).

Continuous, but not intermittent, antipsychotic drug delivery intensifies the pursuit of reward cues.

Science.gov (United States)

Bédard, Anne-Marie; Maheux, Jérôme; Lévesque, Daniel; Samaha, Anne-Noël

2011-05-01

Chronic exposure to antipsychotic medications can persistently change brain dopamine systems. Most studies on the functional significance of these neural changes have focused on motor behavior and few have addressed how long-term antipsychotic treatment might influence dopamine-mediated reward function. We asked, therefore, whether a clinically relevant antipsychotic treatment regimen would alter the incentive motivational properties of a reward cue. We assessed the ability of a Pavlovian-conditioned stimulus to function as a conditioned reward, as well as to elicit approach behavior in rats treated with haloperidol, either continuously (achieved via subcutaneous osmotic minipump) or intermittently (achieved via daily subcutaneous injections). Continuous, but not intermittent, treatment enhanced the ability of amphetamine to potentiate the conditioned reinforcing effects of a cue associated with water. This effect was not related to differences in the ability to attribute predictive value to a conditioned stimulus (as measured by conditioned approach behavior), but was potentially linked to the development of behavioral supersensitivity to amphetamine and to augmented amphetamine-induced immediate early-gene expression (c-fos and Nur77) in dorsal striatopallidal and striatonigral cells. By enhancing the ability of reward cues to control behavior and by intensifying dopamine-mediated striatopallidal and striatonigral cell activity, standard (ie, continuous) antipsychotic treatment regimens might exacerbate drug-seeking and drug-taking behavior in schizophrenia. Achieving regular but transiently high antipsychotic levels in the brain (as modeled in the intermittent condition) might be a viable option to prevent these changes. This possibility should be explored in the clinic.

The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs.

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Nordon, Clementine; Battin, Constance; Verdoux, Helene; Haro, Josef Maria; Belger, Mark; Abenhaim, Lucien; van Staa, Tjeerd Pieter

2017-01-01

A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level. Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist's gender, age, length of practice experience, practice setting and type, countries' Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1) to estimate antipsychotic drugs' effectiveness (defined as the association between patients' outcome at 3 months - dependent variable, continuous - and antipsychotic drug initiation at baseline - drug A vs other antipsychotic drug); 2) to estimate the similarity between clustered data (using the intra-cluster correlation coefficient); and 3) to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term). About 23% of the variance found for patients' outcome was explained by unmeasured confounding at a center level. Psychiatrists' practice experience was found to be associated with patient outcomes ( p =0.04) and modified the relative effect of "drug A" ( p <0.001), independent of center- or patient-related characteristics. Mixed models may be useful to explore how center-related characteristics modify drugs' effect estimates, but require numerous assumptions.

Antipsychotic drugs may worsen metabolic control in type 2 diabetes mellitus

NARCIS (Netherlands)

Spoelstra, JA; Stolk, RP; Cohen, D; Klungel, OH; Erkens, JA; Leufkens, HGM; Grobbee, DE

(B)ackground: Several studies have indicated that type 2 diabetes mellitus is more common among schizophrenic patients than in the general population. In this study, we investigated whether the use of antipsychotic drugs in patients with diabetes leads to worsening of glycemic control. Method: In

Diabetic ketoacidosis associated with atypical antipsychotic drug, clozapine treatment: Report of a case and review of literature

OpenAIRE

Pillai L; Husainy SMK; Ramchandani K

2006-01-01

Atypical antipsychotic drugs are associated with metabolic disturbances like weight gain, type 2 diabetes hyperglycaemia and dyslipedemia, which can result in serious health risk in patients. Diabetic ketoacidosis resulting in serious metabolic acidosis, occurring in a schizophrenic patient on treatment with clozapine is being reported to draw attention this association. Frequent monitoring of the blood sugar and lipids is advised before and during therapy with atypical antipsychotic drugs.

Trends in the Outpatient Utilization of Antipsychotic Drugs in the City of Zagreb in the Ten-Year Period as a Tool to Assess Drug Prescribing Rationality.

Science.gov (United States)

Polić-Vižintin, Marina; Tripković, Ingrid; Štimac, Danijela; Šostar, Zvonimir; Orban, Mirjana

2016-12-01

The aim was to determine distribution and trends in the outpatient utilization of antipsychotics to evaluate the rationality of antipsychotic drug prescribing during the ten year period. The epidemiological method of descriptive and analytical observation was used. Data on drug utilization from Zagreb Municipal Pharmacy were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants per day (DDD/TID) using the World Health Organization Anatomical-Therapeutic-Chemical methodology. The ratio of typical versus atypical antipsychotics served as an indicator on assessing the rationality of the utilization. Data on the use of anticholinergics in the treatment of neuroleptic side effects were also included. Outpatient utilization of antipsychotics showed a declining pattern from 14.17 in 2001 to 8.42 DDD/TID in 2010. The utilization of atypical antipsychotics increased by 60% (from 3.68 to 5.89 DDD/TID), while the utilization of typical antipsychotics decreased by 76% (from 10.49 to 2.53 DDD/TID). The drugs showing the largest increase were olanzapine (from 1.21 to 2.78 DDD/TID) and quetiapine (from 0 to 0.68 DDD/TID). The typical/atypical antipsychotic ratio changed from 1:0.4 in 2001 to 1:2.3 in 2010. A 2.3-fold decrease was recorded in the utilization of anticholinergics (from 2.05 to 0.91 DDD/TID). Total consumption of neuroleptics significantly decreased. A decrease was also recorded in the utilization of anticholinergics. Study results pointed to two favorable features, i.e. low use of typical antipsychotics and the ratio of typical and atypical antipsychotics. Implementation of the new clinical guidelines for nervous system disorders and updating of the list of reimbursable drugs with the addition of new ones contributed to the observed improvement in the prescribing patterns during the study period. Using the WHO ATC/DDD methodology and rationality indicators in the assessment of trends in the outpatient utilization of

Quetiapine versus other atypical antipsychotics for schizophrenia

Science.gov (United States)

Komossa, Katja; Rummel-Kluge, Christine; Schmid, Franziska; Hunger, Heike; Schwarz, Sandra; Srisurapanont, Manit; Kissling, Werner; Leucht, Stefan

2014-01-01

Background In many countries of the industrialised world second generation (’atypical’) antipsychotic drugs have become the first line drug treatment for people with schizophrenia. It is not clear how the effects of the various second generation antipsychotic drugs differ. Objectives To evaluate the effects of quetiapine compared with other second generation antipsychotic drugs for people with schizophrenia and schizophrenia-like psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007), inspected references of all identified studies, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. Selection criteria We included all randomised control trials comparing oral quetiapine with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random-effects model. Main results The review currently includes 21 randomised control trials (RCTs) with 4101 participants. These trials provided data on four comparisons - quetiapine versus clozapine, olanzapine, risperidone or ziprasidone. A major limitation to all findings is the high number of participants leaving studies prematurely (57.6%) and the substantial risk of biases in studies. Efficacy data favoured olanzapine and risperidone compared with quetiapine (PANSS total score versus olanzapine:10 RCTs, n=1449, WMD 3.66 CI 1.93 to 5.39; versus risperidone: 9 RCTs, n=1953, WMD 3.09 CI 1.01 to 5.16), but clinical meaning is unclear

Challenges and opportunities for the development of new antipsychotic drugs.

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Forray, Carlos; Buller, Raimund

2017-11-01

In spite of the significant impact that the serendipitous discovery of drugs with antipsychotic properties had on the care of patients with psychotic disorders, there are significant challenges when aiming at therapeutic goals such as remission, recovery, improved health-related quality of life and functioning. The efficacy and effectiveness of existing antipsychotic drugs fail to address the full spectrum of symptoms and functional deficits that currently prevent patients with psychotic disorders from achieving fulfilling lives. The study of the pharmacological mechanism of action has increased our knowledge on molecular targets and brain circuits related to the antipsychotic properties of this drug class. However, our understanding of how these molecular targets and brain circuits relate to other aspects of disease pathophysiology like cognitive impairment and negative symptoms is incomplete although these are significant clinical unmet needs. Currently, there is still an important knowledge gap between psychopathology and pathophysiology in schizophrenia research. This may have contributed to some recent costly failures of large clinical development programs for drugs targeted at glutamatergic function and nicotinic receptors. The lack of success of these pharmacological approaches to achieve clinical validation raises important questions concerning the underlying hypothesis that guided the choice of molecular targets, and about the predictive validity of translational models that supported the rationale for testing these drugs in clinical studies. From a clinical perspective there is a need to more strongly consider the disease heterogeneity linked to the use of the current diagnostic classification of subjects and to the validity of the psychopathological constructs and assessments that are used to assess clinical outcomes. A paradigm shift in the development of drugs for schizophrenia is needed. This will require among other addressing: the shortcomings of a

Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods

OpenAIRE

Reeves, Gloria M; Keeton, Courtney; Correll, Christoph U; Johnson, Jacqueline L; Hamer, Robert M; Sikich, Linmarie; Hazzard, Lindsey; Alderman, Cheryl; Scheer, Abigail; Mabe, Micah; Kapoor, Sandeep; Sheridan, Eva; Borner, Irmgard; Bussell, Kristin; Pirmohamed, Sara

2013-01-01

Background Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) stu...

Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents.

Science.gov (United States)

El-Hayek, Georges; Bangalore, Sripal; Casso Dominguez, Abel; Devireddy, Chandan; Jaber, Wissam; Kumar, Gautam; Mavromatis, Kreton; Tamis-Holland, Jacqueline; Samady, Habib

2017-03-13

The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (6 months), the strut thickness of the BP-DES (thin 100 μm), or the DAPT duration (≥6 months vs. ≥12 months). BP-DES have similar safety and efficacy profiles to second-generation DP-DES. Published by Elsevier Inc.

Incidence of periprocedural myocardial infarction following stent implantation: Comparison between first- and second-generation drug-eluting stents

NARCIS (Netherlands)

Tandjung, Kenneth; Basalus, Mounir W.Z.; Muurman, Esther; Louwerenburg, Hans W.; van Houwelingen, Gert K.; Stoel, Martin G.; de Man, Frits H.A.F.; Jansen, Hanneke; Huisman, Jennifer; Linssen, Gerard C.M.; Droste, Herman T.; Nienhuis, Mark B.; von Birgelen, Clemens

2012-01-01

Background: First- and second-generation drug-eluting stents (DES) differ in coating materials, which may influence the incidence of periprocedural myocardial infarction (PMI). Objective: To compare the incidence of PMI between first- and second-generation DES, using the current Academic Research

Diabetic control and atypical antipsychotics: a case report

Directory of Open Access Journals (Sweden)

Gaston Romina

2008-05-01

Full Text Available Abstract Introduction People with schizophrenia are at increased risk of developing metabolic disturbances. This risk may be further exacerbated by the use of antipsychotic agents. Research is still ongoing to determine the metabolic impact of antipsychotics on glucose regulation. In this case report we review some of the possible mechanisms of action of antipsychotic medication on glucose regulation. Case presentation We present the case of a 50-year-old man diagnosed with paranoid schizophrenia who developed type 2 diabetes mellitus whilst on treatment with second generation antipsychotics (SGA. His diabetes was controlled by a combination of antidiabetic drugs that were associated with his psychotropic treatment. Due to deterioration in his mental state, the patient was admitted on two occasions to a psychiatric unit during which his prescribed medication (olanzapine and risperidone was discontinued and changed to aripiprazole. On both occasions, the patient suffered hypoglycaemic episodes and his antidiabetic treatment had to be adjusted accordingly. The patient did not require any antidiabetic treatment whilst on aripiprazole during the follow up period. Conclusion Clinicians face regular dilemmas in trying to find the right balance between achieving control over a patient's mental illness and reducing any adverse effects associated with the prescribed medication. In patients receiving concomitant antidiabetic therapy, caution should be exercised when changing from one SGA to another. Whilst more longitudinal data are required, a trial of alternative SGAs, including aripiprazole in those developing type 2 diabetes and impaired glucose tolerance may be a worthwhile therapeutic option.

Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

OpenAIRE

Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

2010-01-01

Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

Simultaneous Determination of Antipsychotic Drugs and Their Active Metabolites by LC-MS-MS and its Application to Therapeutic Drug Monitoring.

Science.gov (United States)

Miroshnichenko, Igor I; Baymeeva, Natalia V

2018-04-07

A quantitative method was developed to support therapeutic drug monitoring of eight antipsychotic drugs: chlorpromazine, haloperidol, zuclopenthixol, clozapine, risperidone, quetiapine, aripiprazole or olanzapine and some active metabolites (dehydroaripiprazole, N-desmethylclozapine and 9-hydroxyrisperidone) in human serum. Separation of the compounds was achieved using a Zorbax SB-C18 (150 mm × 4.6 mm, 5 μm) column and mass-spectrometric detection in multiple reaction monitoring mode. Human blood samples were collected in vacutainer tubes and the analytes were extracted with methyl-tert-butyl ether. The lower limits of quantitation were equal 0.5-1 ng/mL for all analytes. The method was applied with success to serum samples from schizophrenic patients undergoing polypharmacy with two or more different antipsychotic drugs. Precision data, accuracy results were satisfactory, and no interference from other psychotropic drugs was found. Hence, the method is suitable for the TDM of the analytes in psychotic patients' serum.

[Paroxysmal perceptual alteration in comparison with hallucination--a review of its clinical reports and discussion of its pathophysiological mechanism in the present day, when second generation antipsychotics are widely used].

Science.gov (United States)

Watanabe, Ken

2009-01-01

The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985. Since then, many PPA cases have been reported, and its pathophysiological mechanism has been proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors, sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack, patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not real and apprehensive about them. The attack ceases gradually and spontaneously while the patient rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations. It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were prevailing. The occurrence of PPA has been significantly reduced to the present, when second generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these second generation

Off-Label Prescribing of Second-Generation Antipsychotics to Elderly Veterans with Posttraumatic Stress Disorder and Dementia.

Science.gov (United States)

Semla, Todd P; Lee, Austin; Gurrera, Ronald; Bajor, Laura; Li, Mingfei; Miller, Donald R; Smith, Eric G; Wang, Chao; Wan, Yun; Kazis, Lewis E; Bauer, Mark S

2017-08-01

To determine whether elderly veterans with posttraumatic stress disorder (PTSD) and dementia are more likely to be prescribed second-generation antipsychotics (SGAs) than those with PTSD alone. National serial cross-sectional study. Veterans Health Affairs inpatient and outpatient settings. Veterans aged 65 and older with PTSD (excluding schizophrenia or bipolar disorder) with or without concomitant dementia who received care from the Veterans Health Administration between 2003 and 2010 were identified using International Classification of Diseases, Ninth Revision, codes (N = 93,068; 11.1% with dementia). Trends in SGA prescribing and odds of being prescribed an SGA were determined using a multivariable logistic regression model adjusted for clinical, sociodemographic, and geographic covariates. Between 2004 and 2009, SGA prescribing declined annually from 7.0% to 5.1% of elderly veterans with PTSD without dementia and 13.2% to 8.9% in those with dementia; findings over time consistently indicated that veterans with PTSD and dementia had at least twice the odds of being prescribed an SGA as those without PTSD (odds ratios 2.03 (95% confidence interval (CI) = 1.82-2.26) to 2.33 (95% CI = 2.10-2.58). Although the prescribing of SGAs to elderly veterans with PTSD has decreased, prescribing an SGA to those with dementia remained consistently higher than for those with PTSD alone and is problematic given the high prevalence of medical comorbidities in this aging population coupled with the lack of compelling evidence for effectiveness of SGAs in individuals with dementia. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

DEFF Research Database (Denmark)

Pouzet, B; Mow, T; Kreilgaard, Mads

2003-01-01

compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review.

Science.gov (United States)

Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

2010-04-01

After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was

Antipsychotic prescribing in older people.

Science.gov (United States)

Neil, Wendy; Curran, Stephen; Wattis, John

2003-09-01

Antipsychotic medications have made a significant contribution to the care of the mentally ill people over the past 50 years, with good evidence that both typical and atypical agents are effective in the treatment of schizophrenia and related conditions. In addition they are widely used to good effect in other disorders including psychotic depression, dementia and delirium. Both typical and atypical agents may cause severe side-effects and, in the elderly in particular, there is an increased propensity for drug interactions. If used with care, antipsychotics are usually well tolerated, especially the atypical drugs. Although antipsychotics are effective at reducing psychotic symptoms their limitations should be recognised. They do not 'cure' the underlying illness, and the management of psychotic and behavioural symptoms must take into consideration treatment of physical illness as well as psychosocial interventions. In addition, the antipsychotic effect may take one to two weeks to be evident so doses should not be increased too rapidly. Often small doses are effective in the elderly if they are given sufficient time to work. As our understanding of the mechanisms of psychosis improves it is hoped that new drugs will be developed with novel mechanisms of action with improved efficacy and reduced side-effects. There are several drugs in development, some sharing similarities to currently available agents whilst others have novel mechanisms of actions involving glutamate and nicotinic receptors. Pharmacogenetics is also likely to be increasingly important over the next few years. As the genetic basis of many psychiatric disorders becomes more clearly established it is likely that drugs specifically designed for particular sub-groups of receptors will be developed. Finally, although the pharmacological treatment of psychotic disorders in younger people has been given considerable attention, there is a paucity of good quality research on antipsychotic drug use in

Prediabetes in patients treated with antipsychotic drugs.

Science.gov (United States)

Manu, Peter; Correll, Christoph U; van Winkel, Ruud; Wampers, Martien; De Hert, Marc

2012-04-01

In 2010, the American Diabetes Association (ADA) proposed that individuals with fasting glucose level of 100-125 mg/dL (5.6-6.9 mmol/L) or glucose level of 140-199 mg/dL (7.8-11.0 mmol/L) 2 hours after a 75-g oral glucose tolerance test or hemoglobin A(1c) 5.7%-6.4% be classified as prediabetic, indicating increased risk for the emergence of diabetes mellitus. At the same time, the ADA formulated guidelines for the use of metformin for the treatment of prediabetes. To determine the prevalence of prediabetes in a cohort of psychiatrically ill adults receiving antipsychotics and to compare the clinical and metabolic features of prediabetic patients with those of patients with normal glucose tolerance and those with diabetes mellitus. The 2010 ADA criteria were applied to a large, consecutive, single-site European cohort of 783 adult psychiatric inpatients (mean age: 37.6 years) without a history of diabetes who were receiving antipsychotics. All patients in this cross-sectional study underwent measurement of body mass index (BMI), waist circumference, oral glucose tolerance test, and fasting insulin and lipids from November 2003 through July 2007. 413 patients (52.8%) had normal glucose tolerance, 290 (37.0%) had prediabetes, and 80 (10.2%) had diabetes mellitus. The fasting glucose and/or hemoglobin A(1c) criteria were met by 89.7% of prediabetic patients. A statistically significant intergroup gradient from normal glucose tolerance to prediabetes and from prediabetes to diabetes mellitus was observed for waist circumference, triglycerides, fasting insulin levels, and frequency of metabolic syndrome (P = .02 to P prediabetic patients (6.6%) met the 2010 ADA criteria for treatment with metformin. Prediabetes is highly prevalent in adults treated with antipsychotic drugs and correlates with markers of increased intraabdominal adiposity, enhanced lipolysis, and insulin resistance. Criteria for using metformin to prevent the emergence of diabetes mellitus may need to be

Movement disorders in elderly users of risperidone and first generation antipsychotic agents: a Canadian population-based study.

Directory of Open Access Journals (Sweden)

Irina Vasilyeva

Full Text Available Despite concerns over the potential for severe adverse events, antipsychotic medications remain the mainstay of treatment of behaviour disorders and psychosis in elderly patients. Second-generation antipsychotic agents (SGAs; e.g., risperidone, olanzapine, quetiapine have generally shown a better safety profile compared to the first-generation agents (FGAs; e.g., haloperidol and phenothiazines, particularly in terms of a lower potential for involuntary movement disorders. Risperidone, the only SGA with an official indication for the management of inappropriate behaviour in dementia, has emerged as the antipsychotic most commonly prescribed to older patients. Most clinical trials evaluating the risk of movement disorders in elderly patients receiving antipsychotic therapy have been of limited sample size and/or of relatively short duration. A few observational studies have produced inconsistent results.A population-based retrospective cohort study of all residents of the Canadian province of Manitoba aged 65 and over, who were dispensed antipsychotic medications for the first time during the time period from April 1, 2000 to March 31, 2007, was conducted using Manitoba's Department of Health's administrative databases. Cox proportional hazards models were used to determine the risk of extrapyramidal symptoms (EPS in new users of risperidone compared to new users of FGAs.After controlling for potential confounders (demographics, comorbidity and medication use, risperidone use was associated with a lower risk of EPS compared to FGAs at 30, 60, 90 and 180 days (adjusted hazard ratios [HR] 0.38, 95% CI: 0.22-0.67; 0.45, 95% CI: 0.28-0.73; 0.50, 95% CI: 0.33-0.77; 0.65, 95% CI: 0.45-0.94, respectively. At 360 days, the strength of the association weakened with an adjusted HR of 0.75, 95% CI: 0.54-1.05.In a large population of elderly patients the use of risperidone was associated with a lower risk of EPS compared to FGAs.

Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs.

Science.gov (United States)

Andreasen, Nancy C; Pressler, Marcus; Nopoulos, Peg; Miller, Del; Ho, Beng-Choon

2010-02-01

A standardized quantitative method for comparing dosages of different drugs is a useful tool for designing clinical trials and for examining the effects of long-term medication side effects such as tardive dyskinesia. Such a method requires establishing dose equivalents. An expert consensus group has published charts of equivalent doses for various antipsychotic medications for first- and second-generation medications. These charts were used in this study. Regression was used to compare each drug in the experts' charts to chlorpromazine and haloperidol and to create formulas for each relationship. The formulas were solved for chlorpromazine 100 mg and haloperidol 2 mg to derive new chlorpromazine and haloperidol equivalents. The formulas were incorporated into our definition of dose-years such that 100 mg/day of chlorpromazine equivalent or 2 mg/day of haloperidol equivalent taken for 1 year is equal to one dose-year. All comparisons to chlorpromazine and haloperidol were highly linear with R(2) values greater than .9. A power transformation further improved linearity. By deriving a unique formula that converts doses to chlorpromazine or haloperidol equivalents, we can compare otherwise dissimilar drugs. These equivalents can be multiplied by the time an individual has been on a given dose to derive a cumulative value measured in dose-years in the form of (chlorpromazine equivalent in mg) x (time on dose measured in years). After each dose has been converted to dose-years, the results can be summed to provide a cumulative quantitative measure of lifetime exposure. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Occupancy of dopamine D-2 receptors by antipsychotic drugs is related to nicotine addiction in young patients with schizophrenia

NARCIS (Netherlands)

de Haan, Lieuwe; Booij, Jan; Lavalaye, Jules; van Amelsvoort, Therese; Linszen, Don

2006-01-01

Rationale: Occupancy of dopamine D-2 receptors by antipsychotic drugs depends on the individual availability of D-2 receptors and on the dose and type of antipsychotic medication. It has been suggested that a low availability of these receptors may increase the risk for addictive behavior.

Antipsychotic-induced Hyperprolactinemia

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Suheyla Dogan Bulut

2015-06-01

Full Text Available Prolactin provides the growth of the mammary gland during pregnancy and synthesis and preparation of breast milk for lactation. Antipsychotics and antidepressants that are frequently used in psychiatry, cause hyperprolactinemia. The prevalent opinion is that especially typical antipsychotics increase prolactin levels primarily by blocking D2 receptors in the anterior pituitary. The effects of atypical antipsychotics on hyperprolactinemia vary. Hyperprolactinemia causes galactorrhea, gynecomastia, sexual dysfunction, infertility, acne, hirsutism in women, weight gain, obesity and mood changes in addition to menstrual irregularities such as oligomenorrhea, polymenorrhea and amenorrhea. In the long term, hyperprolactinemia may cause reduction in bone density and osteoporosis. Hyperprolactinemia as a side effect of antipsychotics drugs and its treatment will be reviewed in this article. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(2: 109-124

Antipsychotics and Sexual Dysfunction: Sexual Dysfunction - Part III

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Anil Kumar Mysore Nagaraj

2009-11-01

Full Text Available Satisfying sexual experience is an essential part of a healthy and enjoyable life for most people. Antipsychotic drugs are among the various factors that affect optimal sexual functioning. Both conventional and novel antipsychotics are associated with significant sexual side effects. This review has presented various studies comparing different antipsychotic drugs. Dopamine antagonism, increased serum prolactin, serotonergic, adrenergic and cholinergic mechanisms are all proposed to be the mechanisms for sexual dysfunction. Drug treatment for this has not given satisfactory long-term results. Knowledge of the receptor pharmacology of an individual antipsychotic will help to determine whether it is more or less likely to cause sexual side effects and its management.

Zotepine versus other atypical antipsychotics for schizophrenia

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Subramanian, Selvizhi; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Kissling, Werner; Leucht, Stefan; Komossa, Katja

2014-01-01

Background In many parts of the world, particularly in industrialised countries, second generation (atypical) antipsychotic drugs have become first line treatment for people suffering from schizophrenia. The question as to whether the effects of various second generation antipsychotic drugs differ is a matter of debate. Objectives To evaluate the effects of zotepine compared with other second generation antipsychotic drugs for people suffering from schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (November 2009), inspected references of all identified studies for further trials and contacted authors of trials for additional information. Selection criteria We included only randomised clinical controlled trials that compared zotepine with any forms of amisulpride, aripiprazole, clozapine, olanzapine, risperidone, sertindole or ziprasidone in people suffering from only schizophrenia or schizophrenia-like psychoses. Data collection and analysis SS and KK extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated weighted mean differences (MD) again based on a random-effects model. Main results We included three studies (total n=289; 2 RCTs zotepine vs clozapine; 1 RCT zotepine vs clozapine vs risperidone (at 4 mg, 8 mg doses) vs remoxipride. All studies were of limited methodological quality. When zotepine was compared with clozapine, it was clozapine that was found to be more effective in terms of global state (n=59, 1 RCT, RR No clinically significant response 8.23 CI 1.14 to 59.17). Mental state scores also favoured clozapine (n=59, 1 RCT, MD average score (BPRS total, high = poor) 6.00 CI 2.17 to 9.83) and there was less use of antiparkinson medication in the clozapine group (n=116, 2 RCTs, RR 20.96 CI 2.89 to 151.90). In the

Impact of antipsychotic medication on transcranial direct current stimulation (tDCS) effects in schizophrenia patients.

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Agarwal, Sri Mahavir; Bose, Anushree; Shivakumar, Venkataram; Narayanaswamy, Janardhanan C; Chhabra, Harleen; Kalmady, Sunil V; Varambally, Shivarama; Nitsche, Michael A; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

2016-01-30

Transcranial direct current stimulation (tDCS) has generated interest as a treatment modality for schizophrenia. Dopamine, a critical pathogenetic link in schizophrenia, is also known to influence tDCS effects. We evaluated the influence of antipsychotic drug type (as defined by dopamine D2 receptor affinity) on the impact of tDCS in schizophrenia. DSM-IV-TR-diagnosed schizophrenia patients [N=36] with persistent auditory hallucinations despite adequate antipsychotic treatment were administered add-on tDCS. Patients were divided into three groups based on the antipsychotic's affinity to D2 receptors. An auditory hallucinations score (AHS) was measured using the auditory hallucinations subscale of the Psychotic Symptom Rating Scales (PSYRATS). Add-on tDCS resulted in a significant reduction inAHS. Antipsychotic drug type had a significant effect on AHS reduction. Patients treated with high affinity antipsychotics showed significantly lesser improvement compared to patients on low affinity antipsychotics or a mixture of the two. Furthermore, a significant sex-by-group interaction occurred; type of medication had an impact on tDCS effects only in women. Improvement differences could be due to the larger availability of the dopamine receptor system in patients taking antipsychotics with low D2 affinity. Sex-specific differences suggest potential estrogen-mediated effects. This study reports a first-time observation on the clinical utility of antipsychotic drug type in predicting tDCS effects in schizophrenia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antipsychotic-induced somnolence in mothers with schizophrenia.

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Seeman, Mary V

2012-03-01

Although it is known that many antipsychotic drugs, at the doses prescribed for schizophrenia, are sedative and cause daytime drowsiness, the effect of potentially diminished vigilance on parenting parameters has not been studied. The aim of this paper is to advise clinicians about sedative load in mothers who are prescribed antipsychotic medication. A Medline search was conducted into the sedative effects of antipsychotics, with the following search terms: sleep; sedation; somnolence; wakefulness; antipsychotics; schizophrenia, parenting, maternal behavior, and custody. The results showed that antipsychotic drugs differ in their propensity to induce sedation and do so via their effects on a variety of neurotransmitter systems. It is important to note that mothers with schizophrenia risk losing custody of their infants if they are perceived as potentially neglectful because of excessive daytime sleepiness. Clinicians must choose antipsychotic medications carefully and monitor for sedative effects whenever the patient has important responsibilities that require the maintenance of vigilance.

Monitoring of Recommended Metabolic Laboratory Parameters Among Medicaid Recipients on Second-Generation Antipsychotics in Federally Qualified Health Centers.

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Uzal, Natalia E; Chavez, Benjamin; Kosirog, Emily R; Billups, Sarah J; Saseen, Joseph J

2018-02-01

In 2004, a consensus statement outlining recommended metabolic monitoring for patients prescribed second-generation antipsychotics (SGAs) was published. More than a decade later, suboptimal adherence rates to these recommendations continue to be reported, which could lead to long-term and costly complications. To define the prevalence of appropriately monitored Medicaid patients receiving care at federally qualified health centers (FQHCs) prescribed SGAs. This was a retrospective study examining electronic health record and Medicaid claims data to assess the rates of glucose and lipid monitoring for patients prescribed SGAs from January 2014 to August 2016 in a FQHC. Prescription and laboratory claims for patients receiving care at 4 FQHCs were reviewed. Descriptive statistics were used to evaluate the primary outcome. A total of 235 patients were included in the analysis. Patients initiated on SGA therapy (n = 92) had baseline glucose and lipid monitoring rates of 50% and 23%, respectively. The 3-month monitoring rates were 37% for glucose and 26% for lipids, whereas annual rates were 71% and 40%, respectively. Patients continuing SGA therapy (n = 143) had annual glucose and lipid monitoring rates of 67% and 44%. Medicaid patients at FQHCs initially prescribed SGAs have low baseline and 3-month metabolic monitoring, whereas annual monitoring was comparable to previously published studies. Adults receiving chronic care at a FQHC were more likely to receive glucose monitoring. Those with type 2 diabetes mellitus and/or hyperlipidemia were more likely to receive glucose and lipid monitoring.

Some side effects and effcts on physical activity of second-generation antipsychotics: A study in children and adolescents

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Soroor Arman

2014-01-01

Full Text Available Background: This study was designed to investigate the metabolic adverse effects (AEs of second-generation antipsychotics (SGAs and their relationship with physical activity and non-metabolic AE in children and adolescents. Materials and Methods: After exclusion of patients with metabolic syndrome, 62 patients (34 children, 28 adolescents of both genders who were candidates for SGA therapy were selected. Metabolic parameters included fasting blood glucose (FBG, triglyceride (TG, blood pressure (BP, and waist circumference (WC; non-metabolic AEs and physical activity were evaluated at baseline, 1 month, and 3 months after starting the treatment. Results: Mean of post-treatment FBG and TG were significantly higher than the baseline values (P 0.05. The frequency of patients with AbH-TG at the end point was not significantly higher than those with baseline AbH-TG (P = 0.10. Although no patient was obese at baseline, 11 (18% patients developed abdominal obesity at the end point (P 0.05. There was no significant correlation between metabolic and non-metabolic AE (P > 0.05. Frequency of inactive patients was significantly more than the baseline value (P-0.008, and abdominal obesity was significantly more prevalent in less active participants (P = 0.03. Conclusion: The present study showed the AE of SGA on FBG and TG, but no effect on BP and WC. We also found that children are more prone to develop abnormally high FBG.

Antipsychotics and Associated Risk of Out-of-Hospital Cardiac Arrest

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Weeke, Peter; Jensen, Aksel; Folke, Fredrik

2014-01-01

% confidence interval [CI]:1.23-1.89) as was use with typical antipsychotics (OR= 1.66, CI: 1.27-2.17). By contrast, overall atypical antipsychotics drug use was not (OR= 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs were associated with OHCA, haloperidol (OR= 2.43, CI: 1...

[From cradle to grave? Expectations from atypical antipsychotics].

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Frecska, Ede

2005-03-01

Clinical expectations are high toward atypical, second generation antipsychotics (SGAs). Controlled clinical trials supporting the superiority of SGAs over traditional agents are scarce. Meta-analysis of existing data may come for the rescue but that kind of method has its limitations. One of the most meticulous approaches (Davis et al. 2003) reached the conclusion that some, but not all, SGAs are more efficacious than traditional ones. Within the group of distinguished drugs, clozapine and amisulpride have the highest efficacy. The present paper critically overviews the study of the Davis group. Based on in vivo D2 receptor binding data of the new SGAs and the usual post marketing changes of clinical dosing, it is expected that some of the currently and most recently marketed SGAs may show similar superiority.

Recovery of behavioral changes and compromised white matter in C57BL/6 mice exposed to cuprizone: Effects of antipsychotic drugs

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Haiyun eXu

2011-07-01

Full Text Available Recent animal and human studies have suggested that the cuprizone (CPZ, a copper chelator-feeding C57BL/6 mouse may be used as an animal model of schizophrenia. The goals of this study were to see the recovery processes of CPZ-induced behavioral changes and damaged white matter and to examine possible effects of antipsychotic drugs on the recovery processes. Mice were fed a CPZ-containing diet for five weeks then returned to normal food for three weeks, during which period mice were treated with different antipsychotic drugs. Various behaviors were measured at the end of CPZ-feeding phase as well as on the 14th and 21st days after CPZ-withdrawal. The damage to and recovery status of white matter in the brains of mice were examined. Dietary CPZ resulted in white matter damage and behavioral abnormalities in the elevated plus-maze, social interaction and Y-maze test. Elevated plus-maze performance recovered to normal range within two weeks after CPZ withdrawal. But, alterations in social interaction showed no recovery. Antipsychotics did not alter animals’ behavior in either of these tests during the recovery period. Altered performance in the Y-maze showed some recovery in the vehicle group; atypical antipsychotics, but not haloperidol, significantly promoted this recovery process. The recovery of damaged white matter was incomplete during the recovery period. None of the drugs significantly promoted the recovery of damaged white matter. These results suggest that CPZ-induced white matter damage and social interaction deficit may be resistant to the antipsychotic treatment employed in this study. They are in good accordance with the clinical observations that positive symptoms in schizophrenic patients respond well to antipsychotic drugs while social dysfunction is usually intractable.

Models of treatment with antipsychotics of the schizophrenic patients

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Svjetlana Loga-Zec

2005-11-01

Full Text Available The aim of this study were to determine which antipsychotic are currently in use, to establish which doses are administrated to patients, to find out is there a practice of proscribing simultaneously more then one antipsychotic drug, to determine whether antipsychotic are proscribed in divided doses, to establish whether there is, besides antipsychotics, treatment with other medicaments (co-administration, especially with antiparkinsonics. The research (study is epidemiological-clinical prospective, descriptive and analytical and it was conducted at University hospitals in Sarajevo, Tuzla and Mostar. Criteria for inclusion, non-inclusion and exclusion from the study were precisely defined as a mean for formation of sample. Based on this hypothesis were established, zero and alterative. According to zero hypothesis in the treatment of schizophrenia at University hospitals in FBiH new antipsychotic drugs are in use, small doses are proscribed (up to 20 mg, not more then one antipsychotic drug is used simultaneously, antipsychotics are administrated once a day and alongside with antipsychotics other medicaments are not co-administrated, especially antiparkinsons. The results of our study are showing that majority of patients are treated with classical antipsychotics. Minority of patients is treated with atypical neuroleptics like olanzapine, which is proscribed only in Sarajevo. Use of risperidone and ziprasidone is registered also only in Sarajevo, but only small number of patients is treated with these drugs. Most frequent antipsychotics were promazine and haloperidol. The range between minimal and maximal daily dose of promazine was from 50 to 450 mg/daily, and for haloperidol from 1 to 75 mg/daily. Above-mentioned drugs were administrated in an average from two to three times a day. Alongside with antipsychotics, other drugs were used. Most frequent was the use of biperidine in oral and parenteral formulation, as

A review of the evidence for the use of metformin in the treatment of metabolic syndrome caused by antipsychotics.

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Jesus, Cátia; Jesus, Inês; Agius, Mark

2015-09-01

Psychiatric patients requiring therapy with antipsychotics have a greater incidence of becoming overweight or obese compared with the general population. Many of these patients are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidaemia, and other metabolic derangements. The most important and first line of treatment for the metabolic syndrome is lifestyle changes including diet and exercise. However, other approaches like the use of medication (e.g. Metformin) have been also used, mainly when the lifestyle changes are difficult to achieve. Therefore, the treatment of antipsychotic-induced weight gain with metformin may be an option after the lifestyle and dietary changes fail. The use of metformin is still experimental and off license regarding the treatment of metabolic syndrome in Psychiatric patients, however we wished to assess the evidence for its use. Our study is a literature based research. For our research we reviewed 12 Pubmed published articles from 2006 to 2013. Metformin have been reported to counteract effectively antipsychotic-induced body weight gain and has been demonstrated to improve glycaemic control and promote a moderate weight loss in both diabetic and non-diabetic subjects. Metformin use appears to be a benefit when started early in the course of treatment and mostly in young adults newly exposed to antipsychotic drugs.

No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia.

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Goto, Naoki; Yoshimura, Reiji; Kakeda, Shingo; Moriya, Junji; Hori, Hikaru; Hayashi, Kenji; Ikenouchi-Sugita, Atsuko; Nakano-Umene, Wakako; Katsuki, Asuka; Nishimura, Joji; Korogi, Yukunori; Nakamura, Jun

2010-12-01

We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia. Copyright © 2010 Elsevier Inc. All rights reserved.

Persistence of metabolic monitoring for psychiatry inpatients treated with second-generation antipsychotics utilizing a computer-based intervention.

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Lee, J; Dalack, G W; Casher, M I; Eappen, S A; Bostwick, J R

2016-04-01

Monitoring and intervention for metabolic abnormalities secondary to second-generation antipsychotics (SGAs) remain weak areas of performance in mental health care. This study evaluated the sustained impact of a computerized physician order entry (CPOE) pop-up alert designed to improve rates of laboratory metabolic monitoring of patients treated with SGAs in an inpatient psychiatry unit. Interventions carried out by the psychiatry team to manage metabolic abnormalities found on screening were also identified. A retrospective chart review of patients treated with scheduled SGAs at a large Midwestern academic medical centre's inpatient adult psychiatry unit was conducted nearly 4 years after the initial implementation of a pop-up alert. Rates of laboratory monitoring (blood glucose level, haemoglobin A1C [HbA1c], lipid panel) were compared to those following the initial implementation. Medical charts of patients with abnormal laboratory results were also reviewed to summarize interventions made by the psychiatry team to manage identified abnormalities. Patient demographics in the current study population (n = 129) were similar to those in the initial test cohort (n = 157). There was no significant decrease in monitoring of glucose levels and lipid panels (fasting or random). Nine patients with abnormally elevated laboratories were identified. Interventions by the psychiatry team included referrals to appropriate healthcare professionals and initiation of medication. The rate of metabolic monitoring for inpatients on SGA therapy did not significantly change over time with the continued use of the CPOE pop-up alert. Optimal monitoring utilizing a CPOE pop-up alert may allow the psychiatry team, including psychiatric pharmacists, to better manage metabolic conditions. © 2016 John Wiley & Sons Ltd.

[French Society for Biological Psychiatry and Neuropsychopharmacology task force: Formal Consensus for the prescription of depot antipsychotics].

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Samalin, L; Abbar, M; Courtet, P; Guillaume, S; Lancrenon, S; Llorca, P-M

2013-12-01

Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed. Copyright © 2013 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Some novelties and recommendations by swithing antipsychotics

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Nika Aleksandra Kravos

2014-11-01

Full Text Available Clinical outcome of patients with severe mental disorders treated with antipsychotics depends on individual response to therapy, adverse events, physical health, maintaining of physical health and of the patient’s, interpersonal (patient - therapist, health and environmental features. Replacement of antipsychotics is a common therapeutic measure. The response depends on mostly unknown genetic factors, physiological particularities of the patient and its variations. This article summarizes the most important and the most recent pharmacological properties and consequences of cross-action of antipsychotics. It specifies the basic rules and ways of replacing antipsychotic drugs in different clinical situations, and summarizes alerts, recommendations and suggestions when changing antipsychotics.

Association between community pharmacy loyalty and persistence and implementation of antipsychotic treatment among individuals with schizophrenia.

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Zongo, Frank E; Moisan, Jocelyne; Grégoire, Jean-Pierre; Lesage, Alain; Dossa, Anara Richi; Lauzier, Sophie

2018-01-01

Non-adherence is a major obstacle to optimal treatment of schizophrenia. Community pharmacists are in a key position to detect non-adherence and put in place interventions. Their role is likely to be more efficient when individuals are loyal to a single pharmacy. To assess the association between the level of community pharmacy loyalty and persistence with and implementation of antipsychotic drug treatment among individuals with schizophrenia. A cohort study using databases from the Quebec health insurance board (Canada) was conducted among new antipsychotic users insured by Quebec's public drug plan. Level of community pharmacy loyalty was assessed as the number of pharmacies visited in the year after antipsychotics initiation. Persistence was defined as having an antipsychotic supply in the user's possession on the 730 th day after its initiation and implementation as having antipsychotics in the user's possession for ≥80% of the days in the second year after antipsychotics initiation (among persistent only). Generalized linear models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (95%CI). 6,251 individuals were included in the cohort and 54.1% had their drug prescriptions filled in >1 pharmacy. When compared to those who had their prescriptions filled in a single pharmacy, those who had their prescriptions filled in ≥4 different pharmacies were 22% more likely to be non-persistent (aPR = 1.22; 95%CI = 1.10-1.37) and 49% more likely to have an antipsychotic for loyalty in the context of severe mental illness indicates that this healthcare organisation factor might be associated with antipsychotics persistence and implementation. Identification of individuals with low community pharmacy loyalty and initiatives to optimize community pharmacy loyalty could contribute to enhanced persistence and implementation. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of an empiric Bayesian data mining algorithm to reports of pancreatitis associated with atypical antipsychotics.

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Hauben, Manfred

2004-09-01

To compare the results from one frequently cited data mining algorithm with those from a study, which was published in a peer-reviewed journal, that examined the association of pancreatitis with selected atypical antipsychotics observed by traditional rule-based methods of signal detection. Retrospective pharmacovigilance study. The widely studied data mining algorithm known as the Multi-item Gamma Poisson Shrinker (MGPS) was applied to adverse-event reports from the United States Food and Drug Administration's Adverse Event Reporting System database through the first quarter of 2003 for clozapine, olanzapine, and risperidone to determine if a significant signal of pancreatitis would have been generated by this method in advance of their review or the addition of these events to the respective product labels. Data mining was performed by using nine preferred terms relevant to drug-induced pancreatitis from the Medical Dictionary for Regulatory Activities (MedDRA). Results from a previous study on the antipsychotics were reviewed and analyzed. Physicians' Desk References (PDRs) starting from 1994 were manually reviewed to determine the first year that pancreatitis was listed as an adverse event in the product label for each antipsychotic. This information was used as a surrogate marker of the timing of initial signal detection by traditional criteria. Pancreatitis was listed as an adverse event in a PDR for all three atypical antipsychotics. Despite the presence of up to 88 reports/drug-event combination in the Food and Drug Administration's Adverse Event Reporting System database, the MGPS failed to generate a signal of disproportional reporting of pancreatitis associated with the three antipsychotics despite the signaling of these drug-event combinations by traditional rule-based methods, as reflected in product labeling and/or the literature. These discordant findings illustrate key principles in the application of data mining algorithms to drug safety

Effects of Antipsychotic Drugs Haloperidol and Clozapine on Visual Responses of Retinal Ganglion Cells in a Rat Model of Retinitis Pigmentosa.

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Jensen, Ralph J

2016-12-01

In the P23H rat model of retinitis pigmentosa, the dopamine D2 receptor antagonists sulpiride and eticlopride appear to improve visual responses of retinal ganglion cells (RGCs) by increasing light sensitivity of RGCs and transforming abnormal, long-latency ON-center RGCs into OFF-center cells. Antipsychotic drugs are believed to mediate their therapeutic benefits by blocking D2 receptors. This investigation was conducted to test whether haloperidol (a typical antipsychotic drug) and clozapine (an atypical antipsychotic drug) could similarly alter the light responses of RGCs in the P23H rat retina. Extracellular recordings were made from RGCs in isolated P23H rat retinas. Responses of RGCs to flashes of light were evaluated before and during bath application of a drug. Both haloperidol and clozapine increased light sensitivity of RGCs on average by ∼0.3 log unit. For those ON-center RGCs that exhibit an abnormally long-latency response to the onset of a small spot of light, both haloperidol and clozapine brought out a short-latency OFF response and markedly reduced the long-latency ON response. The selective serotonin 5-HT2A antagonist MDL 100907 had similar effects on RGCs. The effects of haloperidol on light responses of RGCs can be explained by its D2 receptor antagonism. The effects of clozapine on light responses of RGCs on the other hand may largely be due to its 5-HT2A receptor antagonism. Overall, the results suggest that antipsychotic drugs may be useful in improving vision in patients with retinitis pigmentosa.

The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs

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Nordon C

2017-12-01

Full Text Available Clementine Nordon,1 Constance Battin,1 Helene Verdoux,2 Josef Maria Haro,3 Mark Belger,4 Lucien Abenhaim,1 Tjeerd Pieter van Staa5 On behalf of the IMI GetReal WP2 Group 1Epidemiological Research, Analytica LASER, Paris, 2Population Health Research Center, Team Pharmaco-Epidemiology, UMR 1219, Bordeaux-2 University, INSERM, Bordeaux, France; 3Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Barcelona, Spain; 4Eli Lilly and Company Limited, Erl Wood Manor, Windlesham, 5Farr Institute, University of Manchester, Manchester, UK Purpose: A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level.Patients and methods: Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist’s gender, age, length of practice experience, practice setting and type, countries’ Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1 to estimate antipsychotic drugs’ effectiveness (defined as the association between patients’ outcome at 3 months – dependent variable, continuous – and antipsychotic drug initiation at baseline – drug A vs other antipsychotic drug; 2 to estimate the similarity between clustered data (using the intra-cluster correlation coefficient; and 3 to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term.Results: About 23% of the variance found for patients’ outcome was explained by unmeasured confounding at a center level. Psychiatrists’ practice experience was found to be associated with patient outcomes (p=0.04 and modified the relative effect of “drug A” (p<0.001, independent of center- or patient

SEXUAL DYSFUNCTION INDUCED BY ANTI-PSYCHOTICS AND ANTI-DEPRESSANTS IN DRUG NAIVE PATIENTS – A COMPARATIVE STUDY

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M. Mohanalakshmi

2017-03-01

Full Text Available BACKGROUND The aim of this study was to determine and compare sexual dysfunction caused by anti-psychotics and anti-depressants in drug naïve patients. MATERIALS AND METHODS Patients diagnosed as drug naïve schizophrenic and depression as per DSM-5 criteria & age between 18-45 years were recruited and allocated into group A (n=30–receiving anti-psychotics & group B (n=30 receiving anti-depressants after informed consent by the patients. Sexual dysfunction was assessed by Arizona Sexual Experiences Scale (ASEX during the initial 2 months of therapy. RESULTS ASEX mean for patients receiving antipsychotics increased from the baseline of 7.97 to 17.23 and the ASEX mean for patients receiving antidepressants increased from baseline of 7.80 to 18.67 with p value of 0.249 which is not statistically significant. Among the antipsychotics haloperidol ASEX mean increased from 7.87 to 18.00 and risperidone mean increased from 8.07 to 16.47 with the p value of 0.335 which is not significant. More patients on haloperidol showed evidence of sexual dysfunction as assessed by ASEX scoring than risperidone though p value was not significant. Among the two antidepressants ASEX score mean for amitriptyline patients increased from 8.07 to 16.47, and that of fluoxetine from 7.53 to 16.47 with the p value of 0.018* statistically significant at α of 0.05 level. CONCLUSION This study shows presence of sexual dysfunction in patients receiving antipsychotics & antidepressants by 2 nd month of therapy though statistically not significant. Fluoxetine group patients developed statistically significant sexual dysfunction. Implications for future research about sexual dysfunction in all new treatments should be strongly taken into account because this side effect adds to the emotional stress and worsening of mental dysfunction.

Atypical antipsychotics and glucose homeostasis.

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Bergman, Richard N; Ader, Marilyn

2005-04-01

needed. A major problem in assessing drug effects is that psychiatric disease itself can cause many of the manifestations leading to diabetes, including weight gain and sedentary lifestyle. While studies in healthy subjects are limited and inconclusive, studies in animal models are more revealing. In the conscious canine model, some atypical antipsychotics cause adiposity, including visceral obesity, a strong risk factor for the metabolic syndrome. Furthermore, while few studies have examined effects of antipsychotics on pancreatic beta-cell function, canine studies demonstrate that expected beta-cell compensation for insulin resistance may be reduced or even eliminated with these agents. Atypical antipsychotics have been shown to contribute to weight gain, which may well reflect increased body fat deposition. Such increased fat is known to cause resistance to insulin action, although more information regarding effect on insulin action is needed. The effect of these drugs on fat distribution has been clearly shown in animal models. It is known that the normal response to insulin resistance is compensatory hyperinsulinemia, which may prevent diabetes. In animals, there is evidence that the hyperinsulinemic compensation is inadequate in the face of atypical antipsychotic agents. It remains to be examined whether failure of adequate pancreatic beta-cell compensation for insulin resistance plays a central role in the pathogenesis of diabetes associated with this class of drugs.

Atypical antipsychotic drugs and diabetes mellitus in the US Food and Drug Administration Adverse Event database: a systematic Bayesian signal detection analysis.

Science.gov (United States)

Baker, Ross A; Pikalov, Andrei; Tran, Quynh-Van; Kremenets, Tatyana; Arani, Ramin B; Doraiswamy, P Murali

2009-01-01

Prior literature suggests that the risk of diabetes-related adverse events (DRAEs) differs between atypical antipsychotics. The present study evaluated the potential association between atypical antipsychotics or haloperidol and diabetes using data from the FDA AERS database. Analysis of AERS data was conducted for clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole or haloperidol with 24 DRAEs from the Medical Dictionary for Regulatory Activities using a Multi-item Gamma Poisson Shrinker (MGPS) data-mining algorithm. Using MGPS, adjusted reporting ratios (Empiric Bayes Geometric Mean or EBGM) and 90% confidence intervals (CIs; EB05-EB95) were calculated to estimate the degree of drug-event association relative to all drugs and events. Logistic regression odds ratios and 90% CIs (LR05-LR95) were calculated for diabetes mellitus events. All six atypicals had an EB05 >/= 2 for at least one DRAE. The most common event was diabetes mellitus (2,784 cases). Adjusted reporting ratios (CIs) for diabetes mellitus were: olanzapine 9.6 (9.2-10.0; 1306 cases); risperidone 3.8 (3.5-4.1; 447 cases); quetiapine 3.5 (3.2-3.9; 283 cases); clozapine 3.1 (2.9-3.3; 464 cases); ziprasidone 2.4 (2.0-2.9; 74 cases); aripiprazole 2.4 (1.9-2.9; 71 cases); haloperidol 2.0 (1.7-2.3; 139 cases). Logistic regression odds ratios agreed with adjusted reporting ratios. In the AERS database, lower associations with DRAEs were seen for haloperidol, aripiprazole and ziprasidone, and higher associations were seen for olanzapine, risperidone, clozapine and quetiapine. Our findings support differential risk of diabetes across atypical antipsychotics, reinforcing the need for metabolic monitoring of patients taking antipsychotics.

First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry.

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Jong-Hwa Ahn

Full Text Available Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES versus first-generation DES in patients with coronary chronic total occlusion (CTO who undergo percutaneous coronary intervention (PCI. The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO.Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557 or second-generation DES (n = 449 were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72 or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99. After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86 and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71 were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE.This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up.

First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro.

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Canfrán-Duque, Alberto; Barrio, Luis C; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A; Busto, Rebeca

2016-03-18

First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1'-dioctadecyl-3,3,3,3'-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes' internal milieu induced by haloperidol affects lysosomal functionality.

[The key role of patient in the antipsychotic therapy: shared decision making, adherence and research].

Science.gov (United States)

Gallingani, Francesca; Piccinni, Carlo; Simeoni, Angela; Poluzzi, Elisabetta; Menchetti, Marco; Berardi, Domenico

2015-11-01

A large number of currently available antipsychotic drugs are included into two main classes: traditional (or first-generation), and atypical (or second-generation) antipsychotics. This wide availability of medicinal products allows, at least in part, to address the need to identify the most appropriate treatment for the individual patient. A precondition for the effectiveness of antipsychotic treatment is the adherence, a multi-determined phenomenon that depends on factors related to the pharmacological properties of each agent and on factors independent from the therapy: among them, therapeutic alliance between patients and medical team, patient's belief in benefits and risks of medicines, and patient's relationship with the family and social environment are the most clearly recognized. The collection of data from patient helps the management of the individual clinical case, but this information could also become a source of data for research. In both cases, data must be collected in a ordered and well-coded way, therefore numerous instruments (like questionnaires and registers) are developing. This approach permits to make a recognition of patient's perception of his health condition, as well as the positive and negative outcomes of his pharmacological treatment. These tools are known in the literature by the name of PROMs (patient-reported outcome measures). From the clinical point of view, the PROMs can reduce the gap between patient and clinician in different therapeutic areas. They also enables the physician to identify the most suitable treatment to the individual patient, to meet his needs and preferences, and to adapt the therapy over time to the changes of his medical condition. About the research, the effects reported by the patient, in terms of both benefits and adverse reactions, represent important information useful to conduct observational studies that better define the benefit-risk profile of drug therapies, especially in psychiatry.

Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats

DEFF Research Database (Denmark)

Oliveras, Ignasi; Sánchez-González, Ana; Sampedro-Viana, Daniel

2017-01-01

acutely administered propsychotic (DOI, MK-801) and antipsychotic drugs (haloperidol, clozapine), as well as apomorphine, on prepulse inhibition (PPI) of startle and locomotor activity (activity cages). RESULTS: RHA-I rats display a consistent deficit of PPI compared with RLA-I rats. The typical...... antipsychotic haloperidol (dopamine D2 receptor antagonist) reversed the PPI deficit characteristic of RHA-I rats (in particular at 65 and 70 dB prepulse intensities) and reduced locomotion in both strains. The atypical antipsychotic clozapine (serotonin/dopamine receptor antagonist) did not affect PPI...

Atypicality of Atypical Antipsychotics

OpenAIRE

Farah, Andrew

2005-01-01

Objective: To review the current definition of atypicality, discuss the unique features of each atypical antipsychotic, and determine whether the available drugs in this class really meet the classical definition of atypicality.

Typical and Atypical Antipsychotic Drugs Increase Extracellular Histamine Levels in the Rat Medial Prefrontal Cortex: Contribution of Histamine H1 Receptor Blockade

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Kjell A Svensson

2012-05-01

Full Text Available Atypical antipsychotics such as clozapine and olanzapine have been shown to enhance histamine turnover and this effect has been hypothesized to contribute to their improved therapeutic profile compared to typical antipsychotics. In the present study, we examined the effects of antipsychotic drugs on histamine (HA efflux in the mPFC of the rat by means of in vivo microdialysis and sought to differentiate the receptor mechanisms which underlie such effects. Olanzapine and clozapine increased mPFC HA efflux in a dose related manner. Increased HA efflux was also observed after quetiapine, chlorpromazine and perphenazine treatment. We found no effect of the selective 5-HT2A antagonist MDL100907, 5-HT2c antagonist SB242084 or the 5-HT6 antagonist Ro 04-6790 on mPFC HA efflux. HA efflux was increased following treatment with selective H1 receptor antagonists pyrilamine, diphenhydramine and triprolidine, the H3 receptor antagonist ciproxifan and the mixed 5HT2A/H1 receptor antagonist ketanserin. The potential novel antipsychotic drug FMPD, which has a lower affinity at H1 receptors than olanzapine, did not affect HA efflux. Similarly, other antipsychotics with lower H1 receptor affinity (risperidone, aripiprazole and haloperidol were also without effect on HA efflux. Perfusion of clozapine and pyrilamine into the TMN, but not the mPFC, increased local HA efflux. Finally, HA efflux after antipsychotic treatment was significantly correlated with affinity at H1 receptors whereas 9 other receptors, including 5-HT2A, were not. These results demonstrate that both typical and atypical antipsychotics increase mPFC histamine efflux and this effect may be mediated via antagonism of histamine H1 receptors.

An epidemiological study of concomitant use of Chinese medicine and antipsychotics in schizophrenic patients: implication for herb-drug interaction.

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Zhang-Jin Zhang

Full Text Available BACKGROUND: Herb-drug interactions are an important issue in drug safety and clinical practice. The aim of this epidemiological study was to characterize associations of clinical outcomes with concomitant herbal and antipsychotic use in patients with schizophrenia. METHODS AND FINDINGS: In this retrospective, cross-sectional study, 1795 patients with schizophrenia who were randomly selected from 17 psychiatric hospitals in China were interviewed face-to-face using a structured questionnaire. Association analyses were conducted to examine correlates between Chinese medicine (CM use and demographic, clinical variables, antipsychotic medication mode, and clinical outcomes. The prevalence of concomitant CM and antipsychotic treatment was 36.4% [95% confidence interval (95% CI 34.2%-38.6%]. Patients using concomitant CM had a significantly greater chance of improved outcomes than non-CM use (61.1% vs. 34.3%, OR = 3.44, 95% CI 2.80-4.24. However, a small but significant number of patients treated concomitantly with CM had a greater risk of developing worse outcomes (7.2% vs. 4.4%, OR = 2.06, 95% CI 2.06-4.83. Significant predictors for concomitant CM treatment-associated outcomes were residence in urban areas, paranoid psychosis, and exceeding 3 months of CM use. Herbal medicine regimens containing Radix Bupleuri, Fructus Gardenia, Fructus Schisandrae, Radix Rehmanniae, Akebia Caulis, and Semen Plantaginis in concomitant use with quetiapine, clozapine, and olanzepine were associated with nearly 60% of the risk of adverse outcomes. CONCLUSIONS: Concomitant herbal and antipsychotic treatment could produce either beneficial or adverse clinical effects in schizophrenic population. Potential herb-drug pharmacokinetic interactions need to be further evaluated.

Antipsychotics and physical attractiveness.

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Seeman, Mary V

2011-10-01

Antipsychotics are effective in treating the symptoms of schizophrenia, but they may induce adverse effects, some of which-those that impact negatively on physical appearance-have not been sufficiently discussed in the psychiatric literature. Through a narrative review, to catalog antipsychotic side effects that interfere with physical attractiveness and to suggest ways of addressing them. PubMed databases were searched for information on the association between "antipsychotic side effects" and "attractiveness" using those two search phrases plus the following terms: "weight," "teeth," "skin," "hair," "eyes," "gait," "voice," "odor." Data from relevant qualitative and quantitative articles were considered, contextualized, and summarized. Antipsychotics, as a group, increase weight and may lead to dry mouth and bad breath, cataracts, hirsutism, acne, and voice changes; they may disturb symmetry of gait and heighten the risk for tics and spasms and incontinence, potentially undermining a person's attractiveness. Clinicians need to be aware of the impact of therapeutic drugs on appearance and how important this issue is to patients. Early in treatment, they need to plan preventive and therapeutic strategies.

Antipsychotic-associated psoriatic rash - a case report

DEFF Research Database (Denmark)

Bujor, Camelia-Eugenia; Vang, Torkel; Nielsen, Jimmi

2017-01-01

BACKGROUND: Antipsychotics are a heterogeneous group of drugs. Although, antipsychotics have been used for years, unexpected side effects may still occur. With this case report we focus on a possible association between psoriasis and antipsychotics. Data on the patient's course of psychiatric...... disease, onset of psoriasis and its evolution were extracted from the patient's medical files. CASE PRESENTATION: We present a case of a 21-year-old female diagnosed with schizophrenia. She was initially treated with quetiapine, and later switched to aripiprazole due to weight gain. After initiation...

Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

Science.gov (United States)

Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

2018-04-01

Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

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Alberto Canfrán-Duque

2016-03-01

Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2 and LBPA (lysobisphosphatidic acid, which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1 and coatomer subunit β (β-COP were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality.

First-Generation Antipsychotic Haloperidol Alters the Functionality of the Late Endosomal/Lysosomal Compartment in Vitro

Science.gov (United States)

Canfrán-Duque, Alberto; Barrio, Luis C.; Lerma, Milagros; de la Peña, Gema; Serna, Jorge; Pastor, Oscar; Lasunción, Miguel A.; Busto, Rebeca

2016-01-01

First- and second-generation antipsychotics (FGAs and SGAs, respectively), have the ability to inhibit cholesterol biosynthesis and also to interrupt the intracellular cholesterol trafficking, interfering with low-density lipoprotein (LDL)-derived cholesterol egress from late endosomes/lysosomes. In the present work, we examined the effects of FGA haloperidol on the functionality of late endosomes/lysosomes in vitro. In HepG2 hepatocarcinoma cells incubated in the presence of 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanineperchlorate (DiI)-LDL, treatment with haloperidol caused the enlargement of organelles positive for late endosome markers lysosome-associated membrane protein 2 (LAMP-2) and LBPA (lysobisphosphatidic acid), which also showed increased content of both free-cholesterol and DiI derived from LDL. This indicates the accumulation of LDL-lipids in the late endosomal/lysosomal compartment caused by haloperidol. In contrast, LDL traffic through early endosomes and the Golgi apparatus appeared to be unaffected by the antipsychotic as the distribution of both early endosome antigen 1 (EEA1) and coatomer subunit β (β-COP) were not perturbed. Notably, treatment with haloperidol significantly increased the lysosomal pH and decreased the activities of lysosomal protease and β-d-galactosidase in a dose-dependent manner. We conclude that the alkalinization of the lysosomes’ internal milieu induced by haloperidol affects lysosomal functionality. PMID:26999125

Self-reported motivation to smoke in schizophrenia is related to antipsychotic drug treatment.

Science.gov (United States)

Barr, Alasdair M; Procyshyn, Ric M; Hui, Philip; Johnson, Joy L; Honer, William G

2008-03-01

The prevalence of smoking in schizophrenia has reliably been reported as being higher than for any other psychiatric disorder. While a number of theories have been proposed to account for such high rates of smoking, little is known about the subjective motivation for why schizophrenia patients smoke in comparison with those without the disease. The aim of the present study was to evaluate and compare smoking motivation in control subjects and schizophrenia patients, and determine if factors such as type of medication or access to cigarettes could contribute to self-reported motivation for smoking. We assessed motivation to smoke in 61 schizophrenia inpatients and 33 non-psychiatric health worker controls at a tertiary care psychiatric facility in a cross-sectional study. Nicotine dependency and smoking behavior were evaluated using the Fagerstrom Test for Nicotine Dependence and a validated questionnaire that assesses motivation for smoking along seven different dimensions. Schizophrenia patients reported a stronger motivation to smoke than controls for reasons related to pleasure from the act of smoking, as well as a need for psychomotor stimulation. Scores on both these factors were significantly associated with daily antipsychotic drug dose. The sedative and anxiolytic effects of smoking were related to anticholinergic load of psychiatric medications. The findings highlight important differences in self-reported motivation to smoke between schizophrenia patients and normals. Antipsychotic drugs may also influence aspects of motivation to smoke.

An explorative study of school performance and antipsychotic medication

NARCIS (Netherlands)

van der Schans, J.; Vardar, S; Cicek, R.; Bos, H. J.; Hoekstra, P. J.; de Vries, T. W.; Hak, E.

2016-01-01

Background: Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. Methods:

Animal behavior models of the mechanisms underlying antipsychotic atypicality.

NARCIS (Netherlands)

Geyer, M.A.; Ellenbroek, B.A.

2003-01-01

This review describes the animal behavior models that provide insight into the mechanisms underlying the critical differences between the actions of typical vs. atypical antipsychotic drugs. Although many of these models are capable of differentiating between antipsychotic and other psychotropic

Sixty Years of Placebo-Controlled Antipsychotic Drug Trials in Acute Schizophrenia: Systematic Review, Bayesian Meta-Analysis, and Meta-Regression of Efficacy Predictors.

Science.gov (United States)

Leucht, Stefan; Leucht, Claudia; Huhn, Maximilian; Chaimani, Anna; Mavridis, Dimitris; Helfer, Bartosz; Samara, Myrto; Rabaioli, Matteo; Bächer, Susanne; Cipriani, Andrea; Geddes, John R; Salanti, Georgia; Davis, John M

2017-10-01

Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences. The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression. The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a "minimal" response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a "good" response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time. Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.

Pharmacodynamics and common drug-drug interactions of the third-generation antiepileptic drugs.

Science.gov (United States)

Stefanović, Srđan; Janković, Slobodan M; Novaković, Milan; Milosavljević, Marko; Folić, Marko

2018-02-01

Anticonvulsants that belong to the third generation are considered as 'newer' antiepileptic drugs, including: eslicarbazepine acetate, lacosamide, perampanel, brivaracetam, rufinamide and stiripentol. Areas covered: This article reviews pharmacodynamics (i.e. mechanisms of action) and clinically relevant drug-drug interactions of the third-generation antiepileptic drugs. Expert opinion: Newer antiepileptic drugs have mechanisms of action which are not shared with the first and the second generation anticonvulsants, like inhibition of neurotransmitters release, blocking receptors for excitatory amino acids and new ways of sodium channel inactivation. New mechanisms of action increase chances of controlling forms of epilepsy resistant to older anticonvulsants. Important advantage of the third-generation anticonvulsants could be their little propensity for interactions with both antiepileptic and other drugs observed until now, making prescribing much easier and safer. However, this may change with new studies specifically designed to discover drug-drug interactions. Although the third-generation antiepileptic drugs enlarged therapeutic palette against epilepsy, 20-30% of patients with epilepsy is still treatment-resistant and need new pharmacological approach. There is great need to explore all molecular targets that may directly or indirectly be involved in generation of seizures, so a number of candidate compounds for even newer anticonvulsants could be generated.

Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery

DEFF Research Database (Denmark)

Mangione, Fernanda Marinho; Biering-Sørensen, Tor; Nochioka, Kotaro

2017-01-01

OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to b...

Choice of antipsychotic treatment by European psychiatry trainees: are decisions based on evidence?

Directory of Open Access Journals (Sweden)

Jauhar Sameer

2012-03-01

Full Text Available Abstract Background Little is known about the factors influencing treatment choice in psychosis, the majority of this work being conducted with specialists (consultant in psychiatry. We sought to examine trainees' choices of treatment for psychosis if they had to prescribe it for themselves, their patients, and factors influencing decision-making. Methods Cross-sectional, semi-structured questionnaire-based study. Results Of the 726 respondents (response rate = 66%, the majority chose second-generation antipsychotics (SGAs if they had to prescribe it for themselves (n = 530, 93% or for their patients (n = 546, 94%. The main factor influencing choice was perceived efficacy, 84.8% (n = 475 of trainees stating this was the most important factor for the patient, and 77.8% (n = 404 stating this was the most important factor for their own treatment. Trainees with knowledge of trials questioning use of SGAs (CATIE, CUtLASS, TEOSS were more likely to choose second-generation antipsychotics than those without knowledge of these trials (χ2 = 3.943; p = 0.047; O.R. = 2.11; 95% C.I. = 1.0-4.48. Regarding psychotherapy, cognitive behavioural therapy (CBT was the most popular choice for self (33.1%; n = 240 and patient (30.9%; n = 224. Trainees were significantly more likely to prefer some form of psychotherapy for themselves rather than patients (χ2 = 9.98; p Conclusions Trainees are more likely to choose second-generation antipsychotic medication for patients and themselves. Despite being aware of evidence that suggests otherwise, they predominantly base these choices on perceived efficacy.

Serum total homocystein, folate and vitamin B12 levels and their correlation with antipsychotic drug doses in adult male patients with chronic schizophrenia.

Science.gov (United States)

Eren, Esin; Yeğin, Ayşenur; Yilmaz, Necat; Herken, Hasan

2010-01-01

Elevated blood levels of homocysteine (hCY) have been associated with schizophrenic male patients. However, controversy remains regarding the association between lowered plasma folate and vitamin B12, hyperhomocysteinemia, and schizophrenia. Sixty-six (66) male patients with chronic schizophrenia were investigated to test the hypotheses that alterations in Hcy, folate, and vitamin B12 levels might be related to the antipsychotic drug doses used in treatment. Serum total homocysteine, folic acid, and vitamin B12 levels were determined by chemiluminescence methods in both patients and control subjects. The patients were grouped according to the antipsychotic drug doses used in their treatment. Patients had higher homocysteine levels but they did not differ from controls in terms of folate and vitamin B12 levels. On the other hand, only folate levels were negatively correlated in the patient group treated with higher therapeutic doses of chlorpromazine equivalents (> 400 mg/day) compared to the patient group with lower doses (< 400 mg/day). Our findings show that higher typical antipsychotic drugs may play a role as modifiying factor for folate metabolism in chronic schizoprenic male patients.

Does mental health staffing level affect antipsychotic prescribing? Analysis of Italian national statistics.

Science.gov (United States)

Starace, Fabrizio; Mungai, Francesco; Barbui, Corrado

2018-01-01

In mental healthcare, one area of major concern identified by health information systems is variability in antipsychotic prescribing. While most studies have investigated patient- and prescriber-related factors as possible reasons for such variability, no studies have investigated facility-level characteristics. The present study ascertained whether staffing level is associated with antipsychotic prescribing in community mental healthcare. A cross-sectional analysis of data extracted from the Italian national mental health information system was carried out. For each Italian region, it collects data on the availability and use of mental health facilities. The rate of individuals exposed to antipsychotic drugs was tested for evidence of association with the rate of mental health staff availability by means of univariate and multivariate analyses. In Italy there were on average nearly 60 mental health professionals per 100,000 inhabitants, with wide regional variations (range 21 to 100). The average rate of individuals prescribed antipsychotic drugs was 2.33%, with wide regional variations (1.04% to 4.01%). Univariate analysis showed that the rate of individuals prescribed antipsychotic drugs was inversely associated with the rate of mental health professionals available in Italian regions (Kendall's tau -0.438, p = 0.006), with lower rates of antipsychotic prescriptions in regions with higher rates of mental health professionals. After adjustment for possible confounders, the total availability of mental health professionals was still inversely associated with the rate of individuals exposed to antipsychotic drugs. The evidence that staffing level was inversely associated with antipsychotic prescribing indicates that any actions aimed at decreasing variability in antipsychotic prescribing need to take into account aspects related to the organization of the mental health system.

Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia

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Zachary Freyberg

2017-07-01

Full Text Available For decades, there have been observations demonstrating significant metabolic disturbances in people with schizophrenia including clinically relevant weight gain, hypertension, and disturbances in glucose and lipid homeostasis. Many of these findings pre-date the use of antipsychotic drugs (APDs which on their own are also strongly associated with metabolic side effects. The combination of APD-induced metabolic changes and common adverse environmental factors associated with schizophrenia have made it difficult to determine the specific contributions of each to the overall metabolic picture. Data from drug-naïve patients, both from the pre-APD era and more recently, suggest that there may be an intrinsic metabolic risk associated with schizophrenia. Nevertheless, these findings remain controversial due to significant clinical variability in both psychiatric and metabolic symptoms throughout patients' disease courses. Here, we provide an extensive review of classic and more recent literature describing the metabolic phenotype associated with schizophrenia. We also suggest potential mechanistic links between signaling pathways associated with schizophrenia and metabolic dysfunction. We propose that, beyond its symptomatology in the central nervous system, schizophrenia is also characterized by pathophysiology in other organ systems directly related to metabolic control.

Antipsychotic Prescriptions for Children Aged 5 Years or Younger

Directory of Open Access Journals (Sweden)

Ana Lòpez-De Fede

2014-10-01

Full Text Available The use of antipsychotics in very young children is of concern given the lack of empirical evidence in their efficacy and long-term impact on children’s health. This study examined the prescription of antipsychotics among children aged ≤5 years enrolled in a state Medicaid program. Secondary data analysis was conducted using the Medicaid administrative data of a southeastern state. Using SAS 9.3, descriptive statistics were performed to examine socio-demographic characteristics, psychiatric diagnoses, off-label use, receipt of medications from multiple psychotropic drug classes, and receipt of non-pharmacologic psychiatric services among children aged ≤5 years who received antipsychotic prescriptions in calendar year (CY 2011. A total of 112 children in the target age group received antipsychotics in CY 2011, the most common prescription being risperidone. The most common listed psychiatric diagnosis was attention deficit hyperactivity disorder. Two in five children received antipsychotics for off-label use. Three in four children also received medications from at least one other psychotropic drug class. More than half did not receive adjunct psychiatric services. State-level policies offering specific guidance and recommendations for antipsychotic use among very young children are urgently needed. Future research is warranted to examine long-term impact of such practices on children’s growth and development.

Comparison of the effectiveness of brand-name and generic antipsychotic drugs for treating patients with schizophrenia in Taiwan.

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Hsu, Chih-Wei; Lee, Sheng-Yu; Wang, Liang-Jen

2018-03-01

The purpose of this nationwide population-based study is to compare the long-term effectiveness of brand-name antipsychotics with generic antipsychotics for treating schizophrenia. We identified patients with schizophrenia who were prescribed antipsychotics from a random sample of one million records from Taiwan's National Health Insurance database, observed between January 1, 2000 and December 31, 2012. Only those with no prior use of antipsychotics for at least 180days were included. We selected patients who were prescribed brand-name risperidone (N=404), generic risperidone (N=145), brand-name sulpiride (N=334), or generic sulpiride (N=991). The effectiveness of the treatments researched in this study consisted of average daily doses, rates of treatment discontinuation, augmentation therapy, and psychiatric hospitalization. We found that compared to patients treated with generic risperidone, those treated with brand-name risperidone required lower daily doses (2.14mg vs. 2.61mg). However, the two groups demonstrated similar rates of treatment discontinuation, augmentation, and psychiatric hospitalization. On the other hand, in comparison with patients prescribed generic sulpiride, those treated with brand-name sulpiride not only required lower daily doses (302.72mg vs. 340.71mg) but also had lower psychiatric admission rates (adjusted hazard ratio: 0.24, 95% confidence interval: 0.10-0.56). In conclusion, for both risperidone and sulpiride, higher daily doses of the respective generic drugs were prescribed than with brand-name drugs in clinical settings. Furthermore, the brand-name sulpiride is more effective at preventing patients from hospitalization than generic sulpiride. These findings can serve as an important reference for clinical practices and healthcare economics for treating schizophrenic patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting Injectable Antipsychotics

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Ludovic Samalin

2016-11-01

Full Text Available The purpose of this study was to identify clinician characteristics associated with higher prescription rates of long-acting injectable (LAI antipsychotics, as well as the sources that influence medical decision-making regarding the treatment of schizophrenia. We surveyed 202 psychiatrists during six regional French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg. Data on the characteristics of practice, prescription rates of antipsychotic, and information sources about their clinical decisions were collected. Most psychiatrists used second-generation antipsychotics (SGAs, and preferentially an oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to 30.4% of schizophrenic patients. The duration and type of practice did not influence the class or formulation of antipsychotics used. The clinicians following the higher percentage of schizophrenic patients were associated with a higher use of LAI antipsychotics and a lower use of oral SGAs. Personal experience, government regulatory approval, and guidelines for the treatment of schizophrenia were the three main contributing factors guiding clinicians’ decision-making regarding the treatment of schizophrenia. The more clinicians follow schizophrenic patients, the more they use LAI antipsychotics. The development of specialized programs with top specialists should lead to better use of LAI antipsychotics in the treatment of schizophrenia.

Molecular Mechanisms of Antipsychotic Drug-Induced Diabetes

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Jiezhong Chen

2017-11-01

Full Text Available Antipsychotic drugs (APDs are widely prescribed to control various mental disorders. As mental disorders are chronic diseases, these drugs are often used over a life-time. However, APDs can cause serious glucometabolic side-effects including type 2 diabetes and hyperglycaemic emergency, leading to medication non-compliance. At present, there is no effective approach to overcome these side-effects. Understanding the mechanisms for APD-induced diabetes should be helpful in prevention and treatment of these side-effects of APDs and thus improve the clinical outcomes of APDs. In this review, the potential mechanisms for APD-induced diabetes are summarized so that novel approaches can be considered to relieve APD-induced diabetes. APD-induced diabetes could be mediated by multiple mechanisms: (1 APDs can inhibit the insulin signaling pathway in the target cells such as muscle cells, hepatocytes and adipocytes to cause insulin resistance; (2 APD-induced obesity can result in high levels of free fatty acids (FFA and inflammation, which can also cause insulin resistance. (3 APDs can cause direct damage to β-cells, leading to dysfunction and apoptosis of β-cells. A recent theory considers that both β-cell damage and insulin resistance are necessary factors for the development of diabetes. In high-fat diet-induced diabetes, the compensatory ability of β-cells is gradually damaged, while APDs cause direct β-cell damage, accounting for the severe form of APD-induced diabetes. Based on these mechanisms, effective prevention of APD-induced diabetes may need an integrated approach to combat various effects of APDs on multiple pathways.

Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment

DEFF Research Database (Denmark)

Sjo, Christina Power; Stenstrøm, Anne Dorte; Bojesen, Anders Bo

2017-01-01

if obesity or metabolic aberration starts in childhood or adolescence. METHODS: Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG......), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were determined through regular follow-ups. RESULTS: The sample included 35 SGA-naive patients aged 7-19 (mean: 15.5) with a diagnosis of psychosis. Over 12 months, the overall rate of MetS changed significantly (from 0% to 20% [p 

First-generation versus second-generation drug-eluting stents in current clinical practice: updated evidence from a comprehensive meta-analysis of randomised clinical trials comprising 31 379 patients

NARCIS (Netherlands)

Navarese, E.P.; Kowalewski, M.; Kandzari, D.; Lansky, A.; Gorny, B.; Koltowski, L.; Waksman, R.; Berti, S.; Musumeci, G.; Limbruno, U.; Schaaf, R.J. van der; Kelm, M.; Kubica, J.; Suryapranata, H.

2014-01-01

BACKGROUND: First-generation drug-eluting stents (DES) have become the most widely used devices worldwide for management of coronary artery disease. As remote follow-up data were becoming available, concerns emerged in regard to their long-term safety. Second-generation DES were designed to overcome

Use of Academic Detailing With Audit and Feedback to Improve Antipsychotic Pharmacotherapy.

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Brunette, Mary F; Cotes, Robert O; de Nesnera, Alexander; McHugo, Gregory; Dzebisashvili, Nino; Xie, Haiyi; Bartels, Stephen J

2018-06-08

Second-generation antipsychotics vary in their propensity to cause serious cardiometabolic side effects. In addition, use of two or more antipsychotics (polypharmacy) may lead to additive side effects and has not been shown to be consistently more effective than monotherapy. This study examined the use of academic detailing with audit and feedback to improve antipsychotic prescribing practices, including antipsychotic polypharmacy and utilization of medication with high or low risk of cardiometabolic side effects ("high risk" or "low risk," respectively). Four intervention sessions were provided over two years to psychiatric care providers at community mental health centers. Segmented regression within the general estimating equation model framework used Medicaid pharmacy claims to examine prescribing patterns before and after the intervention among all beneficiaries (67,721 person-months) over a five-year period. After the intervention, 10.9% of beneficiaries with antipsychotic claims were on polypharmacy, compared with 13.1% before the invention. Use of high-risk and low-risk antipsychotics did not change. The final adjusted polypharmacy model showed that antipsychotic polypharmacy decreased among young adults and adults ages 40 or older compared with beneficiaries ages 30-39 (β=-.02, p=.04, and β=-.02, p=.007, respectively). The raw proportion of beneficiaries on high- and low-risk agents did not change, although final adjusted models demonstrated changes in use of high- and low-risk agents by diagnosis and risk group. Polypharmacy decreased among young and older adults after academic detailing with audit and feedback. Although further research is needed, this low-intensity intervention may help mental health systems reduce antipsychotic polypharmacy.

sigma opiates and certain antipsychotic drugs mutually inhibit (+)-[3H]SKF 10,047 and [3H]haloperidol binding in guinea pig brain membranes

International Nuclear Information System (INIS)

Tam, S.W.; Cook, L.

1984-01-01

The relationship between binding of antipsychotic drugs and sigma psychotomimetic opiates to binding sites for the sigma agonist (+)-[ 3 H]SKF 10,047 (N-allylnormetazocine) and to dopamine D 2 sites was investigated. In guinea pig brain membranes, (+)-[ 3 H]SKF 10,047 bound to single class of sites with a K/sub d/ of 4 x 10 -8 M and a B/sub max/ of 333 fmol/mg of protein. This binding was different from μ, kappa, or delta opiate receptor binding. It was inhibited by opiates that produce psychotomimetic activities but not by opiates that lack such activities. Some antipsychotic drugs inhibited (+)-[ 3 H]SKF 10,047 binding with high to moderate affinities in the following order of potency: haloperidol > perphenazine > fluphenazine > acetophenazine > trifluoperazine > molindone greater than or equal to pimozide greater than or equal to thioridazine greater than or equal to chlorpromazine greater than or equal to triflupromazine. However, there were other antipsychotic drugs such as spiperone and clozapine that showed low affinity for the (+)-[ 3 H]SKF 10,047 binding sites. Affinities of antipsychotic drugs for (+)-[ 3 H]SKF 10,047 binding sites did not correlate with those for [ 3 H]spiperone (dopamine D 2 ) sites. [ 3 H]-Haloperidol binding in whole brain membranes was also inhibited by the sigma opiates pentazocine, cyclazocine, and (+)-[ 3 H]SKF 10,047. In the striatum, about half of the saturable [ 3 H]haloperidol binding was to [ 3 H]spiperone (D 2 ) sites and the other half was to sites similar to (+)-[ 3 H]SKF 10,047 binding sites. 15 references, 4 figures, 1 table

Trends in Antipsychotic Drug Use by Very Young, Privately Insured Children

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Olfson, Mark; Crystal, Stephen; Huang, Cecilia; Gerhard, Tobias

2010-01-01

Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years. Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured…

A Survey of the Tardive Dyskinesia Induced by Antipsychotic Drugs in Patients with Schizophrenia

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Naser tabibi

2010-11-01

Full Text Available "nObjective: Tardive Dyskinesia (TD, is one of the important problems of the patients with schizophrenia. The emergence of these side effects depends on so many factors such as the patients' age and the duration of antipsychotic treatment. By discovering new drugs (Atypical, there has been an outstanding decrease in the emergence of these side effects. The present study investigates the symptoms of TD in the Patients with schizophrenia who were under  treatments for more than 6 months. "nMethod: The sample of this study was 200 Patients with schizophrenia of four wards in Razi hospital (two acute and two chronic wards who were hospitalized in the winter of 2006 and were qualified for this study. The subjects were 101 males and 99 females who were younger than 60 and had received antipsychotic drugs for at least 6 months. After psychiatric interview and filling the demographic questionnaire by the patients, the required information about the drugs and the intensity of the symptoms was acquired. Then clinical and physical examinations of tardive dyskinesia were done. Next, the tardive dyskinesia disorders' check list (AIMS was used. Findings of this cross-sectional, descriptive study were analyzed by SPSS. "nResults: There was a high ratio of 95% between TD and the age factor (P=0.05. There was no relationship between symptoms frequency and duration of treatment (P=0.68. Facial muscles and oral zones were mostly involved in T.D disorder (72%. "nConclusion: No significant difference was observed between nine fold symptoms of T.D in patients who were using traditional drugs and those who were using the new ones (typical and atypical. Findings showed that in the intensity of the symptoms, gender does not play a major role.

The Analgesic Acetaminophen and the Antipsychotic Clozapine Can Each Redox-Cycle with Melanin.

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Temoçin, Zülfikar; Kim, Eunkyoung; Li, Jinyang; Panzella, Lucia; Alfieri, Maria Laura; Napolitano, Alessandra; Kelly, Deanna L; Bentley, William E; Payne, Gregory F

2017-12-20

Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context. The brain has a complex redox context with steep local gradients in O 2 that can promote redox-cycling between melanin and diffusible redox-active chemical species. Here, we performed in vitro reverse engineering studies and report that melanins can redox-cycle with two common redox-active drugs. Experimentally, we used two melanin models: a convenient natural melanin derived from cuttlefish (Sepia melanin) and a synthetic cysteinyldopamine-dopamine core-shell model of neuromelanin. One drug, acetaminophen (APAP), has been used clinically for over a century, and recent studies suggest that low doses of APAP can protect the brain from oxidative-stress-induced toxicity and neurodegeneration, while higher doses can have toxic effects in the brain. The second drug, clozapine (CLZ), is a second generation antipsychotic with polypharmacological activities that remain incompletely understood. These in vitro observations suggest that the redox activities of drugs may be relevant to their modes-of-action, and that melanins may interact with drugs in ways that affect their activities, metabolism, and toxicities.

ATYPICAL ANTIPSYCHOTICS USE IN CHILDREN AND ADOLESCENTS

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Nataša Potočnik-Dajčman

2002-06-01

Full Text Available Background. Classical antipsychotics – neuroleptics are one of the most frequently prescribed psychotropic drugs in child psychiatry. Atypical antipsychotics are used for the same indications – psychotic (schizophrenia as well as unpsychotic disorders (pervasive developmental disorders, mood disorders, conduct disorders and tics disorders. It is surprising that the studies on their use with regard to this age group are rather rare. They are carried out on a small number of samples and only exceptionally double blind. This article summarizes published clinical experience with atypical antipsychotics in children and adolescents. A short overview of pharmacodynamics, pharmacokinetics and side effects is given. Schizophrenia and pervasive developmental disorders are major indications for use of atypical antipsychotics in children and adolescents, but they have also been successfully used for other disorders such as aggressive behaviour, tics and anorexia nervosa.Conclusions. With better side-effect profile, some of the atypical antipsychotics are expected to be doctrinally recognised as the first-line treatment for childhood schizophrenia and pervasive developmental disorders. However, more long-term studies carried out on a larger sample are needed. Atypical antipsychotics are already used in everyday practice as first-line treatment of childhood and adolescents schizophrenia.

Metabolic Syndrome and Antipsychotics: The Role of Mitochondrial Fission/Fusion Imbalance

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Andrea del Campo

2018-04-01

Full Text Available Second-generation antipsychotics (SGAs are known to increase cardiovascular risk through several physiological mechanisms, including insulin resistance, hepatic steatosis, hyperphagia, and accelerated weight gain. There are limited prophylactic interventions to prevent these side effects of SGAs, in part because the molecular mechanisms underlying SGAs toxicity are not yet completely elucidated. In this perspective article, we introduce an innovative approach to study the metabolic side effects of antipsychotics through the alterations of the mitochondrial dynamics, which leads to an imbalance in mitochondrial fusion/fission ratio and to an inefficient mitochondrial phenotype of muscle cells. We believe that this approach may offer a valuable path to explain SGAs-induced alterations in metabolic homeostasis.

Drug-induced parkinsonism: diagnosis and management

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Blanchet PJ

2016-09-01

Full Text Available Pierre J Blanchet,1–3 Veronika Kivenko1–3 1Department of Stomatology, Faculty of Dental Medicine, University of Montreal, 2Andre-Barbeau Movement Disorders Unit, University of Montreal Hospital Center (CHU Montreal, 3Montreal Mental Health University Institute, Montreal, QC, Canada Abstract: Drug-induced parkinsonism (DIP has been known for >60 years. It is the second leading cause of parkinsonism, but still underdiagnosis is likely to influence reported incidence figures. Since DIP is clinically undistinguishable from Lewy-body Parkinson’s disease, any new case of parkinsonism should prompt the search for an offending antipsychotic, hidden neuroleptic, or nonneuroleptic agent that may produce DIP. DIP is reversible upon drug withdrawal in most cases. There is no consensus regarding the duration of the recovery period to allow motor signs to fully remit in order to confirm the diagnosis of DIP following removal of the causative agent, but a drug-free interval of at least 6 months is generally recommended. Interestingly, up to 30% of DIP cases may show persisting or worsening motor signs beyond 6 months following drug withdrawal or adjustment, due to complex postsynaptic and presynaptic factors that may variably interact to negatively influence nigrostriatal dopamine transmission in a so-called “double-hit” hypothesis. The condition significantly impacts on quality of life and increases the risks of morbidity and mortality. Management is challenging in psychiatric patients and requires a team approach to achieve the best outcome. Keywords: neuroleptic drugs, extrapyramidal side effects, second generation antipsychotics, calcium channel blockers, valproic acid, tetrabenazine 

Oral Medication for Agitation of Psychiatric Origin: A Scoping Review of Randomized Controlled Trials.

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Mullinax, Samuel; Shokraneh, Farhad; Wilson, Michael P; Adams, Clive E

2017-10-01

Understanding more about the efficacy and safety of oral second-generation antipsychotic medications in reducing the symptoms of acute agitation could improve the treatment of psychiatric emergencies. The objective of this scoping review was to examine the evidence base underlying expert consensus panel recommendations for the use of oral second-generation antipsychotics to treat acute agitation in mentally ill patients. The Cochrane Schizophrenia Group's Study-Based Register was searched for randomized controlled trials comparing oral second-generation antipsychotics, benzodiazepines, or first-generation antipsychotics with or without adjunctive benzodiazepines, irrespective of route of administration of the drug being compared. Six articles were included in the final review. Two oral second-generation antipsychotic medications were studied across the six included trials. While the studies had relatively small sample sizes, oral second-generation antipsychotics were similarly effective to intramuscular first-generation antipsychotics in treating symptoms of acute agitation and had similar side-effect profiles. This scoping review identified six randomized trials investigating the use of oral second-generation antipsychotic medications in the reduction of acute agitation among patients experiencing psychiatric emergencies. Further research will be necessary to make clinical recommendations due to the overall dearth of randomized trials, as well as the small sample sizes of the included studies. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of antipsychotics in the treatment of depressive disorders

Institute of Scientific and Technical Information of China (English)

Ping WANG; Tianmei SI

2013-01-01

There is a long history of using antipsychotic medications in the treatment of depressive disorders. Atypical antipsychotics, which have fewer side effects than traditional antipsychotics, have been used as monotherapy or adjunctively with antidepressants to treat depressive disorders with or without psychotic symptoms. The antidepressant effect of atypical antipsychotics involves regulation of monoamine, glutamate, gamma-aminobutyric acid (GABA), cortisol, and neurotrophic factors. To date, the United States Food and Drug Administration (USFDA) has approved aripiprazole and quetiapine slow-release tablets as adjunctive treatment for depressive disorders, and the combination of olanzapine and fluoxetine for the treatment of treatment-resistant depression. When using atypical antipsychotics in the treatment of depressed patients, clinicians need to monitor patients for the emergence of adverse effects including extrapyramidal symptoms (EPS), weight gain, and hyperglycemia.

What is it like to take antipsychotic medication? A qualitative study of patients with first-episode psychosis.

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Gray, R; Deane, K

2016-03-01

What is known on the subject? Antipsychotic drugs are an important part of treatment for most patients with first episode psychosis. We do not know much about what it is like to take these drugs from the patient's point of view. What this paper adds to existing knowledge? We talked to 20 young people with psychosis about their experiences of taking antipsychotic drugs. Patients relationship with medication was complex, young people found medication often to be both good and bad at the same time. We were interested in how seemingly trivial issues--colour, taste, size, name--could be very important to young people and could result in them stopping. What are the implications for practice? We think our study highlights the complicated internal struggles that people with first episode psychosis have with medication. Our study highlights how Nurses and Doctors need to try and better understand what it is like to take these drugs and work collaboratively with patients to support them to make informed choices about treatment. Low-dose antipsychotic medication is an important part of treatment for people experiencing a first episode of psychosis. Little is known about this group of patients' experiences of taking medication. A qualitative study of purposively sampled young people experiencing a first episode of psychosis was carried out. A mental health nurse working in the early psychosis team interviewed participants using a structured topic guide. Interviews were subjected to thematic analysis. Interviews were completed with 20 young people. Thematic analysis generated six themes: (1) the drugs do work, (2) the drugs don't work (as well as I'd like), (3) side effects, (4) the indirect effects of medication, (5) rage against the machine and (6) the not trivial issues about medication. Our overarching meta-theme was that young people's experience of taking antipsychotics was complex; medication was often considered good and bad at the same time. Our observations underpin

Cannabidiol as a potential new type of an antipsychotic. A critical review of the evidence

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Cathrin Rohleder

2016-11-01

Full Text Available There is urgent need for the development of mechanistically different and less side-effect prone antipsychotic compounds. The endocannabinoid system has been suggested to represent a potential new target in this indication. While the chronic use of cannabis itself has been considered a risk factor contributing to the development of schizophrenia, triggered by the phytocannabinoid delta-9-tetrahydrocannabinol (Δ9 THC, cannabidiol, the second most important phytocannabinoid, appears to have no psychotomimetic potential. Although results from animal studies are inconsistent to a certain extent and seem to depend on behavioral paradigms, treatment duration and experimental conditions applied, cannabidiol has shown antipsychotic properties in rodents and rhesus monkeys. After some individual treatment attempts, the first randomized, double-blind controlled clinical trial had been conducted and demonstrated that cannabidiol exerts antipsychotic properties in acute schizophrenia comparable to the antipsychotic drug amisulpride accompanied by a superior, placebo-like side effect profile. As the clinical improvement by cannabidiol was significantly associated with elevated anandamide levels, it appears likely that its antipsychotic action is based on mechanisms associated with increased anandamide concentrations. However, a plethora of mechanisms of action has been suggested, but their potential relevance for the antipsychotic effects of cannabidiol needs still to be investigated. The clarification of these mechanisms as well as the establishment of cannabidiol’s antipsychotic efficacy and its hopefully benign side-effect profile remains the subject of a number of previously started clinical trials.

Chronic Kidney Disease in the Second-Generation Drug-Eluting Stent Era: Pooled Analysis of the Korean Multicenter Drug-Eluting Stent Registry.

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Lee, Joo Myung; Kang, Jeehoon; Lee, Euijae; Hwang, Doyeon; Rhee, Tae-Min; Park, Jonghanne; Kim, Hack-Lyoung; Lee, Sang Eun; Han, Jung-Kyu; Yang, Han-Mo; Park, Kyung Woo; Na, Sang-Hoon; Kang, Hyun-Jae; Koo, Bon-Kwon; Kim, Hyo-Soo

2016-10-24

The purpose of this study was to evaluate the clinical impact of chronic kidney disease (CKD) on clinical outcomes in contemporary practice of percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES). Although second-generation DES have improved the safety and efficacy issues in PCI, data regarding the performance of second-generation DES in patients with CKD are still limited. We performed a patient-level pooled analysis on 12,426 patients undergoing PCI using second-generation DES from the Korean Multicenter Drug-Eluting Stent Registry. Endpoints were stent-oriented outcomes (target lesion failure [TLF]) and patient-oriented composite outcomes (POCO) during a median follow-up of 35 months. CKD patients were stratified by the estimated glomerular filtration rate (eGFR) from mild CKD to end-stage renal disease patients, and by the coexistence of diabetes mellitus (DM). A total of 2,927 patients had CKD (23.6%), who showed a significantly higher risk of TLF (adjusted hazard ratio [HR adjust ]: 1.50; 95% confidence interval [CI]: 1.21 to 1.86) and POCO (HR adjust 1.34; 95% CI: 1.17 to 1.55) compared to patients with preserved renal function. Stratified analysis by eGFR showed that TLF was not increased in the mild to moderate CKD, whereas severe CKD and dialysis-dependent patients showed significantly higher risk of TLF (HR adjust 2.44; 95% CI: 1.54 to 3.86; HR adjust 3.58; 95% CI: 2.52 to 5.08, respectively). The eGFR threshold of increased clinical events was 40 to 45 ml/min/1.73 m 2 . Among CKD patients, DM CKD patients showed a higher incidence of TLF compared to non-DM CKD patients (HR adjust : 1.82; 95% CI: 1.32 to 2.52), driven by the increase in target vessel-related events. In the era of second-generation DES, CKD patients were at a significantly higher risk of clinical outcomes only in severe CKD and end-stage renal disease patients. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All

Drug information update. Atypical antipsychotics and neuroleptic malignant syndrome: nuances and pragmatics of the association.

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Sarkar, Siddharth; Gupta, Nitin

2017-08-01

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal adverse event associated with the use of antipsychotics. Although atypical antipsychotics were initially considered to carry no risk of NMS, reports have accumulated over time implicating them in NMS causation. Almost all atypical antipsychotics have been reported to be associated with NMS. The clinical profile of NMS caused by certain atypical antipsychotics such as clozapine has been reported to be considerably different from the NMS produced by typical antipsychotics, with diaphoresis encountered more commonly, and rigidity and tremor encountered less frequently. This article briefly discusses the evidence relating to the occurrence, presentation and management of NMS induced by atypical antipsychotics.

Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST).

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Pijnenborg, G H M; Timmerman, M E; Derks, E M; Fleischhacker, W W; Kahn, R S; Aleman, A

2015-06-01

Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Weight Gain, Schizophrenia and Antipsychotics: New Findings from Animal Model and Pharmacogenomic Studies

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Fabio Panariello

2011-01-01

Full Text Available Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1 the role of polymorphisms in several candidate genes, (2 the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3 the state of development of animal models in this matter. We also outline major areas for future research.

Adiposity-independent hypoadiponectinemia as a potential marker of insulin resistance and inflammation in schizophrenia patients treated with second generation antipsychotics.

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Sapra, Mamta; Lawson, Donna; Iranmanesh, Ali; Varma, Anjali

2016-07-01

The purpose of this study was to explore body fat independent effect of second generation antipsychotics (SGAs) on measures of glucose and adipokine homeostasis, and markers of inflammation. Eight non-diabetic men with schizophrenia (age: 55±3years, BMI: 29.7±1.2kg/m(2)) on SGAs were studied after an overnight fast. DXA and single-cut CT of abdomen were respectively used for the assessment of total body and abdominal fat. Blood samples were collected for measurements of glucose, insulin, leptin, adiponectin, C-reactive protein (CRP), and TNF-α. Data in schizophrenic subjects were compared to eight age (55±2.8years) and BMI (29.6±1.1kg/m(2)) matched healthy men. The results were significant for markedly decreased serum adiponectin in schizophrenia patients (4.6±0.9 vs 11.1±1.5ng/mL, p=0.001). Lower levels of adiponectin in schizophrenia men were associated with significant increases in insulin resistance (4.2±0.7 vs 1.7±0.4, p=0.004), CRP (3.5±1.2 vs 1.2±0.3, p=0.037), and leptin (12±1.4 vs 8.5±1.4ng/mL, p=0.05). Various measures of adiposity, including fat mass index (FMI) and abdominal fat were not different in the two study groups. These findings in the context of comparable age and total body/abdominal fat mass are assumed to be either disease specific, and/or treatment inflicted. The definitive invoking etiology and a presumptive role of hypoadiponectinemia in the development of insulin resistance and increased risk of inflammation warrant future investigation. Published by Elsevier B.V.

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs.

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Riga, Maurizio S; Soria, Guadalupe; Tudela, Raúl; Artigas, Francesc; Celada, Pau

2014-08-01

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (-31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

Safety and effectiveness of drug therapy for the acutely agitated patient (Part 2

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Gianluca Airoldi

2013-04-01

Full Text Available Acute agitation occurs in a variety of medical and psychiatric conditions, and the management of agitated, abusive, or violent patients is a common problem in the emergency department. Rapid control of potentially dangerous behaviors by physical restraint and pharmacologic tranquillization is crucial to ensure the safety of the patient and health-care personnel and to allow diagnostic procedures and treatment of the underlying condition. The purpose of this article (the second in a 2-part series is to review published data on the efficacy and safety of antipsychotic medications currently available for managing situations of this type. Arrhythmias caused by QT-prolonging drugs occur infrequently, and multiple factors are often involved, including concomitant use of other drugs affecting the same pathway (most antipsychotic drugs prolong the QT interval by blocking potassium IKr current in HERG channels of myocardial cells, electrolyte disorders and, possibly, genetic predisposition. Judicious use of typical antipsychotics (mainly haloperidol and benzodiazepines (mainly lorazepam, given intramuscularly alone or in combination, has proved to be safe and effective for controlling acute motor agitation related to psychiatric illness; cocaine, methamphetamine, and ethanol toxicity; ethanol withdrawal; and other factors. They are still widely used and are particularly useful when limited data are available on the patient’s history of cardiovascular disease, current use of medication, and/or the likelihood of illicit drug or alcohol intoxication; when the diagnosis involves medical comorbidity or intoxication; or when there is no specific treatment (e.g., personality disorders, learning disabilities, mental retardation, organic brain damage. If rapid tranquillization is necessary before a formal diagnosis can be made and there are uncertainties regarding the patient’s medical history, lorazepam is often considered the first-line drug of choice. In

Reboxetine Enhances the Olanzapine-Induced Antipsychotic-Like Effect, Cortical Dopamine Outflow and NMDA Receptor-Mediated Transmission

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Marcus, Monica M; Jardemark, Kent; Malmerfelt, Anna; Björkholm, Carl; Svensson, Torgny H

2010-01-01

Preclinical data have shown that addition of the selective norepinephrine transporter (NET) inhibitor reboxetine increases the antipsychotic-like effect of the D2/3 antagonist raclopride and, in parallel, enhances cortical dopamine output. Subsequent clinical results suggested that adding reboxetine to stable treatments with various antipsychotic drugs (APDs) may improve positive, negative and depressive symptoms in schizophrenia. In this study, we investigated in rats the effects of adding reboxetine to the second-generation APD olanzapine on: (i) antipsychotic efficacy, using the conditioned avoidance response (CAR) test, (ii) extrapyramidal side effect (EPS) liability, using a catalepsy test, (iii) dopamine efflux in the medial prefrontal cortex and the nucleus accumbens, using in vivo microdialysis in freely moving animals and (iv) cortical N-methyl--aspartate (NMDA) receptor-mediated transmission, using intracellular electrophysiological recording in vitro. Reboxetine (6 mg/kg) enhanced the suppression of CAR induced by a suboptimal dose (1.25 mg/kg), but not an optimal (2.5 mg/kg) dose of olanzapine without any concomitant catalepsy. Addition of reboxetine to the low dose of olanzapine also markedly increased cortical dopamine outflow and facilitated prefrontal NMDA receptor-mediated transmission. Our data suggest that adjunctive treatment with a NET inhibitor may enhance the therapeutic effect of low-dose olanzapine in schizophrenia without increasing EPS liability and add an antidepressant action, thus in principle allowing for a dose reduction of olanzapine with a concomitant reduction of dose-related side effects, such as EPS and weight gain. PMID:20463659

Antipsychotic Selection for Acute Agitation and Time to Repeat Use in a Psychiatric Emergency Department.

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Gomez, Seth; Dopheide, Julie

2016-11-01

Early recognition and treatment of agitated patients is essential to avoid violence in the psychiatric emergency department (ED). Antipsychotics have established efficacy in managing agitation, yet little is known about how the choice of initial antipsychotic impacts time to repeat use and length of stay (LOS) in the psychiatric ED. To describe the impact of initial antipsychotic selection on time to repeat use and LOS in the psychiatric ED. A chart review identified 388 cases in which patients were administered an antipsychotic for agitation in the psychiatric ED between July 1 and August 31, 2014. Time to repeat use and LOS were compared for intramuscular (IM) haloperidol, other IM antipsychotics, and oral second-generation antipsychotics (SGAs) using the Kruskal-Wallis or Wilcoxon-Mann-Whitney test. Of the 388 cases, 31% (n=122) required repeat medications. Mean time to repeat use for IM haloperidol was 20.1±18.4 hours, which was not significantly different from mean time to repeat use in the groups receiving other IM antipsychotics or oral SGAs (P=0.35). The mean LOS was 29.7±28.7 hours for IM haloperidol, 30.3±36.9 hours for other IM antipsychotics, and 22.6±28.0 hours for oral SGAs. Significant differences in LOS between repeat and nonrepeat users of IM haloperidol and other IM antipsychotics were observed, but not among those who received oral SGAs. Mean time to repeat use ranged from 14 to 20 hours with IM haloperidol, other IM antipsychotics, and oral SGAs without significant differences in time to repeat use in the 3 different groups. Repeat users of IM antipsychotics had a significantly longer LOS in the ED compared with nonrepeat users of IM antipsychotics. However, patients who were initially administered oral SGAs did not have longer LOS in the ED even if a repeat dose was given.

Screening of cardiovascular risk factors in patients with schizophrenia and patients treated with antipsychotic drugs: are we equally exhaustive as with the general population?

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Castillo-Sánchez, Miguel; Fàbregas-Escurriola, Mireia; Bergè-Baquero, Daniel; Fernández-SanMartín, MªIsabel; Goday-Arno, Albert

2017-01-01

Many studies have previously shown increased cardiovascular risk factors related to schizophrenia independently from the use of antipsychotic drugs. However, a poorer effort in clinical detection and management of cardiovascular risk in patients with severe mental illness could also explain these results. To test this hypothesis, we analyzed the differences in screening and incidence of cardiovascular risk factors between schizophrenia, non-schizophrenic patients on treatment with antipsychotic drugs (NS-TAD) and the general population. Data from adult subjects assessed by high-quality register general practitioners from 2006 to 2011 were extracted from the Catalonian SIDIAP database. The schizophrenia, NS-TAD, and control groups were compared in terms of measurements and incidence of diabetes, dyslipidemia, obesity, hypertension, and smoking. A total of 4911 patients in the schizophrenia group, 4157 in NS-TAD group, and 98644 in the control group were included. Schizophrenia patients were screened for dyslipidemia and diabetes more frequently than the control group, while for obesity or hypertension, they were screened equal to controls. Also, as compared to the control group, the NS-TAD group was more frequently screened for obesity with no differences in dyslipidemia and diabetes and less frequently for hypertension. Smoking was less frequently screened in both study groups. The incidence of all risk factors studied in both study groups was higher than or equal to the control group, except for hypertension, which had lower incidence. The lack of screening of risk factors does not appear decisive in the increased cardiovascular risk of patients diagnosed with schizophrenia seen in primary care. Studies evaluating the possible under diagnosis of the risk factors are required. Schizophrenia (SZ); Treatment with antipsychotic drugs (TAD); Cardiovascular risk factor/s (CVRF); Without schizophrenia but on therapy with antipsychotic drugs (NS-TAD); Defined Daily Dose

A pilot randomised controlled trial of community-led ANtipsychotic Drug REduction for Adults with Learning Disabilities.

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McNamara, Rachel; Randell, Elizabeth; Gillespie, David; Wood, Fiona; Felce, David; Romeo, Renee; Angel, Lianna; Espinasse, Aude; Hood, Kerry; Davies, Amy; Meek, Andrea; Addison, Katy; Jones, Glyn; Deslandes, Paul; Allen, David; Knapp, Martin; Thapar, Ajay; Kerr, Michael

2017-08-01

Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. A two-arm individually randomised double-blind placebo-controlled drug reduction trial. Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes

Atypical Antipsychotic Medications and Hyponatremia in Older Adults: A Population-Based Cohort Study

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Sonja Gandhi

2016-04-01

Full Text Available Background: A number of case reports have suggested a possible association between atypical antipsychotic medications and hyponatremia. Currently, there are no reliable estimates of hyponatremia risk from atypical antipsychotic drugs. Objective: The objective of this study was to examine the 30-day risk of hospitalization with hyponatremia in older adults dispensed an atypical antipsychotic drug relative to no antipsychotic use. Design: The design of this study was a retrospective, population-based cohort study. Setting: The setting of this study was in Ontario, Canada, from 2003 to 2012. Patients: Adults 65 years or older with an identified psychiatric condition who were newly dispensed risperidone, olanzapine, or quetiapine in the community setting compared to adults with similar indicators of baseline health who were not dispensed such a prescription. Measurements: The primary outcome was the 30-day risk of hospitalization with hyponatremia. The tracer outcome (an outcome that is not expected to be influenced by the study drugs was the 30-day risk of hospitalization with bowel obstruction. These outcomes were assessed using hospital diagnosis codes. Methods: Using health administrative data, we applied a propensity score technique to match antipsychotic users 1:1 to non-users of antipsychotic drugs (58,008 patients in each group. We used conditional logistic regression to compare outcomes among the matched users and non-users. Results: A total of 104 baseline characteristics were well-balanced between the two matched groups. Atypical antipsychotic use compared to non-use was associated with an increased risk of hospitalization with hyponatremia within 30 days (86/58,008 (0.15 % versus 53/58,008 (0.09 %; relative risk 1.62 (95 % confidence interval (CI 1.15 to 2.29; absolute risk increase 0.06 % (95 % CI 0.02 to 0.10. The limited number of events precluded some additional analyses to confirm if the association was robust. Atypical

Antipsychotic treatment and the risk of hip fracture in subjects with schizophrenia: a 10-year population-based case-control study.

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Wu, Chi-Shin; Chang, Chia-Ming; Tsai, Yu-Ting; Huang, Ya-Wen; Tsai, Hui-Ju

2015-09-01

To investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. Among patients with schizophrenia (ICD-9-CM code 295), 605 cases with hip fracture and 2,828 matched controls were identified from 2002 to 2011 using the National Health Insurance Research Database in Taiwan. The authors conducted a nested case-control study to investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. The modifiable effects of age and gender were evaluated by stratified analysis. In addition, the effects of antipsychotic use, antipsychotic classes, and receptor-binding profiles of antipsychotics, individually, on hip fracture were estimated, and potential confounding factors were adjusted in subsequent analysis. Conditional logistic regressions were applied to determine the effect of antipsychotic treatment on hip fracture. Current antipsychotic use was associated with an increased risk for hip fracture (adjusted odds ratio [AOR] = 1.61; 95% CI, 1.24-2.10). Among current users, new users had a higher risk of hip fracture (AOR = 4.28; 95% CI, 1.76-10.36) than past users (AOR = 1.11; 95% CI, 0.79-1.56). In addition, a significant increased risk of hip fracture was noted in schizophrenia subjects with first-generation antipsychotic use (AOR = 1.59; 95%CI, 1.15-2.20) but not in those with second-generation antipsychotic use (AOR = 1.16; 95% CI, 0.91-1.48). These results extend previous findings and demonstrate an increased risk of hip fracture associated with antipsychotic use in schizophrenia subjects. Further investigation is needed to dissect the underlying mechanisms related to the effect of antipsychotic use on hip fracture in subjects at risk. © Copyright 2015 Physicians Postgraduate Press, Inc.

Pharmacokinetic-pharmacodynamic modeling of antipsychotic drugs in patients with schizophrenia Part I : The use of PANSS total score and clinical utility

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Reddy, Venkatesh Pilla; Kozielska, Magdalena; Suleiman, Ahmed Abbas; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

Background: To develop a pharmacokinetic-pharmacodynamic (PK-PD) model using individual-level data of Positive and Negative Syndrome Scale (PANSS) total score to characterize the antipsychotic drug effect taking into account the placebo effect and dropout rate. In addition, a clinical utility (CU)

Neural basis for the ability of atypical antipsychotic drugs to improve cognition in schizophrenia

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Tomiki eSumiyoshi

2013-10-01

Full Text Available Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT receptors in ameliorating cognitive deficits of schizophrenia.It is noteworthy that atypical antipsychotic drugs, e.g. clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT1A receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence.The neural network underlying the ability of 5-HT1A agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and GABA neurons. A novel strategy for cognitive enhancement in psychosis may be benefitted by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT1A agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g. event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some atypical antipsychotic drugs acting directly or indirectly on 5-HT1A receptors.These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia.

Survey on schizophrenia treatment in Mexico: perception and antipsychotic prescription patterns

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de la Fuente-Sandoval Camilo

2004-04-01

Full Text Available Abstract Background Since the introduction of antipsychotics, especially the so called atypicals, the treatment of schizophrenia has shown important improvements. At the present time, it is preferred to label clozapine and other antipsychotics sharing similar profiles as second-generation antipsychotics (SGAs. These medications have been proposed by some experts as a first line treatment for schizophrenia. It is critical to have reliable data about antipsychotic prescription in Mexico and to create management guidelines based on expert meetings and not only on studies carried out by the pharmaceutical industry. Only this approach will help to make the right decisions for the treatment of schizophrenia. Methods A translated version of Rabinowitz's survey was used to evaluate antipsychotic prescription preferences and patterns in Mexican psychiatrists. The survey questionnaire was sent by mail to 200 psychiatrists from public institutions and private practice in Mexico City and Guadalajara, Mexico. Results Recommendations for antipsychotics daily doses at different stages of the treatment of schizophrenia varied widely. Haloperidol was considered as the first choice for the treatment of positive symptoms. On the contrary, risperidone was the first option for negative symptoms. For a patient with a high susceptibility for developing extrapyramidal symptoms (EPS, risperidone was the first choice. It was also considered that SGAs had advantages over typical antipsychotics in the management of negative symptoms, cognitive impairment and fewer EPS. Besides, there was a clear tendency for prescribing typical antipsychotics at higher doses than recommended and inadequate doses for the atypical ones. Conclusions Some of the obstacles for the prescription of SGAs include their high cost, deficient knowledge about their indications and dosage, the perception of their being less efficient for the treatment of positive symptoms and the resistance of some

Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents.

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Goto, Kosaku; Zhao, Zhijing; Matsumura, Mitsuaki; Dohi, Tomotaka; Kobayashi, Nobuaki; Kirtane, Ajay J; Rabbani, LeRoy E; Collins, Michael B; Parikh, Manish A; Kodali, Susheel K; Leon, Martin B; Moses, Jeffrey W; Mintz, Gary S; Maehara, Akiko

2015-11-01

The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS. Copyright © 2015 Elsevier Inc. All rights reserved.

Antipsychotic prescription patterns and treatment costs of ...

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Peshawar, Pakistan and to analyze the treatment costs associated with these drugs. Methods: One hundred ..... Kendall T. The rise and fall of the atypical antipsychotics. ... size determination in health studies: a practical manual. 1991. 18.

Antipsychotic medications and dental caries in newly diagnosed schizophrenia: A nationwide cohort study.

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Hu, Kai-Fang; Chou, Yu-Hsiang; Wen, Yen-Hsia; Hsieh, Kun-Pin; Tsai, Jui-Hsiu; Yang, Pinchen; Yang, Yi-Hsin; Lin, Chun-Hung Richard

2016-11-30

We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diabetes mellitus and impaired glucose tolerance in patients with schizophrenia, before and after antipsychotic treatment

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Rayees Ahmad Wani

2015-01-01

Full Text Available Background: Treatment with antipsychotics increases the risk of developing diabetes in patients of schizophrenia but this diabetogenic potential of different antipsychotics seems to be different. Moreover, there may be an independent link between schizophrenia and diabetes. So we plan to study the prevalence of glucose dysregulation in patients of schizophrenia before and after treatment with various antipsychotics. Materials and Methods: Fifty patients (32 males and 18 females diagnosed with schizophrenia were evaluated for glucose dysregulation using oral glucose tolerance test, initially (drug naive and after antipsychotic treatment. Age- and sex-matched healthy volunteer group of 50 subjects (35 males and 15 females was taken for comparison. Results were interpreted using American Diabetic Association criteria. Results: Though the glycemic status of the patient group was comparable with healthy controls initially but antipsychotic treatment was associated with glucose dysregulation. For first 6 weeks the antipsychotic (olanzapine, risperidone, haloperidol and aripiprazole-induced glucose dysregulation was comparable, which was seen to be maximum with the olanzapine-treated group at the end of this study, 14 weeks. Conclusion: We conclude that antipsychotic treatment of nondiabetic drug naive schizophrenia patients was associated with adverse effects on glucose regulation. For initial 6 weeks the antipsychotic-induced glucose dysregulation was comparable, which was seen to be maximum with olanzapine at the end of study, i.e. 14 weeks. Keeping this at the back of mind we can stabilize a patient initially with a more effective drug, olanzapine, and later on shift to one with less metabolic side effects.

Antipsychotics, chlorpromazine and haloperidol inhibit voltage-gated proton currents in BV2 microglial cells.

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Shin, Hyewon; Song, Jin-Ho

2014-09-05

Microglial dysfunction and neuroinflammation are thought to contribute to the pathogenesis of schizophrenia. Some antipsychotic drugs have anti-inflammatory activity and can reduce the secretion of pro-inflammatory cytokines and reactive oxygen species from activated microglial cells. Voltage-gated proton channels on the microglial cells participate in the generation of reactive oxygen species and neuronal toxicity by supporting NADPH oxidase activity. In the present study, we examined the effects of two typical antipsychotics, chlorpromazine and haloperidol, on proton currents in microglial BV2 cells using the whole-cell patch clamp method. Chlorpromazine and haloperidol potently inhibited proton currents with IC50 values of 2.2 μM and 8.4 μM, respectively. Chlorpromazine and haloperidol are weak bases that can increase the intracellular pH, whereby they reduce the proton gradient and affect channel gating. Although the drugs caused a marginal positive shift of the activation voltage, they did not change the reversal potential. This suggested that proton current inhibition was not due to an alteration of the intracellular pH. Chlorpromazine and haloperidol are strong blockers of dopamine receptors. While dopamine itself did not affect proton currents, it also did not alter proton current inhibition by the two antipsychotics, indicating dopamine receptors are not likely to mediate the proton current inhibition. Given that proton channels are important for the production of reactive oxygen species and possibly pro-inflammatory cytokines, the anti-inflammatory and antipsychotic activities of chlorpromazine and haloperidol may be partly derived from their ability to inhibit microglial proton currents. Copyright © 2014 Elsevier B.V. All rights reserved.

Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug

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Mizushima Jin

2012-07-01

Full Text Available Abstract Dopamine dysregulation syndrome (DDS consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD. Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

State of the art of drug treatment of schizophrenia and the future position of the novel/atypical antipsychotics.

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Möller, H J

2000-10-01

Neuroleptic medication is the most important part of the treatment regimen for schizophrenic patients. The efficacy of neuroleptics in the acute and long-term treatment of schizophrenia is very well proven and the effect size is comparatively high. After more than 40 years of clinical practice with the classical neuroleptics, several more or less generally accepted rules for the management of drug treatment in schizophrenia have been established. The paper aims to describe these standards, discussing, among other things, developments which have appeared in the last 10 to 20 years, e.g. the tendency to a lower daily dose during acute treatment and the tendency to alternative strategies during long-term treatment. The paper especially also takes into consideration the benefits of the novel/atypical antipsychotics as compared to the classical neuroleptics, which will change the current treatment standards under several aspects--a change which is already ongoing. The novel/atypical antipsychotics will be much better accepted by patients, thus leading to increased compliance, will be associated with a better quality of life and will possibly change the long-term outcome of schizophrenic patients in a very important manner. It should be considered that the so-called novel/atypical neuroleptics do not constitute a homogeneous group but are a group of individual drugs, each with their own advantages and disadvantages. As was the situation with the classical neuroleptics, the physician also has to choose the most adequate drug under consideration of the risk/benefit profile of each drug in relation to the disposition of the individual patient.

Dopamine and incentive learning: a framework for considering antipsychotic medication effects.

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Beninger, Richard J

2006-12-01

Hyperfunction of brain dopamine (DA) systems is associated with psychosis in schizophrenia and the medications used to treat schizophrenia are DA receptor blockers. DA also plays a critical role in incentive learning produced by rewarding stimuli. Using DA as the link, these results suggest that psychosis in schizophrenia can be understood from the point of view of excessive incentive learning. Incentive learning is mediated through the non-declarative memory system and may rely on the striatum or medial prefrontal cortex depending on the task. Typical and atypical antipsychotics differentially affect expression of the immediate early gene c-fos, producing greater activity in the striatum and medial prefrontal cortex, respectively. This led to the hypothesis that performance of schizophrenic patients on tasks that depend on the striatum or medial prefrontal cortex will be differentially affected by their antipsychotic medication. Results from a number of published papers supported this dissociation. Furthermore, the effects of two atypical drugs, clozapine and olanzapine, on c-fos expression were different from another atypical, risperidone that resembles the typical antipsychotics. Similarly, in tests of incentive learning, risperidone acted like the typical antipsychotics. Thus, typical and atypical antipsychotic drugs differed in the types of cognitive performance they affected and, furthermore, members of the atypical class differed in their effects on cognition. It remains the task of researchers and clinicians to sort out the symptoms associated with the endogenous illness from possible iatrogenic symptoms resulting from the antipsychotic medications used to treat schizophrenia.

Performance of a neuro-fuzzy model in predicting weight changes of chronic schizophrenic patients exposed to antipsychotics.

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Lan, T H; Loh, E W; Wu, M S; Hu, T M; Chou, P; Lan, T Y; Chiu, H-J

2008-12-01

Artificial intelligence has become a possible solution to resolve the problem of loss of information when complexity of a disease increases. Obesity phenotypes are observable clinical features of drug-naive schizophrenic patients. In addition, atypical antipsychotic medications may cause these unwanted effects. Here we examined the performance of neuro-fuzzy modeling (NFM) in predicting weight changes in chronic schizophrenic patients exposed to antipsychotics. Two hundred and twenty inpatients meeting DSMIV diagnosis of schizophrenia, treated with antipsychotics, either typical or atypical, for more than 2 years, were recruited. All subjects were assessed in the same study period between mid-November 2003 and mid-April 2004. The baseline and first visit's physical data including weight, height and circumference were used in this study. Clinical information (Clinical Global Impression and Life Style Survey) and genotype data of five single nucleotide polymorphisms were also included as predictors. The subjects were randomly assigned into the first group (105 subjects) and second group (115 subjects), and NFM was performed by using the FuzzyTECH 5.54 software package, with a network-type structure constructed in the rule block. A complete learned model trained from merged data of the first and second groups demonstrates that, at a prediction error of 5, 93% subjects with weight gain were identified. Our study suggests that NFM is a feasible prediction tool for obesity in schizophrenic patients exposed to antipsychotics, with further improvements required.

Atypical antipsychotics: trends in analysis and sample preparation of various biological samples.

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Fragou, Domniki; Dotsika, Spyridoula; Sarafidou, Parthena; Samanidou, Victoria; Njau, Samuel; Kovatsi, Leda

2012-05-01

Atypical antipsychotics are increasingly popular and increasingly prescribed. In some countries, they can even be obtained over-the-counter, without a prescription, making their abuse quite easy. Although atypical antipsychotics are thought to be safer than typical antipsychotics, they still have severe side effects. Intoxications are not rare and some of them have a fatal outcome. Drug interactions involving atypical antipsychotics complicate patient management in clinical settings and the determination of the cause of death in fatalities. In view of the above, analytical strategies that can efficiently isolate atypical antipsychotics from a variety of biological samples and quantify them accurately, sensitively and reliably, are of utmost importance both for the clinical, as well as for the forensic toxicologist. In this review, we will present and discuss novel analytical strategies that have been developed from 2004 to the present day for the determination of atypical antipsychotics in various biological samples.

Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine

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Zhang, Chen; Li, Ming

2011-01-01

Repeated administration of haloperidol and olanzapine causes a progressively enhanced disruption of conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined to the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or PCP (3.2 mg/kg, sc) hyperlocomotion model under haloperidol or olanzapine for five consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated haloperidol or olanzapine treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with haloperidol or olanzapine did not show a stronger inhibition of CAR or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may enter an association with unconditional drug effects via a Pavlovian conditioning process. They may also serve as occasion-setters to modulate the expression of sensitized responses. Because antipsychotic sensitization mimics

Contextual and behavioral control of antipsychotic sensitization induced by haloperidol and olanzapine.

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Zhang, Chen; Li, Ming

2012-02-01

Repeated administration of haloperidol (HAL) and olanzapine (OLZ) causes a progressively enhanced disruption of the conditioned avoidance response (CAR) and a progressively enhanced inhibition of phencyclidine (PCP)-induced hyperlocomotion in rats (termed antipsychotic sensitization). Both actions are thought to reflect intrinsic antipsychotic activity. The present study examined the extent to which antipsychotic-induced sensitization in one model (e.g. CAR) can be transferred or maintained in another (e.g. PCP hyperlocomotion) as a means of investigating the contextual and behavioral controls of antipsychotic sensitization. Well-trained male Sprague-Dawley rats were first repeatedly tested in the CAR or the PCP (3.2 mg/kg, subcutaneously) hyperlocomotion model under HAL or OLZ for 5 consecutive days. Then they were switched to the other model and tested for the expression of sensitization. Finally, all rats were switched back to the original model and retested for the expression of sensitization. Repeated HAL or OLZ treatment progressively disrupted avoidance responding and decreased PCP-induced hyperlocomotion, indicating a robust sensitization. When tested in a different model, rats previously treated with HAL or OLZ did not show a stronger inhibition of CAR-induced or PCP-induced hyperlocomotion than those treated with these drugs for the first time; however, they did show such an effect when tested in the original model in which they received repeated antipsychotic treatment. These findings suggest that the expression of antipsychotic sensitization is strongly influenced by the testing environment and/or selected behavioral response under certain experimental conditions. Distinct contextual cues and behavioral responses may develop an association with unconditional drug effects through a Pavlovian conditioning process. They may also serve as occasion setters to modulate the expression of sensitized responses. As antipsychotic sensitization mimics the clinical

Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

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Galling, B; Vernon, J A; Pagsberg, A K

2018-01-01

adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval...... (CI) = -0.57 to -0.17, P SMD = -0.25, 95% CI = -0.44-0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = -0.......42, 95% CI = -0.77, -0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = -0.71, 95% CI = -1.21, -0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = -0.43, 95% CI = -0...

Effect of Clozapine vs Other Second-Generation Antipsychotics on Hospitalization and Seclusion: A Retrospective Mirror-Image Study in a Japanese Public Psychiatric Hospital.

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Misawa, Fuminari; Suzuki, Takefumi; Fujii, Yasuo

2017-12-01

Clozapine has been regarded as the gold standard for patients with treatment-resistant schizophrenia, but a recent network meta-analysis has questioned its relative superiority over other second-generation antipsychotics (SGAs) such as olanzapine and risperidone. We conducted a retrospective mirror-image study of clozapine vs other SGAs to evaluate real-world effectiveness of clozapine in terms of the duration of hospitalization and seclusion, both of which represent a critical outcome. We included all patients who initiated clozapine at the Yamanashi Prefectural KITA Hospital and had continued to take any SGA(s) other than clozapine for at least 1 year before the initiation of clozapine. We obtained data on hospitalization and seclusion during 1 year of SGA treatment (SGA phase) and 1 year after the treatment was switched to clozapine (clozapine phase). The study included 35 patients (21 men, 31 with schizophrenia, 4 with schizoaffective disorder) with the average ± SD age of 37.3 ± 11.1 years. The results indicated that total hospitalization days did not differ significantly between SGA and clozapine treatment. However, total duration of seclusion was significantly shorter in the clozapine phase than in the SGA phase. Furthermore, the number of patients who were secluded at least once was significantly smaller in the clozapine phase than in the SGA phase. The results were essentially unchanged when outlier patients were excluded and only when patients taking olanzapine and/or risperidone during the SGA phase were considered. Although the findings from this retrospective analysis need to be further tested in prospective trials, they endorse the relative effectiveness of clozapine over other SGAs in the real world.

Differences in body mass index z-scores and weight status in a Dutch pediatric psychiatric population with and without use of second-generation antipsychotics.

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de Hoogd, Sjoerd; Overbeek, Wieske A; Heerdink, Eibert R; Correll, Christoph U; de Graeff, Elisabeth R; Staal, Wouter G

2012-04-01

Weight gain and metabolic adverse effects of second-generation antipsychotics (SGAs) have become a major concern, particularly in youth. However, the specific contribution of SGAs versus other medications or the underlying illness is unclear. In a chart review study of psychiatric outpatients aged ≤ 18 years treated with SGAs and psychiatric controls without lifetime SGA, use body mass index (BMI) z-scores between patients and controls were compared in the entire sample, patients without co-medications, diagnostic subgroups, and age subgroups. In patients with follow-up data, weight z-score change was calculated. Altogether, 592 Caucasian patients aged 4-18 (mean: 10.0) years with a psychiatric diagnosis were included. BMI z-scores in 96 youth treated with SGAs for 9.0 ± 6.1 months were significantly higher than in 496 patients without lifetime SGA use (0.81 ± 1.1 vs. 0.05 ± 1.2; pz-score differences remained significant in all age groups z-score increased significantly from -0.17 ± 1.5 to 0.25 ± 1.4 (p<0.0001) with 12.5% transitioning to overweight or obese status. These data show robust and significant differences in sex- and age-adjusted body weight and weight status in young pediatric Caucasian samples with and without use of SGAs independent of Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) (American Psychiatric Association 2000 ) diagnosis and nonantipsychotic medications. Weight status and metabolic effects of SGAs require careful attention, especially in youth.

Can melatonin prevent or improve metabolic side effects during antipsychotic treatments?

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Porfirio MC

2017-08-01

Full Text Available Maria-Cristina Porfirio,1 Juliana Paula Gomes de Almeida,2 Maddalena Stornelli,1 Silvia Giovinazzo,1 Diane Purper-Ouakil,3 Gabriele Masi4 1Unit of Child Neurology and Psychiatry, “Tor Vergata” University of Rome, Italy; 2Unit of Child Neurology, Irmandade Santa Casa de Misericordia Hospital São Paulo, Brazil; 3Unit of Child and Adolescent Psychiatry, Saint Eloi Hospital, Montpellier, France; 4IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy Abstract: In the last two decades, second-generation antipsychotics (SGAs were more frequently used than typical antipsychotics for treating both psychotic and nonpsychotic psychiatric disorders in both children and adolescents, because of their lower risk of adverse neurological effects, that is, extrapyramidal symptoms. Recent studies have pointed out their effect on weight gain and increased visceral adiposity as they induce metabolic syndrome. Patients receiving SGAs often need to be treated with other substances to counteract metabolic side effects. In this paper, we point out the possible protective effect of add-on melatonin treatment in preventing, mitigating, or even reversing SGAs metabolic effects, improving quality of life and providing safer long-term treatments in pediatric patients. Melatonin is an endogenous indolamine secreted during darkness by the pineal gland; it plays a key role in regulating the circadian rhythm, generated by the suprachiasmatic nuclei (SCN of the hypothalamus, and has many other biological functions, including chronobiotic, antioxidant and neuroprotective properties, anti-inflammatory and free radical scavenging effects, and diminishing oxidative injury and fat distribution. It has been hypothesized that SGAs cause adverse metabolic effects that may be restored by nightly administration of melatonin because of its influence on autonomic and hormonal outputs. Interestingly, atypical anti-psychotics (AAPs can cause

Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic atypicality.

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Heresco-Levy, Uriel

2003-10-01

The neurotransmission mediated by the excitatory amino acids (EAA) glutamate (GLU) and aspartate is of interest to the pharmacotherapy of psychosis due to its role in neurodevelopment and neurotoxicity, its complex interactions with dopaminergic and other neurotransmitter systems and its pivotal importance in recent models of schizophrenia. Accumulating evidence indicates that modulation of glutamatergic neurotransmission may play an important role in the mechanisms of action of atypical antipsychotic drugs. The principles of the phencyclidine (PCP) model of schizophrenia suggest that conventional neuroleptics cannot counteract all aspects of schizophrenia symptomatology, while a more favorable outcome, including anti-negative and cognitive symptoms effects, would be expected with the use of treatment modalities targeting glutamatergic neurotransmission. Clozapine and other presently used atypical antipsychotics differ from conventional neuroleptics in the way they affect various aspects of glutamatergic receptors function. In this context, a specific hypothesis suggesting an agonistic role of clozapine at the N-methyl-D-aspartate (NMDA) subtype of GLU receptors has been postulated. Furthermore, the results of the first generation of clinical trials with glycine (GLY) site agonists of the NMDA receptor in schizophrenia suggest that this type of compounds (1) have efficacy and side effects profiles different than those of conventional neuroleptics and (2) differ in their synergic effects when used in addition to conventional neuroleptics versus clozapine and possibly additional atypical antipsychotics. These findings (1) bring further support to the hypothesis that glutamatergic effects may play an important role in the mechanism of action of atypical antipsychotics, (2) help explain the unique clinical profile of clozapine, and (3) suggest that GLY site agonists of the NMDA receptor may represent a new class of atypical antipsychotic medication. Future research in

Antipsychotic medication for early episode schizophrenia

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Bola, John; Kao, Dennis; Soydan, Haluk; Adams, Clive E

2014-01-01

Background Long-term treatment with antipsychotic medications in early episode schizophrenia spectrum disorders is common, but both short and long-term effects on the illness are unclear. There have been numerous suggestions that people with early episodes of schizophrenia appear to respond differently than those with multiple prior episodes. The number of episodes may moderate response to drug treatment. Objectives To assess the effects of antipsychotic medication treatment on people with early episode schizophrenia spectrum disorders. Search methods We searched the Cochrane Schizophrenia Group register (July 2007) as well as references of included studies. We contacted authors of studies for further data. Selection criteria Studies with a majority of first and second episode schizophrenia spectrum disorders comparing initial antipsychotic medication treatment with placebo, milieu, or psychosocial treatment. Data collection and analysis Working independently, we critically appraised records from 681 studies, of which five studies met inclusion criteria. We calculated risk ratios (RR) and their 95% confidence intervals (CI) where possible. For continuous data, we calculated mean difference (MD). We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results Five studies (combined total n=998) met inclusion criteria. Four studies (n=724) provided leaving the study early data and results suggested that individuals treated with a typical antipsychotic medication are less likely to leave the study early than those treated with placebo (Chlorpromazine: 3 RCTs n=353, RR 0.4 CI 0.3 to 0.5, NNT 3.2, Fluphenaxine: 1 RCT n=240, RR 0.5 CI 0.3 to 0.8, NNT 5; Thioridazine: 1 RCT n=236, RR 0.44 CI 0.3 to 0.7, NNT 4.3, Trifulperazine: 1 RCT n=94, RR 0.96 CI 0.3 to 3.6). Two studies contributed data to assessment of adverse effects and present a general pattern of more frequent side effects among individuals treated with typical antipsychotic medications

Safety and performance of the second generation EnligHTN™ Renal Denervation System in patients with drug-resistant, uncontrolled hypertension.

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Worthley, Stephen G; Wilkins, Gerard T; Webster, Mark W; Montarello, Joseph K; Delacroix, Sinny; Whitbourn, Robert J; Warren, Roderic J

2017-07-01

Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively (p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Curcumin Mitigates the Intracellular Lipid Deposit Induced by Antipsychotics In Vitro.

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Alberto Canfrán-Duque

Full Text Available First- and second-generation antipsychotics (FGAs and SGAs, respectively, both inhibit cholesterol biosynthesis and impair the intracellular cholesterol trafficking, leading to lipid accumulation in the late endosome/lysosome compartment. In this study we examined if curcumin, a plant polyphenol that stimulates exosome release, can alleviate antipsychotic-induced intracellular lipid accumulation.HepG2 hepatocarcinoma cells were treated with antipsychotics or placebo and DiI-labelled LDL for 18 h and then exposed to curcumin for the last 2 h. Cells and media were collected separately and used for biochemical analyses, electron microscopy and immunocytochemistry. Exosomes were isolated from the incubation medium by ultracentrifugation.Curcumin treatment reduced the number of heterolysosomes and shifted their subcellular localization to the periphery, as revealed by electron microscopy, and stimulated the release of lysosomal β-hexosaminidase and exosome markers flotillin-2 and CD63 into the media. The presence of DiI in exosomes released by cells preloaded with DiI-LDL demonstrated the endolysosomal origin of the microvesicles. Furthermore, curcumin increased the secretion of cholesterol as well as LDL-derived DiI and [3H]-cholesterol, in association with a decrease of intracellular lipids. Thus, the disruption of lipid trafficking induced by FGAs or SGAs can be relieved by curcumin treatment. This polyphenol, however, did not mitigate the reduction of cholesterol esterification induced by antipsychotics.Curcumin stimulates exosome release to remove cholesterol (and presumably other lipids accumulated within the endolysosomal compartment, thereby normalizing intracellular lipid homeostasis. This action may help minimize the adverse metabolic effects of antipsychotic treatment, which should now be evaluated in clinical trials.

Adjunctive Treatment of Acute Mania with Risperidone versus Typical Antipsychotics: A Retrospective Study

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Jui-Hsiu Tsai

2005-12-01

Full Text Available Few studies have directly compared atypical antipsychotics (e.g. risperidone with typical antipsychotics as adjunctive therapy in patients hospitalized for acute mania, especially during a lengthy hospital stay. Our retrospective, case-controlled study is a chart review of 64 patients with Diagnostic and Statistical Manual of Mental Disorders, 4th edition, defined bipolar I disorder (current episode, mania. Patients were divided into two groups according to the adjunctive medications used: the risperidone group (mood stabilizers plus risperidone and the control group (mood stabilizers plus typical antipsychotics. Outcome at discharge, medications, adverse drug effects, and length of hospital stay were compared between groups, controlling for gender, age, number of prior admissions, and duration of illness. Results indicated no statistically significant differences between groups in the controlled factors, Global Assessment of Functioning and Clinical Global Impression-Improvement scores, and adverse drug events. Patients in the risperidone group used significantly lower doses of trihexyphenidyl than those in the control group (p < 0.05. Patients treated with risperidone had a shorter hospital stay than those treated with typical antipsychotics (p < 0.01. In conclusion, antipsychotics are effective as adjunctive agents in the treatment of acute mania. The use of risperidone, in particular, decreases the need for anticholinergics and may lead to a shorter hospital stay compared with typical antipsychotics.

Prevalence of Antipsychotic Polypharmacy and Associated Factors among Outpatients with Schizophrenia Attending Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia

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Siranesh Tesfaye

2016-01-01

Full Text Available Background. Despite recommendations by guidelines to avoid combinations of antipsychotics unless after multiple trials of antipsychotic monotherapy, it is quite a common practice to use combinations. This practice leads to unnecessary expenses and exposes the patient to severe drug adverse effects. Methods. An institution based cross-sectional study was conducted from April to May 2014. Systematic random sampling technique was used to select 423 study subjects. Logistic regression analysis was conducted to identify associated factors of antipsychotic polypharmacy among schizophrenia outpatients. Result. The overall prevalence of antipsychotic polypharmacy was found to be 28.2%. Extra pyramidal side effects (AOR = 2.80; 95% CI: 1.38, 5.71, repeated psychiatric hospitalization (AOR = 2.83; 95% CI: 1.45, 5.50, history of substance use (AOR = 2.82; 95% CI: 1.36, 5.88, longer duration of treatment (AOR = 2.10; 95% CI: 1.14, 3.87, and drug nonadherence (AOR = 1.84; 95% CI: 1.14, 2.98 were found to be significantly associated with antipsychotic polypharmacy. Conclusion. Prevalence of antipsychotic polypharmacy was found to be high among the current study participants. Individuals who had extra pyramidal side effects, admission, substance use, duration of treatment, and drug nonadherence were associated with antipsychotic polypharmacy.

Detection of the antipsychotic drug quetiapine in the blood, urine and hair samples of the victim of a drug-facilitated sexual assault

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Johansen, Sys Stybe

2017-01-01

A drug rape facilitated with the sedative antipsychotic drug quetiapine is presented here. A teenage girl and her girlfriend went to the home of an adult couple they had met at a bar. Here, the teenage girl (victim) felt tired after consuming some alcoholic drinks and fell asleep. While she......-three hours after the suspected drug-facilitated sexual assault (DFSA), blood and urine samples were collected and the initial toxicological screening detected quetiapine. Confirmation and quantification by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) revealed...... a concentration of 0.007mg/kg quetiapine in blood and 0.19mg/l in urine. Six months after the DFSA, a hair sample was collected and segmental hair analysis was performed on four washed segments (0-3cm, 3-5cm, 5-7cm, and 7-9cm). The last segment contained 0.011ng/mg of quetiapine, whereas the other segments were...

Antipsychotic use in children and adolescents: a 1-year follow-up study.

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Baeza, Inmaculada; de la Serna, Elena; Calvo-Escalona, Rosa; Morer, Astrid; Merchán-Naranjo, Jessica; Tapia, Cecilia; Martínez-Cantarero, Ma Carmen; Andrés, Patrícia; Alda, José A; Sánchez, Bernardo; Arango, Celso; Castro-Fornieles, Josefina

2014-10-01

The objective of this study was to analyze the initial treatment with antipsychotics (APs) and its changes during the first year of treatment in patients visited in specialized child and adolescent psychiatry departments. Participants were 265 patients, aged 4 to 17 years, who attended consecutively at 4 different centers and were naive of AP or quasi-naive (less than 30 days since the beginning of AP treatment). Type of AP, dosage, and concomitant medication were registered at baseline, 1, 3, 6, and 12 months after beginning the treatment with AP. At baseline, the patients' mean age was 14.4 (2.9) years, and 145 (54.7%) patients were males. Antipsychotics were more prescribed in the following: schizophrenia spectrum disorders (30.2%), disruptive behavior disorders (DBDs) (18.9%), bipolar disorders (14.3%), depressive disorders (12.8%), and eating disorders (11.7%). A total of 93.2% of the patients were on an off-label indication of AP. Risperidone was the AP most prescribed in all the assessments, but differences were observed in the type of AP according to diagnosis. Thus, risperidone was significantly most prescribed in patients with DBD and olanzapine was most prescribed in patients with eating disorders. Olanzapine and quetiapine were the second-generation APs (SGAs) most prescribed after risperidone, and haloperidol was the most prescribed first-generation AP. Up to 8.3% of patients during the follow-up were on AP polypharmacy. Almost 16% patients had a change in its AP treatment during the follow-up, and the main switch was from one SGA to another. Second-generation APs were the APs most prescribed in our sample and approximately 93% of the patients used AP off-label. Risperidone was the most common AP used above all in patients with DBD, whereas olanzapine was most prescribed in patients with eating disorders. Antipsychotic polypharmacy and switch rates were low during the follow-up.

Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.

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Singh, K P; Tripathi, Nidhi

2015-05-01

Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat. Copyright © 2015 Elsevier

Oculomotor and neuropsychological effects of antipsychotic treatment for schizophrenia

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Kristian S. Hill

2009-04-01

Full Text Available Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Anti psychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function. While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development.

Cannabidiol exhibits anxiolytic but not antipsychotic property evaluated in the social interaction test.

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Almeida, Valéria; Levin, Raquel; Peres, Fernanda Fiel; Niigaki, Suzy T; Calzavara, Mariana B; Zuardi, Antônio W; Hallak, Jaime E; Crippa, José A; Abílio, Vanessa C

2013-03-05

Cannabidiol (CBD), a non-psychotomimetic compound of the Cannabis sativa, has been reported to have central therapeutic actions, such as antipsychotic and anxiolytic effects. We have recently reported that Spontaneously Hypertensive Rats (SHRs) present a deficit in social interaction that is ameliorated by atypical antipsychotics. In addition, SHRs present a hyperlocomotion that is reverted by typical and atypical antipsychotics, suggesting that this strain could be useful to study negative symptoms (modeled by a decrease in social interaction) and positive symptoms (modeled by hyperlocomotion) of schizophrenia as well as the effects of potential antipsychotics drugs. At the same time, an increase in social interaction in control animals similar to that induced by benzodiazepines is used to screen potential anxiolytic drugs. The aim of this study was to investigate the effects of CBD on social interaction presented by control animals (Wistar) and SHRs. The lowest dose of CBD (1mg/kg) increased passive and total social interaction of Wistar rats. However, the hyperlocomotion and the deficit in social interaction displayed by SHRs were not altered by any dose of CBD. Our results do not support an antipsychotic property of cannabidiol on symptoms-like behaviors in SHRs but reinforce the anxiolytic profile of this compound in control rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Antipsychotics for fibromyalgia in adults.

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Walitt, Brian; Klose, Petra; Üçeyler, Nurcan; Phillips, Tudor; Häuser, Winfried

2016-06-02

This review is one of a series on drugs used to treat fibromyalgia. Fibromyalgia is a clinically well-defined chronic condition of unknown aetiology characterised by chronic widespread pain that often co-exists with sleep problems and fatigue. It affects approximately 2% of the general population. Up to 70% of patients with fibromyalgia meet the criteria for a depressive or anxiety disorder. People often report high disability levels and poor health-related quality of life. Drug therapy focuses on reducing key symptoms and disability, and improving health-related quality of life. Antipsychotics might reduce fibromyalgia and associated mental health symptoms. To assess the efficacy, tolerability and safety of antipsychotics in fibromyalgia in adults. We searched CENTRAL (2016, Issue 4), MEDLINE and EMBASE to 20 May 2016, together with reference lists of retrieved papers and reviews and two clinical trial registries. We also contacted trial authors. We selected controlled trials of at least four weeks duration of any formulation of antipsychotics used for the treatment of fibromyalgia in adults. We extracted the data from all included studies and two review authors independently assessed study risks of bias. We resolved discrepancies by discussion. We performed analysis using three tiers of evidence. We derived first tier evidence from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for drop-outs, at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with adequate numbers in the comparison, and third tier evidence from data involving small numbers of participants that we considered very likely to be biased or used outcomes of limited clinical utility, or both. We rated the

Positive predictive value of automated database records for diabetic ketoacidosis (DKA in children and youth exposed to antipsychotic drugs or control medications: a tennessee medicaid study

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Bobo William V

2011-11-01

Full Text Available Abstract Background Diabetic ketoacidosis (DKA is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and youth. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard." Methods The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007 in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1 were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA. Results Of 30 potential cases, 27 (90% were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%. Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis. Conclusions Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.

Antipsychotic prescription in children and adolescents: an analysis of data from a German statutory health insurance company from 2005 to 2012.

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Bachmann, Christian J; Lempp, Thomas; Glaeske, Gerd; Hoffmann, Falk

2014-01-17

Despite sparse documentation of their long-term therapeutic effects and side effects, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in recent years, both in the USA and in Europe. No current data are available about antipsychotic prescriptions for this age group in Germany. Data from the largest statutory health insurance fund in Germany (BARMER GEK) were studied to identify antipsychotic prescriptions for children and adolescents (age 0-19 years) from 2005 to 2012 and analyze them with respect to age, sex, drug prescribed, prescribing medical specialty, and any observable secular trends. The percentage of children and adolescents receiving a prescription for an antipsychotic drug rose from 0.23% in 2005 to 0.32% in 2012. In particular, atypical antipsychotic drugs were prescribed more frequently over time (from 0.10% in 2005 to 0.24% in 2012). The rise in antipsychotic prescriptions was particularly marked among 10- to 14-year-olds (from 0.24% to 0.43%) and among 15- to 19-year-olds (from 0.34% to 0.54%). The prescribing physicians were mostly either child and adolescent psychiatrists or pediatricians; the most commonly prescribed drugs were risperidone and pipamperone. Risperidone was most commonly prescribed for patients with hyperkinetic disorders and conduct disorders. In Germany as in other industrialized countries, antipsychotic drugs have come to be prescribed more frequently for children and adolescents in ecent years. The German figures, while still lower than those from North America, are in the middle range of figures from European countries. The causes of the increase should be critically examined; if appropriate, the introduction of prescribing guidelines of a more restrictive nature could be considered.

Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics

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Correll Christoph

2005-05-01

Full Text Available Abstract Background Antipsychotic monotherapy is recognized as the treatment of choice for patients with schizophrenia. Simultaneous treatment with multiple antipsychotics (polypharmacy is suggested by some expert consensus guidelines as the last resort after exhausting monotherapy alternatives. This study assessed the annual rate and duration of antipsychotic monotherapy and its inverse, antipsychotic polypharmacy, among schizophrenia patients initiated on commonly used atypical antipsychotic medications. Methods Data were drawn from a large prospective naturalistic study of patients treated for schizophrenia-spectrum disorders, conducted 7/1997–9/2003. Analyses focused on patients (N = 796 who were initiated during the study on olanzapine (N = 405, quetiapine (N = 115, or risperidone (N = 276. The percentage of patients with monotherapy on the index antipsychotic over the 1-year post initiation, and the cumulative number of days on monotherapy were calculated for all patients and for each of the 3 atypical antipsychotic treatment groups. Analyses employed repeated measures generalized linear models and non-parametric bootstrap re-sampling, controlling for patient characteristics. Results During the 1-year period, only a third (35.7% of the patients were treated predominately with monotherapy (>300 days. Most patients (57.7% had at least one prolonged period of antipsychotic polypharmacy (>60 consecutive days. Patients averaged 195.5 days on monotherapy, 155.7 days on polypharmacy, and 13.9 days without antipsychotic therapy. Olanzapine-initiated patients were significantly more likely to be on monotherapy with the initiating antipsychotic during the 1-year post initiation compared to risperidone (p = .043 or quetiapine (p = .002. The number of monotherapy days was significantly greater for olanzapine than quetiapine (p Conclusion Despite guidelines recommending the use of polypharmacy only as a last resort, the use of antipsychotic

The ticking of the epigenetic clock: antipsychotic drugs in old age

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Adonis Sfera

2016-08-01

Full Text Available AbstractBackground: Exposed to antipsychotic drugs (APDs, older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE, including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs, however they seldom progresses to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear.CNS small vessel disease (SVD is a well-known age-related risk factor for strokes, dementia and sudden death, which may constitute the initial CVAE-predisposing pathology. We therefore propose a two strike CVAE paradigm in which SVD represents the first strike, while exposure to APDs, the second. In this model, both strikes must be present for CVAE to take place, and the neuroimaging load of white matter hyperintensities (WMH may be directly proportional with the CVAE risk.To investigate this hypothesis at the molecular level, we focused on a seemingly unrelated phenomenon: both APDs and SVD were found protective against a similar repertoire of cancers and their spread to the brain (1-4. Since microRNA-29 has shown efficacy against the same malignancies, and has been associated with small vessels pathology, we narrowed our search down to this miR, hypothesizing that the APDs mechanism of action includes miR-29 up-regulation, which in turn facilitates the development of SVD. Aim: to assess whether miR-29 can be utilized as a peripheral blood biomarker for SVD and CVAE risk.Method: we conducted a search of experimentally verified miR-29 target genes utilizing the public domain tools miRanda, RNA22 and Weizemann Institute of Science miRNA Analysis. We identified in total 67 experimentally verified target genes for miR-29 family, 18 of which correlate with microvascular integrity, and may be relevant for CVAE

Association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use

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Ikram, H.; Ahmed, T.M.; Hayat, A.; Ullah, Q.I.; Nawaz, A.

2017-01-01

Objective: To determine the association of metabolic syndrome with atypical antipsychotic drug (olanzapine) short term versus long term use. Study Design: Case control study. Place and Duration of Study: Chemical pathology department Army Medical College Rawalpindi, from Nov 2014 to Oct 2015. Material and Methods: The study was carried out on 240 subjects, 120 cases and 120 controls. For the purpose of the study cases were divided into four groups A, B, C and D according to the duration of drug use. Group A patients included those who the last the drug olanzapine for the last three months. Group B patients included those who were using the drug olanzapine for the last six months. Group C and D included those who were using the drug for last 1 year and more than one year (2-5 years) respectively. By employing non probability convenience sampling technique the data was collected from patients having the diagnosis of psychosis as per DSM IV modified criteria through a proforma and fasting blood samples were drawn. These samples were tested for fasting serum lipid profile and fasting plasma glucose. The data obtained were analyzed using SPSS version 21. For quantitative data Mean and SD were calculated. For qualitative data frequency and percentages were calculated. Qualitative data was compared using chi square test whereas quantitative data was compared using independent sample t-test. Results: There was statistically no significant difference in fasting plasma glucose between group A and B and their controls whereas in group C and D these levels were significantly high as compared to controls. Triglyceride levels were significantly higher and HDL cholesterol levels were significantly lower in all four groups as compared to controls. Comparison of qualitative data which included waist circumference and blood pressure showed statistically no significant rise for group A whereas waist circumference showed insignificant rise and blood pressure showed statistically

DISRUPTION OF CONDITIONED REWARD ASSOCIATION BY TYPICAL AND ATYPICAL ANTIPSYCHOTICS

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Danna, C.L.; Elmer, G.I.

2013-01-01

Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100 μg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3–30 μg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward

A bibliometric analysis of scientific production on atypical antipsychotic drugs from Italy

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López-Muñoz, Francisco; De Berardis, Domenico; Fornaro, Michele; Vellante, Federica; di Giannantonio, Massimo; Povedano-Montero, Francisco J; Póveda Fernández-Martín, Maria; Rubio, Gabriel; Álamo, Cecilio

2017-01-01

A bibliometric study of peer-reviewed scientific publications on atypical antipsychotic drugs (AADs) from Italy is herein presented. We selected the documents from Scopus database. We applied several bibliometric indicators of production and dispersion, including Price’s Law about the increase of scientific literature, and Bradford’s Law. We also calculated the participation index across different countries. The bibliometric data have also been correlated with some social and health data sourcing in Italy, such as total per capita expenditure on health and gross domestic expenditure. A total of 2949 original documents were published within the period 1972-2015. Our results state fulfilment of Price’s Law, with scientific production showing exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The drugs most widely studied were clozapine (257 documents), risperidone (179), and olanzapine (172). Stratification into Bradford zones yielded a nucleus represented by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58 articles, each one). A total of 1091 different journals were evaluated. The publications on AADs in Italy have undergone exponential growth over the studied period, which is in line with the progressively burgeoning on novel AAD releases. No evidence of saturation point was observed.

Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral Disorders with Different Guidelines: The China Food and Drug Administration Versus the FDA.

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Zhu, Xiuqing; Hu, Jinqing; Sun, Bin; Deng, Shuhua; Wen, Yuguan; Chen, Weijia; Qiu, Chang; Shang, Dewei; Zhang, Ming

2018-04-01

This study aims to compare the prevalence of unlicensed and off-label use of antipsychotics among child and adolescent psychiatric outpatients with guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S. Food and Drug Administration (FDA), and to identify factors associated with inconsistencies between the two regulations. A retrospective analysis of 29,326 drug prescriptions for child and adolescent outpatients from the Affiliated Brain Hospital of Guangzhou Medical University was conducted. Antipsychotics were classified as "unlicensed" or "off-label use" according to the latest pediatric license information registered by the CFDA and the FDA or the package inserts of antipsychotics authorized by the CFDA or the FDA for the treatment of pediatric mental and behavioral disorders, respectively. Binary logistic regression analysis was performed to assess factors associated with inconsistencies between the two regulations. The total unlicensed use, according to the CFDA analysis, was higher than that found in the FDA analysis (74.14% vs. 22.04%, p according to the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs. 15.77%, p gender, diagnosis of schizophrenia and schizotypal and delusional disorders, diagnosis of mood [affective] disorders, diagnosis of mental retardation, and diagnosis of psychological development disorders were associated with inconsistent off-label use. The difference in prevalence of total unlicensed and off-label use of antipsychotics between the two regulations was statistically significant. This inconsistency could be partly attributed to differences in pediatric license information and package inserts of antipsychotics. The results indicate a need for further clinical pediatric studies and better harmonization between agencies regarding antipsychotic used in pediatrics.

Easy and low-cost identification of metabolic syndrome in patients treated with second-generation antipsychotics: artificial neural network and logistic regression models.

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Lin, Chao-Cheng; Bai, Ya-Mei; Chen, Jen-Yeu; Hwang, Tzung-Jeng; Chen, Tzu-Ting; Chiu, Hung-Wen; Li, Yu-Chuan

2010-03-01

Metabolic syndrome (MetS) is an important side effect of second-generation antipsychotics (SGAs). However, many SGA-treated patients with MetS remain undetected. In this study, we trained and validated artificial neural network (ANN) and multiple logistic regression models without biochemical parameters to rapidly identify MetS in patients with SGA treatment. A total of 383 patients with a diagnosis of schizophrenia or schizoaffective disorder (DSM-IV criteria) with SGA treatment for more than 6 months were investigated to determine whether they met the MetS criteria according to the International Diabetes Federation. The data for these patients were collected between March 2005 and September 2005. The input variables of ANN and logistic regression were limited to demographic and anthropometric data only. All models were trained by randomly selecting two-thirds of the patient data and were internally validated with the remaining one-third of the data. The models were then externally validated with data from 69 patients from another hospital, collected between March 2008 and June 2008. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of all models. Both the final ANN and logistic regression models had high accuracy (88.3% vs 83.6%), sensitivity (93.1% vs 86.2%), and specificity (86.9% vs 83.8%) to identify MetS in the internal validation set. The mean +/- SD AUC was high for both the ANN and logistic regression models (0.934 +/- 0.033 vs 0.922 +/- 0.035, P = .63). During external validation, high AUC was still obtained for both models. Waist circumference and diastolic blood pressure were the common variables that were left in the final ANN and logistic regression models. Our study developed accurate ANN and logistic regression models to detect MetS in patients with SGA treatment. The models are likely to provide a noninvasive tool for large-scale screening of MetS in this group of patients. (c) 2010 Physicians

Spanish consensus on the risks and detection of antipsychotic drug-related hyperprolactinaemia.

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Montejo, Ángel L; Arango, Celso; Bernardo, Miguel; Carrasco, José L; Crespo-Facorro, Benedicto; Cruz, Juan J; Del Pino, Javier; García Escudero, Miguel A; García Rizo, Clemente; González-Pinto, Ana; Hernández, Ana I; Martín Carrasco, Manuel; Mayoral Cleries, Fermin; Mayoral van Son, Jaqueline; Mories, M Teresa; Pachiarotti, Isabella; Ros, Salvador; Vieta, Eduard

2016-01-01

Iatrogenic hyperprolactinaemia (IHPRL) has been more frequently related to some antipsychotic drugs that provoke an intense blockade of dopamine D2 receptors. There is a wide variation in clinical practice, and perhaps some more awareness between clinicians is needed. Due to the high frequency of chronic treatment in severe mental patients, careful attention is recommended on the physical risk. IHPRL symptoms could be underestimated without routine examination. An intense scientific literature search was performed in order to draw up a multidisciplinary consensus, including different specialists of psychiatry, endocrinology, oncology and internal medicine, and looking for a consensus about clinical risk and detection of IHPRL following evidence-based medicine criteria levels (EBM I- IV). Short-term symptoms include amenorrhea, galactorrhoea, and sexual dysfunction with decrease of libido and erectile difficulties related to hypogonadism. Medium and long-term symptoms related to oestrogens are observed, including a decrease bone mass density, hypogonadism, early menopause, some types of cancer risk increase (breast and endometrial), cardiovascular risk increase, immune system disorders, lipids, and cognitive dysfunction. Prolactin level, gonadal hormones and vitamin D should be checked in all patients receiving antipsychotics at baseline although early symptoms (amenorrhea-galactorrhoea) may not be observed due to the risk of underestimating other delayed symptoms that may appear in the medium term. Routine examination of sexual dysfunction is recommended due to possible poor patient tolerance and low compliance. Special care is required in children and adolescents, as well as patients with PRL levels >50ng/ml (moderate hyperprolactinaemia). A possible prolactinoma should be investigated in patients with PRL levels >150ng/ml, with special attention to patients with breast/endometrial cancer history. Densitometry should be prescribed for males >50 years old

Second generation H1 - antihistamines interaction with food and alcohol-A systematic review.

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Paśko, Paweł; Rodacki, Tomasz; Domagała-Rodacka, Renata; Palimonka, Krzysztof; Marcinkowska, Monika; Owczarek, Danuta

2017-09-01

Histamine is a mediator of many physiological processes. It plays an important role in modulating allergy reactions and immune system responses. H1 receptor is a therapeutic target for drugs applied in allergic diseases such as allergic rhinoconjunctivitis, urticarial, or atopic dermatitis. H1-antihistamines display different chemical structures, pharmacokinetics and a potential for drug-drug and drug-food interactions. Drug-food interactions are known to reduce therapeutic effects of the medicine, as well as to induce a potent adverse drug reactions. Considering it all, a systematic review was conducted to investigate the importance of drug-food interaction for H1-antihistamine drugs. As non-sedating second generation H1-antihistamines remain to be drugs of choice in treating allergic conditions, the review has been focused on this particular class of medicines. The aim of this paper is to examine the evidence of food-drug and food-alcohol interactions for second generation H1-antihistamine drugs. A systematic literature queries were performed in the following databases: Medline (via PubMed), Cochrane Library, Embase and Web of Science (all from their inception date till October 2016). The queries covered nine specific names of second generation anthistamine drugs, namely bilastine, cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mizolastine, and rupatadine, in combinations with such terms as "food", "juice", "grapefruit", "fruits", "alcohol", "pharmacokinetics", and "meal". Additional publications were found by checking all the reference lists. Where none data on drug-food interaction could be found within the investigated databases, a specific drug prescribing information was used. 2326 publications were identified with the database queries. Articles were subjected to analysis by reviewing their title, abstract and full text; duplicated papers were removed. Having collected a complete set of data, a critical review was undertaken

Manual or automated measuring of antipsychotics' chemical oxygen demand.

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Pereira, Sarah A P; Costa, Susana P F; Cunha, Edite; Passos, Marieta L C; Araújo, André R S T; Saraiva, M Lúcia M F S

2018-05-15

Antipsychotic (AP) drugs are becoming accumulated in terrestrial and aqueous resources due to their actual consumption. Thus, the search of methods for assessing the contamination load of these drugs is mandatory. The COD is a key parameter used for monitoring water quality upon the assessment of the effect of polluting agents on the oxygen level. Thus, the present work aims to assess the chemical oxygen demand (COD) levels of several typical and atypical antipsychotic drugs in order to obtain structure-activity relationships. It was implemented the titrimetric method with potassium dichromate as oxidant and a digestion step of 2h, followed by the measurement of remained unreduced dichromate by titration. After that, an automated sequential injection analysis (SIA) method was, also, used aiming to overcome some drawbacks of the titrimetric method. The results obtained showed a relationship between the chemical structures of antipsychotic drugs and their COD values, where the presence of aromatic rings and oxidable groups give higher COD values. It was obtained a good compliance between the results of the reference batch procedure and the SIA system, and the APs were clustered in two groups, with the values ratio between the methodologies, of 2 or 4, in the case of lower or higher COD values, respectively. The SIA methodology is capable of operating as a screening method, in any stage of a synthetic process, being also more environmentally friendly, and cost-effective. Besides, the studies presented open promising perspectives for the improvement of the effectiveness of pharmaceutical removal from the waste effluents, by assessing COD values. Copyright © 2018 Elsevier Inc. All rights reserved.

Serotonin-1A receptor gene polymorphism and the ability of antipsychotic drugs to improve attention in schizophrenia.

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Sumiyoshi, Tomiki; Tsunoda, Masahiko; Higuchi, Yuko; Itoh, Toru; Seo, Tomonori; Itoh, Hiroko; Suzuki, Michio; Kurachi, Masayoshi

2010-05-01

The purpose of this study was to determine if the functional single nucleotide polymorphisms of rs6259 C(-1019)G in the promoter region, which regulates serotonin 5-HT(1A) receptor transcription, affects the ability of antipsychotic drugs to improve attention in patients with schizophrenia. Subjects were neuroleptic-free and meeting DSM-IV-TR criteria for schizophrenia. Psychopathology and attention were evaluated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) at baseline and 3 months after treatment with atypical antipsychotic drugs (AAPDs). DNA was extracted from peripheral blood following standard procedures. Genotyping was performed with HS-Taq assay (LaboPass). Data were available from 30 subjects (male/female=19/11), in which 17 had the CC genotype, three had the GG genotype, and 10 were heterozygous. The 3-month treatment with AAPDs was associated with significant improvements in positive and negative symptoms, but not attention as measured by SANS-Attention subscale in the entire subject group. There were no significant differences in the degree of improvements of SAPS and SANS scores between the CC genotype group and the (C/G plus G/G) combined group. On the other hand, improvement of attention was significantly greater for the former group compared to the latter group (P<0.016), suggesting a detrimental influence of the G-allele. These results provide additional support to the role of 5-HT(1A) receptors in some of the cognitive disturbances of schizophrenia. Further studies with a larger number of subjects are warranted.

Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

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Moore R Andrew

2007-08-01

were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence. Conclusion Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine. There is insufficient data confidently to distinguish between different atypical antipsychotics.

Early Nonresponse Determined by the Clinical Global Impressions Scale Predicts Poorer Outcomes in Youth with Schizophrenia Spectrum Disorders Naturalistically Treated with Second-Generation Antipsychotics

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Stentebjerg-Olesen, Marie; Jeppesen, Pia; Pagsberg, Anne K

2013-01-01

Abstract Objective: The use of early response/nonresponse (ER/ENR) to antipsychotics as a predictor for ultimate response/nonresponse (UR/UNR) may help decrease inefficacious treatment continuation. However, data have been limited to adults, and ER/ENR has only been determined using time-consuming...

Risperidone versus typical antipsychotic medication for schizophrenia.

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Hunter, R H; Joy, C B; Kennedy, E; Gilbody, S M; Song, F

2003-01-01

Risperidone is one of the 'new generation' antipsychotics. As well as its reputed tendency to cause fewer movement disorders than the older drugs such as chlorpromazine and haloperidol, it is claimed that risperidone may improve negative symptoms. To evaluate the effects of risperidone for schizophrenia in comparison to 'conventional' neuroleptic drugs. The original electronic searches of Biological Abstracts (1980-1997), Cochrane Schizophrenia Group's Register (1997), The Cochrane Library (1997, Issue 1), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were updated with a new electronic search of the same databases in 2002. The search term used in the update was identical to that used in 1997. Any new studies or relevant references were added to the review. In addition, references of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were also contacted. All randomised trials comparing risperidone to any 'conventional' neuroleptic treatment for people with schizophrenia or other similar serious mental illnesses. Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Where possible, sensitivity analyses on dose of risperidone, haloperidol and duration of illness were undertaken for the primary outcomes of clinical improvement, side effects (movement disorders) and acceptability of treatment. For homogeneous dichotomous data the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) were calculated on an intention-to-treat basis. In the short-term, risperidone was more likely to produce an improvement in the Positive and Negative Syndrome Scale (PANSS) when compared with haloperidol (n=2368, 9 RCTs, RR not 20% improved 0.72 CI 0.59 to 0.88 NNT 8). A similar, favourable outcome for risperidone was

Effects of Antipsychotics on Secular Mortality Trends in Patients With Alzheimer's Disease

DEFF Research Database (Denmark)

Nielsen, René Ernst; Valentin, Jan B; Lolk, Annette

2018-01-01

OBJECTIVE: To investigate secular changes in mortality rates between patients with Alzheimer's disease (AD) and the general population as well as changes in antipsychotic drug treatment and the association between drug treatment and mortality in patients with AD in Denmark during a 12-year study...

Neurodevelopmental outcomes in infants exposed in utero to antipsychotics: a systematic review of published data.

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Gentile, Salvatore; Fusco, Maria Luigia

2017-06-01

The proportion of pregnancies exposed to either second-generation antipsychotics (SGAs) or first-generation antipsychotics (FGAs) varies between 0.3%-2% of all pregnancies, but, until now, little is known about the potential neurobehavioral teratogenicity of antipsychotics. Assessing this safety facet is the aim of this article. PubMed, Scopus, and Google Scholar were searched for eligible articles. PubMed (1954 to May 2016) was searched using several medical subject headings, variously combined. PubMed search results were also limited using the search filter for human studies published in English. Scopus and Google Scholar searches were filtered for article title (antipsychotics/neuroleptics, pregnancy). After excluding duplicates, 9,250 articles were identified and 29 met the following inclusion criteria: only articles that provided original/primary data on neurodevelopmental outcome in human offspring older than 4 months of age, independently of the study design, were selected for review. Indeed, some relevant neurodevelopmental milestones are achieved at this time. Length of study and neurodevelopmental assessment methodology did not influence the study selection. Unfortunately, published data on neurodevelopmental teratogenicity of SGAs mainly derive from case reports and small case-series studies. Even findings emerging from case-control and prospective/retrospective studies are of limited clinical relevance because of their small sample sizes. Limited data are also available on FGAs. Hence, we have to conclude that the long-term neurodevelopmental outcomes for children exposed in utero remain unclear. Low to very low quality evidence of retrieved data makes impossible to confirm or exclude potential long-lasting untoward effects on infant neurocognitive development associate with antenatal exposure to either SGAs or FGAs.

Fluvoxamine for aripiprazole-associated akathisia in patients with schizophrenia: a potential role of sigma-1 receptors

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Hashimoto Kenji

2010-03-01

Full Text Available Abstract Background Second-generation antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPSs than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interplay of several neurotransmitter systems might play a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors are shown to regulate a number of neurotransmitter systems in the brain. Methods We report on two cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the antipsychotic drug aripiprazole. Results The global score on the Barnes Akathisia Scale in the two patients with schizophrenia treated with aripiprazole decreased after fluvoxamine monotherapy. Conclusion Doctors may wish to consider fluvoxamine as an alternative approach in treating akathisia associated with antipsychotic drugs such as aripiprazole.

Selective attention and mismatch negativity in antipsychotic-naïve, first-episode schizophrenia patients before and after 6 months of antipsychotic monotherapy.

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Oranje, B; Aggernaes, B; Rasmussen, H; Ebdrup, B H; Glenthøj, B Y

2017-09-01

Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2 receptors than for serotonergic 5-HT2A receptors, on electrophysiological parameters of attention was investigated in a group of antipsychotic-naïve, first-episode schizophrenia patients compared with a group of age- and gender-matched healthy controls. A total of 34 first-episode, antipsychotic-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow-up, whereas controls received no treatment. Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only ameliorated in patients treated with above median dosages of quetiapine. Patients had lower P3B amplitude, yet showed similar levels of processing negativity and N100 amplitude compared with healthy controls, both at baseline and follow-up. The results indicate that deficits in MMN, P200 and P3B amplitude are present at early stages of schizophrenia, although depending on the paradigm used. Furthermore, the results indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits, and only in those subjects on higher dosages.

Risk of stent thrombosis among bare-metal stents, first-generation drug-eluting stents, and second-generation drug-eluting stents: results from a registry of 18,334 patients.

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Tada, Tomohisa; Byrne, Robert A; Simunovic, Iva; King, Lamin A; Cassese, Salvatore; Joner, Michael; Fusaro, Massimiliano; Schneider, Simon; Schulz, Stefanie; Ibrahim, Tareq; Ott, Ilka; Massberg, Steffen; Laugwitz, Karl-Ludwig; Kastrati, Adnan

2013-12-01

This study sought to compare the risk of stent thrombosis among patients treated with bare-metal stents (BMS), first-generation drug-eluting stents (G1-DES), and second-generation drug-eluting stents (G2-DES) for a period of 3 years. In patients undergoing coronary stenting, there is a scarcity of long-term follow-up data on cohorts large enough to compare rates of stent thrombosis across the stent generations. A total of 18,334 patients undergoing successful coronary stent implantation from 1998 to 2011 at 2 centers in Munich, Germany, were included in this study. Patients were stratified into 3 groups according to treatment with BMS, G1-DES, and G2-DES. The cumulative incidence of definite stent thrombosis at 3 years was 1.5% with BMS, 2.2% with G1-DES, and 1.0% with G2-DES. On multivariate analysis, G1-DES compared with BMS showed a significantly higher risk of stent thrombosis (odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.47 to 2.86; p stent thrombosis compared with BMS (OR: 0.82; 95% CI: 0.56 to 1.19; p = 0.30). Beyond 1 year, the risk of stent thrombosis was significantly increased with G1-DES compared with BMS (OR: 4.72; 95% CI: 2.01 to 11.1; p stenting, compared with BMS, there was a significant excess risk of stent thrombosis at 3 years with G1-DES, driven by an increased risk of stent thrombosis events beyond 1 year. G2-DES were associated with a similar risk of stent thrombosis compared with BMS. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

An explorative study of school performance and antipsychotic medication.

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van der Schans, J; Vardar, S; Çiçek, R; Bos, H J; Hoekstra, P J; de Vries, T W; Hak, E

2016-09-21

Antipsychotic therapy can reduce severe symptoms of psychiatric disorders, however, data on school performance among children on such treatment are lacking. The objective was to explore school performance among children using antipsychotic drugs at the end of primary education. A cross-sectional study was conducted using the University Groningen pharmacy database linked to academic achievement scores at the end of primary school (Dutch Cito-test) obtained from Statistics Netherlands. Mean Cito-test scores and standard deviations were obtained for children on antipsychotic therapy and reference children, and statistically compared using analyses of covariance. In addition, differences in subgroups as boys versus girls, ethnicity, household income, and late starters (start date within 12 months of the Cito-test) versus early starters (start date > 12 months before the Cito-test) were tested. In all, data from 7994 children could be linked to Cito-test scores. At the time of the Cito-test, 45 (0.6 %) were on treatment with antipsychotics. Children using antipsychotics scored on average 3.6 points lower than the reference peer group (534.5 ± 9.5). Scores were different across gender and levels of household income (p starters were significantly higher than starters within 12 months (533.7 ± 1.7 vs. 524.1 ± 2.6). This first exploration showed that children on antipsychotic treatment have lower school performance compared to the reference peer group at the end of primary school. This was most noticeable for girls, but early starters were less affected than later starters. Due to the observational cross-sectional nature of this study, no causality can be inferred, but the results indicate that school performance should be closely monitored and causes of underperformance despite treatment warrants more research.

Very late stent thrombosis with second generation drug eluting stents compared to bare metal stents: Network meta-analysis of randomized primary percutaneous coronary intervention trials.

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Philip, Femi; Stewart, Susan; Southard, Jeffrey A

2016-07-01

The relative safety of drug-eluting stents (DES) and bare-metal stents (BMS) in primary percutaneous coronary intervention (PPCI) in ST elevation myocardial infarction (STEMI) continues to be debated. The long-term clinical outcomes between second generation DES and BMS for primary percutaneous coronary intervention (PCI) using network meta-analysis were compared. Randomized controlled trials comparing stent types (first generation DES, second generation DES, or BMS) were considered for inclusion. A search strategy used Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion criteria, and sample characteristics were extracted. Network meta-analysis was used to pool direct (comparison of second generation DES to BMS) and indirect evidence (first generation DES with BMS and second generation DES) from the randomized trials. Twelve trials comparing all stents types including 9,673 patients randomly assigned to treatment groups were analyzed. Second generation DES was associated with significantly lower incidence of definite or probable ST (OR 0.59, 95% CI 0.39-0.89), MI (OR 0.59, 95% CI 0.39-0.89), and TVR at 3 years (OR 0.50: 95% CI 0.31-0.81) compared with BMS. In addition, there was a significantly lower incidence of MACE with second generation DES versus BMS (OR 0.54, 95% CI 0.34-0.74) at 3 years. These were driven by a higher rate of TVR, MI and stent thrombosis in the BMS group at 3 years. There was a non-significant reduction in the overall and cardiac mortality [OR 0.83, 95% CI (0.60-1.14), OR 0.88, 95% CI (0.6-1.28)] with the use of second generation DES versus BMS at 3 years. Network meta-analysis of randomized trials of primary PCI demonstrated lower incidence of MACE, MI, TVR, and stent thrombosis with second generation DES compared with BMS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Conference report: Belgian consensus on metabolic problems associated with atypical antipsychotics].

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De Nayer, A; De Hert, M; Scheen, A; Van Gaal, L; Peuskens, J

2007-01-01

The current literature supports that schizophrenia (and bipolar disorders) appear to be associated with a higher prevalence of type 2 diabetes. Because of the silent nature of diabetes mellitus, and the fact that schizophrenic patients are not screened comprehensively for the disease, the true prevalence of hyperglycemia and diabetes may be substantially underestimated. Notably, it has been suggested that schizophrenia as such carries an increased risk, as certain characteristics of schizophrenic patients such as unhealthy life style promote the diabetes risk. This risk may be increased by antipsychotic drug treatment, as was already suggested for first-generation antipsychotics (FGA). The amount of literature on the association of SGA and metabolic disorders is much larger however, although well-controlled prospective data are sparse. Reports comprise abnormal glucose regulation, exacerbation of existing type 1 and 2 diabetes, new-onset pseudo-type 1 or type 2 diabetes, diabetic ketoacidosis, coma and death. In large-scale studies (mostly retrospective), reviews and meta-analyses, the association was not found for all drugs. According to recent reviews, the risk of developing diabetes was highest for clozapine and olanzapine, followed by quetiapine and risperidone. The hierarchy of liability of weight gain, or differential effects on insulin resistance was also in the described order. Apart from disturbances in glucose metabolism, further frequent metabolic abnormalities in schizophrenic patients on SGA include features of the metabolic syndrome. Antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, while agents such as haloperidol, risperidone and ziprasidone were associated with reductions in plasma triglycerides. Amisulpride, aripiprazole and ziprasidone seem to carry the lowest risk for weight gain, diabetes and effects on insulin resistance. As a consequence, there is a shift in attention toward physical health

Differences in psychotropic drug prescriptions among ethnic groups in the Netherlands.

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Wittkampf, Laura Christina; Smeets, Hugo M; Knol, Mirjam J; Geerlings, Mirjam I; Braam, Arjan W; De Wit, Niek J

2010-08-01

Psychotropic drug use in Europe and the USA has increased in the past 20 years. The rise in mental health-care use instigated a debate about possible differences in prevalence rates between different ethnic groups in the Netherlands, although the exact differences were unknown. The aim of this study was to determine whether these minority groups were more or less likely than the native population to receive psychotropic drugs. A descriptive population study was conducted using the Agis Health Database, containing demographic and health-care consumption data of approximately 1.5 million inhabitants of the Netherlands. Rates of prescriptions of psychotropic drugs from 2001 to 2006 and adjusted odds ratios for psychotropic drug prescriptions among native Dutch, Turkish and Moroccan ethnic groups were calculated. These data were analysed using logistic regression, after being adjusted for age, gender and socioeconomic status. The mean year prevalence of psychotropic drug prescriptions from 2001 to 2006 was 14.0%. Except for a decrease in anxiolytic drugs, the prescriptions of psychotropic drugs increased from 2001 to 2006. These trends were the same for all of the ethnic groups considered. Among both the Moroccan and Turkish populations, there was a higher risk of antidepressant and antipsychotic drug prescriptions, and a pronounced lower risk of ADHD medication and lithium prescriptions compared to the native population. Among the Turkish population, the risk of anxiolytic drug prescriptions was greater than in the native population. Compared to the native population in the Netherlands, first- and second-generation Turkish and Moroccan immigrants had an increased risk of antidepressant and antipsychotic drug prescriptions and a decreased risk of ADHD medication and Lithium prescriptions. Further research is needed to clarify whether patients of different ethnic backgrounds with the same symptoms receive similar diagnosis and adequate treatment.

Effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care.

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Stargardt, Tom; Weinbrenner, Susanne; Busse, Reinhard; Juckel, Georg; Gericke, Christian A

2008-06-01

In two recent randomised clinical trials, a meta-analysis and in an effectiveness study analysing routine data from the U.S. Veterans Administration the superiority of the newer atypical drugs over typical antipsychotic drugs, concerning both their efficacy and their side-effect profile, has been questioned. To analyse the effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care. Cohort study using routine care data from a statutory sickness fund with 5.4 million insured in Germany. To be included, patients had to be discharged with a diagnosis of schizophrenia in 2003 and fulfil membership criteria. Main outcome measures were rehospitalisation rates, mean hospital bed days, mean length of stay, cost of inpatient and pharmaceutical care to the sickness fund during follow-up and medication used to treat side-effects. 3121 patients were included into the study. There were no statistically significant differences in the effectiveness of atypical and typical antipsychotics on rehospitalisation during follow-up (rehospitalisation rate ratio 1.07, 95% confidence interval 0.86 to 1.33). However, there were consistent observations of atypical antipsychotics being more effective for severe cases of schizophrenia (14.6% of study population; >61 prior bed days per year in 2000-2002) in the follow-up period, whereas for the other severity strata typical antipsychotics seemed more effective in reducing various rehospitalisation outcomes. Patients treated with atypical antipsychotics received significantly less prescriptions for anticholinergics or tiaprid (relative risk 0.26, 95% confidence interval 0.18 to 0.38). The effectiveness of atypical antipsychotics for schizophrenia on rehospitalisation measures appeared similar to that of typical antipsychotics. With the exception of severe cases, the higher costs for atypical antipsychotics were not offset by savings from reduced inpatient care. Major limitations include the lack of

Temporomandibular disorders in patients with schizophrenia using antipsychotic agents: a discussion paper

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de Araújo AN

2014-03-01

Full Text Available Arão Nogueira de Araújo,1 Marion Alves do Nascimento,1 Eduardo Pondé de Sena,1,2 Abrahão Fontes Baptista3,4 1Postgraduate Program in Interactive Processes of Organs and Systems, 2Department of Pharmacology, Institute of Health Sciences, 3Department of Biomorphology, Institute of Health Sciences, 4Postgraduate Program in Medicine and Health, Federal University of Bahia, Salvador, Brazil Abstract: Patients with psychiatric problems show a tendency to develop temporomandibular disorders (TMD. Particularly, patients with schizophrenia are quite likely to have signs and symptoms of TMD due to the impairment of their oral health, the use of antipsychotic drugs, and other general health problems. In nonschizophrenic populations, TMD have been considered as the main cause of nondental pain in the orofacial region, involving mechanisms associated with changes in masticatory activity at the cortical and neuromuscular levels. Individuals with schizophrenia do not usually complain of pain, and TMD is misdiagnosed in this population. In this paper, we aimed to review the clinical aspects of TMD in people with schizophrenia on antipsychotic drug therapy. Keywords: schizophrenia, temporomandibular joint, pain, antipsychotic agents

The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia

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Stefanović Vesna

2015-01-01

Full Text Available Background/Aim. Immune system disorder, including inflammation, takes a significant place when considering still unclear etiology of schizophrenia. The aim of this study was to determine the blood levels of nonspecific inflammation markers in the first episode of schizophrenia and their relation to the therapy response. Methods. In this study we determined the blood levels of nonspecific inflammation markers: white blood cells count (WBC, C-reactive protein (CRP, erythrocytes sedimentation rate (ESR and the elements of differential white blood cell counts (or the leukocyte formula: granulocytes (Gra, lymphocytes (Lym and monocytes (Mon, in the first episode of schizofrenia, in 78 patients hospitalized at the Clinic for Psychiatric Disorders “Dr Laza Lazarević” in Belgrade. The levels were measured at admission to the clinic, as well as after 4 weeks of antipsychotic treatment. The Positive and negative syndrome scale for schizophrenia (PANSS was applied to measure the severity of psychopathology and response to the treatment. Results. During the first episode of schizophrenia, before initiation of antipsychotic treatment, the frequency of abnormal values was high (≥ 25% of the patients for the following non-specific inflammation markers: WBC, CRP, ESR and Gra, in the leukocyte formula, but dropped after 4 weeks of antipsychotic treatment at the level of high statistical significance for WBC and Gra (p < 0.001. The ESR remained unchanged in as many as 50% of the patients even after 4-week antipsychotic treatment, at the level of statistical significance in the non-responders compared to the responders (p = 0.045. Conclusion. The obtained results indicate that in the first episode of schizophrenia the blood levels of non-specific inflammation markers (WBS, CRP, ESR and Gra from the leukocyte formula were high in the subpopulation of patients with the tendency towards normalization of inflammation parameters after a 4-week antipsychotic

Almost all antipsychotics result in weight gain: a meta-analysis.

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Maarten Bak

Full Text Available INTRODUCTION: Antipsychotics (AP induce weight gain. However, reviews and meta-analyses generally are restricted to second generation antipsychotics (SGA and do not stratify for duration of AP use. It is hypothesised that patients gain more weight if duration of AP use is longer. METHOD: A meta-analysis was conducted of clinical trials of AP that reported weight change. Outcome measures were body weight change, change in BMI and clinically relevant weight change (7% weight gain or loss. Duration of AP-use was stratified as follows: ≤6 weeks, 6-16 weeks, 16-38 weeks and >38 weeks. Forest plots stratified by AP as well as by duration of use were generated and results were summarised in figures. RESULTS: 307 articles met inclusion criteria. The majority were AP switch studies. Almost all AP showed a degree of weight gain after prolonged use, except for amisulpride, aripiprazole and ziprasidone, for which prolonged exposure resulted in negligible weight change. The level of weight gain per AP varied from discrete to severe. Contrary to expectations, switch of AP did not result in weight loss for amisulpride, aripiprazole or ziprasidone. In AP-naive patients, weight gain was much more pronounced for all AP. CONCLUSION: Given prolonged exposure, virtually all AP are associated with weight gain. The rational of switching AP to achieve weight reduction may be overrated. In AP-naive patients, weight gain is more pronounced.

Primary Care Physician Perspectives about Antipsychotics and Other Medications for Symptoms of Dementia.

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Kerns, J William; Winter, Jonathan D; Winter, Katherine M; Boyd, Terry; Etz, Rebecca S

2018-01-01

Guidelines, policies, and warnings have been applied to reduce the use of medications for behavioral and psychological symptoms of dementia (BPSD). Because of rare dangerous side effects, antipsychotics have been singled out in these efforts. However, antipsychotics are still prescribed "off label" to hundreds of thousands of seniors residing in nursing homes and communities. Our objective was to evaluate how and why primary-care physicians (PCPs) employ nonpharmacologic strategies and drugs for BPSD. Semi-structured interviews analyzed via template, immersion and crystallization, and thematic development of 26 PCPs (16 family practice, 10 general internal medicine) in full time primary-care practice for at least 3 years in Northwestern Virginia. PCPs described 4 major themes regarding BPSD management: (1) nonpharmacologic methods have substantial barriers; (2) medication use is not constrained by those barriers and is perceived as easy, efficacious, reasonably safe, and appropriate; (3) pharmacologic policies decrease the use of targeted medications, including antipsychotics, but also have unintended consequences such as increased use of alternative risky medications; and (4) PCPs need practical evidence-based guidelines for all aspects of BPSD management. PCPs continue to prescribe medications because they meet patient-oriented goals and because PCPs perceive drugs, including antipsychotics and their alternatives, to be more effective and less dangerous than evidence suggests. To optimally treat BPSD, PCPs need supportive verified prescribing guidelines and access to nonpharmacologic modalities that are as affordable, available, and efficacious as drugs; these require and deserve significant additional research and payer support. Community PCPs should be included in BPSD policy and guideline development. © Copyright 2018 by the American Board of Family Medicine.

Second-harmonic generation in second-harmonic fiber Bragg gratings.

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Steel, M J; de Sterke, C M

1996-06-20

We consider the production of second-harmonic light in gratings resonant with the generated field, through a Green's function approach. We recover some standard results and obtain new limits for the uniform grating case. With the extension to nonuniform gratings, we find the Green's function for the second harmonic in a grating with an arbitrary phase shift at some point. We then obtain closed form approximate expressions for the generated light for phase shifts close to π/2 and at the center of the grating. Finally, comparing the uniform and phase-shifted gratings with homogeneous materials, we discuss the enhancement in generated light and the bandwidth over which it occurs, and the consequences for second-harmonic generation in optical fiber Bragg gratings.

Chronic Antipsychotic Treatment in the Rat – Effects on Brain Interleukin-8 and Kynurenic Acid

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Markus K. Larsson

2015-01-01

Full Text Available Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6, olanzapine (2 mg/kg, n = 6, and clozapine (20 mg/kg, n = 6 or saline ( n = 6 for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.

Antipsychotic-associated weight gain: management strategies and impact on treatment adherence

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Dayabandara M

2017-08-01

Full Text Available Madhubhashinee Dayabandara, Raveen Hanwella, Suhashini Ratnatunga, Sudarshi Seneviratne, Chathurie Suraweera, Varuni A de Silva Department of Psychiatry, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka Abstract: Antipsychotic-induced weight gain is a major management problem for clinicians. It has been shown that weight gain and obesity lead to increased cardiovascular and cerebrovascular morbidity and mortality, reduced quality of life and poor drug compliance. This narrative review discusses the propensity of various antipsychotics to cause weight gain, the pharmacologic and nonpharmacologic interventions available to counteract this effect and its impact on adherence. Most antipsychotics cause weight gain. The risk appears to be highest with olanzapine and clozapine. Weight increases rapidly in the initial period after starting antipsychotics. Patients continue to gain weight in the long term. Children appear to be particularly vulnerable to antipsychotic-induced weight gain. Tailoring antipsychotics according to the needs of the individual and close monitoring of weight and other metabolic parameters are the best preventive strategies at the outset. Switching to an agent with lesser tendency to cause weight gain is an option, but carries the risk of relapse of the illness. Nonpharmacologic interventions of dietary counseling, exercise programs and cognitive and behavioral strategies appear to be equally effective in individual and group therapy formats. Both nonpharmacologic prevention and intervention strategies have shown modest effects on weight. Multiple compounds have been investigated as add-on medications to cause weight loss. Metformin has the best evidence in this respect. Burden of side effects needs to be considered when prescribing weight loss medications. There is no strong evidence to recommend routine prescription of add-on medication for weight reduction. Heterogeneity of study methodologies and other

Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

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Pimentel, Camilla B; Donovan, Jennifer L; Field, Terry S; Gurwitz, Jerry H; Harrold, Leslie R; Kanaan, Abir O; Lemay, Celeste A; Mazor, Kathleen M; Tjia, Jennifer; Briesacher, Becky A

2015-02-01

To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. Forty-one NHs in Connecticut. NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

[Prevention and Treatment of Common Acute Adverse Effects With Antipsychotic Use in Adults With Schizophrenia Diagnosis].

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Arenas Borrero, Álvaro Enrique; Gómez Restrepo, Carlos; Bohórquez Peñaranda, Adriana Patricia; Vélez Traslaviña, Ángela; Castro Díaz, Sergio Mario; Jaramillo González, Luis Eduardo; García Valencia, Jenny

2014-01-01

To determine the most adequate strategies for the prevention and treatment of the acute adverse effects of the use of antipsychotics. A clinical practice guideline was elaborated under the parameters of the Methodological Guide of the Ministerio de Salud y Protección Social to identify, synthesize and evaluate the evidence and make recommendations about the treatment and follow-up of adult patients with schizophrenia. A systematic literature search was carried out. The evidence was presented to the Guideline Developing Group and recommendations, employing the GRADE system, were produced. The non-pharmacological interventions such as nutritional counseling by a nutritionist, exercise and psychotherapy are effective in preventing weight gain with the use of antipsychotics. (Kg Weight reduction in DM of -3.05 (-4.16, -1.94)). The antipsychotic change from olanzapine to aripiprazole showed weight loss and decreased BMI (decreased weight in KG DM -3.21 (-9.03, -2.61). The use of beta blockers was ineffective in reducing akathisia induced by antipsychotic; using as outcome the 50% reduction of symptoms of akathisia comparing beta-blockers with placebo RR was 1.4 (0.59, 1.83). It is recommended to make psychotherapeutic accompaniment and nutrition management of overweight for patients with weight gain. If these alternatives are ineffective is suggested to change the antipsychotic or consider starting metformin. For the management of drug-induced akathisia it is recommended to decrease the dose of the drug and the addition of lorazepam. It is recommended using 5mg biperiden IM or trihexyphenidyl 5mg orally in case of secondary acute dystonia and for the treatment of antipsychotic-induced parkinsonism to decrease the dose of antipsychotic or consider using 2 - 4mg/day of biperiden or diphenhydramine 50mg once daily. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia.

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Tomelleri, Luisa; Jogia, Jigar; Perlini, Cinzia; Bellani, Marcella; Ferro, Adele; Rambaldelli, Gianluca; Tansella, Michele; Frangou, Sophia; Brambilla, Paolo

2009-12-01

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology.

Relationship of symptomatology, gender, and antipsychotic drug treatment with plasma homovanillic acid in schizophrenia.

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Zhang, Z J; Reynolds, G P; Ramchand, C; Peet, M; Shah, S

2001-01-01

To study the role of dopamine neurotransmission in schizophrenia and its drug treatment by assessing the relationship of plasma homovanillic acid (pHVA), a major central dopamine metabolite to various clinical parameters in schizophrenic patients. pHVA was measured by high-performance liquid chromatography with electrochemical detection in a large cohort of both medicated and unmedicated DSM-IV schizophrenic patients. Prior to the measurement of pHVA, the patients were rated on the schedule for the assessment of positive and negative symptoms (PANSS). (1) pHVA in 46 patients receiving antipsychotic drugs was decreased, and in 58 drug-free patients increased, (7.4+/-2.7) microg/L and (10+/-4) microg/L compared with a matched control group (9 microg/L+/-3 microg/L, n=62) (ANOVA F=8.57, df=2, P pHVA was higher in the patients with a more negative symptom profile. (2) No significant correlation of pHVA with overall SAPS or SANS scores was apparent in the drug-free patients, although within the SANS subscales, a significant relationships to anhedonia-asociality (r=0.32, P pHVA with negative symptoms (r=0.42, P < 0.05) while females showed no significant relationship with any PANSS subscales. The results suggest that an increased dopaminergic metabolism is apparent in (male) schizophrenic patients with predominantly negative symptoms, supporting reports that this change in neuronal activity may be related to the neuropathological abnormalities seen in the disease, which may differ between males and females. Such neuronal deficits of developmental origin may thus result in an elevation/disinhibition of central dopamine metabolism in schizophrenia.

Brain Connectivity Studies in Schizophrenia: Unravelling the Effects of Antipsychotics

DEFF Research Database (Denmark)

Nejad, A.B.; Ebdrup, Bjørn Hylsebeck; Glenthøj, Birte Yding

2012-01-01

Impaired brain connectivity is a hallmark of schizophrenia brain dysfunction. However, the effect of drug treatment and challenges on the dysconnectivity of functional networks in schizophrenia is an understudied area. In this review, we provide an overview of functional magnetic resonance imaging...... studies examining dysconnectivity in schizophrenia and discuss the few studies which have also attempted to probe connectivity changes with antipsychotic drug treatment. We conclude with a discussion of possible avenues for further investigation....

Patient, Physician and Organizational Influences on Variation in Antipsychotic Prescribing Behavior.

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Tang, Yan; Chang, Chung-Chou H; Lave, Judith R; Gellad, Walid F; Huskamp, Haiden A; Donohue, Julie M

2016-03-01

Physicians face the choice of multiple ingredients when prescribing drugs in many therapeutic categories. For conditions with considerable patient heterogeneity in treatment response, customizing treatment to individual patient needs and preferences may improve outcomes. To assess variation in the diversity of antipsychotic prescribing for mental health conditions, a necessary although not sufficient condition for personalizing treatment. To identify patient caseload, physician, and organizational factors associated with the diversity of antipsychotic prescribing. Using 2011 data from Pennsylvania's Medicaid program, IMS Health's HCOSTM database, and the AMA Masterfile, we identified 764 psychiatrists who prescribed antipsychotics to 10 patients. We constructed three physician-level measures of diversity/concentration of antipsychotic prescribing: number of ingredients prescribed, share of prescriptions for most preferred ingredient, and Herfindahl-Hirschman index (HHI). We used multiple membership linear mixed models to examine patient caseload, physician, and healthcare organizational predictors of physician concentration of antipsychotic prescribing. There was substantial variability in antipsychotic prescribing concentration among psychiatrists, with number of ingredients ranging from 2-17, share for most preferred ingredient from 16%-85%, and HHI from 1,088-7,270. On average, psychiatrist prescribing behavior was relatively diversified; however, 11% of psychiatrists wrote an average of 55% of their prescriptions for their most preferred ingredient. Female prescribers and those with smaller shares of disabled or serious mental illness patients had more concentrated prescribing behavior on average. Antipsychotic prescribing by individual psychiatrists in a large state Medicaid program varied substantially across psychiatrists. Our findings illustrate the importance of understanding physicians' prescribing behavior and indicate that even among specialties

Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011.

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Guthrie, Bruce; Clark, Stella A; Reynish, Emma L; McCowan, Colin; Morales, Daniel R

2013-01-01

Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact. Segmented regression time-series analysis 2001-2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing. The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI -6.6 to -5.2) and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs. The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates are falling

Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.

Science.gov (United States)

Meltzer, H Y; Matsubara, S; Lee, J C

1989-10-01

The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding sites were determined. The atypical antipsychotics had significantly lower pKi values for the D-2 but not 5-HT2 binding sites. There was a trend for a lower pKi value for the D-1 binding site for the atypical APD. The 5-HT2 and D-1 pKi values were correlated for the typical APD whereas the 5-HT2 and D-2 pKi values were correlated for the atypical APD. A stepwise discriminant function analysis to determine the independent contribution of each pKi value for a given binding site to the classification as a typical or atypical APD entered the D-2 pKi value first, followed by the 5-HT2 pKi value. The D-1 pKi value was not entered. A discriminant function analysis correctly classified 19 of 20 of these compounds plus 14 of 17 additional test compounds as typical or atypical APD for an overall correct classification rate of 89.2%. The major contributors to the discriminant function were the D-2 and 5-HT2 pKi values. A cluster analysis based only on the 5-HT2/D2 ratio grouped 15 of 17 atypical + one typical APD in one cluster and 19 of 20 typical + two atypical APDs in a second cluster, for an overall correct classification rate of 91.9%. When the stepwise discriminant function was repeated for all 37 compounds, only the D-2 and 5-HT2 pKi values were entered into the discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatments for acute bipolar depression: meta-analyses of placebo-controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics.

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Selle, V; Schalkwijk, S; Vázquez, G H; Baldessarini, R J

2014-03-01

Optimal treatments for bipolar depression, and the relative value of specific drugs for that purpose, remain uncertain, including agents other than antidepressants. We searched for reports of placebo-controlled, monotherapy trials of mood-stabilizing anticonvulsants, second-generation antipsychotics, or lithium for acute major depressive episodes in patients diagnosed with type I or II bipolar disorder and applied random-effects meta-analysis to evaluate their efficacy, comparing outcomes based on standardized mean drug-placebo differences (SMD) in improvement, relative response rates (RR), and number-needed-to-treat (NNT). We identified 24 trials of 10 treatments (lasting 7.5 weeks, with ≥ 50 collaborating sites/trial) that met eligibility criteria: lamotrigine (5 trials), quetiapine (5), valproate (4), 2 each for aripiprazole, olanzapine, ziprasidone, and 1 each for carbamazepine, lithium, lurasidone, and olanzapine-fluoxetine. Overall, pooled drug-over-placebo responder-rate superiority (RR) was moderate (29% [CI: 19-40%]), and NNT was 8.2 (CI: 6.4-11). By SMD, apparent efficacy ranked: olanzapine + fluoxetine ≥ valproate > quetiapine > lurasidone > olanzapine, aripiprazole, and carbamazepine; ziprasidone was ineffective, and lithium remains inadequately studied. Notably, drugs were superior to placebo in only 11/24 trials (5/5 with quetiapine, 2/4 with valproate), and only lamotrigine, quetiapine and valproate had > 2 trials. Treatment-associated mania-like reactions were uncommon (drugs: 3.7%; placebo: 4.7%). Controlled trials of non-antidepressant treatments for bipolar depression remain scarce, but findings with olanzapine-fluoxetine, lurasidone, quetiapine, and perhaps carbamazepine and valproate were encouraging; lithium requires adequate testing. © Georg Thieme Verlag KG Stuttgart · New York.

The role of atypical antipsychotics for treatment of Tourette's syndrome: an overview.

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Budman, Cathy L

2014-07-01

Tourette's syndrome (TS) is a neuropsychiatric disorder of childhood onset characterized by multiple motor and phonic tics that fluctuate over time. Tic symptoms often improve by late adolescence, but some children and adults with TS may experience significant tic-related morbidity, including social and family problems, academic difficulties, and pain. When more conservative interventions are not successful, and when certain psychiatric co-morbidities further complicate the clinical profile, treating TS with an atypical antipsychotic medication may be a reasonable second-tier approach. However, the evidence supporting efficacy and safety of the atypical antipsychotics for treatment of tics is still very limited. The objective of this paper is to provide an updated overview of the role of atypical antipsychotics for treatment of TS, with evidence-based guidance on their use. Evidence for efficacy of different typical and atypical antipsychotics for treatment of tics was examined by conducting a systematic, keyword-related search of 'atypical antipsychotics' and 'Tourette's syndrome' in PubMed (National Library of Medicine, Washington, DC, USA). Four recent treatment consensus publications were also reviewed. This review focused on literature published from 2000 to 2013 and on available randomized controlled trials in TS. Evidence supporting the use of atypical antipsychotics for treatment of TS is limited. There are few randomized medication treatment trials in TS (i.e. risperidone, aripiprazole, ziprasidone), which employed varying methodologies, thereby restricting meaningful comparisons among studies. Future collaborations among clinical sites with TS expertise employing high-quality study design may better elucidate the role of atypical antipsychotics for treatment of TS.

Heterogeneity of response to antipsychotics from multiple disorders in the schizophrenia spectrum.

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Garver, D L; Holcomb, J A; Christensen, J D

2000-12-01

Antipsychotic response after the initiation of neuroleptic treatment shows wide variation in schizophrenic patient populations. In this overview, the authors suggest that the variance in antipsychotic drug response within schizophrenia can be reduced by resolving the schizophrenias into several discrete "endophenotypes," each with different etiologic underpinnings. Studies relating differences in the relative speed or completeness of antipsychotic response to differences in distribution of 2 biological markers with possible etiologic significance are reviewed. Such studies had assessed recently hospitalized, neuroleptic-free patients undergoing exacerbation of nonaffective psychotic disorders. Prior to initiation of neuroleptic, the cohort of patients had been assessed for the quantity of the dopamine metabolite homovanillic acid in plasma (pHVA) and had undergone the first of 2 magnetic resonance imaging (MRI) studies for analyses of ventricle volumes. A second MRI was subsequently performed during a period of (partial) remission to determine within-patient stability of ventricular volumes. These selected studies assessed the distribution of pHVA and distribution of rates of ventricular change, with non-normal distributions resolved by K-means clustering. The speed and completeness of neuroleptic-induced antipsychotic response were related to 3 clusters of patients delineated by modal distributions of pHVA and of apparent rates of ventricular change. At least 3 unique "endophenotypes" of the "group of the schizophrenias" can be defined with respect to speed and completeness of antipsychotic response. Each endophenotype appears to show at least one unique biological feature that differentiates it from a normal comparison group. A rapidly responsive psychosis was associated with excessive production of dopamine, as identifiable by elevation of pHVA and a "good-prognosis" course. A delayed-response psychosis had low-to-normal pHVA, clinically demonstrated persistent

Patterns of clozapine and other antipsychotics prescriptions in patients with treatment-resistant schizophrenia in community mental health centers in São Paulo, Brazil

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Ana Stella de Azevedo Silveira

2015-12-01

Full Text Available Abstract Background Despite of its global underuse, clozapine is still the golden standard antipsychotic for patients with treatment-resistant schizophrenia (TRS. Objective To evaluate the patterns of clozapine and other antipsychotic drugs prescription in TRS in community mental health centers in São Paulo, Brazil. Methods A multiple-choice questionnaire was applied to fifteen psychiatrists at five centers inquiring about patients’ clinical condition, adherence to oral treatment and current antipsychotic treatment. History of previous and current antipsychotic treatment was collected through medical chart review. Results Out of 442 schizophrenia patients, 103 (23.3% fulfilled the criteria for TRS. Fifty-eight patients (56.3% were receiving polypharmacy; 30 (29.1% were on atypical antipsychotic monotherapy, 14 (13.6% were on typical antipsychotic monotherapy, 25 (24.3% were taking depot antipsychotic medication and only 22 (21.4% were receiving clozapine. Discussion As well as in other parts of the world, many TRS patients (78.6% receive other drugs instead of clozapine in São Paulo, the best evidence-based medication for patients with TRS. The government should make every effort to provide medical training and the equipment and logistic support to adequately serve those who could benefit from clozapine treatment at the community health centers.

A Non-Interventional Naturalistic Study of the Prescription Patterns of Antipsychotics in Patients with Schizophrenia from the Spanish Province of Tarragona.

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Ana M Gaviria

Full Text Available The analysis of prescribing patterns in entire catchment areas contributes to global mapping of the use of antipsychotics and may improve treatment outcomes.To determine the pattern of long-term antipsychotic prescription in outpatients with schizophrenia in the province of Tarragona (Catalonia-Spain.A naturalistic, observational, retrospective, non-interventional study based on the analysis of registries of computerized medical records from an anonymized database of 1,765 patients with schizophrenia treated between 2011 and 2013.The most used antipsychotic was risperidone, identified in 463 (26.3% patients, followed by olanzapine in 249 (14.1%, paliperidone in 225 (12.7%, zuclopenthixol in 201 (11.4%, quetiapine in 141 (8%, aripiprazole in 100 (5.7%, and clozapine in 100 (5.7%. Almost 8 out of 10 patients (79.3% were treated with atypical or second-generation antipsychotics. Long-acting injectable (LAI formulations were used in 44.8% of patients. Antipsychotics were generally prescribed in their recommended doses, with clozapine, ziprasidone, LAI paliperidone, and LAI risperidone being prescribed at the higher end of their therapeutic ranges. Almost 7 out of 10 patients (69.6% were on antipsychotic polypharmacy, and 81.4% were on psychiatric medications aside from antipsychotics. Being prescribed quetiapine (OR 14.24, 95% CI 4.94-40.97, LAI (OR 9.99, 95% CI 6.45-15.45, psychiatric co-medications (OR 4.25, 95% CI 2.72-6.64, and paliperidone (OR 3.13, 95% CI 1.23-7.92 were all associated with an increased likelihood of polypharmacy. Being prescribed risperidone (OR 0.54, 95% CI 0.35-0.83 and older age (OR 0.98, 95% CI 0.97-0.99 were related to a low polypharmacy probability.Polypharmacy is the most common pattern of antipsychotic use in this region of Spain. Use of atypical antipsychotics is extensive. Most patients receive psychiatric co-medications such as anxiolytics or antidepressants. Polypharmacy is associated with the use of quetiapine or

The modern role of antipsychotics for the treatment of agitation and psychosis in Alzheimer's disease.

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Creese, Byron; Da Silva, Miguel Vasconcelos; Johar, Iskandar; Ballard, Clive

2018-05-21

Antipsychotics have long been the mainstay of treatment for agitation and psychosis in Alzheimer's disease. Despite their current use successive studies have shown that they only confer a modest benefit which must be balanced against their well-established serious side effects (extrapyramidal symptoms, stroke, accelerated cognitive decline and mortality). Areas covered: This review outlines the current guidance on antipsychotic usage and the evidence of their continued usage against a backdrop of emerging pharmacological treatments and an increasing emphasis on the importance of non-pharmacological interventions. Expert commentary: The current justification for antipsychotic use in the context of the changing landscape of prescribing and provide a view on the most promising alternative candidates to this class of drug are appraised.

Second harmonic generation and sum frequency generation

International Nuclear Information System (INIS)

Pellin, M.J.; Biwer, B.M.; Schauer, M.W.; Frye, J.M.; Gruen, D.M.

1990-01-01

Second harmonic generation and sum frequency generation are increasingly being used as in situ surface probes. These techniques are coherent and inherently surface sensitive by the nature of the mediums response to intense laser light. Here we will review these two techniques using aqueous corrosion as an example problem. Aqueous corrosion of technologically important materials such as Fe, Ni and Cr proceeds from a reduced metal surface with layer by layer growth of oxide films mitigated by compositional changes in the chemical makeup of the growing film. Passivation of the metal surface is achieved after growth of only a few tens of atomic layers of metal oxide. Surface Second Harmonic Generation and a related nonlinear laser technique, Sum Frequency Generation have demonstrated an ability to probe the surface composition of growing films even in the presence of aqueous solutions. 96 refs., 4 figs

Neuroleptic malignant syndrome following catatonia: Vigilance is the price of antipsychotic prescription

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Thomas J Reilly

2017-03-01

Full Text Available Objectives: To describe a case of neuroleptic malignant syndrome following antipsychotic treatment of catatonia, highlighting the potentially serious complications of this rare adverse drug reaction. Methods: We present a case report of a patient who developed this syndrome with various sequelae. Results: The patient developed neuroleptic after being treated with lorazepam and olanzapine for catatonia. He subsequently developed the complications of rhabdomyolysis, acute kidney injury, pulmonary embolism, urinary retention and ileus. He received high-dose lorazepam, anticoagulation and intravenous fluids. Antipsychotic medication in the form of haloperidol was reinstated with no adverse effect, and he went on to make a full recovery. Conclusions: This case illustrates the potential life-threatening complications of neuroleptic malignant syndrome and the need for a low index of clinical suspicion. It also highlights the lack of evidence for treatment of catatonia, including the use of antipsychotics.

Web Tools: The Second Generation

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Pascopella, Angela

2008-01-01

Web 2.0 tools and technologies, or second generation tools, help districts to save time and money, and eliminate the need to transfer or move files back and forth across computers. Many Web 2.0 tools help students think critically and solve problems, which falls under the 21st-century skills. The second-generation tools are growing in popularity…

QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

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Piccinelli Marco

2005-01-01

Full Text Available Abstract Background Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine or lithium. An Electrocardiogram (ECG was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms however this was not the case in Group 1 (-1 ± 30 ms (Repeated measures ANOVA p Conclusions No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a

Measurement of treatment adherence with antipsychotic agents in patients with schizophrenia

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Xinhua S Ren

2009-09-01

Full Text Available Xinhua S Ren1,2,3, Lawrence Herz4,5, Shirley Qian1,2,3, Eric Smith3,4, Lewis E Kazis1,2,31The Center for the Assessment of Pharmaceutical Practices (CAPP, Boston University School of Public Health, Boston, MA, USA; 2Department of Health Policy and Management, Boston University School of Public Health, Boston, MA, USA; 3Center for Health Quality, Outcomes, and Economic Research, Bedford Veterans Affairs Medical Center, Bedford, MA, USA; 4Division of Psychiatry, Boston University School of Medicine, Boston, MA, USA; 5Mental Health Service Line, Bedford VA Medical Center, Bedford, MA, USAAbstract: The importance of medication adherence in sustaining control of schizophrenic symptoms has generated a great deal of interest in comparing levels of treatment adherence with different antipsychotic agents. However, the bulk of the research has yielded results that are often inconsistent. In this prospective, observational study, we assessed the measurement properties of 3 commonly used, pharmacy-based measures of treatment adherence with antipsychotic agents in schizophrenia using data from the Veterans Health Administration during 2000 to 2005. Patients were selected if they were on antipsychotics and diagnosed with schizophrenia (N = 18,425. A gap of ≥30 days (with no filled index medication was used to define discontinuation of treatment as well as medication “episodes,” or the number of times a patient returned to the same index agent after discontinuation of treatment within a 1-year period. The study found that the 3 existing measures differed in their approaches in measuring treatment adherence, suggesting that studies using these different measures would generate different levels of treatment adherence across antipsychotic agents. Considering the measurement problems associated with each existing approach, we offered a new, medication episode-specific approach, which would provide a fairer comparison of the levels of treatment adherence

Antipsychotic Polypharmacy among Children and Young Adults in Office-Based or Hospital Outpatient Department Settings

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Minji Sohn

2017-11-01

Full Text Available The purpose of the study was three-fold: (1 to estimate the national trends in antipsychotic (AP polypharmacy among 6- to 24-year-old patients in the U.S.; (2 to identify frequently used AP agents and mental disorder diagnoses related to AP polypharmacy; and (3 to assess the strength of association between AP polypharmacy and patient/provider characteristics. We used publicly available ambulatory health care datasets to evaluate AP polypharmacy in office-based or hospital outpatient department settings to conduct a cross-sectional study. First, national visit rates between 2007 and 2011 were estimated using sampling weights. Second, common diagnoses and drugs used in AP polypharmacy were identified. Third, a multivariate logistic regression model was developed to assess the strength of association between AP polypharmacy and patient and provider characteristics. Between 2007 and 2011, approximately 2% of office-based or hospital outpatient department visits made by 6- to 24-year-old patients included one or more AP prescriptions. Of these visits, 5% were classified as AP polypharmacy. The most common combination of AP polypharmacy was to use two or more second-generation APs. Also, bipolar disorder and schizophrenia were the two most frequent primary mental disorder diagnoses among AP polypharmacy visits. The factors associated with AP polypharmacy were: older age (young adults, black, having one or more non-AP prescriptions, and having schizophrenia or ADHD.

Antipsychotic treatment for children and adolescents with schizophrenia spectrum disorders

DEFF Research Database (Denmark)

Pagsberg, Anne Katrine; Tarp, Simon; Glintborg, D

2014-01-01

INTRODUCTION: Antipsychotic treatment in early-onset schizophrenia (EOS) lacks a rich evidence base, and efforts to rank different drugs concerning their efficacy have not proven any particular drug superior. In contrast to the literature regarding adult-onset schizophrenia (AOS), comparative...... allocate children and adolescents presenting with schizophrenia or a related non-affective psychotic condition to an intervention group or to a control group. Two reviewers will-independently and in duplicate-screen titles and abstracts, complete full text reviews to determine eligibility, and subsequently...

Treatment patterns and clinical characteristics prior to initiating depot typical antipsychotics for nonadherent schizophrenia patients

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Montgomery William

2009-07-01

Full Text Available Abstract Background Nonadherence with antipsychotic medication is an important clinical and economic problem in the treatment of schizophrenia. This study identified treatment patterns and clinical characteristics that immediately precede the initiation of depot typical antipsychotics in the usual treatment of schizophrenia patients with a recent history of nonadherence with oral antipsychotic regimens. Methods Data were drawn from a large, multisite, 3-year prospective noninterventional observational study of persons treated for schizophrenia in the United States, which was conducted between 7/1997 and 9/2003. The analytical sample included patients who, in the 6 months prior to enrollment, were considered nonadherent with oral antipsychotics and were not treated with depot antipsychotics (N = 314. Patients who were subsequently initiated on typical depots during the 3-year follow-up were compared with patients who continued therapy with only oral antipsychotic agents. Group comparisons were made on patient baseline characteristics and precedent variables that were assessed 1 to 6 months prior to depot initiation. Patient assessments were made at predetermined intervals throughout the 3-year study using standard psychiatric measures, a patient-reported questionnaire, and medical record information. Results A small proportion of patients (12.4% who were recently nonadherent with oral antipsychotics were subsequently initiated on depot therapy during the 3-year study. Compared to patients treated with only oral antipsychotics, those subsequently initiated on a depot were significantly more likely to be hospitalized at depot initiation or the previous 30 days, to have recent involvement with the criminal justice system (arrests, recent illicit drug use, recent switching or augmentation of oral antipsychotics, and recent treatment with oral typical antipsychotics. Conclusion Despite prior nonadherence with oral antipsychotic medication, only a

Selective attention and mismatch negativity in antipsychotic-naïve, first-episode schizophrenia patients before and after 6 months of antipsychotic monotherapy

DEFF Research Database (Denmark)

Oranje, B.; Aggernaes, B.; Rasmussen, H.

2017-01-01

-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow......-up, whereas controls received no treatment. Results Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only......Background Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2...

Incident users of antipsychotics

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Baandrup, Lone; Kruse, Marie

2016-01-01

PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine...

Two Sudden and Unexpected Deaths of Patients with Schizophrenia Associated with Intramuscular Injections of Antipsychotics and Practice Guidelines to Limit the Use of High Doses of Intramuscular Antipsychotics

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Nasratullah Wahidi

2016-01-01

Full Text Available Intravenous haloperidol has been associated with torsades de pointes (TdP. These two sudden deaths were probable adverse drug reactions (ADRs following intramuscular (IM antipsychotics. The autopsies described lack of heart pathology and were highly compatible with the possibility of TdP in the absence of risk factors other than the accumulation of antipsychotics with a high serum peak after the last injection, leading to death within hours. The first case was a 27-year-old African-American male with schizophrenia but no medical issues. His death was probably caused by repeated IM haloperidol injections of 10 mg (totaling 35 mg in 2 days. The second case involves a 42-year-old African-American female with metabolic syndrome. Her probable cause of death was the last ziprasidone IM injection of 20 mg in addition to (1 three extra haloperidol doses (2 hours before the ziprasidone injection, 5 mg oral haloperidol; approximately 21 hours earlier, 5 mg oral haloperidol; and 2 days prior, one 10 mg IM haloperidol injection, (2 10 mg/day of scheduled oral haloperidol for 6 days before death, and (3 a long-acting paliperidone injection of 156 mg 18 days before death. The study of haloperidol glucuronidation and its impairment in some African-Americans is urgently recommended.

The impact of reference pricing and extension of generic substitution on the daily cost of antipsychotic medication in Finland.

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Koskinen, Hanna; Ahola, Elina; Saastamoinen, Leena K; Mikkola, Hennamari; Martikainen, Jaana E

2014-12-01

To assess the impact of reference pricing and extension of generic substitution on the daily cost of antipsychotic drugs in Finland during the first year after its launch. Furthermore, the additional impact of reference pricing on prior implemented generic substitution is assessed. A retrospective analysis was performed between 2006 and 2010. A segmented linear regression analysis of interrupted time series was used to estimate changes in the levels and trends in the cost of one day of treatment. Of the study drugs, clozapine belonged to generic substitution already at the start of the study period while olanzapine and quetiapine were included in generic substitution alongside with reference pricing in 2009. Risperidone was included in generic substitution in 2008, before reference pricing. A substantial decrease in the daily cost of all four antipsychotic substances was seen after one year of the implementation of reference pricing and the extension of generic substitution. The impact ranged from -29.9% to -66.3%, and it was most substantial on the daily cost of olanzapine. Also in the daily cost of risperidone a substantial decrease of -43.3% was observed. However, most of these savings, -32.6%, were generated by generic substitution which had been adopted prior. Reference pricing and the extension of generic substitution produced substantial savings on antipsychotic medication costs during the first year after its launch, but the intensity of the impact differed between active substances. Furthermore, our results suggest that the additional cost savings from reference pricing after prior implemented generic substitution, are comparatively low.

Pharmacokinetic-pharmacodynamic analysis of antipsychotics-induced extrapyramidal symptoms based on receptor occupancy theory incorporating endogenous dopamine release.

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Matsui-Sakata, Akiko; Ohtani, Hisakazu; Sawada, Yasufumi

2005-06-01

We aimed to analyze the risks of extrapyramidal symptoms (EPS) induced by typical and atypical antipsychotic drugs using a common pharmacokinetic-pharmacodynamic (PK-PD) model based on the receptor occupancy. We collected the data for EPS induced by atypical antipsychotics, risperidone, olanzapine and quetiapine, and a typical antipsychotic, haloperidol from literature and analyzed the following five indices of EPS, the ratio of patients obliged to take anticholinergic medication, the occurrence rates of plural extrapyramidal symptoms (more than one of tremor, dystonia, hypokinesia, akathisia, extrapyramidal syndrome, etc.), parkinsonism, akathisia, and extrapyramidal syndrome. We tested two models, i.e., a model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition and a model not considering the endogenous dopamine release, and used them to examine the relationship between the D2 receptor occupancy of endogenous dopamine and the extent of drug-induced EPS. The model incorporating endogenous dopamine release better described the relationship between the mean D2 receptor occupancy of endogenous dopamine and the extent of EPS than the other model, as assessed by the final sum of squares of residuals (final SS) and Akaike's Information Criteria (AIC). Furthermore, the former model could appropriately predict the risks of EPS induced by two other atypical antipsychotics, clozapine and ziprasidone, which were not incorporated into the model development. The developed model incorporating endogenous dopamine release owing to 5-HT2A receptor inhibition may be useful for the prediction of antipsychotics-induced EPS.

Correlation between plasma homovanillic acid levels and the response to atypical antipsychotics in male patients with schizophrenia.

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Kaneda, Yasuhiro; Kawamura, Ichiro; Ohmori, Tetsuro

2005-01-01

The authors investigated the effects of atypical antipsychotic drugs-olanzapine, perospirone, and quetiapine-on plasma homovanillic acid (pHVA) in male patients with chronic schizophrenia. In this prospective, open-label study, the subjects were 30 inpatients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia. The authors switched patients from typical antipsychotic drugs to olanzapine, perospirone, or quetiapine. Each patient gave informed consent for the research. pHVA was assessed before and after switching medications. After the switch, the authors found a significant improvement in psychotic symptoms, nonsignificant improvement in extrapyramidal symptoms, and a nonsignificant reduction in pHVA. In addition, the baseline pHVA correlated positively with the score changes from baseline in the Brief Psychiatric Rating Scale (BPRS) total, positive, and negative symptoms in the group with a whole sample and in the olanzapine-treated group, and with the score changes in the BPRS total and positive symptoms in the quetiapine-treated group. Our findings indicated that the preswitching pHVA levels could be used to predict changes in the psychotic symptoms of male patients with chronic schizophrenia when switching to atypical antipsychotic drugs.

Central and Peripheral Mechanisms of Antipsychotic Medication-Induced Metabolic Dysregulation

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2016-10-01

may also significantly contribute to our fundamental understanding of obesity and lead to novel treatments. Since APD-induced metabolic disturbances...York, NY 10032 Department of Psychology , Yeshiva University, New York, NY 10016 Sponsor: Jonathan A. Javitch Background: Antipsychotic drugs...Zachary Freyberg Departments of Psychiatry, Pharmacology & Medicine, Columbia University, New York, NY 10032 Department of Psychology , Yeshiva

Differential impact of two risk communications on antipsychotic prescribing to people with dementia in Scotland: segmented regression time series analysis 2001-2011.

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Bruce Guthrie

Full Text Available Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact.Segmented regression time-series analysis 2001-2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing.The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI -6.6 to -5.2 and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs.The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and unintended outcomes. Although rates

Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

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Maher, Alicia R; Theodore, George

2012-06-01

Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses of atypical antipsychotics. Since that time, numerous studies have been published evaluating these therapies in various new off-label uses; new or increased adverse effects have been observed with off-label uses; new atypical antipsychotics have been approved; and previously off-label uses have been approved for some atypical antipsychotics. Hence, AHRQ published an updated review in September 2011 that summarized the benefits and harms of atypical antipsychotics in the treatment of attention-deficit hyperactivity disorder/attention deficit disorder (ADHD), anxiety, behavioral disturbances of dementia and severe geriatric agitation, depression, eating disorders, insomnia, obsessive-compulsive disorder (OCD), personality disorder, post-traumatic stress disorder (PTSD), substance use and dependence disorders, and Tourette's syndrome. The new report also investigated topics for which data in the previous report were found to be insufficient to make conclusions, including

Antipsychotic treatment among youth in foster care.

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Dosreis, Susan; Yoon, Yesel; Rubin, David M; Riddle, Mark A; Noll, Elizabeth; Rothbard, Aileen

2011-12-01

Despite national concerns over high rates of antipsychotic medication use among youth in foster care, concomitant antipsychotic use has not been examined. In this study, concomitant antipsychotic use among Medicaid-enrolled youth in foster care was compared with disabled or low-income Medicaid-enrolled youth. The sample included 16 969 youths younger than 20 years who were continuously enrolled in a Mid-Atlantic state Medicaid program and had ≥1 claim with a psychiatric diagnosis and ≥1 antipsychotic claim in 2003. Antipsychotic treatment was characterized by days of any use and concomitant use with ≥2 overlapping antipsychotics for >30 days. Medicaid program categories were foster care, disabled (Supplemental Security Income), and Temporary Assistance for Needy Families (TANF). Multicategory involvement for youths in foster care was classified as foster care/Supplemental Security Income, foster care/TANF, and foster care/adoption. We used multivariate analyses, adjusting for demographics, psychiatric comorbidities, and other psychotropic use, to assess associations between Medicaid program category and concomitant antipsychotic use. Average antipsychotic use ranged from 222 ± 110 days in foster care to only 135 ± 101 days in TANF (P foster care only and 24% in foster care/adoption compared with youths in the foster care system.

Association Study of 60 Candidate Genes with Antipsychotic-induced Weight Gain in Schizophrenia Patients.

Science.gov (United States)

Ryu, S; Huh, I-S; Cho, E-Y; Cho, Y; Park, T; Yoon, S C; Joo, Y H; Hong, K S

2016-03-01

This study aimed to investigate the association of multiple candidate genes with weight gain and appetite change during antipsychotic treatment. A total of 233 single nucleotide polymorphisms (SNPs) within 60 candidate genes were genotyped. BMI changes for up to 8 weeks in 84 schizophrenia patients receiving antipsychotic medication were analyzed using a linear mixed model. In addition, we assessed appetite change during antipsychotic treatment in a different group of 46 schizophrenia patients using the Drug-Related Eating Behavior Questionnaire. No SNP showed a statistically significant association with BMI or appetite change after correction for multiple testing. We observed trends of association (PGHRL showed suggestive evidence of association with not only weight gain (P=0.001) but also appetite change (P=0.042). Patients carrying the GG genotype of rs696217 exhibited higher increase in both BMI and appetite compared to patients carrying the GT/TT genotype. Our findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients. © Georg Thieme Verlag KG Stuttgart · New York.

Emergency Department Visits Involving Misuse and Abuse of the Antipsychotic Quetiapine: Results from the Drug Abuse Warning Network (DAWN

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Margaret E. Mattson

2015-01-01

Full Text Available Case reports in medical literature suggest that the atypical antipsychotic quetiapine, a medication not previously considered to have abuse potential, is now being subject to misuse and abuse (MUA; ie, taken when not prescribed for them or used in a way other than instructed by their health professional. Here we present systematic, nationally representative data from the 2005 to 2011 Drug Abuse Warning Network (DAWN for prevalence of emergency department (ED visits among the U.S. general population involving quetiapine and related to MUA, suicide attempts, and adverse reactions. Nationally, quetiapine-related ED visits increased 90% between 2005 and 2011, from 35,581 ED visits to 67,497. DAWN data indicate that when used without medical supervision for recreational/self-medication purposes, quetiapine poses health risks for its users, especially among polydrug users and women. These findings suggest that the medical and public health communities should increase vigilance concerning this drug and its potential for MUA.

Second generation γ-secretase modulators exhibit different modulation of Notch β and Aβ production.

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Wanngren, Johanna; Ottervald, Jan; Parpal, Santiago; Portelius, Erik; Strömberg, Kia; Borgegård, Tomas; Klintenberg, Rebecka; Juréus, Anders; Blomqvist, Jenny; Blennow, Kaj; Zetterberg, Henrik; Lundkvist, Johan; Rosqvist, Susanne; Karlström, Helena

2012-09-21

The γ-secretase complex is an appealing drug target when the therapeutic strategy is to alter amyloid-β peptide (Aβ) aggregation in Alzheimer disease. γ-Secretase is directly involved in Aβ formation and determines the pathogenic potential of Aβ by generating the aggregation-prone Aβ42 peptide. Because γ-secretase mediates cleavage of many substrates involved in cell signaling, such as the Notch receptor, it is crucial to sustain these pathways while altering the Aβ secretion. A way of avoiding interference with the physiological function of γ-secretase is to use γ-secretase modulators (GSMs) instead of inhibitors of the enzyme. GSMs modify the Aβ formation from producing the amyloid-prone Aβ42 variant to shorter and less amyloidogenic Aβ species. The modes of action of GSMs are not fully understood, and even though the pharmacology of GSMs has been thoroughly studied regarding Aβ generation, knowledge is lacking about their effects on other substrates, such as Notch. Here, using immunoprecipitation followed by MALDI-TOF MS analysis, we found that two novel, second generation GSMs modulate both Notch β and Aβ production. Moreover, by correlating S3-specific Val-1744 cleavage of Notch intracellular domain (Notch intracellular domain) to total Notch intracellular domain levels using immunocytochemistry, we also demonstrated that Notch intracellular domain is not modulated by the compounds. Interestingly, two well characterized, nonsteroidal anti-inflammatory drugs (nonsteroidal anti-inflammatory drug), R-flurbiprofen and sulindac sulfide, affect only Aβ and not Notch β formation, indicating that second generation GSMs and nonsteroidal anti-inflammatory drug-based GSMs have different modes of action regarding Notch processing.

The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

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Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

2012-03-01

Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

Change in Prolactin Levels in Pediatric Patients Given Antipsychotics for Schizophrenia and Schizophrenia Spectrum Disorders: A Network Meta-Analysis

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Chakrapani Balijepalli

2018-01-01

Full Text Available Background. Treatment of schizophrenia with first- and second-generation antipsychotics has been associated with elevated prolactin levels, which may increase the risk for prolactin-related adverse events. Methods. Randomized controlled trials (RCTs included in a recent systematic review were considered for this analysis. A Bayesian network meta-analysis was used to compare changes in prolactin levels in pediatric patients diagnosed with schizophrenia or schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs. Results. Five RCTs, including 989 patients combined, have evaluated the changes in prolactin for pediatric patients after 6 weeks of treatment with risperidone, quetiapine, aripiprazole, olanzapine, and paliperidone. In the overall study population, treatment with risperidone was associated with the highest increase in mean prolactin levels compared to other SGAs. Patients treated with risperidone 4–6 mg/day were found to experience the greatest increases (55.06 ng/ml [95% CrI: 40.53–69.58] in prolactin levels, followed by risperidone 1–3 mg/day, paliperidone 3–6 mg/day, and paliperidone 6–12 mg/day. Conclusions. This study shows that there are differences in SGAs ability to cause hyperprolactinemia. Further, there is clear evidence of safety concerns with risperidone and paliperidone treatment in adolescent schizophrenia patients. Registration. PROSPERO CRD42014009506.

ABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice

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Natalia Brzozowska

2016-05-01

Full Text Available Cannabidiol (CBD is currently being investigated as a novel therapeutic for the treatment of CNS disorders like schizophrenia and epilepsy. ABC transporters such as P-glycoprotein (P-gp and breast cancer resistance protein (Bcrp mediate pharmacoresistance in these disorders. P-gp and Bcrp are expressed at the blood brain barrier (BBB and reduce the brain uptake of substrate drugs including various antipsychotics and anticonvulsants. It is therefore important to assess whether CBD is prone to treatment resistance mediated by P-gp and Bcrp. Moreover, it has become common practice in the drug development of CNS agents to screen against ABC transporters to help isolate lead compounds with optimal pharmacokinetic properties. The current study aimed to assess whether P-gp and Bcrp impacts the brain transport of CBD by comparing CBD tissue concentrations in wild-type (WT mice versus mice devoid of ABC transporter genes. P-gp knockout (Abcb1a/b−∕−, Bcrp knockout (Abcg2−∕−, combined P-gp/Bcrp knockout (Abcb1a/b−∕−Abcg2−∕− and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points. CBD results were compared with the positive control risperidone and 9-hydroxy risperidone, antipsychotic drugs that are established ABC transporter substrates. Brain and plasma concentrations of CBD were not greater in P-gp, Bcrp or P-gp/Bcrp knockout mice than WT mice. In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice. These results suggest that CBD is not a substrate of P-gp or Bcrp and may be free from the complication of reduced brain uptake by these transporters. Such findings provide favorable evidence for the therapeutic development of CBD in the treatment of various CNS disorders.

Second harmonic generation imaging

CERN Document Server

2013-01-01

Second-harmonic generation (SHG) microscopy has shown great promise for imaging live cells and tissues, with applications in basic science, medical research, and tissue engineering. Second Harmonic Generation Imaging offers a complete guide to this optical modality, from basic principles, instrumentation, methods, and image analysis to biomedical applications. The book features contributions by experts in second-harmonic imaging, including many pioneering researchers in the field. Written for researchers at all levels, it takes an in-depth look at the current state of the art and possibilities of SHG microscopy. Organized into three sections, the book: Provides an introduction to the physics of the process, step-by-step instructions on how to build an SHG microscope, and comparisons with related imaging techniques Gives an overview of the capabilities of SHG microscopy for imaging tissues and cells—including cell membranes, muscle, collagen in tissues, and microtubules in live cells—by summarizing experi...

Twenty-four months of antipsychotic treatment in children and adolescents with first psychotic episode: discontinuation and tolerability.

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Noguera, Ana; Ballesta, Patricia; Baeza, Immaculada; Arango, Celso; de la Serna, Elena; González-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Carmen; Otero, Soraya; Castro-Fornieles, Josefina

2013-08-01

The Child and Adolescent First-Episode Psychosis Study is a longitudinal study of early-onset first psychotic episodes. This report describes the naturalistic psychopharmacological treatment administered during a 24-month follow-up period, as well as discontinuation rates, reasons for discontinuation, and adverse effects. The sample comprised 110 patients, aged 9 to 17 years, with a first psychotic episode. Pharmacological treatment, changes, reasons for discontinuation, and the UKU (Udvalg for Kliniske Undersogelser) Side Effect Rating Scale were registered at 6, 12, and 24 months of follow-up. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, were the most commonly used. The discontinuation rate was 44.5% at 6 months, 59.1% at 12 months, and 70.9% at 24 months. Discontinuation rates or reasons for discontinuation (adverse reaction, insufficient response, and other) did not differ significantly between antipsychotics. At 6 months, significant differences were found in body mass index increase and body mass index z score increase, which were higher with olanzapine, and in neurological effects, which were higher with risperidone; at 12 and 24 months, these differences were no longer significant. High maintenance rates were found in the clozapine group, although they had higher scores on the autonomic subscale of the UKU. A long follow-up period reveals high discontinuation rates similar to those observed in adults, particularly during the first year. No differences were found between antipsychotics. Differences in adverse effects were found at 6 months but not subsequently after changes in treatment. Clozapine had a high maintenance rate, and its tolerability was comparable to that of other antipsychotics.

Making the leap from daily oral dosing to long-acting injectables: lessons from the antipsychotics.

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Remenar, Julius F

2014-06-02

There are now long-acting versions of six antipsychotic drugs on the U.S. market, and with them, five unique combinations of molecular form and delivery strategy long-acting-injectable-antipsychotics (LAIAs) show evidence of reduced relapses of schizophrenia, but their introduction has been slow, taking at least nine years after the approval of each oral drug. Oily solutions of lipophilic prodrugs were the first to enter the LAIA market, but they relied on esterification of a hydroxyl handle that was lost with the emergence of the atypical antipsychotics. A review of the literature and patents shows that companies tested many different approaches before reaching the currently marketed versions, including aqueous suspensions of poorly soluble salts, polymeric microspheres, and new approaches to making prodrugs. Yet, very little has been published to support faster development of safe long-acting injectables (LAIs). This review introduces some of the critical considerations in creating an LAI; then it analyzes the existing products and discusses areas where further research is needed. The available literature suggests that lipophilic prodrugs may be inherently safer than poorly soluble salts as LAIs. Other areas needing additional study include (1) the range of physical properties acceptable for LAIs and the effect of prodrug tail length in achieving them, and (2) the role of physiological responses at the injection site in the release of drug from a depot.

Differential Impact of Two Risk Communications on Antipsychotic Prescribing to People with Dementia in Scotland: Segmented Regression Time Series Analysis 2001–2011

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Guthrie, Bruce; Clark, Stella A.; Reynish, Emma L.; McCowan, Colin; Morales, Daniel R.

2013-01-01

Background Regulatory risk communications are an important method for disseminating drug safety information, but their impact varies. Two significant UK risk communications about antipsychotic use in older people with dementia were issued in 2004 and 2009. These varied considerably in their content and dissemination, allowing examination of their differential impact. Methods Segmented regression time-series analysis 2001–2011 for people aged ≥65 years with dementia in 87 Scottish general practices, examining the impact of two pre-specified risk communications in 2004 and 2009 on antipsychotic and other psychotropic prescribing. Results The percentage of people with dementia prescribed an antipsychotic was 15.9% in quarter 1 2001 and was rising by an estimated 0.6%/quarter before the 2004 risk communication. The 2004 risk communication was sent directly to all prescribers, and specifically recommended review of all patients prescribed relevant drugs. It was associated with an immediate absolute reduction in antipsychotic prescribing of 5.9% (95% CI −6.6 to −5.2) and a change to a stable level of prescribing subsequently. The 2009 risk communication was disseminated in a limited circulation bulletin, and only specifically recommended avoiding initiation if possible. There was no immediate associated impact, but it was associated with a significant decline in prescribing subsequently which appeared driven by a decline in initiation, with the percentage prescribed an antipsychotic falling from 18.4% in Q1 2009 to 13.5% in Q1 2011. There was no widespread substitution of antipsychotics with other psychotropic drugs. Conclusions The two risk communications were associated with reductions in antipsychotic use, in ways which were compatible with marked differences in their content and dissemination. Further research is needed to ensure that the content and dissemination of regulatory risk communications is optimal, and to track their impact on intended and

Testing of bioactive-nanovesicles on hepatotoxicity of atypical antipsychotics via digital holography.

Science.gov (United States)

Ozturk Kirbay, Fatma; Geyik, Caner; Guler, Emine; Yesiltepe, Ozan; Gumus, Zinar Pinar; Odaci Demirkol, Dilek; Coskunol, Hakan; Timur, Suna

2017-04-01

Atypical antipsychotic drugs induce hepatic toxicity. Thus, it is of importance to eliminate the side effects of these drugs. Herein we describe the preparation of nanoemulsions with a dietary supplement; wheat germ oil (WGO), to ameliorate the liver damage induced by clozapine and olanzapine. THLE-2 cell line was used as a model to investigate the effects of these nanoemulsions on cell viability as well as antioxidative efficiency after antipsychotic insult. In this context, a conventional cell culture method; MTT was used along with a novel cellular imaging technique called digital holography (DH) to evaluate cell viability. Obtained data confirmed that both clozapine and olanzapine induced the liver damage in in vitro model and WGO nanoemulsions were found to be effective on cells and eliminate the cytotoxic effects of these drugs. Briefly, this study has some outputs as follows; it showed that different dietary supplements can be used in such formulations instead of their pristine forms to increase bioavailability. Also, DH was successfully applied for the monitoring of cell viability and it could be a promising approach as the reactive-free cytotoxicity test. Copyright © 2017 Elsevier B.V. All rights reserved.

Second generation biofuels: Economics and policies

International Nuclear Information System (INIS)

Carriquiry, Miguel A.; Du Xiaodong; Timilsina, Govinda R.

2011-01-01

This study reviews economics of production of second generation biofuels from various feedstocks, including crop and wood/forestry residues, lignocellulosic energy crops, jatropha, and algae. The study indicates that while second generation biofuels could significantly contribute to the future energy supply mix, cost is a major barrier to its commercial production in the near to medium term. Depending upon type of biofuels, feedstock prices and conversion costs, the cost of cellulosic ethanol is found to be two to three times higher than the current price of gasoline on an energy equivalent basis. The median cost (across the studies reviewed) of biodiesel produced from microalgae, a prospective feedstock, is seven times higher than the current price of diesel, although much higher cost estimates have been reported. As compared with the case of first generation biofuels, in which feedstock can account for over two-thirds of the total costs, the share of feedstock in the total costs is relatively lower (30-50%) in the case of second generation biofuels. While significant cost reductions are needed for both types of second generation biofuels, the critical barriers are at different steps of the production process. For cellulosic ethanol, the biomass conversion costs needs to be reduced. On the other hand, feedstock cost is the main issue for biodiesel. At present, policy instruments, such as fiscal incentives and consumption mandates have in general not differentiated between the first and second generation biofuels except in the cases of the US and EU. The policy regime should be revised to account for the relative merits of different types of biofuels. - Highlights: → Second generation biofuels could significantly contribute to the future energy supply mix. → Cost is a major barrier to its the commercial production in the near to medium term. → The policy regime should be revised to account for the relative merits of different biofuels.

Second generation biofuels: Economics and policies

Energy Technology Data Exchange (ETDEWEB)

Carriquiry, Miguel A., E-mail: miguelc@iastate.edu [Center for Agricultural and Rural Development, Iowa State University (United States); Du Xiaodong, E-mail: xdu23@wisc.edu [Department of Agricultural and Applied Economics, University of Wisconsin-Madison (United States); Timilsina, Govinda R., E-mail: gtimilsina@worldbank.org [Development Research Group, The World Bank (United States)

2011-07-15

This study reviews economics of production of second generation biofuels from various feedstocks, including crop and wood/forestry residues, lignocellulosic energy crops, jatropha, and algae. The study indicates that while second generation biofuels could significantly contribute to the future energy supply mix, cost is a major barrier to its commercial production in the near to medium term. Depending upon type of biofuels, feedstock prices and conversion costs, the cost of cellulosic ethanol is found to be two to three times higher than the current price of gasoline on an energy equivalent basis. The median cost (across the studies reviewed) of biodiesel produced from microalgae, a prospective feedstock, is seven times higher than the current price of diesel, although much higher cost estimates have been reported. As compared with the case of first generation biofuels, in which feedstock can account for over two-thirds of the total costs, the share of feedstock in the total costs is relatively lower (30-50%) in the case of second generation biofuels. While significant cost reductions are needed for both types of second generation biofuels, the critical barriers are at different steps of the production process. For cellulosic ethanol, the biomass conversion costs needs to be reduced. On the other hand, feedstock cost is the main issue for biodiesel. At present, policy instruments, such as fiscal incentives and consumption mandates have in general not differentiated between the first and second generation biofuels except in the cases of the US and EU. The policy regime should be revised to account for the relative merits of different types of biofuels. - Highlights: > Second generation biofuels could significantly contribute to the future energy supply mix. > Cost is a major barrier to its the commercial production in the near to medium term. > The policy regime should be revised to account for the relative merits of different biofuels.

Potentiation of latent inhibition by haloperidol and clozapine is attenuated in Dopamine D2 receptor (Drd-2)-deficient mice: Do antipsychotics influence learning to ignore irrelevant stimuli via both Drd-2 and non-Drd-2 mechanisms?

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O’Callaghan, Matthew J; Bay-Richter, Cecilie; O’Tuathaigh, Colm MP; Heery, David M; Waddington, John L; Moran, Paula M

2014-01-01

Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner’s ‘two-headed’ model indicates that antipsychotics not only reverse LI disruption, ‘disrupted LI’, but also potentiate LI when low/absent in controls, ‘persistent’ LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2-/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1-/- and wild-type mice, indicating no such moderation in Drd1-/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis. PMID:25122042

Evaluation of patients on sertindole treatment after failure of other antipsychotics: A retrospective analysis

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Hansen Karina

2008-03-01

Full Text Available Abstract Background Use of the atypical antipsychotic sertindole was suspended for four years due to safety concerns. During the suspension, the regulatory authorities required further studies, including this one, to be conducted. The purpose of this study was to determine if a subset of patients with psychotic illness exists which particularly benefits from sertindole treatment after failure of other antipsychotic drugs, including atypical antipsychotics. Methods This was a retrospective single-arm observational crossover study of 344 patients, who served as their own controls. Patients mainly from the Sertindole Safety Study who had shown good response to sertindole, and who had followed up to four alternating six month periods of treatment with sertindole and other antipsychotics, were included. (In Period 1 patients took non-sertindole treatment, in Period 2, sertindole was taken, in Period 3, patients reverted to non-sertindole treatment, and in Period 4, sertindole was taken again. Patient records for each period of treatment were assessed for objective data: number and duration of hospitalizations due to worsening of psychotic symptoms; the amount of self-harming behaviour; indicators of social status. Retrospective evaluation of changes in clinical symptoms from the patients' records was also conducted. Dates and reasons for stopping and/or switching medication were also recorded. Results There was improvement in all objective measured parameters during the periods of sertindole treatment. In particular, the average number of hospitalizations per year due to worsening of psychotic symptoms was reduced in the following way in the group studied over four treatment periods: Period 1 (non-sertindole treatment 3.4; Period 2 (sertindole treatment 1.0; Period 3 (non-sertindole treatment 2.0; Period 4 (sertindole treatment 1.8. The duration of hospitalizations also decreased significantly during the periods of sertindole treatment. Results

Relationships among neurocognition, symptoms and functioning in patients with schizophrenia: a path-analytic approach for associations at baseline and following 24 weeks of antipsychotic drug therapy

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Keefe Richard SE

2009-07-01

Full Text Available Abstract Background Neurocognitive impairment and psychiatric symptoms have been associated with deficits in psychosocial and occupational functioning in patients with schizophrenia. This post-hoc analysis evaluates the relationships among cognition, psychopathology, and psychosocial functioning in patients with schizophrenia at baseline and following sustained treatment with antipsychotic drugs. Methods Data were obtained from a clinical trial assessing the cognitive effects of selected antipsychotic drugs in patients with schizophrenia. Patients were randomly assigned to 24 weeks of treatment with olanzapine (n = 159, risperidone (n = 158, or haloperidol (n = 97. Psychosocial functioning was assessed with the Heinrichs-Carpenter Quality of Life Scale [QLS], cognition with a standard battery of neurocognitive tests; and psychiatric symptoms with the Positive and Negative Syndrome Scale [PANSS]. A path-analytic approach was used to evaluate the effects of changes in cognitive functioning on subdomains of quality of life, and to determine whether such effects were direct or mediated via changes in psychiatric symptoms. Results At baseline, processing speed affected functioning mainly indirectly via negative symptoms. Positive symptoms also affected functioning at baseline although independent of cognition. At 24 weeks, changes in processing speed affected changes in functioning both directly and indirectly via PANSS negative subscale scores. Positive symptoms no longer contributed to the path-analytic models. Although a consistent relationship was observed between processing speed and the 3 functional domains, variation existed as to whether the paths were direct and/or indirect. Working memory and verbal memory did not significantly contribute to any of the path-analytic models studied. Conclusion Processing speed demonstrated direct and indirect effects via negative symptoms on three domains of functioning as measured by the QLS at baseline and

[Augmented antipsychotic therapy with pantogam active in patients with schizophrenia].

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Medvedev, V E; Frolova, V I; Gushanskaya, E V; Ter-Israelyan, A U

2015-01-01

to study the efficacy of the GABA-ergic drug pantogam active (D-, L-gopantenic acid) in patients with schizophrenia treated with typical neuroleptics and to assess the rate of treatment response and tolerability of the drug. A sample consisted of 70 patients with schizophrenia stratified into main (n=35) and control (n=35) groups. All patients received one of typical antipsychotics (haloperidol, zuclopenthixol, promazine or perphenazine). Patients of the main group received in addition pantogam active in dose of 1200-1800 mg daily. The maximum allowed dose of 1800 mg daily was used in 62.9% of the patients. The long-term combined therapy with the addition of D-, L-gopantenic acid (pantogam activ) allowed to achieve clinical improvement earlier (on 8th week in the main group versus 16th week in the control group). The frequency and severity of secondary negative symptoms associated with antipsychotic therapy were decreased as well. The high efficacy and tolerability of the combined therapy allow to improve quality of life in patients with schizophrenia and their compliance to treatment as well as to reduce costs of medical care.

The switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of cognitive deficits. A pilot study in individuals with schizophrenia

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Sánchez-Moreno José

2010-06-01

Full Text Available Abstract Background Atypical antipsychotics provide better control of the negative and affective symptoms of schizophrenia when compared with conventional neuroleptics; nevertheless, their heightened ability to improve cognitive dysfunction remains a matter of debate. This study aimed to examine the changes in cognition associated with long-term antipsychotic treatment and to evaluate the effect of the type of antipsychotic (conventional versus novel antipsychotic drugs on cognitive performance over time. Methods In this naturalistic study, we used a comprehensive neuropsychological battery of tests to assess a sample of schizophrenia patients taking either conventional (n = 13 or novel antipsychotics (n = 26 at baseline and at two years after. Results Continuous antipsychotic treatment regardless of class was associated with improvement on verbal fluency, executive functions, and visual and verbal memory. Patients taking atypical antipsychotics did not show greater cognitive enhancement over two years than patients taking conventional antipsychotics. Conclusions Although long-term antipsychotic treatment slightly improved cognitive function, the switch from conventional to atypical antipsychotic treatment should not be based exclusively on the presence of these cognitive deficits.

Lurasidone-β-cyclodextrin complexes: Physicochemical characterization and comparison of their antidepressant, antipsychotic activities against that of self microemulsifying formulation

Science.gov (United States)

Londhe, Vaishali Y.; Deshmane, Aishwarya B.; Singh, Sarita R.; Kulkarni, Yogesh A.

2018-04-01

Lurasidone hydrochloride (LHD) is an atypical antipsychotic drug has poor aqueous solubility and low bioavailability (9-19%). This study describes effect of different methods of complex formation with β-cyclodextrin (BCD) on enhancement of dissolution and on antidepressant, antipsychotic effects of LHD. Other purpose of this study is to compare pharmacodynamic effects of complexes with that of self microemulsifying drug delivery system of LHD (SMEDDS). Inclusion complexes (IC) of LHD and BCD were prepared by physical mixing (PM), kneading (KN) and spray drying (SD) in a 1:1 M ratio. These complexes were characterized by different techniques. KN and SD showing enhancement in dissolution, were compared with SMEDDS using Forced swim test (FST) and Tail suspension test (TST) for antidepressant action and Paw test for antipsychotic activity. Characterization of complexes confirmed interaction between LHD and BCD. Enhancement in dissolution is seen in following order SD > KN > PM > LHD. In all three animal models, SD, KN and SMEDDS showed statistically significant effect (p LHD.

Central nervous system effects of the second-generation antihistamines marketed in Japan--review of inter-drug differences using the proportional impairment ratio (PIR-.

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Tatsuya Isomura

Full Text Available BACKGROUND: Second-generation antihistamines (AHs have, in general, fewer sedative effects than the first-generation. However, important inter-drug differences remain in the degree of cognitive and/or psychomotor impairment. The extent to which a particular compound causes disruption can be conveniently compared, to all other AHs, using the Proportional Impairment Ratio (PIR. Although the PIR can differentiate the relative impairment caused by individual drugs, there is no indication of the reliability of the ratios obtained. OBJECTIVE: To calculate the PIRs -together with 95% confidence intervals (CIs, as an index of reliability- and compare AHs currently, or soon to be, available in Japan, with respect to their intrinsic capacity to cause impairment. METHODS: Results from studies of cetirizine, desloratadine, ebastine, fexofenadine, levocetirizine, loratadine, mequitazine, and olopatadine were included in the PIR calculations. All data utilised came from crossover studies in healthy volunteers which were randomised and placebo and positive-internal controlled. Existing databases from studies reporting the sedative effects of AHs on objective (speed, accuracy, memory and subjective (feeling psychometrics were augmented, via results from suitable studies published after the previous reviews. The null value for a PIR was one. RESULTS: A total of 45 studies were finally included for this review. Of the AHs assessed, fexofenadine, ebastine, and levocetirizine showed a PIR for objective tests of 0. However, only fexofenadine (PIR = 0.49 had an upper limit of the 95% CI of less than 1. Fexofenadine, levocetirizine, desloratadine, olopatadine, loratadine, and mequitazine all had a PIR for subjective ratings of 0, but the upper limits of the 95% CIs were all in excess of 1, although fexofenadine (PIR = 2.57 was the lowest. CONCLUSIONS: The results show that there are differences between second-generation AHs in the extent of sedation produced

Terminal illness and the increased mortality risk of conventional antipsychotics in observational studies: a systematic review.

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Luijendijk, Hendrika J; de Bruin, Niels C; Hulshof, Tessa A; Koolman, Xander

2016-02-01

Numerous large observational studies have shown an increased risk of mortality in elderly users of conventional antipsychotics. Health authorities have warned against use of these drugs. However, terminal illness is a potentially strong confounder of the observational findings. So, the objective of this study was to systematically assess whether terminal illness may have biased the observational association between conventional antipsychotics and risk of mortality in elderly patients. Studies were searched in PubMed, CINAHL, Embase, the references of selected studies and articles referring to selected studies (Web of Science). Inclusion criteria were (i) observational studies that estimated (ii) the risk of all-cause mortality in (iii) new elderly users of (iv) conventional antipsychotics compared with atypical antipsychotics or no use. Two investigators assessed the characteristics of the exposure and reference groups, main results, measured confounders and methods used to adjust for unmeasured confounders. We identified 21 studies. All studies were based on administrative medical and pharmaceutical databases. Sicker and older patients received conventional antipsychotics more often than new antipsychotics. The risk of dying was especially high in the first month of use, and when haloperidol was administered per injection or in high doses. Terminal illness was not measured in any study. Instrumental variables that were used were also confounded by terminal illness. We conclude that terminal illness has not been adjusted for in observational studies that reported an increased risk of mortality risk in elderly users of conventional antipsychotics. As the validity of the evidence is questionable, so is the warning based on it. Copyright © 2015 John Wiley & Sons, Ltd.

A low TSH profile predicts olanzapine-induced weight gain and relief by adjunctive topiramate in healthy male volunteers

NARCIS (Netherlands)

Evers, Simon S; van Vliet, André; van Vugt, Barbara; Scheurink, Antonius; van Dijk, Gertjan

2016-01-01

Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side

Sibutramine in the treatment of antipsychotic-induced weight gain: a pilot study in patients with schizophrenia.

Science.gov (United States)

Biedermann, Falko; Fleischhacker, W Wolfgang; Kemmler, Georg; Ebenbichler, Christoph F; Lechleitner, Monika; Hofer, Alex

2014-05-01

Weight gain represents a frequent side effect of antipsychotic drug treatment. The current trial investigated the effect of add-on treatment with sibutramine in schizophrenia outpatients who had gained more than 7% of weight during the course of treatment. This 24-week placebo-controlled study evaluated the effects of sibutramine added to ongoing antipsychotic treatment. Weight, waist-hip ratio, BMI, blood pressure/pulse and ECG were monitored regularly. In addition, several laboratory tests were performed. Psychopathological symptoms and side effects were assessed frequently. Fifteen patients were assigned randomly to add-on treatment with sibutramine 10 mg or placebo. The two groups did not differ in weight, sociodemographic, or clinical data. Eleven patients were considered for statistical analysis. Significant weight loss was observed in the sibutramine group (mean = -6.1 kg), whereas patients on placebo experienced a mean weight gain of 1.9 kg. A reduction in HbA1c was apparent in the sibutramine but not in the placebo group. No significant between-group differences were found in changes in psychopathology or drug safety. This pilot trial suggests that adjunctive treatment with sibutramine may be safe and effective in schizophrenic patients with antipsychotic-induced weight gain.

Second generation registry framework.

Science.gov (United States)

Bellgard, Matthew I; Render, Lee; Radochonski, Maciej; Hunter, Adam

2014-01-01

Information management systems are essential to capture data be it for public health and human disease, sustainable agriculture, or plant and animal biosecurity. In public health, the term patient registry is often used to describe information management systems that are used to record and track phenotypic data of patients. Appropriate design, implementation and deployment of patient registries enables rapid decision making and ongoing data mining ultimately leading to improved patient outcomes. A major bottleneck encountered is the static nature of these registries. That is, software developers are required to work with stakeholders to determine requirements, design the system, implement the required data fields and functionality for each patient registry. Additionally, software developer time is required for ongoing maintenance and customisation. It is desirable to deploy a sophisticated registry framework that can allow scientists and registry curators possessing standard computing skills to dynamically construct a complete patient registry from scratch and customise it for their specific needs with little or no need to engage a software developer at any stage. This paper introduces our second generation open source registry framework which builds on our previous rare disease registry framework (RDRF). This second generation RDRF is a new approach as it empowers registry administrators to construct one or more patient registries without software developer effort. New data elements for a diverse range of phenotypic and genotypic measurements can be defined at any time. Defined data elements can then be utilised in any of the created registries. Fine grained, multi-level user and workgroup access can be applied to each data element to ensure appropriate access and data privacy. We introduce the concept of derived data elements to assist the data element standards communities on how they might be best categorised. We introduce the second generation RDRF that

Study on effects of an atypical antipsychotic agent, quetiapine, on regional cerebral blood flow with 99mTc-ECD SPECT in drug-naive or unmedicated schizophrenic patients

International Nuclear Information System (INIS)

Monkawa, Akikazu

2007-01-01

The objective of this study was to investigate the underlying mechanisms of intracerebral actions or clinical efficacies of quetiapine, an atypical antipsychotic agent and a multi-action receptor targeting agent (MARTA), and the influences of quetiapine on absolute regional cerebral blood flows (rCBFs) of schizophrenic patients. Correlations between rCBFs and psychotic symptoms were also examined. Subjects comprised 12 patients who met the ICD-10 criteria for schizophrenia. All patients were drug-naive or unmedicated. Using single photon emission computed tomography (SPECT) with 99m Tc-ethyl cysteinate dimer (ECD), rCBFs were measured. Psychotic symptoms were evaluated with positive and negative syndrome scale (PANSS). The evaluations of SPECT and PANSS were repeated before and after oral 2-week administration of quetiapine 300 mg/day in all patients and after subsequent 2-week administration of quetiapine 600 mg/day in 6 patients. Administration of quetiapine yielded no significant changes in rCBFs at any dose. And there were no significant correlations between the scores of PANSS and the values of rCBFs in any region, though the scores of PANSS decreased after qutiapine administration. It has been reported that, a typical antipsychotic agent, haloperidol, and an atypical antipsychotic agent, risperidone, decrease rCBFs in the cerebral cortex in dose-dependently in drug-naive or unmedicated schizophrenic patients. This phenomenon is considered to be attributable to a secondary inactivation of the cerebral cortex due to D2 receptor blockade of haloperidol or risperidone in the striatum through the cortico-striatal-thalamic pathway. In the frame of this hypothesis, results of this study may relate to the lower degree of D2 blockade induced by quetiapine than that produced by haloperidol and risperidone. (author)

Stimulant and atypical antipsychotic medications for children placed in foster homes.

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L Oriana Linares

Full Text Available The purpose of this study is to examine the use of prescribed psychoactive medications in a prospective cohort of children shortly after they entered foster homes; and to identify demographics, maltreatment history, psychiatric diagnoses including ADHD comorbidity, and level of aggression that contribute to prescribed use of stimulant and atypical antipsychotic medication over time.The sample included N = 252 children (nested in 95 sibling groups followed for three years up to 4 yearly waves.Nearly all (89% met criteria for at least one of eight psychiatric diagnoses and 31% (75/252 used one or more prescribed psychoactive medications. Over half (55% were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD; of these 38% used stimulants and 36% used atypical antipsychotics. Of the 75 medicated children, 19% received ≥3 different classes of drugs over the course of the study. Stimulants (69% and atypical antipsychotics (65% were the most frequently used drugs among medicated children. Adjusted odds ratios (AOR showed that male gender (AOR = 3.2; 95% CI = 1.5-9.3, African American vs Latino ethnicity (AOR = 5.4; 95% CI = 2.1-14.2, ADHD regardless of Oppositional Defiant (ODD or Conduct (CD comorbidity (AOR = 6.0, 95% CI = 1.3-27.5, ODD or CD (AOR = 11.1, 95% CI = 2.1-58.6, and Separation Anxiety (AOR = 2.0, 95% CI = 1.0-4.0 psychiatric disorders were associated with the use of prescribed stimulants; while male gender (AOR = 3.8, 95% CI = 1.5-9.3, African American vs Latino (AOR = 5.1, 95% CI = 1.2-9.2 or Mixed/Other ethnicity (AOR = 3.3, 95% CI = 1.9-13.7, ADHD regardless of ODD or CD comorbidity (AOR = 5.8, 95% CI = 1.2-28.7, ODD or CD (AOR = 13.9, 95% CI = 3.3-58.5, Major Depression/Dysthymia (AOR = 2.8, 95% CI = 1.1-6.7 psychiatric disorders, and history of sexual abuse (AOR = 4.6, 95% CI = 1.3-18.4 were associated with the use of

Low dosage of aripiprazole induced neuroleptic malignant syndrome after interaction with other neuroleptic drugs

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Albino Petrone

2013-09-01

Full Text Available Aripiprazole is a 2nd generation antipsychotic medication, atypical neuroleptic used for treatment of schizophrenia improving symptoms such as hallucinations, delusions, and disorganized thinking. A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS has been reported in association with administration of antipsychotic drugs, including aripiprazole. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. The disease is characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. We report on a 63-year old woman with depression syndrome who developed neuroleptic malignant syndrome after twelve days of aripripazole 5 mg per day. Our case is added to the small number already described and suggests the need for caution when aripripazole is added to increase the effect of other antipsychotics.

Minimizing Cardiovascular Adverse Effects of Atypical Antipsychotic Drugs in Patients with Schizophrenia

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Fadi T. Khasawneh

2014-01-01

Full Text Available The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients.

Treatment of antipsychotic-associated obesity with a GLP-1 receptor agnoist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study - the TAO study

DEFF Research Database (Denmark)

Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Materials and methods: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs...

Crosstalk between insulin and dopamine signaling: A basis for the metabolic effects of antipsychotic drugs.

Science.gov (United States)

Nash, Abigail I

2017-10-01

In the setting of rising rates of obesity and metabolic syndrome, characterized in part by hyperinsulinemia, it is increasingly important to understand the mechanisms that contribute to insulin dysregulation. The higher risk for metabolic syndrome imparted by antipsychotic medication use highlights one such mechanism. Though there is great variation in the number and types of signaling pathways targeted by these medications, the one common mechanism of action is through dopamine. Dopamine's effects on insulin signaling begin at the level of insulin secretion from the pancreas and continue through the central nervous system. In a reciprocal fashion, insulin also affects dopamine signaling, with specific effects on dopamine reuptake from the synapse. This review probes the dopamine-insulin connection to provide a comprehensive examination of how antipsychotics may contribute towards insulin resistance. Published by Elsevier B.V.

Unresolved Issues for Utilization of Atypical Antipsychotics in Schizophrenia: Antipsychotic Polypharmacy and Metabolic Syndrome

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Sang Won Jeon

2017-10-01

Full Text Available Atypical antipsychotics (AAP are the prevailing form of schizophrenia treatment today due to their low side effects and superior efficacy. Nevertheless, some issues still need to be addressed. First, there are still a large number of patients with treatment-resistant schizophrenia (TRS, which has led to a growing trend to resort to AAP polypharmacy with few side effects. Most clinical treatment guidelines recommend clozapine monotherapy in TRS, but around one third of schizophrenic patients fail to respond to clozapine. For these patients, with clozapine-resistant schizophrenia AAP polypharmacy is a common strategy with a continually growing evidence base. Second, AAP generally have great risks for developing metabolic syndrome, such as weight gain, abnormality in glucose, and lipid metabolism. These metabolic side effects have become huge stumbling blocks in today’s schizophrenia treatment that aims to improve patients’ quality of life as well as symptoms. The exact reasons why this particular syndrome occurs in patients treated with AAP is as yet unclear though factors such as interaction of AAP with neurotransmitter receptors, genetic pholymorphisms, type of AAPs, length of AAP use, and life style of schizophrenic patients that may contribute to its development. The present article aimed to review the evidence underlying these key issues and provide the most reasonable interpretations to expand the overall scope of antipsychotics usage.

Schizophrenia, antipsychotics and risk of hip fracture

DEFF Research Database (Denmark)

Sørensen, Holger J; Jensen, Signe O W; Nielsen, Jimmi

2013-01-01

In a nationwide study using linkage of Danish hospital registers we examined predictors of hip fracture (ICD-10: S72) in 15,431 patients with schizophrenia (ICD-10: F20 or ICD-8: 295) and 3,807,597 population controls. Shorter education, disability pension, lifetime alcohol abuse, somatic co......-morbidity, antipsychotics (IRR=1.19; 95% CI 1.15-1.24), antidepressant (IRR=1.18; 95% CI 1.16-1.20), anticholinergics (IRR=1.29; 95% CI 1.22-1.36), benzodiazepines (IRR=1.06; 95% CI 1.04-1.08) and corticosteroids (IRR=1.44; 95% CI 1.36-1.53) were significant predictors. In 556 persons with schizophrenia and hip fracture...... (matched to 1:3 to schizophrenia controls without hip fracture), antipsychotic polypharmacy predicted hip fracture. Analyses among antipsychotic monotherapy patients showed no differential effect of individual antipsychotics. A dose-response relationship of hip fracture and lifetime antipsychotics...

Antipsychotic treatment in child and adolescent first-episode psychosis: a longitudinal naturalistic approach.

Science.gov (United States)

Castro-Fornieles, Josefina; Parellada, Mara; Soutullo, César A; Baeza, Immaculada; Gonzalez-Pinto, Ana; Graell, Montserrat; Paya, Beatriz; Moreno, Dolores; de la Serna, Elena; Arango, Celso

2008-08-01

The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a naturalistic longitudinal study of early-onset first psychotic episodes. This report describes the antipsychotic treatment during the first year and compares the most frequently used agents after 6 months. Participants were 110 patients, aged 9-17 years, with a first psychotic episode attended consecutively at six different centers. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions (CGI), Disability Assessment Schedule (DAS), and Global Assessment of Function (GAF) scales were administered at baseline and at 6 months and the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale only at 6 months. Diagnoses at baseline were 38.2% psychotic disorder not otherwise specified, 39.1% schizophrenia-type disorder, 11.8% depressive disorder with psychotic symptoms, and 10.9% bipolar disorder, manic episode with psychotic symptoms. The most frequently used antipsychotic agents were risperidone (n = 50), quetiapine (n = 18), and olanzapine (n = 16). Patients who were prescribed olanzapine or quetiapine had more negative and general symptoms. Using the baseline score as covariate, no significant differences were found in the reductions on any scale in patients treated with risperidone, quetiapine, or olanzapine for 6 months. Weight increase was greater with olanzapine than with risperidone (p = 0.020) or quetiapine (p = 0.040). More neurological side effects appeared with risperidone than with olanzapine (p = 0.022). All side effects were mild or moderate. Second-generation antipsychotics, especially risperidone, quetiapine, and olanzapine, are the most used in our context in first psychotic episodes in children and adolescents. These three obtain similar clinical improvement, but differ in their side effects.

Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

Science.gov (United States)

Berna, F; Misdrahi, D; Boyer, L; Aouizerate, B; Brunel, L; Capdevielle, D; Chereau, I; Danion, J M; Dorey, J M; Dubertret, C; Dubreucq, J; Faget, C; Gabayet, F; Lancon, C; Mallet, J; Rey, R; Passerieux, C; Schandrin, A; Schurhoff, F; Tronche, A M; Urbach, M; Vidailhet, P; Llorca, P M; Fond, G

2015-12-01

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications. Copyright © 2015 Elsevier B.V. All rights reserved.

Second Generation Waste Package Design Study

International Nuclear Information System (INIS)

Armijo, J.S.; Misra, M.; Kar, Piyush

2007-01-01

The following describes the objectives of Project Activity 023 ''Second Generation Waste Package Design Study'' under DOE Cooperative Agreement DE-FC28-04RW12232. The objectives of this activity are: to review the current YMP baseline environment and establish corrosion test environments representative of the range of dry to intermittently wet conditions expected in the drifts as a function of time; to demonstrate the oxidation and corrosion resistance of A588 weathering steel and reference Alloy 22 samples in the representative dry to intermittently dry conditions; and to evaluate backfill and design features to improve the thermal performance analyses of the proposed second-generation waste packages using existing models developed at the University of Nevada, Reno(UNR). The work plan for this project activity consists of three major tasks: Task 1. Definition of expected worst-case environments (humidity, liquid composition and temperature) at waste package outer surfaces as a function of time, and comparison with environments defined in the YMP baseline; Task 2. Oxidation and corrosion tests of proposed second-generation outer container material; and Task 3. Second Generation waste package thermal analyses. Full funding was not provided for this project activity

Atypical antipsychotics: recent research findings and applications to clinical practice: Proceedings of a symposium presented at the 29th Annual European College of Neuropsychopharmacology Congress, 19 September 2016, Vienna, Austria.

Science.gov (United States)

Murray, Robin; Correll, Christoph U; Reynolds, Gavin P; Taylor, David

2017-03-01

Available evidence suggests that second-generation atypical antipsychotics are broadly similar to first-generation agents in terms of their efficacy, but may have a more favourable tolerability profile, primarily by being less likely to cause extrapyramidal symptoms. However, atypical antipsychotics are variably associated with disturbances in the cardiometabolic arena, including increased body weight and the development of metabolic syndrome, which may reflect differences in their receptor binding profiles. Effective management of schizophrenia must ensure that the physical health of patients is addressed together with their mental health. This should therefore involve consideration of the specific tolerability profiles of available agents and individualization of treatment to minimize the likelihood of adverse metabolic sequelae, thereby improving long-term adherence and optimizing overall treatment outcomes. Alongside this, modifiable risk factors (such as exercise, diet, obesity/body weight and smoking status) must be addressed, in order to optimize patients' overall health and quality of life (QoL). In addition to antipsychotic-induced side effects, the clinical management of early nonresponders and psychopharmacological approaches for patients with treatment-resistant schizophrenia remain important unmet needs. Evidence suggests that antipsychotic response starts early in the course of treatment and that early nonresponse accurately predicts nonresponse over the longer term. Early nonresponse therefore represents an important modifiable risk factor for poor efficacy and effectiveness outcomes, since switching or augmenting antipsychotic treatment in patients showing early nonresponse has been shown to improve the likelihood of subsequent treatment outcomes. Recent evidence has also demonstrated that patients showing early nonresponse to treatment with lurasidone at 2 weeks may benefit from an increase in dose at this timepoint without compromising

Antipsychotic Medications in Major Depression and the Association with Treatment Satisfaction and Quality of Life: Findings of Three National Surveys on Use of Psychotropics in China Between 2002 and 2012

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Yu-Xi Wang

2015-01-01

Conclusions: Concurrent antipsychotic use was found in about one in four treated depressed patients in China, which has increased over a 10-year period. Considering the association of drug-induced side effects and the lack of patients′ and relatives′ satisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of the use of antipsychotics in depression is needed.

The effects of typical and atypical antipsychotics on the electrical activity of the brain in a rat model

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Oytun Erbaş

2013-09-01

Full Text Available Objective: Antipsychotic drugs are known to have strongeffect on the bioelectric activity in the brain. However,some studies addressing the changes on electroencephalography(EEG caused by typical and atypical antipsychoticdrugs are conflicting. We aimed to compare the effectsof typical and atypical antipsychotics on the electricalactivity in the brain via EEG recordings in a rat model.Methods: Thirty-two Sprague Dawley adult male ratswere used in the study. The rats were divided into fivegroups, randomly (n=7, for each group. The first groupwas used as control group and administered 1 ml/kg salineintraperitoneally (IP. Haloperidol (1 mg/kg (group 2,chlorpromazine (5 mg/kg (group 3, olanzapine (1 mg/kg(group 4, ziprasidone (1 mg/ kg (group 5 were injectedIP for five consecutive days. Then, EEG recordings ofeach group were taken for 30 minutes.Results: The percentages of delta and theta waves inhaloperidol, chlorpromazine, olanzapine and ziprasidonegroups were found to have a highly significant differencecompared with the saline administration group (p<0.001.The theta waves in the olanzapine and ziprasidonegroups were increased compared with haloperidol andchlorpromazine groups (p<0.05.Conclusion: The typical and atypical antipsychotic drugsmay be risk factor for EEG abnormalities. This studyshows that antipsychotic drugs should be used with caution.J Clin Exp Invest 2013; 4 (3: 279-284Key words: Haloperidol, chlorpromazine, olanzapine,ziprasidone, EEG, rat

Psychotropic and neurotropic drugs and neurotransmitter receptors

International Nuclear Information System (INIS)

Takahashi, Ryo

1986-01-01

Neurotransmitters are important in nervous and mental diseases because of their part in the pathogenesis of such diseases; at the same time, they play significant roles in the actions of effective therapeutic drugs. Studies of the mechanisms involved in the actions of such drugs not only generate useful methods to elucidate the pathogenesis of nervous and mental disorders but also serve as indispensable means of developing new drugs. In this field, investigations using both animal models of certain diseases and healthy animals are essential. Development of these animal models is urgently required. In this workshop, studies were presented of the mechanisms of action of major neuropsychotropic drugs such as anxiolytics, antidepressants, and antipsychotics, assessed in terms of the parts played by neurotransmitters and receptors. (Auth.)

Effect of GLP-1 Receptor Agonist Treatment on Body weight in Obese Antipsychotic-treated Patients with Schizophrenia

DEFF Research Database (Denmark)

Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V

2017-01-01

AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects like obesity...... and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia. MATERIAL AND METHODS......: Antipsychotic-treated, obese, non-diabetic, schizophrenia spectrum patients were randomized to double-blinded adjunctive treatment with once-weekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for three months. The primary outcome was body weight loss after treatment and repeated measures...

Glucometabolic hormones and cardiovascular risk markers in antipsychotic-treated patients.

Science.gov (United States)

Ebdrup, Bjørn H; Knop, Filip K; Madsen, Anna; Mortensen, Henrik B; Søgaard, Birgitte; Holst, Jens J; Szecsi, Pal B; Lublin, Henrik

2014-09-01

Treatment with antipsychotic drugs is widely associated with metabolic side effects such as weight gain and disturbed glucose metabolism, but the pathophysiologic mechanisms are unclear. Fifty nondiabetic (fasting plasma glucose ≤ 7.0 mmol/L), antipsychotic-treated male patients (ICD-10 diagnosis code F20, F21, F22, F25, F28, or F60; mean ± SD age = 33.0 ± 6.7 years; body mass index [BMI; kg/m²] = 26.0 ± 4.7; waist circumference = 95.9 ± 13.3 cm; glycated hemoglobin A1c [HbA1c] = 5.7% ± 0.3%) and 93 age- and waist circumference-matched healthy male controls (age = 33 ± 7.3 years; BMI = 26.1 ± 3.9; waist circumference = 94.6 ± 11.9 cm; HbA1c = 5.7% ± 0.3%) participated in this cross-sectional study. Blood was sampled in the fasting state and 90 minutes after ingestion of a standardized liquid meal (2,268 kJ). The primary outcomes were glucometabolic hormones and cardiovascular risk markers. Data were collected between March 2008 and February 2010. Compared to healthy controls, patients were characterized by elevated fasting levels of proinsulin, C-peptide, and glucose-dependent insulinotropic polypeptide (GIP) (P risk profile. The appetite-regulating hormones GLP-1 and ghrelin appear not to be influenced by antipsychotic treatment. Our findings provide new clinical insight into the pathophysiology associated with metabolic side effects of antipsychotic treatment and put emphasis on the importance of implementing metabolic screening into psychiatric practice. ClinicalTrials.gov identifier NCT00627757. © Copyright 2014 Physicians Postgraduate Press, Inc.

Attitudes toward antipsychotic treatment among patients with bipolar disorders and their clinicians: a systematic review

Directory of Open Access Journals (Sweden)

Sajatovic M

2017-08-01

may reflect a relative lack of experience using antipsychotics in patients with bipolar disorder. Conclusion: Although data are very limited, perceived tolerability and efficacy concerns shape both patient and clinician attitudes toward use of antipsychotic drugs in bipolar disorder. Additional studies are warranted. Keywords: bipolar disorder, antipsychotics, systematic review, attitudes

Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients

DEFF Research Database (Denmark)

Baandrup, Lone; Allerup, Peter; Lublin, H

2010-01-01

polypharmacy, socioeconomic status and functional level of patients. The intervention was aimed at psychiatric healthcare providers and consisted of 1 day of didactic lectures, six 3-h educational outreach visits and an electronic reminder during drug prescribing. RESULTS: Between-group use of antipsychotic...

Plasma wave and second harmonic generation

International Nuclear Information System (INIS)

Sodha, M.S.; Sharma, J.K.; Tewari, D.P.; Sharma, R.P.; Kaushik, S.C.

1978-01-01

An investigation is made of a plasma wave at pump wave frequency and second harmonic generation caused by a self induced transverse inhomogeneity introduced by a Gaussian electromagnetic beam in a hot collisionless plasma. In the presence of a Gaussian beam the carriers get redistributed from the high field region to the low field region by ponderomative force and a transverse density gradient is established in the plasma. When the electric vector of the main beam is parallel to this density gradient, a plasma wave at the pump wave frequency is generated. In addition to this the transverse intensity gradient of the electromagnetic wave also contributes significantly to the plasma wave generation. The power of the plasma wave exhibits a maximum and minimum with the power of the pump wave (at z = 0). The generated plasma wave interacts with the electromagnetic wave and leads to the generation of a second harmonic. Furthermore, if the initial power of the pump wave is more than the critical power for self-focusing, the beam gets self-focused and hence the generated plasma wave and second harmonic which depend upon the background electron concentration and power of the main beam also get accordingly modified. (author)

What is the role of sedating antidepressants, antipsychotics, and anticonvulsants in the management of insomnia?

Science.gov (United States)

McCall, Catherine; McCall, W Vaughn

2012-10-01

Psychiatric medications such as antidepressants, antipsychotics, and anticonvulsants are commonly prescribed by physicians for the off-label use of improving sleep. Reasons for preferential prescription of these medications over FDA-approved insomnia drugs may include a desire to treat concurrent sleep problems and psychiatric illness with a single medication, and/or an attempt to avoid hypnotic drugs due to their publicized side effects. However, there have been few large studies demonstrating the efficacy and safety of most off-label medications prescribed to treat insomnia. In addition, many of these medications have significant known side effect profiles themselves. Here we review the pertinent research studies published in recent years on antidepressant, antipsychotic, and anticonvulsant medications frequently prescribed for sleep difficulties. Although there have been few large-scale studies for most of these medications, some may be appropriate in the treatment of sleep issues in specific well-defined populations.

Handwriting Movement Kinematics for Quantifying EPS in Patients Treated with Atypical Antipsychotics

Science.gov (United States)

Caligiuri, Michael P.; Teulings, Hans-Leo; Dean, Charles E.; Niculescu, Alexander B.; Lohr, James B.

2009-01-01

Ongoing monitoring of neuroleptic-induced extrapyramidal side effects (EPS) is important to maximize treatment outcome, improve medication adherence and reduce re-hospitalization. Traditional approaches for assessing EPS such as parkinsonism, tardive akathisia, or dyskinesia rely upon clinical ratings. However, these observer-based EPS severity ratings can be unreliable and are subject to examiner bias. In contrast, quantitative instrumental methods are less subject to bias. Most instrumental methods have only limited clinical utility because of their complexity and costs. This paper describes an easy-to-use instrumental approach based on handwriting movements for quantifying EPS. Here, we present findings from psychiatric patients treated with atypical (second generation) antipsychotics. The handwriting task consisted of a sentence written several times within a 2 cm vertical boundary at a comfortable speed using an inkless pen and digitizing tablet. Kinematic variables including movement duration, peak vertical velocity and the number of acceleration peaks, and average normalized jerk (a measure of smoothness) for each up or down stroke and their submovements were analyzed. Results from 59 psychosis patients and 46 healthy comparison subjects revealed significant slowing and dysfluency in patients compared to controls. We observed differences across medications and daily dose. These findings support the ecological validity of handwriting movement analysis as an objective behavioral biomarker for quantifying the effects of antipsychotic medication and dose on the motor system. PMID:20381875

Design of a long-term antipsychotic in situ forming implant and its release control method and mechanism.

Science.gov (United States)

Wang, Lexi; Wang, Aiping; Zhao, Xiaolei; Liu, Ximing; Wang, Dan; Sun, Fengying; Li, Youxin

2012-05-10

Two kinds of in situ forming implants (ISFIs) of atypical antipsychotics, risperidone and its 9-hydroxy active metabolite, paliperidone, using poly(lactide-co-glycolide)(PLGA) as carrier, were investigated. Significant difference was observed in the solution-gel transition mechanism of the two systems: homogeneous system of N-methyl-2-pyrrolidone (NMP) ISFI, in which drug was dissolved, and heterogeneous system of dimethyl sulfoxide (DMSO) ISFI, in which drug was dispersed. Fast solvent extractions were found in both systems, but in comparison with the high drug release rate from homogeneous system of drug/polymer/NMP, a fast solvent extraction from the heterogeneous system of drug/polymer/DMSO was not accompanied by a high drug release rate but a rapid solidification of the implant, which resulted in a high drug retention, well-controlled initial burst and slow release of the drug. In vivo study on beagle dogs showed a more than 3-week sustained release with limited initial burst. Pharmacologic evaluation on optimized paliperidone ISFIs presented a sustained-suppressing effect from 1 day to 38 day on the MK-801 induced schizophrenic behavior mice model. A long sustained-release antipsychotic ISFI of 50% drug loading and controlled burst release was achieved, which indicated a good potential in clinic application. Copyright © 2012 Elsevier B.V. All rights reserved.

Translational PKPD modeling in schizophrenia: linking receptor occupancy of antipsychotics to efficacy and safety

NARCIS (Netherlands)

Pilla Reddy, Venkatesh; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes

2012-01-01

Objectives: To link the brain dopamine D2 receptor occupancy (D2RO) of antipsychotic drugs with clinical endpoints of efficacy and safety to assess the therapeutic window of D2RO. Methods: Pharmacokinetic-Pharmacodynamic (PK-PD) models were developed to predict the D2 receptor occupancy of

Increased use of antipsychotic long-acting injections with community treatment orders.

Science.gov (United States)

Patel, Maxine X; Matonhodze, Jane; Baig, Mirza K; Gilleen, James; Boydell, Jane; Holloway, Frank; Taylor, David; Szmukler, George; Lambert, Tim; David, Anthony S

2011-04-01

Community treatment orders (CTOs) are increasingly being used, despite a weak evidence base, and problems continue regarding Second Opinion Appointed Doctor (SOAD) certification of medication. The aim of the current study was to describe current CTO usage regarding patient characteristics, prescribed medication and CTO conditions. A 1-year prospective cohort study with consecutive sampling was conducted for all patients whose CTO was registered in a large mental health trust. Only the first CTO for each patient was included. Measures included sociodemographic variables, psychiatric diagnosis, CTO date of initiation and conditions, psychotropic medication and date of SOAD certification for medication. This study was conducted in the first year of CTO legislation in England and Wales. A total of195 patients were sampled (mean age 40.6 years, 65% male, 52% black ethnic origin). There was significant geographical variability in rates of CTO use (χ(2) = 11.3, p = 0.012). A total of 53% had their place of residence specified as a condition and 29% were required to allow access into their homes. Of those with schizophrenia, 64% were prescribed an antipsychotic long-acting injection (LAI). Of the total group, 7% received high-dose antipsychotics, 10% were prescribed two antipsychotics and only 15% received SOAD certification in time. There was geographical and ethnic variation in CTO use but higher rates of hospital detention in minority ethnic groups may be contributory. Most patients were prescribed antipsychotic LAIs and CTO conditions may not follow the least restrictive principle.

Hiponatremia in the practice of a psychiatrist. Part 1: SIADH syndrome and drug-induced hyponatremia.

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Stelmach Ewa

2017-06-01

Full Text Available Introduction. Hyponatremia is an important part of psychiatric practice. In order to analyze its causes and symptoms, the literature on hyponatremia in psychiatric patients has been reviewed. The work has been divided into two separate manuscripts. In the first one the authors discuss the syndrome of inappropriate antidiuretic hormone secretion (SIADH and hyponatremia occurring with the use of psychotropic drugs (antidepressants, antipsychotics, normotimics, while the second paper discusses research on psychogenic polydipsia. The causes of hyponatremia in patients treated in psychiatric wards include: water intoxication associated with polydipsia, somatic comorbidities, side effect of internal medicine and psychiatric drugs. The most common mechanism leading in these cases to hyponatremia is the syndrome of inappropriate secretion of vasopressin (SIADH. The SIADH syndrome is a group of symptoms, first described in 1967 by Schwartz and Bartter in The American Journal of Medicine, which results from the hypersecretion of antidiuretic hormone, also called vasopressin, which causes patients to develop normovolemic hyponatremia. The phenomenon of drug-induced hyponatremia in psychiatric practice is generally observed with the use of antidepressants, antipsychotics and anti-epileptic drugs (used in psychiatry as normotimic drugs.

Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study

DEFF Research Database (Denmark)

Ishøy, Pelle Lau; Knop, Filip Krag; Broberg, Brian Villumsen

with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity. Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised...

Concomitant NSAID use during antipsychotic treatment and risk of 2-year relapse - a population-based study of 16,253 incident patients with schizophrenia

DEFF Research Database (Denmark)

Köhler, Karl Ole; Petersen, Liselotte; Benros, Michael Eriksen

2016-01-01

OBJECTIVE: Clinical trials have indicated antipsychotic effects of non-steroidal anti-inflammatory drugs (NSAIDs) among incident patients with schizophrenia. We aimed to study, in a population-based setting, whether concomitant use of NSAIDs or paracetamol, changed 2-year relapse risk...... for schizophrenia. METHODS: We identified all incident patients with schizophrenia in Denmark diagnosed 1996-2012 initiating antipsychotic treatment within the year after diagnosis. We calculated concomitant treatment intervals for antipsychotic and NSAID or paracetamol use. Hazard rate ratios (HRR) were estimated...... using Cox regression adjusted for important covariates. MAIN OUTCOME MEASURES: 2-year relapse, i.e. (re)-hospitalizations with schizophrenia. RESULTS: Among 16,235 incident patients with schizophrenia using antipsychotics, 1480 (9.1%) used NSAIDs and 767 (4.7%) paracetamol. Concomitant use of NSAIDs...

Gamma-aminobutyric acid agonists for antipsychotic-induced tardive dyskinesia.

Science.gov (United States)

Alabed, Samer; Latifeh, Youssef; Mohammad, Husam Aldeen; Bergman, Hanna

2018-04-17

Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. Gamma-aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD. 1. Primary objectiveThe primary objective was to determine whether using non-benzodiazepine GABA agonist drugs for at least six weeks was clinically effective for the treatment of antipsychotic-induced TD in people with schizophrenia, schizoaffective disorder or other chronic mental illnesses.2. Secondary objectivesThe secondary objectives were as follows.To examine whether any improvement occurred with short periods of intervention (less than six weeks) and, if this did occur, whether this effect was maintained at longer periods of follow-up.To examine whether there was a differential effect between the various compounds.To test the hypothesis that GABA agonist drugs are most effective for a younger age group (less than 40 years old). We searched the Cochrane Schizophrenia Group Trials Register (last searched April 2017), inspected references of all identified studies for further trials, and, when necessary, contacted authors of trials for additional information. We included randomised controlled trials of non-benzodiazepine GABA agonist drugs in people with antipsychotic-induced TD and schizophrenia or other chronic mental illness. Two review authors independently selected and critically appraised studies, extracted and analysed data on an intention-to-treat basis. Where possible and appropriate we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous data we calculated mean differences (MD). We assumed that people who left early had no improvement. We contacted investigators to obtain missing information. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. We included 11 studies that randomised 343 people. Overall, the risk of bias

Atypical antipsychotics in the treatment of early-onset schizophrenia

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Hrdlicka M

2015-04-01

Full Text Available Michal Hrdlicka, Iva Dudova Department of Child Psychiatry, Charles University Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic Abstract: Atypical antipsychotics (AAPs have been successfully used in early-onset schizophrenia (EOS. This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. Keywords: early-onset schizophrenia, atypical antipsychotics, efficacy, onset of action, weight gain

Possible Oxcarbazepine Inductive Effects on Aripiprazole Metabolism: A Case Report.

Science.gov (United States)

McGrane, Ian R; Loveland, Joshua G; de Leon, Jose

2017-01-01

Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness. A limited number of reports are available which discuss reduced atypical antipsychotic concentrations secondary to oxcarbazepine CYP3A4 induction. We report a young boy taking oxcarbazepine (1200 mg/d) who presented with an unexpectedly low serum aripiprazole concentration. Utilizing therapeutic drug monitoring, pharmacogenetic testing, and a tool to evaluate drug-drug interactions, we estimate that oxcarbazepine possibly reduced his serum aripiprazole concentration by 68%. Our report is important, as it is the first to describe a drug-drug interaction between oxcarbazepine and aripiprazole. This report should encourage the completion of in vitro and clinical studies and the publication of case reports describing the possible inductive effects of oxcarbazepine on atypical antipsychotics (including cariprazine, lurasidone, quetiapine, aripiprazole, brexpiprazole, iloperidone, and risperidone) mediated by induction of the CYP3A4 metabolic pathway.

Generation and characterization of atto second pulses

International Nuclear Information System (INIS)

Mairesse, Y.

2005-07-01

Atto-second pulse trains in the extreme ultraviolet range can be produced by high-order harmonic generation, by focusing an intense femtosecond pulse in a rare gas jet. In this thesis, we present a temporal characterization of this radiation on the femtosecond and atto-second timescales. By transposing a spectral interferometry technique commonly used in the infrared range (SPIDER), we make a complete single-shot characterization of the temporal profile of individual harmonics, on the femtosecond timescale. In a second part, we study experimentally the atto-second structure of the harmonic radiation, and demonstrate a temporal drift in the emission: the lowest harmonics are emitted before the highest ones. This chirp, which is directly related to the electron dynamics in the generation process, imposes a lower limit to the duration that can be achieved by increasing the spectral range. We show how generating conditions can be optimized in order to enhance the synchronization in the emission, and how atto-second pulses can be re-compressed. Last, we propose a new technique for the complete characterization of arbitrary atto-second pulses: FROGCRAB. This method would allow simultaneous measurements of the femtosecond and atto-second structures of the radiation, and thus a complete knowledge of the atto-second light source in the perspective of applications. (author)

Stimulant and Atypical Antipsychotic Medications For Children Placed in Foster Homes

Science.gov (United States)

Linares, L. Oriana; Martinez-Martin, Nuria; Castellanos, F. Xavier

2013-01-01

Objectives The purpose of this study is to examine the use of prescribed psychoactive medications in a prospective cohort of children shortly after they entered foster homes; and to identify demographics, maltreatment history, psychiatric diagnoses including ADHD comorbidity, and level of aggression that contribute to prescribed use of stimulant and atypical antipsychotic medication over time. Methods The sample included N = 252 children (nested in 95 sibling groups) followed for three years up to 4 yearly waves. Results Nearly all (89%) met criteria for at least one of eight psychiatric diagnoses and 31% (75/252) used one or more prescribed psychoactive medications. Over half (55%) were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD); of these 38% used stimulants and 36% used atypical antipsychotics. Of the 75 medicated children, 19% received ≥3 different classes of drugs over the course of the study. Stimulants (69%) and atypical antipsychotics (65%) were the most frequently used drugs among medicated children. Adjusted odds ratios (AOR) showed that male gender (AOR = 3.2; 95% CI = 1.5–9.3), African American vs Latino ethnicity (AOR = 5.4; 95% CI = 2.1–14.2), ADHD regardless of Oppositional Defiant (ODD) or Conduct (CD) comorbidity (AOR = 6.0, 95% CI = 1.3–27.5), ODD or CD (AOR = 11.1, 95% CI = 2.1–58.6), and Separation Anxiety (AOR = 2.0, 95% CI = 1.0–4.0) psychiatric disorders were associated with the use of prescribed stimulants; while male gender (AOR = 3.8, 95% CI = 1.5–9.3), African American vs Latino (AOR = 5.1, 95% CI = 1.2–9.2) or Mixed/Other ethnicity (AOR = 3.3, 95% CI = 1.9–13.7), ADHD regardless of ODD or CD comorbidity (AOR = 5.8, 95% CI = 1.2–28.7), ODD or CD (AOR = 13.9, 95% CI = 3.3–58.5), Major Depression/Dysthymia (AOR = 2.8, 95% CI = 1.1–6.7) psychiatric disorders, and history of sexual abuse (AOR = 4.6, 95

Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

International Nuclear Information System (INIS)

Memo, M.; Battaini, F.; Spano, P.F.; Trabucchi, M.

1981-01-01

It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D 1 receptors, associated with adenylyl cyclase activity, and D 2 receptor, uncoupled to a cyclic APM generating system. In order to understand the role of D 1 and D 2 receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D 1 receptors, and sulpiride, a selective antagonist to D 2 receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D 2 receptors. In fact under these conditions 3 H-(-)-sulpiride binding, which is a marker of D 2 receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D 2 receptors. Moreover, sulpiride does not induce supersensitivity of the D 1 receptors, characterized by 3 H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by 3 H-spiroperidol and 3 H-(-)-sulpiride binding. These findings suggest that D 1 and D 2 receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements. (author)

Antipsychotic activity of aqueous ethanolic extract of Tinospora Cordifolia in amphetamine challenged mice model

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Bindu nee Giri Jain

2010-01-01

Full Text Available Tinospora cordifolia is reported to have CNS active principle and is used for the treatment of various neurological disorders. Hence, the effect of aqueous ethanolic extract of Tinospora cordifolia was investigated for its putative antipsychotic activity using amphetamine challenged mice model. Haloperidol (1 mg/kg i.p. was administered acutely to mice as standard drug. Control animals received vehicle (10% DMSO. The in vivo receptor binding studies were carried out to correlate the antipsychotic activity of the extract with its capacity to bind to the DAD2 receptor. The results in SLA showed that the hydro alcoholic extract of the stems of Tinospora cordifolia at a dose level of 250 mg/kg and 500 mg/kg showed no significant antipsychotic activity in amphetamine induced hyperactivity in mice when compared to standard. Extract alone treated group at a dos level of 250 mg/kg and 500 mg/kg showed a decreased in locomotor activity when compared to the control. The plant extract increased the DAD2 receptor binding in a dose dependent manner in treated mice compared to the control group.

Antipsychotic-like effect of the muscarinic acetylcholine receptor agonist BuTAC in non-human primates.

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Maibritt B Andersen

Full Text Available Cholinergic, muscarinic receptor agonists exhibit functional dopamine antagonism and muscarinic receptors have been suggested as possible future targets for the treatment of schizophrenia and drug abuse. The muscarinic ligand (5R,6R-6-(3-butylthio-1,2,5-thiadiazol-4-yl-1-azabicyclo[3.2.1]octane (BuTAC exhibits high affinity for muscarinic receptors with no or substantially less affinity for a large number of other receptors and binding sites, including the dopamine receptors and the dopamine transporter. In the present study, we wanted to examine the possible antipsychotic-like effects of BuTAC in primates. To this end, we investigated the effects of BuTAC on d-amphetamine-induced behaviour in antipsychotic-naive Cebus paella monkeys. Possible adverse events of BuTAC, were evaluated in the same monkeys as well as in monkeys sensitized to antipsychotic-induced extrapyramidal side effects. The present data suggests that, the muscarinic receptor ligand BuTAC exhibits antipsychotic-like behaviour in primates. The behavioural data of BuTAC as well as the new biochemical data further substantiate the rationale for the use of muscarinic M1/M2/M4-preferring receptor agonists as novel pharmacological tools in the treatment of schizophrenia.

Variation in Dopamine D2 and Serotonin 5-HT2A Receptor Genes is Associated with Working Memory Processing and Response to Treatment with Antipsychotics.

Science.gov (United States)

Blasi, Giuseppe; Selvaggi, Pierluigi; Fazio, Leonardo; Antonucci, Linda Antonella; Taurisano, Paolo; Masellis, Rita; Romano, Raffaella; Mancini, Marina; Zhang, Fengyu; Caforio, Grazia; Popolizio, Teresa; Apud, Jose; Weinberger, Daniel R; Bertolino, Alessandro

2015-06-01

Dopamine D2 and serotonin 5-HT2A receptors contribute to modulate prefrontal cortical physiology and response to treatment with antipsychotics in schizophrenia. Similarly, functional variation in the genes encoding these receptors is also associated with these phenotypes. In particular, the DRD2 rs1076560 T allele predicts a lower ratio of expression of D2 short/long isoforms, suboptimal working memory processing, and better response to antipsychotic treatment compared with the G allele. Furthermore, the HTR2A T allele is associated with lower 5-HT2A expression, impaired working memory processing, and poorer response to antipsychotics compared with the C allele. Here, we investigated in healthy subjects whether these functional polymorphisms have a combined effect on prefrontal cortical physiology and related cognitive behavior linked to schizophrenia as well as on response to treatment with second-generation antipsychotics in patients with schizophrenia. In a total sample of 620 healthy subjects, we found that subjects with the rs1076560 T and rs6314 T alleles have greater fMRI prefrontal activity during working memory. Similar results were obtained within the attentional domain. Also, the concomitant presence of the rs1076560 T/rs6314 T alleles also predicted lower behavioral accuracy during working memory. Moreover, we found that rs1076560 T carrier/rs6314 CC individuals had better responses to antipsychotic treatment in two independent samples of patients with schizophrenia (n=63 and n=54, respectively), consistent with the previously reported separate effects of these genotypes. These results indicate that DRD2 and HTR2A genetic variants together modulate physiological prefrontal efficiency during working memory and also modulate the response to antipsychotics. Therefore, these results suggest that further exploration is needed to better understand the clinical consequences of these genotype-phenotype relationships.

Multiple Antipsychotic Medication Use in Autism Spectrum Disorder.

Science.gov (United States)

Wink, Logan K; Pedapati, Ernest V; Horn, Paul S; McDougle, Christopher J; Erickson, Craig A

2017-02-01

The purpose of this study was to explore the use of multiple antipsychotic medications in patients with autism spectrum disorder (ASD) by reviewing the longitudinal medication management of 1100 patients consecutively treated for behavioral symptoms associated with ASD at a tertiary care specialty clinic. We identified all patients with ASD treated with daily doses of two or more antipsychotics for at least two visits at our clinic. For each patient meeting inclusion criteria, diagnostic and demographic data were collected. To evaluate clinical need and effectiveness of antipsychotic medications in this sample, we reviewed symptoms targeted with each antipsychotic medication and concomitant medications prescribed. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scale ratings had been completed at the time of each visit, and the duration of treatment with antipsychotic medications was determined. To evaluate the safety and tolerability of antipsychotic medication use in ASD, we reviewed reported adverse effects and calculated body mass index (BMI) change with treatment. Seventy patients met the inclusion criteria (6.4% of our sample). The majority of patients were moderately to severely ill Caucasian males, as determined by baseline mean CGI-S of 4.7 (SD = 0.8), and were diagnosed with autistic disorder and comorbid intellectual disability. The mean age was 15.1 years (SD = 10.9), the primary targeted symptoms were agitation/irritability, physical aggression, and self-injury. The majority of patients remained on two or more antipsychotics for >1 year. In this population, patients demonstrated greater symptomatic improvement and generally tolerated treatment without significant adverse effects. The use of two or more antipsychotic medications may be increasingly common in patients with ASD. This retrospective study demonstrates that this treatment approach may be of some clinical benefit, and is generally well

Cost-effectiveness of an atypical conventional antipsychotic in South Africa: An economic evaluation of quetiapine versus haloperidol in the treatment of patients partially responsive to previous antipsychotics

Directory of Open Access Journals (Sweden)

Robin Emsley

2004-10-01

Full Text Available Background. The introduction of a new generation of atypical antipsychotic agents has raised difficult economic and ethical questions, particularly in lower-income countries. The reported tolerability and efficacy advantages of the atypical antipsy- chotics over their conventional predecessors have to be weighed against their higher acquisition costs. Pharmaco-eco- nomic studies conducted in Western countries consistently report cost advantages or cost neutrality for these new agents. However, considerable differences in health care service pro- vision make it difficult to generalise these findings to South Africa. Method. We compared the direct costs (private and public sector of treating schizophrenia with an atypical antipsychotic quetiapine, and with a conventional antipsychotic haloperidol, by adapting a decision-analytic pharmaco-economic model for South African circumstances. The sample comprised patients partially responsive to antipsychotics, who had partic- ipated in a multinational randomised controlled trial compar- ing the efficacy and safety of quetiapine versus haloperidol. Results. The estimated total direct cost for the treatment with quetiapine in South Africa was slightly less than for haloperidol for various models in both the private and the public sectors. Conclusions. Significant differences in health care provision make pharmaco-economic studies conducted in other coun- tries invalid for South African circumstances. Previously queti- apine treatment did not result in direct cost savings in South Africa. However, the recently introduced legislation to estab- lish single exit prices for medications has resulted in the cost of quetiapine treatment declining by 36.7% and that of haloperi- dol by 13%. This has translated into an overall direct cost sav- ing for quetiapine in both the private and public sector models. This, together with additional indirect advantages of the atypi- cal antipsychotics such as improved quality of

Review and analysis of hospitalization costs associated with antipsychotic nonadherence in the treatment of schizophrenia in the United States.

Science.gov (United States)

Sun, Shawn X; Liu, Gordon G; Christensen, Dale B; Fu, Alex Z

2007-10-01

To review the literature addressing the economic outcomes of nonadherence in the treatment of schizophrenia, and to utilize the review results to provide an update on the economic impact of hospitalizations among schizophrenia patients related to antipsychotic nonadherence. A structured search of EMBASE, Ovid MEDLINE, PubMed and PsycINFO for years 1995-2007 was conducted to identify published English-language articles addressing the economic impact of antipsychotic nonadherence in schizophrenia. The following key words were used in the search: compliance, noncompliance, adherence, nonadherence, relapse, economic, cost, and schizophrenia. A bibliographic search of retrieved articles was performed to identify additional studies. For a study to be included, the date of publication had to be from 1/1/1995 to 6/1/2007, and the impact of nonadherence had to be measured in terms of direct healthcare costs or inpatient days. Subsequently, an estimate of incremental hospitalization costs related to antipsychotic non adherence was extrapolated at the US national level based on the reviewed studies (nonadherence rate and hospitalization rate) and the National Inpatient Sample of Healthcare Cost and Utilization Project (average daily hospitalization costs). Seven studies were identified and reviewed based on the study design, measurement of medication nonadherence, study setting, and cost outcome results. Despite the varied adherence measures across studies, all articles reviewed showed that antipsychotic nonadherence was related to an increase in hospitalization rate, hospital days or hospital costs. We also estimated that the national rehospitalization costs related to antipsychotic nonadherence was $1479 million, ranging from $1392 million to $1826 million in the US in 2005. The estimate of rehospitalization costs was restricted to schizophrenia patients from the Medicaid program. Additionally, the studies we reviewed did not capture the newer antipsychotic drugs

Improv Chat: Second Response Generation for Chatbot

OpenAIRE

Wei, Furu

2018-01-01

Existing research on response generation for chatbot focuses on \\textbf{First Response Generation} which aims to teach the chatbot to say the first response (e.g. a sentence) appropriate to the conversation context (e.g. the user's query). In this paper, we introduce a new task \\textbf{Second Response Generation}, termed as Improv chat, which aims to teach the chatbot to say the second response after saying the first response with respect the conversation context, so as to lighten the burden ...

Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark

DEFF Research Database (Denmark)

Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian

2017-01-01

to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population...

Atypical antipsychotic usage among Asian Americans and Pacific Islanders.

Science.gov (United States)

Takeshita, Junji; Goebert, Deborah; Else, Iwalani; Carlton, Barry; Matsu, Courtenay; Guerrero, Anthony

2014-09-01

Previous studies have shown significant ethnic differences in prescribing patterns of two or more antipsychotics. This study examined changes in atypical and typical antipsychotic prescriptions among Asian Americans and Pacific Islanders. Five hundred consecutive charts were reviewed for antipsychotics at the time of admission and discharge from each of two inpatient psychiatric facilities in Hawai'i. Multiple antipsychotic prescription rates were 9% at intake and 6% at discharge. For the ethnic groups studied, there were no statistically significant differences by patient ethnicity regarding antipsychotics at intake (χ(2) = 29.2, df = 21, P = .110) or discharge (χ(2) = 20.5, df = 24, P = .667). There were no significant differences in prescription and polypharmacy patterns among Asian Americans and Pacific Islanders ethnic groups in this study.

Current status of atypical antipsychotics for the treatment of fibromyalgia.

Science.gov (United States)

Rico-Villademoros, F; Calandre, E P; Slim, M

2014-06-01

The treatment of fibromyalgia requires pharmacological and nonpharmacological therapies. The pharmacological treatment of fibromyalgia is limited to a few drugs that have been demonstrated to be moderately effective in some but not all dimensions of the disease. Therefore, the search for new drugs to treat this condition is warranted. Atypical antipsychotics offered an attractive alternative because they had been shown to be active against several key symptoms of fibromyalgia. The results of open-label studies, however, appear to indicate that atypical antipsychotics are poorly tolerated in patients with fibromyalgia, and only quetiapine XR has been studied in randomized controlled trials. Quetiapine XR has demonstrated effectiveness in treating comorbid major depression, anxiety and sleep disturbance. However, in two randomized controlled trials, quetiapine XR was not differentiated from placebo and failed to demonstrate noninferiority to amitriptyline in terms of improving overall symptomatology. The effect of quetiapine XR on pain and its usefulness as part of a combination pharmacological regimen should be further evaluated. Overall, the use of quetiapine (initiated at a low dose and slowly titrated) in fibromyalgia should be limited to patients with comorbid major depression or patients who are currently receiving other treatments and have unresolved and disabling depressive and/or anxiety symptoms. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.

Wood Quality of Acacia Hybrid and Second-Generation Acacia mangium

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Ismail Jusoh

2013-11-01

Full Text Available Two new tree variants, namely Acacia hybrid and second-generation Acacia mangium, have been introduced in plantation forests in Sarawak, Malaysia, and their wood qualities were examined. The mean basic density of Acacia hybrid was comparable with Acacia mangium. However basic density and strength properties of second-generation A. mangium were significantly lower compared to Acacia hybrid. The mean fibre length and fibre wall thickness in the hybrid were found to be greater than that of second-generation A. mangium. Fibre diameter and fibre lumen diameter of Acacia hybrid were smaller compared to second-generation A. mangium. Runkel and slenderness ratios of Acacia hybrid and second-generation A. mangium fibres showed that they were suitable for pulp and paper production. Acacia hybrid was more resistant to Coptotermes curvignathus attack than second-generation A. mangium. A laboratory soil block test showed that Acacia hybrid and second-generation A. mangium were moderately durable timbers. In summary, marked differences in wood properties and qualities were observed between Acacia hybrid and second-generation A. mangium.

The Psychopharmacology of Agitation: Consensus Statement of the American Association for Emergency Psychiatry Project BETA Psychopharmacology Workgroup

Directory of Open Access Journals (Sweden)

Michael P. Wilson

2012-04-01

Full Text Available Agitation is common in the medical and psychiatric emergency department, and appropriate management of agitation is a core competency for emergency clinicians. In this article, the authors review the use of a variety of first-generation antipsychotic drugs, second-generation antipsychotic agents, and benzodiazepines for treatment of acute agitation, and propose specific guidelines for treatment of agitation associated with a variety of conditions, including acute intoxication, psychiatric illness, delirium, and multifocal or idiopathic causes. Pharmacologic treatment of agitation should be based on an assessment of the most likely cause for the agitation. If agitation results from a medical condition or delirium, clinicians should first attempt to treat this underlying cause instead of simply medicating with antipsychotics or benzodiazepines. [West J Emerg Med. 2012;13(1:26–34.

Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia

DEFF Research Database (Denmark)

Ishøy, Pelle L; Knop, Filip K; Broberg, Brian V

2017-01-01

and placebo groups experienced significant ( P  = .004), however similar ( P  = .98), weight losses of 2.24 ± 3.3 and 2.23 ± 4.4 kg, respectively, after 3 months of treatment. CONCLUSIONS: Treatment with exenatide once-weekly did not promote weight loss in obese, antipsychotic-treated patients......AIMS: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2 receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects...... such as obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia. MATERIAL...

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

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Eduardo Henrique Teixeira

2013-01-01

Full Text Available Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA. All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.

Use of Fixed Dose Combination (FDC) Drugs in India: Central Regulatory Approval and Sales of FDCs Containing Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), Metformin, or Psychotropic Drugs

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McGettigan, Patricia; Roderick, Peter; Mahajan, Rushikesh; Kadam, Abhay; Pollock, Allyson M.

2015-01-01

Background In 2012, an Indian parliamentary committee reported that manufacturing licenses for large numbers of fixed dose combination (FDC) drugs had been issued by state authorities without prior approval of the Central Drugs Standard Control Organization (CDSCO) in violation of rules, and considered that some ambiguity until 1 May 2002 about states’ powers might have contributed. To our knowledge, no systematic enquiry has been undertaken to determine if evidence existed to support these findings. We investigated CDSCO approvals for and availability of oral FDC drugs in four therapeutic areas: analgesia (non-steroidal anti-inflammatory drugs [NSAIDs]), diabetes (metformin), depression/anxiety (anti-depressants/benzodiazepines), and psychosis (anti-psychotics). Methods and Findings This was an ecologic study with a time-trend analysis of FDC sales volumes (2007–2012) and a cross-sectional examination of 2011–2012 data to establish the numbers of formulations on the market with and without a record of CDSCO approval (“approved” and “unapproved”), their branded products, and sales volumes. Data from the CDSCO on approved FDC formulations were compared with sales data from PharmaTrac, a database of national drug sales. We determined the proportions of FDC sales volumes (2011–2012) arising from centrally approved and unapproved formulations and from formulations including drugs banned/restricted internationally. We also determined the proportions of centrally approved and unapproved formulations marketed before and after 1 May 2002, when amendments were made to the drug rules. FDC approvals in India, the United Kingdom (UK), and United States of America (US) were compared. For NSAID FDCs, 124 formulations were marketed, of which 34 (27%) were centrally approved and 90 (73%) were unapproved; metformin: 25 formulations, 20 (80%) approved, five (20%) unapproved; anti-depressants/benzodiazepines: 16 formulations, three (19%) approved, 13 (81%) unapproved

Side effects as influencers of treatment outcome.

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Sharif, Zafar

2008-01-01

Research relative to the efficacy of a therapeutic agent commands a clinician's greatest interest, but treatment decisions are made based on optimizing efficacy and tolerability/safety considerations. Second-generation atypical antipsychotic drugs are a study in the importance of taking a careful look at the full benefit-risk profile of each drug. The disorders that atypical antipsychotics are approved to treat--schizophrenia, schizoaffective disorder, and bipolar disorder--are associated with an increased rate of certain medical comorbidities compared to the general population. Between-drug differences in efficacy are relatively modest for the atypicals, or between atypicals and conventionals, while differences in safety and tolerability are larger and more clinically relevant. The current article will provide a brief summary of safety-related issues that influence treatment outcome and choice of drug.

Second-Generation Prisoners and the Transmission of Domestic Violence.

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Will, Joanna L; Loper, Ann B; Jackson, Shelly L

2016-01-01

Adult inmates who experienced the incarceration of a parent, known as "second-generation prisoners," experience unique challenges and are at heightened risk for experiencing other adversities throughout the life span. Our study investigated one specific, and previously unexplored, type of adversity--domestic violence--within a sample of 293 incarcerated adults. We examined the relation between generation status (first- or second-generation prisoners), childhood exposure to domestic violence, and participation in adult relationship violence prior to incarceration. Results indicate that prisoners who had been exposed to domestic violence in childhood were more likely to engage in intimate partner violence resulting in inflicted and received injury. Relative to first-generation prisoners, second-generation prisoners reported more childhood domestic violence exposure and were more likely to have been injured by a relationship partner. However, this relation between second-generation status and injury victimization was mediated by domestic violence exposure. These results support an intergenerational pattern of domestic violence and suggest that second-generation prisoners are a unique population worthy of future investigation and mental health intervention. © The Author(s) 2014.

[Antipsychotic Treatment of the Adult Patient in the Acute Phase of Schizophrenia].

Science.gov (United States)

Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos; García Valencia, Jenny; Jaramillo González, Luis Eduardo; de la Hoz, Ana María; Arenas, Álvaro; Tamayo Martínez, Nathalie

2014-01-01

To determine the efficacy and safety of different antipsychotic drugs in the management of patients diagnosed with schizophrenia in the acute phase. To formulate evidence-based recommendations on the antipsychotic (AP) drug management strategies for the treatment of the adult diagnosed with schizophrenia in the acute phase. Clinical practice guidelines were prepared, using the guidelines of the Methodology Guide of the Ministry of Health and Social Protection, in order to identify, synthesise, and evaluate the evidence and formulate recommendations as regards the management and follow-up of adult patients diagnosed with schizophrenia. The evidence of the NICE 82 guideline was adopted and updated, which answered the question on the management of the acute phase of adults with a diagnosis of schizophrenia. The evidence and its level were presented to the Guideline Development Group (GDG) in order to formulate recommendations following the methodology proposed by the GRADE approach. Clozapine, olanzapine, risperidone, ziprasidone, amisulpride, paliperidone, haloperidol, quetiapine, and aripiprazole were more effective than placebo for the majority of psychotic symptoms and the abandonment of treatment, but asenapine was not. Paliperidone, risperidone, quetiapine, clozapine, and olanzapine showed significant increases in weight compared to placebo. Haloperidol, risperidone, ziprasidone, and paliperidone had a higher risk of extrapyramidal symptoms than placebo. There was a significant risk of sedation or drowsiness with, risperidone, haloperidol, ziprasidone, quetiapine, olanzapine, and clozapine in the comparisons with placebo. Of the results of the comparisons between AP, it was shown that clozapine and paliperidone had a clinically significant effect compared to haloperidol and quetiapine, respectively. Olanzapine and risperidone had a lower risk of abandoning the treatment in general, and due to adverse reactions in two comparisons of each one, haloperidol was the

Identifying a predictive model for response to atypical antipsychotic monotherapy treatment in south Indian schizophrenia patients.

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Gupta, Meenal; Moily, Nagaraj S; Kaur, Harpreet; Jajodia, Ajay; Jain, Sanjeev; Kukreti, Ritushree

2013-08-01

Atypical antipsychotic (AAP) drugs are the preferred choice of treatment for schizophrenia patients. Patients who do not show favorable response to AAP monotherapy are subjected to random prolonged therapeutic treatment with AAP multitherapy, typical antipsychotics or a combination of both. Therefore, prior identification of patients' response to drugs can be an important step in providing efficacious and safe therapeutic treatment. We thus attempted to elucidate a genetic signature which could predict patients' response to AAP monotherapy. Our logistic regression analyses indicated the probability that 76% patients carrying combination of four SNPs will not show favorable response to AAP therapy. The robustness of this prediction model was assessed using repeated 10-fold cross validation method, and the results across n-fold cross-validations (mean accuracy=71.91%; 95%CI=71.47-72.35) suggest high accuracy and reliability of the prediction model. Further validations of these results in large sample sets are likely to establish their clinical applicability. Copyright © 2013 Elsevier Inc. All rights reserved.

A "second generation" of ministry leadership.

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Giammalvo, Peter J

2005-01-01

Catholic health care leaders differ from others in the field in that "they are expected to serve as Jesus served, teach as Jesus taught, and lead as Jesus led, in order to heal as Jesus healed." The Catholic health ministry today is led largely by laypeople-what might be called the "first generation" of lay leaders. This first generation was privileged in that it was tutored by and worked alongside women and men religious. Those religious are now mostly gone from the ministry, and that first generation of lay leaders will also be retiring in the not too distant future. Leadership will then pass to a "second generation," laypeople who have not worked alongside religious. How is this new generation to learn "to heal as Jesus healed"? Catholic Health East (CHE), Newtown Square, PA, has developed a program explicitly directed at the recruitment and development of second-generation leaders. In its efforts to fill a position, the system first assembles a preferred-candidate profile, based on 15 competencies, including seven core competencies. CHE then employs a recruitment process based on behavioral event interviewing. All involved stakeholders participate in the interviews.

Reporting sexual function disorders caused by antipsychotic drugs : is there a role for the community pharmacy?

NARCIS (Netherlands)

Rijcken, CAW; Dekens-Konter, JAM; Knegtering, H; de Jong-van den Berg, LTW

2001-01-01

Sexual function disorders are frequent adverse effects of antipsychotic use. These effects can lead to non-compliance to medication, which dramatically worsen the outcome of the psychotic disease. Detecting sexual dysfunction by the carers may be difficult, since feelings of embarrassment may occur

Impulsivity and novel object recognition test of rat model for vascular cognitive impairment after antipsychotics treatment

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Ronny T Wirasto

2016-12-01

Full Text Available ABSTRACT Vascular cognitive impairment (VCI is a common condition in which no standard treatment has been approved. VCI is often accompanied by behavioral problems which require psychiatric interventions. The common therapeutic agent used for the acute management is antipsychotic injections. Current findings showed that atypical antipsychotic possess better safety profile for treating behavioral problems related to VCI compared to typical antipsychotic. In this study, we induced VCI in Sprague Dawley rats between 6-8 weeks old using bilateral carotid communist artery occlusion technique. The subjects were divided into 4 treatment groups: sham, olanzapine, haloperidol, and risperidone groups. Subjects received intramuscular injections of subsequent drugs for 3 days post VCI induction. Impulsive behavior and object recognition were examined using cliff jumping test and novel object recognition test. The analyses results showed that impulsive behavior was lower in the olanzapine and haloperidol groups compared to sham group, although it was not statistically significant (p = 0.651. The results also showed that there were no significant differences in the time spent exploring old and novel objects in all groups (p = 0.945;0.637 respectively. In conclusion, antipsychotic injection might not be effective to control impulsive behavior post VCI induction.

Antibacterial activity of antipsychotic agents, their association with lipid nanocapsules and its impact on the properties of the nanocarriers and on antibacterial activity.

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Hassan Nehme

Full Text Available Bacterial antibiotic resistance is an emerging public health problem worldwide; therefore, new therapeutic strategies are needed. Many studies have described antipsychotic compounds that present antibacterial activity. Hence, the aims of this study were to evaluate the in vitro antibacterial activity of antipsychotics belonging to different chemical families, to assess the influence of their association with lipid nanocapsules (LNCs on their antimicrobial activity as well as drug release and to study the uptake of LNCs by bacterial cells. Antibacterial activity was evaluated against Gram-positive Staphylococcus aureus and Gram negative Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii by minimum inhibitory concentration (MIC assay, and the capability of killing tested microorganisms was evaluated by time kill assay. LNCs were prepared by phase inversion method, and the antipsychotic agents were incorporated using pre-loading and post-loading strategies. Only phenothiazines and thioxanthenes showed antibacterial activity, which was independent of antibiotic-resistance patterns. Loading the nanocarriers with the drugs affected the properties of the former, particularly their zeta potential. The release rate depended on the drug and its concentration-a maximum of released drug of less than 40% over 24 hours was observed for promazine. The influence of the drug associations on the antibacterial properties was concentration-dependent since, at low concentrations (high nanocarrier/drug ratio, the activity was lost, probably due to the high affinity of the drug to nanocarriers and slow release rate, whereas at higher concentrations, the activity was well maintained for the majority of the drugs. Chlorpromazine and thioridazine increased the uptake of the LNCs by bacteria compared with blank LNCs, even below the minimum inhibitory concentration.

Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment.

Science.gov (United States)

Spellmann, Ilja; Riedel, Michael; Städtler, Julia; Zill, Peter; Obermeier, Michael; Cerovecki, Anja; Dehning, Sandra; Schennach, Rebecca; Epple, Maria; Opgen-Rhein, Markus; Müller, Norbert; Bondy, Brigitta; Möller, Hans-Jürgen; Musil, Richard

2017-07-01

NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics. Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. 167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed. Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

Persistent akathisia masquerading as agitated depression after use of ziprasidone in the treatment of bipolar depression

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Penders TM

2013-04-01

Full Text Available Thomas M Penders,1 Salina Agarwal,2 Rachel Rohaidy11Department of Psychiatric Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA; 2Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USAAbstract: There has been increasing recognition that the second-generation antipsychotic drugs can produce extrapyramidal side effects. This case reports the development of severe akathisia in a patient being treated with ziprasidone for bipolar depression. The case illustrates that this symptom can be easily mistaken for worsening agitated depression. Akathisia may produce considerable distress and elevate suicide risk. Such symptoms may persist for weeks and be refractory to discontinuation of the offending agent or to pharmacological interventions commonly used to mitigate this reaction.Keywords: extrapyramidal, second-generation, affective, antipsychotic, suicide, mood disorder

New users of antipsychotic medication

DEFF Research Database (Denmark)

Baandrup, L; Kruse, M

2016-01-01

patterns and labor market affiliation, considering both authority approved and off-label prescriptions and the relation to polypharmacy. METHODS: Register-based cohort study using a dataset of 71,254 new antipsychotic users with a psychiatric diagnosis. Labor market affiliation and duration of welfare...... payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services. RESULTS: The majority of new antipsychotic users...

Sex differences in concomitant medication with benzodiazepines or antidepressants in first-break schizophrenic patients treated with antipsychotic medication

NARCIS (Netherlands)

Rijcken, C.A.W.; Knegtering, H; Bruggeman, R; Tobi, H; de Jong-van den Berg, Lolkje Theodora Wilhelmina

2005-01-01

During a first episode of psychosis, treatment with antipsychotic drugs can improve both positive and negative symptoms. If sufficient amelioration does not occur, adding psychotropic comedication may result in a favorable outcome. To establish sex differences in psychotropic comedication use, we

Risperidone long-acting injection: a review of its long term safety and efficacy

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Michael K Rainer

2008-08-01

Full Text Available Michael K RainerMemory-Clinic and Psychiatric Department, Donauspital, Vienna, AustriaAbstract: A long-acting form of the second-generation antipsychotic drug risperidone is now broadly available for the treatment of schizophrenia and closely related psychiatric conditions. It combines the advantage of previously available depot formulations for first-generation drugs with the favorable characteristics of the modern “atypical” antipsychotics, namely higher efficacy in the treatment of the negative symptoms of schizophrenia and reduced motor disturbances. Published clinical studies show an objective clinical efficacy (as per psychiatric symptom scores and relapse data that exceeds that of oral atypical antipsychotics when patients are switched to the long-acting injectable form, a low incidence of treatment-emergent extrapyramidal side effects, and very good acceptance by patients. Available data for maintenance treatment of bipolar disorder show equivalence with the oral form instead of superiority, but are still limited. As it seems likely that efficacy benefits are mostly due to the fact that the injectable form reduces the demand for patient compliance to one physician visit every 2 weeks instead of self-administration on a daily or twice-daily basis, additional potential could exist in other psychiatric disorders where atypical antipsychotic drugs are of benefit but where patient adherence to treatment schedules is typically low.Keywords: risperidone, schizophrenia, psychotic disorders, patient compliance; delayed-action preparations, injections, intramuscular

Second-generation migrants: Europe and the United States

NARCIS (Netherlands)

Crul, M.R.J.; Schneider, J.; Ness, I.; Bellwood, P.

2013-01-01

The public debate about the second generation in Europe has taken a dramatic shift in the last five years. The riots in the banlieues in France, involving mostly Algerian and Moroccan second-generation youth, pitched the cherished republican model into deep crisis. In the Netherlands, arguments

Biological substantiation of antipsychotic-associated pneumonia: Systematic literature review and computational analyses.

Science.gov (United States)

Sultana, Janet; Calabró, Marco; Garcia-Serna, Ricard; Ferrajolo, Carmen; Crisafulli, Concetta; Mestres, Jordi; Trifirò', Gianluca

2017-01-01

Antipsychotic (AP) safety has been widely investigated. However, mechanisms underlying AP-associated pneumonia are not well-defined. The aim of this study was to investigate the known mechanisms of AP-associated pneumonia through a systematic literature review, confirm these mechanisms using an independent data source on drug targets and attempt to identify novel AP drug targets potentially linked to pneumonia. A search was conducted in Medline and Web of Science to identify studies exploring the association between pneumonia and antipsychotic use, from which information on hypothesized mechanism of action was extracted. All studies had to be in English and had to concern AP use as an intervention in persons of any age and for any indication, provided that the outcome was pneumonia. Information on the study design, population, exposure, outcome, risk estimate and mechanism of action was tabulated. Public repositories of pharmacology and drug safety data were used to identify the receptor binding profile and AP safety events. Cytoscape was then used to map biological pathways that could link AP targets and off-targets to pneumonia. The literature search yielded 200 articles; 41 were included in the review. Thirty studies reported a hypothesized mechanism of action, most commonly activation/inhibition of cholinergic, histaminergic and dopaminergic receptors. In vitro pharmacology data confirmed receptor affinities identified in the literature review. Two targets, thromboxane A2 receptor (TBXA2R) and platelet activating factor receptor (PTAFR) were found to be novel AP target receptors potentially associated with pneumonia. Biological pathways constructed using Cytoscape identified plausible biological links potentially leading to pneumonia downstream of TBXA2R and PTAFR. Innovative approaches for biological substantiation of drug-adverse event associations may strengthen evidence on drug safety profiles and help to tailor pharmacological therapies to patient risk

The effect of atypical antipsychotics on brain N-acetylaspartate levels in antipsychotic-naïve first-episode patients with schizophrenia: a preliminary study

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Grošić V

2014-07-01

Full Text Available Vladimir Grošić,1 Petra Folnegovic Grošić,2 Petra Kalember,3,4 Maja Bajs Janović,2 Marko Radoš,3,4 Mate Mihanović,1 Neven Henigsberg3,51Psychiatric Hospital Sveti Ivan, Zagreb, 2University Hospital Center Zagreb, University of Zagreb, Zagreb, 3Polyclinic Neuron, Croatian Institute for Brain Research, Zagreb, 4Department of Neuropharmacology and Behavioral Pharmacology, Croatian Institute for Brain Research, University of Zagreb, Zagreb, 5Vrapče University Hospital, University of Zagreb, Zagreb, CroatiaPurpose: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics.Patients and methods: Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using 1H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London – Drexel University, Letter–Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced.Results: After 12 study months, the N-acetylaspartate/creatine (NAA/Cr level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008 and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005. On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months.Conclusion: One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn’t result

Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.

Science.gov (United States)

Bettinger, Tawny L; Shuler, Garyn; Jones, Donnamaria R; Wilson, James P

2007-02-01

Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.

Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics

Energy Technology Data Exchange (ETDEWEB)

Memo, M; Battaini, F; Spano, P F; Trabucchi, M [University of Brescia, (Italy). Dept. of Pharmacology

1981-01-01

It is now generally recognized that dopamine receptors excist in the CNS as different subtypes: D/sub 1/ receptors, associated with adenylyl cyclase activity, and D/sub 2/ receptor, uncoupled to a cyclic AMP generating system. In order to understand the role of D/sub 1/ and D/sub 2/ receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D/sub 1/ receptors, and sulpiride, a selective antagonist to D/sub 2/ receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D/sub 2/ receptors. In fact under these conditions /sup 3/H-(-)-sulpiride binding, which is a marker of D/sub 2/ receptor function, does not increase in rat striatum, while the long-term administration of sulpiride, itself produces supersensitivity of D/sub 2/ receptors. Moreover, sulpiride does not induce supersensitivity of the D/sub 1/ receptors, characterized by /sup 3/H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral leison of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by /sup 3/H-spiroperidol and /sup 3/H-(-)-sulpiride binding. These findings suggest that D/sub 1/ and D/sub 2/ receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements.

Metabolic syndrome and psychiatrists' choice of follow-up interventions in patients treated with atypical antipsychotics in Denmark and Sweden

DEFF Research Database (Denmark)

Larsen, J. T.; Fagerquist, M.; Holdrup, M.

2011-01-01

rate of metabolic syndrome did not elicit much decisive action on the part of the treating psychiatrists; the most frequent action taken was dietary and exercise advice (in 75% of subjects), while in 54% and 19% of subjects a laboratory follow-up and blood pressure follow-up were advised respectively......Introduction: The aim of the present study was to obtain point prevalence estimates of the metabolic syndrome according to the NCEP III criteria in a sample of patients with schizophrenia spectrum disorders treated with atypical antipsychotic drugs in Denmark and Sweden, and to assess...... for at least 3 months with atypical antipsychotic drugs. Results: The metabolic syndrome as per medical history was present in 1% of 582 evaluable patients at baseline. After performing laboratory measurements and applying the NCEP III criteria, metabolic syndrome was confirmed in 43% of subjects. The high...

Early antiretroviral therapy and potent second-line drugs could decrease HIV incidence of drug resistance.

Science.gov (United States)

Shen, Mingwang; Xiao, Yanni; Rong, Libin; Meyers, Lauren Ancel; Bellan, Steven E

2017-06-28

Early initiation of antiretroviral therapy (ART) reduces the risk of drug-sensitive HIV transmission but may increase the transmission of drug-resistant HIV. We used a mathematical model to estimate the long-term population-level benefits of ART and determine the scenarios under which earlier ART (treatment at 1 year post-infection, on average) could decrease simultaneously both total and drug-resistant HIV incidence (new infections). We constructed an infection-age-structured mathematical model that tracked the transmission rates over the course of infection and modelled the patients' life expectancy as a function of ART initiation timing. We fitted this model to the annual AIDS incidence and death data directly, and to resistance data and demographic data indirectly among men who have sex with men (MSM) in San Francisco. Using counterfactual scenarios, we assessed the impact on total and drug-resistant HIV incidence of ART initiation timing, frequency of acquired drug resistance, and second-line drug effectiveness (defined as the combination of resistance monitoring, biomedical drug efficacy and adherence). Earlier ART initiation could decrease the number of both total and drug-resistant HIV incidence when second-line drug effectiveness is sufficiently high (greater than 80%), but increase the proportion of new infections that are drug resistant. Thus, resistance may paradoxically appear to be increasing while actually decreasing. © 2017 The Author(s).

Managing cardiovascular disease risk in patients treated with antipsychotics: a multidisciplinary approach

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Shulman M

2014-10-01

Full Text Available Matisyahu Shulman,1 Avraham Miller,2 Jason Misher,3 Aleksey Tentler4 1Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, NY, USA; 2The Ruth and Bruce Rappaport Faculty of Medicine, The Technion Israel Institute of Technology, Haifa, Israel; 3Department of Medicine, Hofstra North Shore-LIJ School of Medicine, Hempstead, NY, USA; 4Department of Internal Medicine, Rutgers New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA Background: The use of antipsychotic medication in the United States and throughout the world has greatly increased over the last fifteen years. These drugs have significant side effect burdens, many of them relating to cardiovascular health. Objective: To review the available evidence on the major cardiovascular issues that arise in patients taking antipsychotic medication. Method: A PubMed literature review was performed to identify recent meta-analyses, review articles, and large studies. Further articles were identified through cited papers and based on expert consultation when necessary. Results: Clinical guidance on the following adverse effects and antipsychotics was reviewed: electrocardiogram (ECG changes, (specifically, prolonged QT and risk of torsades de pointes, weight gain, dyslipidemia, metabolic syndrome, and myocarditis. Specific attention was paid to monitoring guidelines and treatment options in the event of adverse events, including dose change, medication switch, or adjuvant therapy. Keywords: schizophrenia, prolonged QT, increased mortality, weight gain, myocarditis

Antipsychotics and the risk of sudden cardiac death

NARCIS (Netherlands)

Straus, S.M.J.M.; Bleumink, G.S.; Dieleman, J.P.; van der Lei, J.; 't Jong, G.W.; Kingma, J. Herre; Sturkenboom, M.C J M; Stricker, B.H C

2004-01-01

Background Antipsychotics have been associated with prolongation of the corrected QT interval and sudden cardiac death. Only a few epidemiological studies have investigated this association. We performed a case-control study to investigate the association between use of antipsychotics and sudden

Patient perspectives on antipsychotic treatments and their association with clinical outcomes

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Hong Liu-Seifert

2010-09-01

Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

Transmit beamforming for optimal second-harmonic generation.

Science.gov (United States)

Hoilund-Kaupang, Halvard; Masoy, Svein-Erik

2011-08-01

A simulation study of transmit ultrasound beams from several transducer configurations is conducted to compare second-harmonic imaging at 3.5 MHz and 11 MHz. Second- harmonic generation and the ability to suppress near field echoes are compared. Each transducer configuration is defined by a chosen f-number and focal depth, and the transmit pressure is estimated to not exceed a mechanical index of 1.2. The medium resembles homogeneous muscle tissue with nonlinear elasticity and power-law attenuation. To improve computational efficiency, the KZK equation is utilized, and all transducers are circular-symmetric. Previous literature shows that second-harmonic generation is proportional to the square of the transmit pressure, and that transducer configurations with different transmit frequencies, but equal aperture and focal depth in terms of wavelengths, generate identical second-harmonic fields in terms of shape. Results verify this for a medium with attenuation f1. For attenuation f1.1, deviations are found, and the high frequency subsequently performs worse than the low frequency. The results suggest that high frequencies are less able to suppress near-field echoes in the presence of a heterogeneous body wall than low frequencies.

The evolution of antipsychotic switch and polypharmacy in natural practice--a longitudinal perspective.

Science.gov (United States)

Tsutsumi, Chisa; Uchida, Hiroyuki; Suzuki, Takefumi; Watanabe, Koichiro; Takeuchi, Hiroyoshi; Nakajima, Shinichiro; Kimura, Yoshie; Tsutsumi, Yuichiro; Ishii, Koichi; Imasaka, Yasushi; Kapur, Shitij

2011-08-01

Most patients with schizophrenia first start with a single antipsychotic, and yet most finally end up 'switching' or using 'polypharmacy'. The objective of this study was to examine the evolution of antipsychotic switch and polypharmacy in the real-world from a longitudinal perspective. A systematic review of longitudinal antipsychotic prescriptions in 300 patients with schizophrenia (ICD-10) for up to 2 years after their first visit to one of the 4 participating psychiatric clinics in Tokyo, Japan between January, 2007 and June, 2008, was conducted. Reasons for prescription change were also examined. The evolution of switching and polypharmacy was studied, and prescribed doses were compared to suggested dose ranges by the Texas Medication Algorithm Project (TMAP). 208 patients started their antipsychotic treatment with monotherapy. 34.1% of the patients gave up monotherapy with an initial antipsychotic to move to antipsychotic switch (27.4%) and/or polypharmacy (17.8%) within 2 years. The main reason for antipsychotic switch was 'ineffectiveness'; interestingly, this happened despite the fact that the monotherapy dose was below the recommended range in 47.4% of the antipsychotic switch. In a subgroup of 100 patients who started as antipsychotic-free, 2-year prevalence rates of switching and antipsychotic polypharmacy were 27.0% and 18.0%, respectively, and polypharmacy was resorted to after a median of 1 antipsychotic had been tried for 84 days (median). These findings raise a concern that physicians may perform an antipsychotic switch without exploring the entire dose range and resort to antipsychotic polypharmacy without trying an adequate number of antipsychotics. Copyright © 2011 Elsevier B.V. All rights reserved.

New approaches for the management of bipolar disorder: role of sublingual asenapine in the treatment of mania

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Warren CG

2013-05-01

Full Text Available Calvert G Warren,1 Steven L Dubovsky1,21Department of Psychiatry, State University of New York at Buffalo, Buffalo, NY, USA; 2Departments of Psychiatry and Medicine, University of Colorado, Boulder, CO, USAAbstract: Bipolar disorder is a prevalent disorder that tends to become progressive without treatment and with inadequate treatment. Second generation (atypical antipsychotic drugs have increasingly been used as adjunctive treatment or monotherapy for mania, but they have the potential for significant adverse effects and their role in maintenance treatment remains unclear. Asenapine is a new atypical antipsychotic medication formulated in a sublingual preparation that has been studied for mania but not maintenance therapy. Evidence indicating efficacy, adverse effects, and potential benefits and drawbacks of using asenapine in the treatment of bipolar disorder based on currently available published data are summarized.Keywords: bipolar disorder, antipsychotic drug, mania, maintenance, sublingual

Issues in the management of acute agitation: how much current guidelines consider safety?

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Bruno ePacciardi

2013-05-01

Full Text Available Agitated behavior constitutes up to 10% of emergency psychiatric interventions. Pharmacological tranquilization is often used as a valid treatment for agitation but a strong evidence base does not underpin it. Available literature shows different recommendations, supported by research data, theoretical considerations or clinical experience. Rapid tranquilization is mainly based on parenteral drug treatment and the few existing guidelines on this topic, when suggesting the use of first generation antipsychotics and benzodiazepines, include drugs with questionable tolerability profile such as chlorpromazine, haloperidol, midazolam and lorazepam. In order to systematically evaluate safety concerns related to the adoption of such guidelines, we reviewed them independently from principal diagnosis while examining tolerability data for suggested treatments. There is a growing evidence about safety profile of second generation antipsychotics for rapid tranquilization but further controlled studies providing definitive data in this area are urgently needed.

Treatment of Young People With Antipsychotic Medications in the United States.

Science.gov (United States)

Olfson, Mark; King, Marissa; Schoenbaum, Michael

2015-09-01

Despite concerns about rising treatment of young people with antipsychotic medications, little is known about trends and patterns of their use in the United States. To describe antipsychotic prescription patterns among young people in the United States, focusing on age and sex. A retrospective descriptive analysis of antipsychotic prescriptions among patients aged 1 to 24 years was performed with data from calendar years 2006 (n = 765,829), 2008 (n = 858,216), and 2010 (n = 851,874), including a subset from calendar year 2009 with service claims data (n = 53,896). Data were retrieved from the IMS LifeLink LRx Longitudinal Prescription database, which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population. The percentage of young people filling 1 or more antipsychotic prescriptions during the study year by sex and age group (younger children, 1-6 years; older children, 7-12 years; adolescents, 13-18 years; and young adults, 19-24 years) was calculated. Among young people with antipsychotic use, percentages with specific clinical psychiatric diagnoses and 1 or more antipsychotic prescriptions from a psychiatrist and from a child and adolescent psychiatrist were also determined. The percentages of young people using antipsychotics in 2006 and 2010, respectively, were 0.14% and 0.11% for younger children, 0.85% and 0.80% for older children, 1.10% and 1.19% for adolescents, and 0.69% and 0.84% for young adults. In 2010, males were more likely than females to use antipsychotics, especially during childhood and adolescence: 0.16% vs 0.06% for younger children, 1.20% vs 0.44% for older children, 1.42% vs 0.95% for adolescents, and 0.88% vs 0.81% for young adults. Among young people treated with antipsychotics in 2010, receiving a prescription from a psychiatrist was less common among younger children (57.9%) than among other age groups (range, 70.4%-77.9%). Approximately 29.3% of

Changes in antipsychotics and other psychotropic drugs during a 30-month lifestyle intervention among outpatients with schizophrenia

DEFF Research Database (Denmark)

Hojlund, Mikkel; Elliott, Anja Friis; Madsen, Nikolaj Juul

2017-01-01

BACKGROUND: Patients with schizophrenia have high risk of early death from diabetes and cardiovascular diseases, partly because of poor lifestyle and partly because of long-lasting exposure to antipsychotic treatment. AIMS: To investigate the influence of a lifestyle intervention program on chang...

Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day Adventists and Baptists in Denmark.

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Rasmussen, Peter; Johansen, Christoffer; Hvidt, Niels Christian; Kørup, Alex Kappel; Søndergaard, Jens; Thygesen, Lau Caspar

2017-10-01

Earlier it has been found that female Seventh-day Adventists (SDA) and Baptists have an increased incidence of psychiatric affective disorders, in contrast to findings that religious practice is associated with better health. In this study, we examined whether the increase in incidence is due to less use of prescribed antidepressants, sedatives and antipsychotics by members of these religious societies than by the general population. In a cohort study, we examined records of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender-matched members of the general population between 1995 and 2010 in the Danish Prescription Register and compared the prevalence and incidence of use of antidepressants, sedatives and antipsychotics. The prevalence of antidepressant use by women was lower in 1998 but no different from that in controls in 2003 and 2008; the prevalence of antidepressant use by men was higher in both 1998 and 2008 than in the Danish population. The incidence of antidepressant use was lower for female members in 1996-2000, but no difference was observed in the other periods. The prevalence and incidence of use of sedatives and antipsychotics did not consistently differ from those of the general population. The prevalence and incidence of use of antidepressants, sedatives and antipsychotics by female SDA and Baptists were not consistently lower than in the general Danish population. Our findings hence do not explain the increased incidence of psychiatric disorders among female members of these Danish religious societies.

Herbert: A Second Generation Mobile Robot.

Science.gov (United States)

1988-01-01

PROJECT. TASK S Artificial Inteligence Laboratory AREA A WORK UNIT NUMBERS ’ ~ 545 Technology Square Cambridge, MA 02139 11. CONTROLLING OFFICE NAME...AD-AI93 632 WMRT: A SECOND GENERTION MOBILE ROWT(U) / MASSACHUSETTS IMST OF TECH CAMBRIDGE ARTIFICIAL INTELLIGENCE LAB R BROOKS ET AL .JAN l8 Al-M...MASSACHUSETTS INSTITUTE OF TECHNOLOGY ARTIFICIAL INTELLIGENCE LABORATORY A. I. Memo 1016 January, 1988 HERBERT: A SECOND GENERATION MOBILE ROBOT Rodney A

Symmetry properties of second harmonics generated by antisymmetric Lamb waves

Science.gov (United States)

Zhu, Wujun; Xiang, Yanxun; Liu, Chang-Jun; Deng, Mingxi; Xuan, Fu-Zhen

2018-03-01

Symmetry properties of second harmonics generated by antisymmetric primary Lamb waves are systematically studied in this work. In theory, the acoustic field of second harmonic Lamb waves is obtained by using the perturbation approximation and normal modal method, and the energy flux transfer from the primary Lamb waves to second harmonics is mainly explored. Symmetry analyses indicate that either the symmetric or antisymmetric Lamb waves can merely generate the symmetric second harmonics. Finite element simulations are performed on the nonlinear Lamb wave propagation of the antisymmetric A0 mode in the low frequency region. The signals of the second harmonics and the symmetric second harmonic s0 mode are found to be exactly equivalent in the time domain. The relative acoustic nonlinearity parameter A2/A12 oscillates with the propagation distance, and the oscillation amplitude and spatial period are well consistent with the theoretical prediction of the A0-s0 mode pair, which means that only the second harmonic s0 mode is generated by the antisymmetric primary A0 mode. Experiments are further conducted to examine the cumulative generation of symmetric second harmonics for the antisymmetric-symmetric mode pair A3-s6. Results show that A2/A12 increases linearly with the propagation distance, which means that the symmetric second harmonic s6 mode is generated cumulatively by the antisymmetric primary A3 mode. The present investigation systematically corroborates the proposed theory that only symmetric second harmonics can be generated accompanying the propagation of antisymmetric primary Lamb waves in a plate.

A novel role for dopamine signaling in the pathogenesis of bone loss from the atypical antipsychotic drug risperidone in female mice.

Science.gov (United States)

Motyl, Katherine J; Beauchemin, Megan; Barlow, Deborah; Le, Phuong T; Nagano, Kenichi; Treyball, Annika; Contractor, Anisha; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

2017-10-01

Atypical antipsychotic (AA) drugs, including risperidone (RIS), are used to treat schizophrenia, bipolar disorder, and autism, and are prescribed off-label for other mental health issues. AA drugs are associated with severe metabolic side effects of obesity and type 2 diabetes. Cross-sectional and longitudinal data also show that risperidone causes bone loss and increases fracture risk in both men and women. There are several potential mechanisms of bone loss from RIS. One is hypogonadism due to hyperprolactinemia from dopamine receptor antagonism. However, many patients have normal prolactin levels; moreover we demonstrated that bone loss from RIS in mice can be blocked by inhibition of β-adrenergic receptor activation with propranolol, suggesting the sympathetic nervous system (SNS) plays a pathological role. Further, when, we treated ovariectomized (OVX) and sham operated mice daily for 8weeks with RIS or vehicle we demonstrated that RIS causes significant trabecular bone loss in both sham operated and OVX mice. RIS directly suppressed osteoblast number in both sham and OVX mice, but increased osteoclast number and surface in OVX mice alone, potentially accounting for the augmented bone loss. Thus, hypogonadism alone cannot explain RIS induced bone loss. In the current study, we show that dopamine and RIS are present in the bone marrow compartment and that RIS can exert its effects directly on bone cells via dopamine receptors. Our findings of both direct and indirect effects of AA drugs on bone are relevant for current and future clinical and translational studies investigating the mechanism of skeletal changes from AA drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-stay psychiatric patients: a prospective study revealing persistent antipsychotic-induced movement disorder.

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P Roberto Bakker

Full Text Available OBJECTIVE: The purpose of this study was to assess the frequency of persistent drug-induced movement disorders namely, tardive dyskinesia (TD, parkinsonism, akathisia and tardive dystonia in a representative sample of long-stay patients with chronic severe mental illness. METHOD: Naturalistic study of 209, mainly white, antipsychotic-treated patients, mostly diagnosed with psychotic disorder. Of this group, the same rater examined 194 patients at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. RESULTS: The frequencies of persistent movement disorders in the sample were 28.4% for TD, 56.2% for parkinsonism, 4.6% for akathisia and 5.7% for tardive dystonia. Two-thirds of the participants displayed at least one type of persistent movement disorder. CONCLUSIONS: Persistent movement disorder continues to be the norm for long-stay patients with chronic mental illness and long-term antipsychotic treatment. Measures are required to remedy this situation.

Generative Research on Second Language Acquisition.

Science.gov (United States)

Eubank, Lynn

1995-01-01

Reviews recent trends in generative research on second language acquisition, focusing on the role of universal grammar, parameter resetting, and anaphoric binding. An annotated bibliography discusses five important works in the field. (61 references) (MDM)

Cost-effectiveness Analysis of Antipsychotic Combination Therapy in Schizophrenia Inpatients

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Rizky Abdulah

2017-03-01

Full Text Available Schizophrenia is one of mental disorders with high cost and lifetime morbidity risk. Hence, it is necessary to analyze the cost-effectiveness of various combinations of antipsychotics. The aim of this study was to analyze the most cost-effective group of antipsychotic combinations in schizophrenia inpatients in West Java Psychiatric Hospital during 2012–2013. Data were collected retrospectively from medical record of patients who used antipsychotics clozapine-haloperidol or clozapine-risperidone therapy. Direct medical costs were obtained from antipsychotics costs, costs of medical treatment, medical expenses, hospitalization costs, and administrative costs. The results showed that the average cost-effectiveness ratio of antipsychotic clozapine-haloperidol was Rp126.898/day and Rp132.781/day for the combination of clozapine-haloperidol and clozapine-risperidone, respectively. Considering length of stay as the therapy effectiveness, it can be concluded that the combination of clozapine-haloperidol is more cost-effective than clozapine-risperidone.

Spatial mode discrimination using second harmonic generation

DEFF Research Database (Denmark)

Delaubert, Vincent; Lassen, Mikael Østergaard; Pulford, David

2007-01-01

Second harmonic generation can be used as a technique for controlling the spatial mode structure of optical beams. We demonstrate experimentally the generation of higher order spatial modes, and that it is possible to use nonlinear phase matching as a predictable and robust technique for the conv...

Neurological Adverse Effects of Antipsychotics in Children and Adolescents.

Science.gov (United States)

Garcia-Amador, Margarita; Merchán-Naranjo, Jessica; Tapia, Cecilia; Moreno, Carmen; Castro-Fornieles, Josefina; Baeza, Inmaculada; de la Serna, Elena; Alda, José A; Muñoz, Daniel; Andrés Nestares, Patricia; Cantarero, Carmen Martínez; Arango, Celso

2015-12-01

The aim of this study was to evaluate demographic, clinical, and treatment factors that may impact on neurological adverse effects in naive and quasi-naive children and adolescents treated with antipsychotics. This was a 1-year, multicenter, observational study of a naive and quasi-naive pediatric population receiving antipsychotic treatment. Two subanalyses were run using the subsample of subjects taking the 3 most used antipsychotics and the subsample of antipsychotic-naive subjects. Total dyskinesia score (DyskinesiaS) and total Parkinson score (ParkinsonS) were calculated from the Maryland Psychiatric Research Center Involuntary Movement Scale, total UKU-Cognition score was calculated from the UKU Side Effect Rating Scale. Risk factors for tardive dyskinesias (TDs) defined after Schooler-Kaine criteria were studied using a logistic regression. Two hundred sixty-five subjects (mean age, 14.4 [SD, 2.9] years) with different Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I disorders were recruited. DyskinesiaS (P < 0.001) and ParkinsonS (P < 0.001) increased at 1-year follow-up. Risperidone was associated with higher increases in DyskinesiaS compared with quetiapine (P < 0.001). Higher increases in ParkinsonS were found with risperidone (P < 0.001) and olanzapine (P = 0.02) compared with quetiapine. Total UKU-Cognition Score decreased at follow-up. Findings were also significant when analyzing antipsychotic-naive subjects. Fifteen subjects (5.8%) fulfilled Schooler-Kane criteria for TD at follow-up. Younger age, history of psychotic symptoms, and higher cumulative exposure time were associated with TD at follow-up. Antipsychotics increased neurological adverse effects in a naive and quasi-naive pediatric population and should be carefully monitored. Risperidone presented higher scores in symptoms of dyskinesia and parkinsonism. Quetiapine was the antipsychotic with less neurological adverse effects. Younger subjects, psychosis, and

Can a digital medicine system improve adherence to antipsychotic treatment?

Science.gov (United States)

Papola, D; Gastaldon, C; Ostuzzi, G

2018-06-01

A substantial proportion of people with mental health conditions do not adhere to prescribed pharmacological treatments. Poor adherence is probably one of the most critical elements contributing to relapse in people with schizophrenia and other severe mental disorders. In order to tackle this global issue, in November 2017 the Food and Drug Administration approved a tablet formulation of the atypical antipsychotic aripiprazole embedded with a novel digital adherence-assessment device. In this commentary, we critically appraised the potential beneficial and harmful consequences of this new digital formulation of aripiprazole, and we highlighted expected implications for clinical practice.

[Psychoactive drugs and costs in the Madrid III (Valdemoro) prison].

Science.gov (United States)

Algora-Donoso, I; Varela-González, O

2008-01-01

Annual pharmaceutical expenditures in prisons increases dramatically and the rising costs of psychoactive drugs have especially contributed to this. These drugs are often prescribed in order to find therapeutic uses in the field of personality disorders, addictions, and dysfunctional behaviours that are not included in the authorized indications (compassionate use). This study has enabled a detailed description of the use of psychoactive drugs at the Madrid III prison, a centre with one of the lowest levels of pharmaceutical expenditure in this autonomous community. During a two-week period, all prescriptions of psychoactive drugs were collected and registered along with data of several possible conditioning factors. 20.5% of the population was receiving some kind of psychoactive drug; 76% of those inmates undergoing treatment were receiving one or two substances; 65% were taking anxiolytics, 38% antidepressants and 27% antipsychotics. The total amount of psychoactive drugs consumed was 9,840 defined daily doses, 46% of which were anxiolytics, 17% antidepressants and 14% antipsychotics. The total cost of the fortnight's treatment was euros 5,379 with a saving of euro 611 due to requesting and selecting offers carried out by the pharmacist. 72% of the costs were spent on anti-psychotics and the newer psychoactive drugs, representing 66% of the prescriptions, accounted for 98% of expenditure. The prescriber was one of the key influential factors over the amount, type and cost of the treatments. There are signs that compassionate use of current antipsychotics and antiepileptics, and newer antidepressants are a main cause of the dramatic increase in the costs, with cost-efficiency not always clearly demonstrated. These results are not an isolated fact restricted only to prisons, as demonstrated by consumption data published by the National Health System in the same year.

The second generation in Europe and the United States : How is the transatlantic debate relevant for further research on the European second generation?

NARCIS (Netherlands)

Thomson, Mark; Crul, Maurice

This introductory paper to the special issue of JEMS on the second generation in Europe reviews some of the key themes underpinning the growing interest in the second generation, and asks what 'integration' actually means in contemporary debates about immigration and settlement. The authors attempt

The second generation in Europe and the United States. How is the transatlantic debate relevant for further research on the European second generation?

NARCIS (Netherlands)

Crul, M.R.J.; Thomsen, M.

2007-01-01

This introductory paper to the special issue of JEMS on the second generation in Europe reviews some of the key themes underpinning the growing interest in the second generation, and asks what 'integration' actually means in contemporary debates about immigration and settlement. The authors attempt

Model of Management (Mo.Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and recovery with long-acting injectable antipsychotics (LAIs).

Science.gov (United States)

Brugnoli, Roberto; Rapinesi, Chiara; Kotzalidis, Georgios D; Marcellusi, Andrea; Mennini, Francesco S; De Filippis, Sergio; Carrus, Dario; Ballerini, Andrea; Francomano, Antonio; Ducci, Giuseppe; Del Casale, Antonio; Girardi, Paolo

2016-01-01

Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long-acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery. To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia. After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence. The

Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

DEFF Research Database (Denmark)

Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

2012-01-01

CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE....... Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01154829....... To investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...

A Pharmacovigilance Study in First Episode of Psychosis: Psychopharmacological Interventions and Safety Profiles in the PEPs Project.

Science.gov (United States)

Bioque, Miquel; Llerena, Adrián; Cabrera, Bibiana; Mezquida, Gisela; Lobo, Antonio; González-Pinto, Ana; Díaz-Caneja, Covadonga M; Corripio, Iluminada; Aguilar, Eduardo J; Bulbena, Antoni; Castro-Fornieles, Josefina; Vieta, Eduard; Lafuente, Amàlia; Mas, Sergi; Parellada, Mara; Saiz-Ruiz, Jerónimo; Cuesta, Manuel J; Bernardo, Miguel

2016-04-01

The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, Psecurity issues, support future research of determinate pharmacological strategies for the treatment of early phases of psychosis, such as the role of clozapine, long-acting injectable antipsychotics, antipsychotic combination, and the use of benzodiazepines. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Towards Second and Third Generation Web-Based Multimedia

NARCIS (Netherlands)

J.R. van Ossenbruggen (Jacco); J.P.T.M. Geurts (Joost); F.J. Cornelissen; L. Rutledge (Lloyd); L. Hardman (Lynda)

2001-01-01

textabstractFirst generation Web-content encodes information in handwritten (HTML) Web pages. Second generation Web content generates HTML pages on demand, e.g. by filling in templates with content retrieved dynamically from a database or transformation of structured documents using style sheets

Second-generation HTS conductors

CERN Document Server

2010-01-01

The discovery of high temperature superconductors (HTS) in 1986 by two IBM scientists led to an unprecedented explosion of research and development efforts world-wide because of the significant potential for practical applications offered by these materials. However, the early euphoria created by the exciting prospects was dampened by the daunting task of fabricating these materials into useful forms with acceptable superconducting properties. Progress towards this goal has been hindered by many intrinsic materials problems, such as weak-links, flux-creep, and poor mechanical properties. The above problems led to the development of the Second-Generation of HTS wires. Three methods were invented to produce flexible metallic substrates, which were also crystallographically biaxially textured, and resembled a long, mosaic single crystal. The first method invented is the Ion-Beam-Assisted-Deposition (IBAD). The second method developed was the Inclined-Substrate-Deposition (ISD). The third method invented is calle...

Drug: D07623 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available 01942 ... Iminobenzyl antipsychotic Chemical group: DG01312 ... Tricyclic antidepressant, Iminodibenzyl derivativ... D07623 Drug Carpipramine (INN) ... C28H38N4O D07623.gif ... Neuropsychiatric agent ... DG

Disorganizing experiences in second- and third-generation holocaust survivors.

Science.gov (United States)

Scharf, Miri; Mayseless, Ofra

2011-11-01

Second-generation Holocaust survivors might not show direct symptoms of posttraumatic stress disorder or attachment disorganization, but are at risk for developing high levels of psychological distress. We present themes of difficult experiences of second-generation Holocaust survivors, arguing that some of these aversive experiences might have disorganizing qualities even though they do not qualify as traumatic. Based on in-depth interviews with 196 second-generation parents and their adolescent children, three themes of disorganizing experiences carried across generations were identified: focus on survival issues, lack of emotional resources, and coercion to please the parents and satisfy their needs. These themes reflect the frustration of three basic needs: competence, relatedness, and autonomy, and this frustration becomes disorganizing when it involves stability, potency, incomprehensibility, and helplessness. The findings shed light on the effect of trauma over the generations and, as such, equip therapists with a greater understanding of the mechanisms involved.

Patient compliance with drug therapy in schizophrenia. Economic and clinical issues.

Science.gov (United States)

Lindström, E; Bingefors, K

2000-08-01

The effectiveness of drug treatment in clinical practice is considerably lower than the efficacy shown in controlled studies. The lower effectiveness in practice presumably leads to lower cost effectiveness of drug treatment in real-life situations compared with that demonstrated by studies based on results from controlled trials. Improved cost effectiveness in routine clinical practice would be a significant advantage in the treatment of schizophrenia, one of the most costly diseases in society. The aetiology of schizophrenia is unknown, and there is no cure. The main aims of therapy with antipsychotic medication include the effective relief of symptoms without the introduction of adverse effects or serious adverse events, improved quality of life, cost effectiveness and a positive long term outcome. The older classical antipsychotic drugs do not always meet these requirements because of their well-known limitations, such as a lack of response in a subgroup of individuals with schizophrenia and intolerable adverse effects. There has long been a need for new antipsychotics that can ameliorate more symptoms and have no or few adverse effects. Some of the recently introduced antipsychotics have been shown to be more effective in certain clinical situations and to have a more favourable adverse effect profile than the classical antipsychotics. A major factor contributing to the lower effectiveness of drug treatment is noncompliance, which may be very high in schizophrenia. There are several factors influencing compliance, including drug type and formulation, patient, disease status, physician, health care system, community care and family. There have been very few studies of compliance improvement strategies in schizophrenia or, indeed, in medicine in general. Current methods are relatively complex and there are differing opinions on their effectiveness. There are several ways to increase compliance in schizophrenia--the evidence is strongest for psychoeducative

TADIR: a second-generation 480 x 4 TDI FLIR

Science.gov (United States)

Sarusi, Gabby

1997-08-01

'TADIR' is an El-Op's new second generation thermal imager based on 480 by 4 TDI MCT detector operated in the 8 - 10.5 micrometer spectral range. Although the prototype configuration design of TADIR is aimed toward the light weight low volume applications, TADIR is a generic modular technology of which the future El-Op second generation FLIR applications will be derived from. Beside the detector, what put the system in the second generation category are the state of the art features implemented in every component. This paper describes the system concept and design consideration have been taken during the development of its components.

Superwellness Program: a cognitive-behavioral therapy-based group intervention to reduce weight gain in patients treated with antipsychotic drugs

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Laura R. Magni

2017-03-01

Full Text Available Objective: To assess the effectiveness of a cognitive-behavioral therapy-based intervention (Superwellness Program on weight gain compared with a treatment-as-usual (TAU approach in patients treated with antipsychotics, and to evaluate the relationship between body mass index (BMI variation and clinical variables. Method: Eighty-five patients treated with antipsychotics were allocated across two groups, experimental (n=59 and control (n=26. The Superwellness Program (experimental group consisted of 32 twice-weekly 1-hour sessions, conducted by a psychologist and a nutritionist/nurse, concurrently with moderate food intake and moderate physical activity plans. Sociodemographic, clinical, and biological variables were collected at baseline, at the end of intervention (16 weeks, and after 6 months. Results: BMI change from baseline differed significantly between the experimental and control groups, with a larger decrease in the experimental group (F = 5.5, p = 0.021. Duration of illness moderated the effect of treatment on BMI (p = 0.026. No significant (p = 0.499 effect of intervention during the follow-up period was found. Interestingly, the intervention indirectly induced a significant (p = 0.024 reduction in metabolic risk by reducing BMI. Conclusion: A cognitive-behavioral therapy-based intervention could be useful in reducing weight in a clinical population taking antipsychotics, with consequent benefit to physical and mental health.

Drug Elucidation: Invertebrate Genetics Sheds New Light on the Molecular Targets of CNS Drugs

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Donard S. Dwyer

2014-07-01

Full Text Available Many important drugs approved to treat common human diseases were discovered by serendipity, without a firm understanding of their modes of action. As a result, the side effects and interactions of these medications are often unpredictable, and there is limited guidance for improving the design of next-generation drugs. Here, we review the innovative use of simple model organisms, especially Caenorhabditis elegans, to gain fresh insights into the complex biological effects of approved CNS medications. Whereas drug discovery involves the identification of new drug targets and lead compounds/biologics, and drug development spans preclinical testing to FDA approval, drug elucidation refers to the process of understanding the mechanisms of action of marketed drugs by studying their novel effects in model organisms. Drug elucidation studies have revealed new pathways affected by antipsychotic drugs, e.g., the insulin signaling pathway, a trace amine receptor and a nicotinic acetylcholine receptor. Similarly, novel targets of antidepressant drugs and lithium have been identified in C. elegans, including lipid-binding/transport proteins and the SGK-1 signaling pathway, respectively. Elucidation of the mode of action of anesthetic agents has shown that anesthesia can involve mitochondrial targets, leak currents and gap junctions. The general approach reviewed in this article has advanced our knowledge about important drugs for CNS disorders and can guide future drug discovery efforts.

[Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia].

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Quitian Reyes, Hoover; Arciniegas Barrera, Jair Alberto; Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos

2016-01-01

Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

In Silico Identification and In Vitro and In Vivo Validation of Anti-Psychotic Drug Fluspirilene as a Potential CDK2 Inhibitor and a Candidate Anti-Cancer Drug.

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Xi-Nan Shi

Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related deaths worldwide. Surgical resection and conventional chemotherapy and radiotherapy ultimately fail due to tumor recurrence and HCC's resistance. The development of novel therapies against HCC is thus urgently required. The cyclin-dependent kinase (CDK pathways are important and well-established targets for cancer treatment. In particular, CDK2 is a key factor regulating the cell cycle G1 to S transition and a hallmark for cancers. In this study, we utilized our free and open-source protein-ligand docking software, idock, prospectively to identify potential CDK2 inhibitors from 4,311 FDA-approved small molecule drugs using a repurposing strategy and an ensemble docking methodology. Sorted by average idock score, nine compounds were purchased and tested in vitro. Among them, the anti-psychotic drug fluspirilene exhibited the highest anti-proliferative effect in human hepatocellular carcinoma HepG2 and Huh7 cells. We demonstrated for the first time that fluspirilene treatment significantly increased the percentage of cells in G1 phase, and decreased the expressions of CDK2, cyclin E and Rb, as well as the phosphorylations of CDK2 on Thr160 and Rb on Ser795. We also examined the anti-cancer effect of fluspirilene in vivo in BALB/C nude mice subcutaneously xenografted with human hepatocellular carcinoma Huh7 cells. Our results showed that oral fluspirilene treatment significantly inhibited tumor growth. Fluspirilene (15 mg/kg exhibited strong anti-tumor activity, comparable to that of the leading cancer drug 5-fluorouracil (10 mg/kg. Moreover, the cocktail treatment with fluspirilene and 5-fluorouracil exhibited the highest therapeutic effect. These results suggested for the first time that fluspirilene is a potential CDK2 inhibitor and a candidate anti-cancer drug for the treatment of human hepatocellular carcinoma. In view of the fact that fluspirilene has a long history

Increasing use of atypical antipsychotics and anticonvulsants during pregnancy

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Epstein, Richard A.; Bobo, William V.; Shelton, Richard C.; Arbogast, Patrick G.; Morrow, James A.; Wang, Wei; Chandrasekhar, Rameela; Cooper, William O.

2013-01-01

Purpose To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants and lithium during pregnancy. Methods Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. Results During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1,000 pregnancies (β = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. Conclusions There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted. PMID:23124892

Policies for second generation biofuels: current status and future challenges

Energy Technology Data Exchange (ETDEWEB)

Egger, Haakan; Greaker, Mads; Potter, Emily

2011-07-01

Current state-of-the-art knowledge concludes that green house gas (GHG) emissions must be controlled and reduced within the next 30-40 years. The transport sector contributes almost a fifth of the current global emissions, and its share is likely to increase in the future. The US and a number of European countries have therefore introduced various support schemes for research and development (RandD) of low emission fuels that can potentially replace the current fossil fuels. One such alternative is biofuels. The advantage of biofuels are that it is easy to introduce into the transport sector. On the other hand, recent research papers question whether the supply of feedstock is sufficient, and to what extent biofuels lead to GHG emission reductions. This report reviews the current status of second generation biofuels. Second generation biofuels are made from cellulose, which according to our survey of the literature, is in more abundant supply than the first generation biofuels feedstocks. Furthermore, it seems to have the potential to reduce GHG emissions from the transport sector without leading to devastating land use changes, which recent critique has held against first generation biofuels. Given that governments have decided to support RandD of low emission fuels, we ask the following questions: Should second generation biofuels receive RandD support to the same extent as other low emission fuels like hydrogen? How should support schemes for second generation biofuels be designed? Second generation biofuels can be divided according to the production process into thermo-chemical and bio-chemical. With respect to the thermo-chemical process the potential for cost reductions seems to be low. On the other hand, ethanol made from cellulose using the biochemical conversion process is far from a ripe technology. Expert reports point to several potential technological breakthroughs which may reduce costs substantially. Hence, cellulosic ethanol, should receive direct

Second harmonic generation in resonant optical structures

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Eichenfield, Matt; Moore, Jeremy; Friedmann, Thomas A.; Olsson, Roy H.; Wiwi, Michael; Padilla, Camille; Douglas, James Kenneth; Hattar, Khalid Mikhiel

2018-01-09

An optical second-harmonic generator (or spontaneous parametric down-converter) includes a microresonator formed of a nonlinear optical medium. The microresonator supports at least two modes that can be phase matched at different frequencies so that light can be converted between them: A first resonant mode having substantially radial polarization and a second resonant mode having substantially vertical polarization. The first and second modes have the same radial order. The thickness of the nonlinear medium is less than one-half the pump wavelength within the medium.