Gandhi, Sonja; McArthur, Eric; Reiss, Jeffrey P.; Mamdani, Muhammad M.; Hackam, Daniel G.; Weir, Matthew A.; Garg, Amit X
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-ba...
Sangeeta Narayan; Kimberly L. Sterling; McCombs, Jeffrey S.
Background: The California Medicaid Program (Medi-Cal) provided open access to atypical antipsychotics in October 1997. This study investigated the impact of open access to atypical antipsychotics on the costs and duration of therapy for patients with bipolar disorders. Methods: Paid claims data from Medi-Cal were used to identify episodes of treatment using antipsychotics, antidepressants, mood stabilizers, or selected anticonvulsants initiated by patients with bipolar disorders. Episodes of...
L Oriana Linares
Full Text Available 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% CI = 1.3-18.4 were
Ashish Chauhan*, Amit Mittal, Pradeep Kumar Arora
history and development, epidemiology, etiology of psychosis along with treatment with antipsychotics (especially on atypical antipsychotics, their global market, pharmaco-economics, mechanism of action and recent advancements in atypical antipsychotic medications, antipsychotic drugs which are currently under clinical development along with Ayurvedic, Homeopathic, Chinese, Unani treatment for psychosis.
Gregoor, Jochem G.; van der Weide, Jan; Loovers, Harriet M.; van Megen, Harold J.; Egberts, Toine C.; Heerdink, Eibert R.
Background Treatment with atypical antipsychotic agents is often complicated by dyslipidemia, which is a risk factor for cardiovascular disease. Objectives To determine whether the LEPR Q223R, the LEP -2548G/A, and the HTR2C -759C/T polymorphisms are associated with dyslipidemia in patients using at
Sharath Chandra S P
Full Text Available Antipsychotic medications constitute a diverse series of heterocyclic compounds that are used to treat psychotic problems, particularly schizophrenia and bipolar affective disorders. Heterocyclic molecules such as benzisoxazole derivatives, especially 3-(piperidin-4-yl-1,2-benzisoxazole have been widely used as antipsychotic drugs. Atypical antipsychotic drugs which are derived from benzisoxazole include risperidone, iloperidone and paliperidone.
Unwin, Gemma L.; Deb, Shoumitro
The use of medications to manage problem behaviours is widespread. However, robust evidence to support their use seems to be lacking. The aim was to review research evidence into the efficacy of atypical antipsychotic medication in managing problem behaviour in children with intellectual disabilities and borderline intelligence. A systematic…
Ying Qiu; Fu, Alex Z; Gordon G. Liu; Christensen, Dale B.
Background: A large body of clinical studies have demonstrated the efficacy of atypical antipsychotic use in the treatment of bipolar disorder. Facing increasing budget pressure, third-party payers, such as state Medicaid programmes in the US, are demanding better understanding of the medical costs beyond atypical antipsychotic drug costs alone in treating bipolar disorder. Objective: To examine healthcare costs associated with the atypical antipsychotic treatments for bipolar disorder from a...
Full Text Available This study describes a patient diagnosed as a case of bipolar affective disorder complaining of bothersome incidence of pedal edema 1 month after the initiation of atypical antipsychotic regimen with risperidone and quetiapine. All hematological and biochemical profiles were found to be normal. On discontinuation of risperidone, the condition remained unresolved even after 2 weeks, and the edema progressed reaching her calves. On tapering the dose of quetiapine, she started showing gradual improvement in edematous condition. Quetiapine was slowly discontinued. No further recurrence of edema occurred, and hence, no further medication changes were implemented. Pedal edema was found to be resolved within weeks of dechallenge of the regimen. Naranjo adverse drug reaction probability scale gave a score of 7 which denotes "probable" adverse drug reaction with quetiapine.
Full Text Available Atypical antipsychotics cause less frequently extrapyramidal system symptoms, neuroleptic malignant syndrome and hyperprolactinemia than typical antipsychotics. However hematological side effects such as leukopenia and neutropenia could occur during treatment with atypical antipsychotics. These side effects could lead to life threatening situations and the mortality rate due to drug related agranulocytosis is about 5-10%. There are several hypothesis describing the mechanisms underlying drug induced leukopenia and/or neutropenia such as direct toxic effects of these drugs upon the bone marrow or myeloid precursors, immunologic destruction of the granulocytes or supression of the granulopoiesis. Clozapine is the antipsychotic agent which has been most commonly associated with agranulocytosis. A nitrenium ion which is formed by the bioactivation of clozapine is thought to have an important role in the pathophysiogy of this adverse effect. Aside from clozapine, there are several case reports reporting an association between olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole and leukopenia. We did not find any study or case report presenting amisulpride or sulpride related hematological side effects in our literature search. Patients who had hematological side effects during their previous antipsychotic drug treatments and who had lower baseline blood leukocyte counts, have higher risk to develop leukopenia or neutropenia during their current antipsychotic treatment. Once leukopenia and neutropenia develops, drugs thought to be responsible for this side effect should be discontinued or dosages should be lowered. In some cases iniatition of lithium or G-CSF (granulocyte colony-stimulating factor therapy may be helpful in normalizing blood cell counts. Clinicans should avoid any combination of drugs known to cause hematological side effects. Besides during antipsychotic treatment, infection symptoms such as fever, cough, sore throat or
Full Text Available Abstract Background Although much progress has been made on antipsychotic drug development, precise mechanisms behind the action of typical and atypical antipsychotics are poorly understood. Methods We performed genome-wide expression profiling to study effects of typical antipsychotics and atypical antipsychotics in the postmortem liver of schizophrenia patients using microarrays (Affymetrix U133 plus2.0. We classified the subjects into typical antipsychotics (n = 24 or atypical antipsychotics (n = 26 based on their medication history, and compared gene expression profiles with unaffected controls (n = 34. We further analyzed individual antipsychotic effects on gene expression by sub-classifying the subjects into four major antipsychotic groups including haloperidol, phenothiazines, olanzapine and risperidone. Results Typical antipsychotics affected genes associated with nuclear protein, stress responses and phosphorylation, whereas atypical antipsychotics affected genes associated with golgi/endoplasmic reticulum and cytoplasm transport. Comparison between typical antipsychotics and atypical antipsychotics further identified genes associated with lipid metabolism and mitochondrial function. Analyses on individual antipsychotics revealed a set of genes (151 transcripts, FDR adjusted p Conclusion Typical antipsychotics and atypical antipsychotics affect different genes and biological function in the liver. Typical antipsychotic phenothiazines exert robust effects on gene expression in the liver that may lead to liver toxicity. The genes found in the current study may benefit antipsychotic drug development with better therapeutic and side effect profiles.
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
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.
BACKGROUND Many nursing home (NH) residents are prescribed atypical antipsychotics despite US Food and Drug Administration warnings of increased risk of death in older adults with dementia. Aggressive pharmaceutical marketing has been cited as a potential cause, although data are scarce. The objectives of this study were to describe the current extent and type of pharmaceutical marketing in NHs in one state, and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. DESIGN Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. SETTING 41 NHs in Connecticut. PARTICIPANTS NH administrators, directors of nursing and medical directors (n = 93, response rate 75.6%). MEASUREMENTS 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 semi-structured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. RESULTS Leadership at 46.3% of NHs (19/41) reported pharmaceutical marketing encounters, consisting of educational training, written/Internet-based materials and/or sponsored training. No association was detected between the level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. CONCLUSION NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. PMID:25688605
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
Full Text Available Abstract Background There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia. This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation, a recognized index of medication effectiveness in the treatment of schizophrenia. Methods We used data from a large, 3-year, observational, non-randomized, multisite study of schizophrenia, conducted in the U.S. between 7/1997 and 9/2003. Patients who were initiated on oral atypical antipsychotics (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone or oral typical antipsychotics (low, medium, or high potency were compared on time to all-cause medication discontinuation for 1 year following initiation. Treatment group comparisons were based on treatment episodes using 3 statistical approaches (Kaplan-Meier survival analysis, Cox Proportional Hazards regression model, and propensity score-adjusted bootstrap resampling methods. To further assess the robustness of the findings, sensitivity analyses were performed, including the use of (a only 1 medication episode for each patient, the one with which the patient was treated first, and (b all medication episodes, including those simultaneously initiated on more than 1 antipsychotic. Results Mean time to all-cause medication discontinuation was longer on atypical (N = 1132, 256.3 days compared to typical antipsychotics (N = 534, 197.2 days; p Conclusion In the usual care of schizophrenia patients, time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level. Findings were primarily driven by clozapine and olanzapine, and to a lesser extent by risperidone. Furthermore, only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine, a medium
Alpak, Gokay; Demir, Bahadir; Aksoy, Ihsan; Kaya, Hilal; Unal, Ahmet; Bulbul, Feridun; Savas, Haluk A.
Objective: Bipolar disorder (BD) is a chronic psychiatric disorder which shows difficulties in the process of diagnosis and treatment. One of the biggest problems in BD maintenance therapy is to ensure medication compliance. Long-acting injectable (LAI) antipsychotic medications have important advantages in such cases. In this study we aimed to include both LAI atypical and typical antipsychotics and to compare the clinical status, number of hospitalization, and side effects of pre and post-t...
Moore R Andrew
Full Text Available Abstract Background Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics. Methods We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library, and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration. Results In five trials (2,206 patients participants presented with a depressive episode, and in 25 trials (6,174 patients the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12. With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22 in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10. In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials, somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics
López-Muñoz, Francisco; Shen, Winston W.; Pae, Chi-un; Moreno, Raquel; Rubio, Gabriel; Molina, Juan D.; Noriega, Concha; Pérez-Nieto, Miguel A.; Huelves, Lorena; Álamo, Cecilio
Objective We have carried out a bibliometric study on the scientific publications in relation to atypical or second-generation antipsychotic drugs (SGAs) in South Korea. Methods With the EMBASE and MEDLINE databases, we selected those publications made in South Korea whose title included the descriptors atypic* (atypical*) antipsychotic*, second-generation antipsychotic*, clozapine, risperidone, olanzapine, ziprasidone, quetiapine, sertindole, aripiprazole, paliperidone, amisulpride, zotepine...
Full Text Available Pietro Gareri,1 Cristina Segura-García,2 Valeria Graziella Laura Manfredi,1 Antonella Bruni,2 Paola Ciambrone,2 Gregorio Cerminara,2 Giovambattista De Sarro,2 Pasquale De Fazio2 1Elderly Health Care, Azienda Sanitaria Provinciale Catanzaro, Catanzaro, Italy; 2Department of Health Sciences, University “Magna Græcia” of Catanzaro, Catanzaro, Italy Abstract: The use of atypical antipsychotic drugs in the elderly has become wider and wider in recent years; in fact, these agents have novel receptor binding profiles, good efficacy with regard to negative symptoms, and reduced extrapyramidal symptoms. However, in recent years, the use of both conventional and atypical antipsychotics has been widely debated for concerns about their safety in elderly patients affected with dementia and the possible risks for stroke and sudden death. A MEDLINE search was made using the words elderly, atypical antipsychotics, use, schizophrenia, psychosis, mood disorders, dementia, behavioral disorders, and adverse events. Some personal studies were also considered. This paper reports the receptor binding profiles and the main mechanism of action of these drugs, together with their main use in psychiatry and the possible adverse events in elderly people. Keywords: atypical antipsychotics, dementia, elderly, psychosis, mood disorders, side effects
Fountoulakis, Konstantinos N; Nimatoudis, Ioannis; Iacovides, Apostolos; Kaprinis, George
Introduction With the introduction of newer atypical antipsychotic agents, a question emerged, concerning their use as complementary pharmacotherapy or even as monotherapy in mental disorders other than psychosis. Material and method MEDLINE was searched with the combination of each one of the key words: risperidone, olanzapine and quetiapine with key words that refered to every DSM-IV diagnosis other than schizophrenia and other psychotic disorders, bipolar disorder and dementia and memory d...
Full Text Available Silvio Caccia,1 Luca Pasina,2 Alessandro Nobili21Laboratory of Drug Metabolism, “Mario Negri” Institute for Pharmacological Research, Milan, Italy; 2Laboratory of Quality, Assessment of Geriatric Therapies and Services, “Mario Negri” Institute for Pharmacological Research, Milan, ItalyAbstract: The optimal treatment of schizophrenia poses a challenge to develop more effective treatments and safer drugs, to overcome poor compliance, discontinuation and frequent switching with available antipsychotics. Iloperidone is a new dopamine type 2/serotonin type 2A (D2/5-HT2A antagonist structurally related to risperidone, expected to give better efficacy with less extrapyramidal symptoms than D2 receptor antagonist antipsychotics. In double-blind phase III trials iloperidone reduced the symptoms of schizophrenia at oral doses from 12 to 24 mg. It was more effective than placebo in reducing positive and negative syndrome total score and Brief Psychiatric Rating scale scores; it was as effective as haloperidol and risperidone in post-hoc analysis. Its long-term efficacy was equivalent to that of haloperidol. The most common adverse events were dizziness, dry mouth, dyspepsia and somnolence, with few extrapyramidal symptoms and metabolic changes in short- and long-term studies in adults. Akathisia was rare, but prolongation of the corrected QT (QTc interval was comparable to haloperidol and ziprasidone, which is of particular concern. Further comparative studies are needed to clarify the benefit/risk profile of iloperidone and its role in the treatment of schizophrenia.Keywords: iloperidone, pharmacology, pharmacokinetics, efficacy, safety
Full Text Available Abstract Background Deep venous Thrombosis is a serious, possible life threatening event which is often ignored in psychiatric Settings. Purpose In this paper three cases of deep venous Thrombosis (DVT following the use of olanzapine and risperidone are presented. Methods The data of Three patients was collected from hospital records. Results The patients were in good general physical health and had no personal or familial history of DVT. The patients were not overweight (BMI Conclusion Risk of DVT exists in patients under treatment with atypical antipsychotics in spite of no pre existing risk factor.
Glenthoj, Andreas; Glenthøj, Birte Yding; Mackeprang, Torben; Pagsberg, Anne K; Hemmingsen, Ralf; Jernigan, Terry L; Baaré, William Frans Christian
The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and...... altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin.......The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and...... 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of...
Baandrup, L; Kruse, M
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...... received welfare payments for prolonged periods of time during the observation period, even more so for individuals treated with antipsychotic polypharmacy or other antipsychotic combination regimens. The risk of permanently leaving the labor market was also associated with antipsychotic combination...
Stip, Emmanuel; Mancini-Marie, Adham
Objective: To investigate which cognitive and affective features contribute most to responder/non-responder group separation during a switching trial with atypical antipsychotic. Design: A prospective open trial with an atypical antipsychotic (olanzapine). Patients: One hundred and thirty-four patients meeting diagnostic criteria for…
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.
Full Text Available Ken O'Day,1 Krithika Rajagopalan,2 Kellie Meyer,1 Andrei Pikalov,2 Antony Loebel21Xcenda, Palm Harbor, FL, 2Sunovion Pharmaceuticals, Marlborough, MA, USABackground: The purpose of this study was to evaluate the long-term cost-effectiveness (including hospitalizations and cardiometabolic consequences of atypical antipsychotics among adults with schizophrenia.Methods: A 5-year Markov cohort cost-effectiveness model, from a US payer perspective, was developed to compare lurasidone, generic risperidone, generic olanzapine, generic ziprasidone, aripiprazole, and quetiapine extended-release. Health states included in the model were patients: on an initial atypical antipsychotic; switched to a second atypical antipsychotic; and on clozapine after failing a second atypical antipsychotic. Incremental cost-effectiveness ratios (ICERs assessed incremental cost/hospitalization avoided. Effectiveness inputs included discontinuations, hospitalizations, weight change, and cholesterol change from comparative clinical trials for lurasidone and for aripiprazole, and the Clinical Antipsychotic Trials of Intervention Effectiveness for other comparators. Atypical antipsychotic-specific relative risk of diabetes obtained from a retrospective analysis was used to predict cardiometabolic events per Framingham body mass index risk equation. Mental health costs (relapsing versus nonrelapsing patients and medical costs associated with cardiometabolic consequences (cardiovascular events and diabetes management were obtained from published sources. Atypical antipsychotic costs were estimated from Red Book® prices at dose(s reported in clinical data sources used in the model (weighted average dose of lurasidone and average dose for all other comparators. Costs and outcomes were discounted at 3%, and model robustness was tested using one-way and probabilistic sensitivity analyses.Results: Ziprasidone, olanzapine, quetiapine extended-release, and aripiprazole were dominated
Full Text Available Atypical antipsychotics are an important advance in the treatment of schizophrenia and other psychiatric illness, and have become widely used as first - line pharmacotherapy for psychosis. This study is a longitudinal prospective observational study of ADRs of Atypical Antipsychotic drugs in patients of psychiatric illness. Information of ADRs was data based and collected from OPD. The noted ADRs were assessed by using Naranjo’s probability assessment scale, and WHO (UMC causality assessment scale. Majority of patients in this study belonged to 21 - 30 years age group which was 24% of the total. According to the severity of ADRs, majority of cases were reported of having weight gain 38. 46% followed by sedation 19. 23%, dry mouth 13. 46% and orthostatic hypote nsion 5. 76%. 88. 47% were reported as type A and 11. 53% were reported as type B. Definite (certain relationship was established in 30. 40% patients while probable in 57. 62% and 11. 53% ADRs were categorized as possible. The ADRs can be prevented by col lecting reliable information about their frequencies and possible risk factors.
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
Full Text Available Excessive weight gain, hyperglycemia, type 2 diabetes and hyperlipidemia are significant clinical adverse effects that appear as a result of the treatment with second generation atypical antipsychotic drugs. These drugs possibly cause weight gain by stimulating appetite and increasing insulin resistance. Amantadine, nizatidine, ranitidine, famotidine, topiramate, reboxetine and metformin are notified as the effective drugs which were used in order to prevent the weight gain due to atypical antipsychotic drugs. As an antidiabetic agent, metformin draws attention due to reducing weight gain and correcting insulin resistance. The aim of this paper was to evaluate studies searching fort he effect of metformin on weight-gain due to atypical antipsychotics.
Ahmadkhaniha, Hamid-Reza; Bani-Hashem, Shahab; Ahmadzad-Asl, Masoud
Objective: The present study aimed to review the relapse rate in patients with schizophrenia treated with orally taken atypical agents (serotonin dopamine antagonists, SDAs) and depot preparation of conventional (typical) antipsychotics. Methods: In this historical cohort study, mean relapse per month (MRM) index, duration between initiation of antipsychotic treatment and the first relapse episode, and the time gap between successive relapses were compared between 84 patients on SDAs-except c...
Eduardo Henrique Teixeira
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.
Ernst, Carrie L; Goldberg, Joseph F
There has been growing concern about the potential iatrogenic effects of several newer psychotropic drugs on reproductive health safety in women. Areas of particular concern in this regard include (1) controversies about a potential association between the use of valproate and development of polycystic ovary syndrome (PCOS), (2) the safety of use of newer psychotropic medications during pregnancy, and (3) safety issues with these medications in women while breastfeeding. This review summarizes current information about each of these areas. In particular, existing data suggest that (1) PCOS very likely represents a complex neuroendocrine disorder with multiple determinants; (2) menstrual irregularities may be a frequently seen phenomenon in women with bipolar illness, at least partially independent of psychotropic drug therapy; (3) potential central nervous system teratogenicity remains substantial during first-trimester exposure to valproate or carbamazepine; (4) with newer agents used for bipolar disorder and schizophrenia, safety data during pregnancy, while not definitive, are most abundant with olanzapine and with lamotrigine; relatively less is known about systematic pregnancy outcomes with other atypical antipsychotics or newer anticonvulsants; and (5) risks for neonatal safety during lactation continue to appear substantial with lithium, are of potential concern with lamotrigine and clozapine, are quite likely minimal with valproate or carbamazepine, and are indeterminate with most other new anticonvulsants or atypical antipsychotics. Recommendations are presented for clinical management in each of these instances. PMID:11913676
Mendhekar, D.N.; Jiloha, R.C.; M M Mehndiratta; War, L.
There are several reports available on neuroleptic malignant syndrome (NMS) associated with risperidone but when a more stringent criterion is applied there are only a few. Report on challenge and rechallenge with various atypical antipsychotic drugs in re-emergence of post NMS psychosis is scanty. Our aim of presenting this is to highlight the differential response of various atypical antipsychotic drugs in the treatment of post NMS psychosis. This paper reports a young male with mild mental...
Rasimas, J.J.; Liebelt, Erica L.
Medications are being used with greater frequency to address pediatric mental health problems, and in recent years atypical antipsychotic (AAP) prescriptions have increased more than any other class. Acute care practitioners must be aware of the pharmacology of AAPs and the conditions, on- and off-label, for which they are prescribed. This involves identifying and managing side effects that manifest both mentally and physically. Although “atypicality” confers a lower risk of movement side effects compared to conventional agents, children are more sensitive than adults to extrapyramidal reactions. Like adults, they also may present with toxic sedation, confusion, cardiovascular dysfunction, and metabolic derangements. Evaluation and management of these toxicities requires an index of suspicion, a careful symptom and medication history, physical examination, and targeted interventions. This review is designed to orient the emergency practitioner to the challenging task of recognizing and treating adverse effects related to acute and chronic atypical antipsychotic exposure in children. PMID:23471213
Han, Changsu; Pae, Chi-Un
Asian and western countries differ in the prevalence, symptom manifestation, diagnostic procedures, patient recognition and treatments of major depressive disorder (MDD), according to a number of studies. Ethnic differences in pharmacological profiles are also important in the prescription of certain antipsychotic medications because they may impact treatment outcomes and adverse events. Differential pharmacokinetic and pharmacodynamic properties of antipsychotics may be practically useful in the control of specific depressive symptoms. Furthermore, patient compliance with prescribed medications has been found to be different across races and ethnicities. Therefore, this article explores practical clinical issues for the use of atypical antipsychotics in patients with MDD, focusing on ethno-cultural differences. PMID:23709361
Full Text Available Abstract Background A number of reports showed en encouraging remediation in some patients' executive deficits thanks to the use of 'information processing strategies'. Moreover the impact of antipsychotics on cognitive functions of the schizophrenics is an important issue, especially if an integrated psychosocial treatment is needed. The aim of this paper is to evaluate different executive performance and response to verbalization, a strategy of the Wisconsin Card Sorting Test (WCST remediation, in subjects on classical vs atypical antipsychotic (AP treatment. Methods Sixty-three schizophrenic subjects undertook the WCST under standard and modified (verbalization administration. Subjects were stratified by the kind of WCST response (i.e. good, poor and remediable and AP treatment (i.e. atypical vs. classical. Results Subjects on atypical APs showed a better performance than those on classical ones. More poor performers who did not remediate were seen in the sample with classical Aps while subjects who remediated the performance were seen in the subgroup with atypical APs only. An increase of perseverative and total errors was seen in poor performers subjects on classical APs. Conclusion Subjects on atypicals showed a better cognitive pattern in terms of WCST performance. Since the naturalistic assignment of medication we cannot draw conclusions about its effect on cognitive performance and its interaction with cognitive remediation potential. However the data lead us to hypothesize that subjects with potential room for remediation did so with the atypical APs.
Full Text Available Objective: to comparatively investigate – by means of computer simulations – the economic cost and clinical outcomes of five atypical oral antipsychotic agents (ziprasidone, olanzapina, risperidone, paliperidone and aripiprazolo.Methods: a cyclical stochastic model representing patient evolution, taking into account main adverse reactions (akathisia, weight gain and extra-pyramidal ARs, drug efficacy on psychosis stabilization and probability of relapse, was developed. Ten different scenarios were compared, each starting with one of the considered antipsychotics, prescribed either at home or in a hospital setting. Switching to another medication was allowed until no untried drugs were available, in which case clozapine treatment or admission to a Psychiatric Therapeutic Rehabilitation Center were irreversibly assigned. Model inputs were probabilities of ARs, probabilities of stabilization and probabilities of destabilization (assumed equal for all; as well as costs attributable to drugs, hospitalization, outpatient care and costs adverse reactions in terms of concomitant medications. Sources for the inputs were the trials reported in the most recent literature (from the year 2000, selected based on the homogeneity of the observational period and antipsychotic dosage used.Results: in each scenario, the hospitalization cost represented the highest component of the overall cost (approximately 67%. Assuming equal drug effectiveness, ziprasidone fared better than all other considered competitors, showing the lowest average annual costs per patient (and also the lowest average annual hospitalization costs as well as the largest numbers of controlled months without adverse reactions, independently of the initial setting. Conclusions: the most important determinant of total cost appears to be hospitalization, whose cost is about 600% higher than the medications cost. Medication effectiveness and tolerability remain however of utmost importance for
Kwon, Jun Soo; Kim, Sung Nyun; Han, Jaewook; Lee, Sang Ick; Chang, Jae Seung; Choi, Jung-Seok; Lee, Heon-Jeong; Cho, Seong Jin; Jun, Tae-Youn; Lee, Seung-Hwan; Han, Changsu; Lee, Kyoung-Uk; Lee, Kyung Kyu; Lee, EunJung
Patient satisfaction with treatment is an important clinical index associated with the efficacy and adherence of treatment in schizophrenia. Although switching from oral antipsychotics to the long-acting injectable formulation may improve convenience, patient satisfaction has not been studied extensively. We carried out a 21-week, multicenter, randomized, open-label comparative study. A total of 154 patients with schizophrenia unsatisfied with current oral atypical antipsychotics were assigned randomly to either immediate or delayed switching to paliperidone palmitate, the long-acting injectable formulation of paliperidone. The Medication Satisfaction Questionnaire (MSQ) and the Treatment Satisfaction Questionnaire for Medication (TSQM) were used to evaluate patient satisfaction with treatment, whereas the Positive and Negative Syndrome Scale (PANSS) and the Personal and Social Performance (PSP) scale were used to evaluate efficacy. From baseline to the final assessment, the MSQ score increased significantly in both groups, and the increase was greatest after the first administration of paliperidone palmitate in the immediate switch group. The scores of TSQM effectiveness, convenience, and global satisfaction as well as the PSP total score increased significantly, whereas the PANSS total score decreased significantly in both groups. The immediate switch group showed a significant improvement in the TSQM convenience score compared with the delayed switch group on oral antipsychotics during the comparison period. Most adverse events were minor and tolerable. In short, switching from oral atypical antipsychotics to paliperidone palmitate because of poor satisfaction significantly improved patient satisfaction, with comparable efficacy and tolerability. PMID:26196188
Full Text Available Tuanthon Boonlue,1,2 Suphat Subongkot,1,2 Piyameth Dilokthornsakul,3,4 Ronnachai Kongsakon,5 Oraluck Pattanaprateep,6 Orabhorn Suanchang,7 Nathorn Chaiyakunapruk3,8–10 1Clinical Pharmacy Division, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand; 2The College of Pharmacotherapy of Thailand, Nonthaburi, Thailand; 3Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 4Center for Pharmaceutical Outcomes Research, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA; 5Department of Psychiatry, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 6Department of Health Informatics, Ramathibodi Hospital, Mahidol University, 7Department of Pharmacy, Somdet Chaopraya Institute of Psychiatry, Bangkok, Thailand; 8School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 9School of Population Health, University of Queensland, Brisbane, Australia; 10School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA Background: Several clinical practice guidelines suggest using atypical over typical antipsychotics in patients diagnosed with schizophrenia. Nevertheless, cost-containment policy urged restricting usage of atypical antipsychotics and switching from atypical to typical antipsychotics. Objective: This study aimed to evaluate clinical and economic impacts of switching from atypical to typical antipsychotics in schizophrenia patients in Thailand. Methods: From October 2010 through September 2013, a retrospective cohort study was performed utilizing electronic database of two tertiary hospitals. Schizophrenia patients aged 18 years or older and being treated with atypical antipsychotics were included. Patients were classified as atypical antipsychotic switching group if they switched to typical antipsychotics after 180 days of continual
Howland, Robert H
Atypical antipsychotic drugs are not all alike with respect to their pharmacologies, therapeutic uses, and side eff ects, although many clinicians lump them together and do not distinguish among them. Risk assessment for the potential use of a drug, such as aripiprazole (Abilify), should not focus on any particular adverse effect, but rather should consider risk assessment in a broader context. Specifically, what are the alternatives, and what are their inherent risk profiles? What is the risk of no treatment? Side eff ects commonly associated with a particular drug or class of drugs can also occur with other drugs. For any drug prescribed for any reason, prescribers should document discussion about common and potentially serious adverse effects, as well as document clinical monitoring. Alternative treatments and their inherent risks, along with the risks of not taking medication for a particular condition, should also be discussed with patients and documented. PMID:25346958
Allan H. Young
Full Text Available Antidepressant therapies, such as selective serotonin reuptake inhibitors (SSRIs, are current first-line treatments for Major Depressive Disorder. However, over 50% of treated patients show an inadequate response to initial antidepressant therapy. If the therapeutic outcomes from two antidepressant therapies are suboptimal, potentially resulting in Treatment Resistant Depression, subsequent strategies include switching to another antidepressant or augmenting treatment by combining with other agents. When combined with SSRIs, atypical antipsychotics have supplementary action on dopaminergic and noradrenergic systems. Studies on combined treatment with atypical antipsychotics have shown significantly increased remission rates, shortened response times, and favorable side effects. Augmentation of antidepressants with atypical antipsychotics is now an acceptable treatment strategy which leads to increased remission rates and better outcomes for patients.
Martín-Blanco, Ana; Patrizi, Barbara; Villalta, Laia; Gasol, Xero; Soler, Joaquim; Gasol, Miquel; Pascual, Juan C
Many individuals with borderline personality disorder (BPD) receive medical treatment in clinical practice, although to date, there are no drugs specifically available for BPD. The recent Cochrane guideline suggests a benefit from using second-generation antipsychotics such as olanzapine or aripiprazole; nevertheless, side effects limit their use. Asenapine is a novel FDA-approved atypical antipsychotic for schizophrenia and bipolar disorder. However, it has not yet been tested for BPD. The goal of this observational open-label study was to assess the safety, tolerability and efficacy of asenapine in a series of cases of patients with BPD. Twelve individuals with BPD were recruited and treated with asenapine during an 8-week period. Eight individuals completed the study; a significant improvement was observed in the CGI-BPD (P<0.001) and BSL-23 (P<0.048) scales for BPD symptomatology. Besides, there was a significant improvement in the general psychopathology domains (BPRS, P<0.004), whereas no significant differences were observed in depressive symptoms. No serious adverse effects were reported and a significant weight reduction was observed (P=0.002). Asenapine appears to be a safe and effective agent in the treatment of patients with BPD, especially when other alternatives are not tolerated. These preliminary findings should be replicated in a controlled clinical trial. PMID:23962963
Kiran G Piparva
Full Text Available Background: Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS. However, these drugs have separate set of adverse drug reactions (ADRs. Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment. Materials and Methods: A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex, who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients′ responses were recorded in the case record form. Results: Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93 were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4-6 mg/day and olanzepine (at 10-15 mg/day, gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2-3 months after treatment course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3-9 months use. Conclusion: The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized.
Tatara, Ayaka; Shimizu, Saki; Masui, Atsushi; Tamura, Miyuki; Minamimoto, Shoko; Mizuguchi, Yuto; Ochiai, Midori; Mizobe, Yusuke; Ohno, Yukihiro
Blonanserin is a new atypical antipsychotic drug that shows high affinities to dopamine D2 and 5-HT2 receptors; however, the mechanisms underlying its atypicality are not fully understood. In this study, we evaluated the antipsychotic properties of AD-6048, a primary metabolite of blonanserin, to determine if it contributes to the atypicality of blonanserin. Subcutaneous administration of AD-6048 (0.3-1mg/kg) significantly inhibited apomorphine (APO)-induced climbing behavior with an ED50 value of 0.200mg/kg, the potency being 1/3-1/5 times that of haloperidol (HAL). AD-6048 did not cause extrapyramidal side effects (EPS) even at high doses (up to 10mg/kg, s.c.), whereas HAL at doses of 0.1-3mg/kg (s.c.) significantly induced bradykinesia and catalepsy in a dose-dependent manner. Thus, the therapeutic index (potency ratios of anti-APO action to that of EPS induction) of AD-6048 was much higher than that of haloperidol, illustrating that AD-6048 per se possesses atypical antipsychotic properties. In addition, immunohistochemical analysis of Fos protein expression revealed that both AD-6048 and HAL significantly increased Fos expression in the shell part of the nucleus accumbens and the striatum. However, in contrast to HAL which preferentially enhanced striatal Fos expression, AD-6048 showed a preferential action to the nucleus accumbens. These results indicate that AD-6048 acts as an atypical antipsychotic, which seems to at least partly contribute to the atypicality of blonanserin. PMID:26363311
Wakamatsu, Akihide; Aoki, Kazuo; Sakiyama, Yojiro; Ohnishi, Takashi; Makoto SUGITA
Lower fluctuation, i.e., lower peak-to-trough plasma-concentration variation at steady-state pharmacokinetics, has several advantages for the treatment of schizophrenia with antipsychotics. The reduction of peak concentration can decrease the risk of dose-dependent side effects, such as extrapyramidal symptom and somnolence, and by contrast the increase in trough concentration can decrease the incidence of lack of efficacy due to subtherapeutic drug concentration. Using a one-compartment simu...
Gregoor, Jochem G; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J G M; Egberts, Antoine C G; Heerdink, Eibert R
Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications. PMID:19142102
Full Text Available 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.
Tan, Lin; Tan, Lan; Wang, Hui-Fu; Wang, Jun; Tan, Chen-Chen; Tan, Meng-Shan; Meng, Xiang-Fei; Wang, Chong; Yu, Jin-Tai
Introduction A wide variety of atypical antipsychotic drugs (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone and clozapine) are widely used in the management of neuropsychiatric symptoms, which are commonly seen in dementia, but results from randomised controlled trials (RCTs) on the efficacy and safety of these agents are conflicting. We aimed to quantify the efficacy and safety of atypical antipsychotic drugs on neuropsychiatric symptoms in dementia patients. Methods PubMed, ...
Full Text Available Introduction: Considering lack of accepted guideline in cases of Parkinson’s disease-related visual hallucinations with poor response or intolerance to antipsychotics, and their possible cholinergic pathogenesis, the trial with cholinesterase inhibitors seems to be legitimated. Material and methods: Five patients with PD (with or without dementia complicated by VH and unresponsive to atypical antipsychotics were offered a 12-week, open-label trial of a cholinesterase inhibitor. Results: All 5 subjects completed the trial with no major adverse effects and, noteworthy, no discontinuations due to adverse events. VH resolved in 4 subjects and were markedly diminished in one person. Neither changes in UPDRS scores nor exaggeration of subjective complaints about extrapyramidal symptoms were noted during treatment. Conclusions: Cholinesterase inhibitors, rivastigmine or donepezil, might represent a useful alternative to antipsychotics for patients with PD accompanied by VH even in the absence of dementia.
Hepburn, Kirsten; Brzozowska, Malgorzata Monika
The atypical antipsychotic agent clozapine, although an effective treatment for schizophrenia, is linked with metabolic adverse effects. We report a case of diabetic ketoacidosis and very severe hypertriglyceridaemia associated with clozapine use, in a patient with type 2 diabetes mellitus, who was successfully treated with continuous insulin infusion and fluids. As clozapine proved to be the most efficacious in controlling the patient's psychotic symptoms, the patient has been continued on clozapine despite its known metabolic side effects. Importantly the patient has achieved satisfactory long-term lipid and glycaemic control. The current recommendations related to the metabolic care for patients treated with atypical antipsychotic agents as well as the mechanisms behind abnormal glucose and lipid regulation with clozapine therapy are discussed. PMID:27507689
The current review raises the question of the place of long-acting injectable (LAI) atypical antipsychotics for the treatment of first-episode schizophrenia in current and future guidelines. After exposing the different points of view adopted in the former, the author presents the clinical trials conducted with LAI atypicals in this indication, as well as the surveys related to psychiatrists'opinion regarding the use of these drugs in early schizophrenia. Pros and cons of this therapeutic option are discussed and suggestions are made for further guidelines. PMID:24084422
Park, Young-Min; Lee, Seung-Hwan; Lee, Bun-Hee; Lee, Kyu Young; Lee, Kye-Seong; Kang, Seung-Gul; Lee, Hwa-Young; Kim, Won
The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (phyperprolactinemia and macroprolactinemia in psychiatric patients. PMID:27010188
Sandeep Raha; Taylor, Valerie H.; Holloway, Alison C.
There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both incr...
Hussein, Osamah; Izikson, Lidia; Bathish, Yunis; Dabur, Enas; Hanna, Alaa; Zidan, Jamal
Some of the medications used for the management of schizophrenia are associated with clinically significant increases in weight and adverse alterations in serum lipid levels. The aim of the study was to investigate the effect of short-term (two months) treatment with atypical anti-psychotics on coronary heart disease risk factors, including the functional properties of high-density lipoprotein (HDL), in psychiatric patients. Nineteen patients diagnosed with schizophrenia, schizoaffective, and bipolar disorder and ten healthy volunteers were enrolled in the study. In the present study blood was drawn at baseline and after two months of atypical anti-psychotic treatment. Wilcoxon non-parametric-test was used to examine differences in the psychotic group before and two months after treatment.Waist circumference and oxidative stress in psychiatric patients were higher compared with the control group. Serum-mediated cholesterol efflux capacity was lower in psychotic patients compared to controls. Two months of anti-psychotic therapy was associated with increased abdominal obesity, decreased paraoxonase lactonase activity, but with no further change in serum-mediated cholesterol efflux from macrophages. Psychotic patients have low serum-mediated cholesterol efflux from macrophages as a parameter of HDL functionality. Atypical anti-psychotic treatment for two months increased metabolic derangements in these patients but without further decrement in serum-mediated cholesterol efflux. PMID:26253619
Veysey, Bonita M.; Stenius, Vanja; Mazade, Noel; Schacht, Lucille
Medications are central to the psychiatric armamentorium in U.S. jails and prisons. Psychiatric medications are used both to stabilize acute symptoms as well as maintain mental health once symptoms are reduced. Both jails and prisons rely heavily on traditional antipsychotics, but both have a full array of atypical medications in their…
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
An observational and comparative study was conducted to compare the functional outcome between the patients treated with conventional antipsychotic agent haloperidol and typical antipsychotic agent, Risperidone (Risperidal). A total of 32 patients were included in the study with established schizophrenia according to (DSM iv). The data was processed on SSPE 10th version. The primary outcome measure was the improvement of negative symptoms of schizophrenia and secondary outcome measure was to observe the superiority of the atypical drug Risperid one over conventional agent haloperidol regarding side effects. Patients were assessed at baseline, 2nd and 8th week, using four tools of assessment. For treatment group receiving haloperidol mean was 47.2+-11.50 at 8th week and for Risperidone treatment group mean was 43+-14.68. The P values for all the parameters in the Clozapine group were significant as compared to haloperidol. (author)
Pesa, Jacqueline A.; Muser, Erik; Montejano, Leslie B.; Smith, David M.; Meyers, Oren I.
Background Non-adherence to antipsychotic therapy among patients with schizophrenia is a key driver of relapse, which can lead to costly inpatient stays. Long-acting injectables (LAIs) may improve adherence, thus reducing hospitalizations, but inpatient cost reductions need to be balanced against higher drug acquisition costs of LAIs. Real-world evidence is needed to help quantify the economic value of oral atypical antipsychotics compared with LAIs. Objective The objective of this study was ...
Kwon, Jun Soo; Kim, Sung Nyun; Han, Jaewook; Lee, Sang Ick; Chang, Jae Seung; Choi, Jung-Seok; Lee, Heon-Jeong; Cho, Seong Jin; Jun, Tae-Youn; Lee, Seung-Hwan; Han, Changsu; Lee, Kyoung-Uk; Lee, Kyung Kyu; Lee, Eunjung
Patient satisfaction with treatment is an important clinical index associated with the efficacy and adherence of treatment in schizophrenia. Although switching from oral antipsychotics to the long-acting injectable formulation may improve convenience, patient satisfaction has not been studied extensively. We carried out a 21-week, multicenter, randomized, open-label comparative study. A total of 154 patients with schizophrenia unsatisfied with current oral atypical antipsychotics were assigne...
Marzola, Enrica; Desedime, Nadia; Giovannone, Cristina; Amianto, Federico; Fassino, Secondo; Abbate-Daga, Giovanni
Anorexia nervosa (AN) is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs) in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings. PMID:25922939
Full Text Available Anorexia nervosa (AN is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder. We aimed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors (SSRIs in adult inpatients affected by AN. We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014. Patients were evaluated upon admission and discharge. We investigated eating symptomatology, and both general and eating psychopathology using: Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Yale-Brown-Cornell Eating Disorders Scale. The charts of 75 patients were included in this study. The sample resulted equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs. Notwithstanding a few baseline clinical differences, upon discharge all groups were significantly improved on all measures. Interestingly, aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size. The body of evidence on medication management in AN is in dismal condition. Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well. Nevertheless, to date very little data is available on this topic. Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions. Randomized controlled trials are warranted to confirm these encouraging findings.
Full Text Available BACKGROUND: Schizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels. METHODS: In the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP. MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs. RESULTS: We found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024. CONCLUSIONS: The association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.
Ana Maria Volpato
Full Text Available Objective: Atypical antipsychotics (AAPs promote obesity and insulin resistance. In this regard, the main objective of this study was to present potential mechanisms and evidence concerning side effects of atypical antipsychotics in humans and rodents. Method: A systematic review of the literature was performed using the MEDLINE database. We checked the references of selected articles, review articles, and books on the subject. Results: This review provides consistent results concerning the side effects of olanzapine (OL and clozapine (CLZ, whereas we found conflicting results related to other AAPs. Most studies involving humans describe the effects on body weight, adiposity, lipid profile, and blood glucose levels. However, it seems difficult to identify an animal model replicating the wide range of changes observed in humans. Animal lineage, route of administration, dose, and duration of treatment should be carefully chosen for the replication of the findings in humans. Conclusions: Patients undergoing treatment with AAPs are at higher risk of developing adverse metabolic changes. This increased risk must be taken into account when making decisions about treatment. The influence of AAPs on multiple systems is certainly the cause of such effects. Specifically, muscarinic and histaminergic pathways seem to play important roles.
Full Text Available Atypical antipsychotics are associated with metabolic syndrome, primarily associated with weight gain. The effects of Ziprasidone, an atypical antipsychotic, on metabolic syndrome has yet to be evaluated. Here in, we evaluated lipid accumulation and behavioral changes in a new experimental model, the nematode Caenorhabditis elegans (C. elegans. Behavioral parameters in the worms were evaluated 24 h after Ziprasidone treatment. Subsequently, lipid accumulation was examined using Nile red, LipidTox green and BODIPY labeling. Ziprasidone at 40 µM for 24 h effectively decreased the fluorescence labeling of all markers in intestinal cells of C. elegans compared to control (0.16% dimethyl sulfoxide. Ziprasidone did not alter behaviors related to energetic balance, such as pharynx pumping, defecation cycles and movement. There was, however, a reduction in egg-production, egg-laying and body-length in nematodes exposed to Ziprasidone without any changes in the progression of larval stages. The serotoninergic pathway did not appear to modulate Ziprasidone's effects on Nile red fluorescence. Additionally, Ziprasidone did not alter lipid accumulation in daf-16 or crh-1 deletion mutants (orthologous of the transcription factors DAF-16 and CREB, respectively. These results suggest that Ziprasidone alters reproductive behavior, morphology and lipid reserves in the intestinal cells of C. elegans. Our results highlight that the DAF-16 and CREB transcription factors are essential for Ziprasidone-induced fat store reduction.
Rigler, Sally K.; Shireman, Theresa I.; Cook-Wiens, Galen J.; Ellerbeck, Edward F.; Whittle, Jeffrey C.; Mehr, David R.; Mahnken, Jonathan D.
Objectives to determine whether antipsychotic medication initiation is associated with subsequent fracture in nursing home residents, whether fracture rates differ between first-generation versus second-generation antipsychotic use, and whether fracture rates differ among users of haloperidol, risperidone, olanzapine, and quetiapine. Design time-to-event analyses were conducted in a retrospective cohort using linked Medicaid, Medicare, Minimum Data Set and Online Survey, Certification and Reporting data sets. Setting and Participants nursing home residents aged ≥ 65 years in CA, FL, MO, NJ and PA. Measurements fracture outcomes (any fracture; hip fracture) in first-versus second-generation antipsychotic users, and specifically among users of haloperidol, risperidone, olanzapine and quetiapine. Comparisons incorporated propensity scores that included patient-level variables (demographics, comorbidity, diagnoses, weight, fall history, concomitant medications, cognitive performance, physical function, aggressivebehavior) and facility-level variables (nursing home size, ownership factors, staffing levels). Results Among 8,262 subjects (within 4,131 pairs), 4.3% suffered any fracture during observation with 1% having a hip fracture during an average follow up period of 93 ± 71 days; range 1 to 293 days). Antipsychotic initiation was associated with any fracture (hazard ratio (HR) 1.39, p=0.004) and with hip fracture (HR 1.76, p=0.024). The highest risk was found for hip fracture when antipsychotic use was adjusted for dose(HR=2.96; p=0.008). However, no differences in time-to-fracture were found in first-versus second-generation agents or across competing individual drugs. Conclusion Antipsychotic initiation is associated with fracture in nursing home residents, but risk does not differ across commonly used antipsychotics. PMID:23590366
Pyne, Jeffrey M.; Fischer, Ellen P.; Gilmore, LaNissa; McSweeney, Jean C.; Stewart, Katharine E.; Mittal, Dinesh; Bost, James E.; Valenstein, Marcia
Objective: A substantial gap exists between patients and their mental health providers about patient's perceived barriers, facilitators, and motivators (BFMs) for taking antipsychotic medications. This article describes how we used an intervention mapping (IM) framework coupled with qualitative and quantitative item-selection methods to…
Full Text Available Patients with schizophrenia have a smaller volume of cortex than healthy controls. Nevertheless, the substrate of such deficit is not well understood A progressive loss of cortical GM in schizophrenia seemed supported by early studies with magnetic resonance imaging (MRI in which patients received typical drugs between the baseline and final scans. However, recent MRI results challenge this notion and suggest that structural changes may depend, at least in part, on the type of treatment received. These data may be relevant for a correct interpretation of the substrate of cortical volume deficit in schizophrenia. If that deficit can be even reversed by treatment, as suggested by recent studies, a neuronal substrate seems unlikely. Several lines of evidence instead support that glia cells may have a role in cortical structural and functional deficits in schizophrenia, which would be also in agreement with recent longitudinal results with MRI in patients treated with atypical antipsychotics. These evidences are reviewed in this paper.
Jørgensen, Anders; Knorr, Ulla Benedichte Søsted; Soendergaard, Mia Greisen;
BACKGROUND: Schizophrenia is associated with increased cardiovascular morbidity and mortality. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, and the L-arginine:ADMA ratio are markers of endothelial dysfunction that predict mortality and adverse outcome in...... a range of cardiovascular disorders. Increased ADMA levels may also lead to increased oxidative stress. We hypothesized that ADMA and the L-arginine:ADMA ratio are increased in somatically healthy schizophrenia patients treated with atypical antipsychotics (AAP), and that the ADMA and the L......-arginine: ADMA ratio are positively correlated to measures of oxidative stress. METHODS: We included 40 schizophrenia patients treated with AAP, but without somatic disease or drug abuse, and 40 healthy controls. Plasma concentrations of ADMA and L-arginine were determined by high-performance liquid...
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.
Full text: Aim: Since regional cerebral blood flow (rCBF) findings in schizophrenic patients are inconsistent, the aim of our study was to evaluate and compare rCBF in the first episode of schizophrenia, before and after atypical antipsychotic treatment. Method: 21 patients who met criteria for schizophrenia were assessed PANSS score and tomographic brain perfusion (SPECT). The treatment was administered for 10-12 weeks and the dose was 4.8mg/day Risperidone, 11.6mg/day Olanzepine, 440mg/day Quetiapine. After finishing treatment all patients underwent a control SPECT study. Results: PANSS scores revealed two groups: group A-14 patients with predominant positive symptoms; 9 received Olanzapine and 5 Quetiapine. In group B -7 patients with predominant negative symptoms received Risperidone. Positive symptoms were associated with hypoperfusion in posterior parietal regions and superior temporal gyrus, bilaterally; for negative symptoms we found hypoperfusion in prefrontal cortex, predominantly in left side and a hyper perfusion in left basal ganglia. All patients that received atypical antipsychotic drugs had clinical improvement and decreases in PANSS scores; the control SPECT analysis revealed the same cortical changes as first studies in 15 patients and an increase of the rCBF in frontal lobes for 4 patients. 14 patients we noticed an increased rCBF at subcortical level, especially in left caudate nuclei. Conclusions: We found nonspecific features of rCBF in patients with first episode of schizophrenia, suggesting a perfusion dynamic balance rather than a fixed model. Those aspects are much more related to clinical symptoms, than to the therapeutical response. The rCBF changes in subcortical level after treatment (64.4% increase of rCBF; 35.6% not modified), can have a good prognostic value for therapeutic response. (author)
Karthik, M. S.; Nisha Warikoo; Subho Chakrabarti; Sandeep Grover; Parmanand Kulhara
Background: Given the paucity of research in this area, this study attempted to assess attitudes toward antipsychotic medications and its correlates among patients with schizophrenia, either on first-generation antipsychotics (FGAs) or second-generation antipsychotics (SGAs) medications. Materials and Methods: Structured assessments of attitudes to antipsychotics, psychopathology, insight and side-effects were carried out in 120 patients with DSM-IV schizophrenia; 89 of these were on SGAs and...
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
Ichikawa, Junji; Chung, Young-Chul; Dai, Jin; Meltzer, Herbert Y
Antipsychotic drugs (APD)s and anticonvulsant mood-stabilizers are now frequently used in combination with one another in treating both schizophrenia and bipolar disorder. We have recently reported that the atypical APDs, e.g. clozapine and risperidone, as well as the anticonvulsant mood-stabilizers, valproic acid (VPA), zonisamide, and carbamazepine, but not the typical APD haloperidol, increase dopamine (DA) release in rat medial prefrontal cortex (mPFC). The increased DA release was partially (atypical APDs) or completely (mood-stabilizers) blocked by the serotonin (5-HT)1A receptor antagonist WAY100635. Diminished prefrontal cortical DA activity may contribute to cognitive impairment in virtually all the patients with schizophrenia and, perhaps, bipolar disorder. Thus, the enhanced release of cortical DA by these agents may be beneficial in this regard. It is, therefore, of considerable interest to determine whether combined administration of these agents augments prefrontal cortical DA release, and if so, whether the increase is dependent upon 5-HT1A receptor activation. VPA (50 mg/kg), which was insufficient by itself to increase prefrontal cortical DA release, potentiated the ability of clozapine (20 mg/kg) and risperidone (1 mg/kg) to increase DA release in the mPFC, but not in the nucleus accumbens (NAC). VPA (50 mg/kg) also potentiated haloperidol (0.5 mg/kg)-induced DA release in the mPFC; this increase was completely abolished by WAY100635 (0.2 mg/kg). These results suggest that, in combination with VPA, both typical and atypical APDs produce greater increases in prefrontal cortical DA release than either type of drug alone via a mechanism dependent upon 5-HT(1A) receptor activation. Furthermore, they provide a strong rationale for testing for possible clinical synergism of an APD and anticonvulsant mood-stabilizer in improving the cognitive deficits present in patients with schizophrenia and bipolar disorder. PMID:16061211
Pilla Reddy, Venkatesh; Suleiman, Ahmed; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; Liu, Jing; de Greef, Rik; Groothuis, Genoveva; Danhof, Meindert; Proost, Johannes
Objectives: It has been suggested that atypical antipsychotics (ATAPs), are more effective towards negative symptoms than typical antipsychotics (TAPs) in schizophrenic patients.[1,2] To quantify the above statement, we aimed i) to develop a PK-PD model that characterizes the time course of PANSS sc
Seyed Sina Ahmadi abhari
Full Text Available "nObjective: "n The lithium concentration in the plasma is assumed to give someindication as to the concentration of this ion in different organ cells especially incentral nervous system. While the practical value of intracellular lithium measurement is controversial however, erythrocytes have proved to be useful for studying lithium concentration and its transport across the membrane. There are some reports suggesting that neuroleptic drugs are able to affect the erythrocyte lithium concentration (ELCs, although these studies have yielded inconsistent results. "nMethod: In the present study the effect of risperidone and olanzapine as atypical antipsychotic and haloperidol as standard typical antipsychotic on lithium ratio in 46 acute manic patients was studied. ELCs were measured using atomic absorption spectrophotometer. Clinical response was evaluated by using Young mania rating scale (YMRS. "nResults: No significant difference was found between LRs and dose or type of antipsychotics. Also there were no significant differences between LRs and clinical response or remission. "nConclusion: The concurrent use of an atypical antipsychotics and lithium may not significantly alter the lithium transport in the erythrocyte and presumably in the nerve cells. A more comprehensive study is warranted to confirm the results of this study.
Woo, Young Sup; Bahk, Won-Myong; Park, Young-Min; Chung, Sangkeun; Yoon, Bo-Hyun; Won, Seunghee; Lee, Jeong Goo; Lee, Hwang-Bin; Kim, Won; Jeong, Jong-Hyun; Lee, Kwanghun; Kim, Moon-Doo
We evaluated the effectiveness of aripiprazole among bipolar patients who had switched to this medication as a result of difficulty maintaining on their prestudy atypical antipsychotics (AAPs) because of subsyndromal mood symptoms or intolerance. This study included 77 bipolar patients who were in syndromal remission with an AAP as monotherapy or with an AAP combined with a mood stabilizer(s) who needed to switch from their present AAP because of subsyndromal symptoms or intolerance. At 24 weeks after switching to aripiprazole, the remission rates on the Montgomery-Åsberg Depression Rating Scale (MADRS) and on both the MADRS and the Young Mania Rating Scale were increased significantly in the full sample and in the inefficacy subgroup. In the inefficacy subgroup, the MADRS score change was significant during the 24 weeks of study. Total cholesterol and prolactin decreased significantly after switching to aripiprazole. The proportion of patients who had abnormal values for central obesity and hypercholesterolemia decreased significantly from baseline to week 24. These findings suggest that a change from the current AAP to aripiprazole was associated with improvement in subsyndromal mood symptoms and several lipid/metabolic or safety profile parameters in patients with bipolar disorder with tolerability concerns or subsyndromal mood symptoms. PMID:27487259
O'Day K; Rajagopalan K; Meyer K; Pikalov A; Loebel A
Ken O'Day,1 Krithika Rajagopalan,2 Kellie Meyer,1 Andrei Pikalov,2 Antony Loebel21Xcenda, Palm Harbor, FL, 2Sunovion Pharmaceuticals, Marlborough, MA, USABackground: The purpose of this study was to evaluate the long-term cost-effectiveness (including hospitalizations and cardiometabolic consequences) of atypical antipsychotics among adults with schizophrenia.Methods: A 5-year Markov cohort cost-effectiveness model, from a US payer perspective, was developed to compare lurasidone, generic...
Ken O'Day,1 Krithika Rajagopalan,2 Kellie Meyer,1 Andrei Pikalov,2 Antony Loebel21Xcenda, Palm Harbor, FL, 2Sunovion Pharmaceuticals, Marlborough, MA, USABackground: The purpose of this study was to evaluate the long-term cost-effectiveness (including hospitalizations and cardiometabolic consequences) of atypical antipsychotics among adults with schizophrenia.Methods: A 5-year Markov cohort cost-effectiveness model, from a US payer perspective, was developed to compare lurasidone, gen...
O’Day, Ken; Rajagopalan, Krithika; Meyer, Kellie; Pikalov, Andrei; Loebel, Antony
Background The purpose of this study was to evaluate the long-term cost-effectiveness (including hospitalizations and cardiometabolic consequences) of atypical antipsychotics among adults with schizophrenia. Methods A 5-year Markov cohort cost-effectiveness model, from a US payer perspective, was developed to compare lurasidone, generic risperidone, generic olanzapine, generic ziprasidone, aripiprazole, and quetiapine extended-release. Health states included in the model were patients: on an ...
Xiao, Yongling; Muser, Erik; Fu, Dong-Jing; Lafeuille, Marie-Hélène; Pilon, Dominic; Emond, Bruno; Wu, Allen; Duh, Mei Sheng; Lefebvre, Patrick
Background Compared to oral atypical antipsychotics (OAAs), long-acting injectable antipsychotics require less frequent administration, and thus may improve adherence and reduce risk of relapse in schizoaffective disorder (SAD) patients. Objective To evaluate the impact of once monthly paliperidone palmitate (PP) versus OAAs on healthcare resource utilization, Medicaid spending, and hospital readmission among SAD patients. Methods Using FL, IA, KS, MS, MO, and NJ Medicaid data (January 2009-December 2013), adults with ≥2 SAD diagnoses initiated on PP or OAA (index date) were identified. Baseline characteristics and outcomes were assessed during the 12month pre- and post-index periods, respectively. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to reduce confounding and compare the estimated treatment effect for PP versus OAA. Results A total of 10,778 OAA-treated patients and 876 PP-treated patients were selected. Compared to OAAs, PP was associated with significantly lower medical costs (PSM: mean monthly cost difference [MMCD] = -$383, p < 0.001; IPTW: MMCD = -$403, p = 0.016), which offset the higher pharmacy costs associated with PP (PSM: MMCD = $270, p < 0.001; IPTW: MMCD = $350, p < 0.001) and resulted in similar total healthcare cost (PSM: MMCD = -$113, p = 0.414; IPTW: MMCD = -$53, p = 0.697) for PP versus OAA. Reduced risk of hospitalization (PSM: incidence rate ratio [IRR] = 0.85, p = 0.128; IPTW: IRR = 0.96, p = 0.004) and fewer hospitalization days (PSM: IRR = 0.74, p = 0.008; IPTW: IRR = 0.85, p < 0.001) were observed in PP versus OAA patients. Among hospitalized patients, PP was associated with a lower risk of 30 day hospital readmission compared to OAA (IPTW: odds ratio = 0.89, p = 0.041). Limitations The Medicaid data may not be representative of the nation or other states, and includes pre-rebate pharmacy costs
Full Text Available OBJECTIVE: Previous research has shown that a better therapeutic relationship (TR predicts more positive attitudes towards antipsychotic medication, but did not address whether it is also linked with actual adherence. This study investigated whether the TR is associated with adherence to antipsychotics in patients with schizophrenia. METHODS: 134 clinicians and 507 of their patients with schizophrenia or a related psychotic disorder participated in a European multi-centre study. A logistic regression model examined how the TR as rated by patients and by clinicians is associated with medication adherence, adjusting for clinician clustering and symptom severity. RESULTS: Patient and clinician ratings of the TR were weakly inter-correlated (r(s = 0.13, p = 0.004, but each was independently linked with better adherence. After adjusting for patient rated TR and symptom severity, each unit increase in clinician rated TR was associated with an increase of the odds ratio of good compliance by 65.9% (95% CI: 34.6% to 104.5%. After adjusting for clinician rated TR and symptom severity, for each unit increase in patient rated TR the odds ratio of good compliance was increased by 20.8% (95% CI: 4.4% to 39.8%. CONCLUSIONS: A better TR is associated with better adherence to medication among patients with schizophrenia. Patients' and clinicians' perspectives of the TR are both important, but may reflect distinct aspects.
de Araújo, Aurigena Antunes; de Araújo Dantas, Diego; do Nascimento, Gemma Galgani; Ribeiro, Susana Barbosa; Chaves, Katarina Melo; de Lima Silva, Vanessa; de Araújo, Raimundo Fernandes; de Souza, Dyego Leandro Bezerra; de Medeiros, Caroline Addison Carvalho Xavier
This cross-sectional study compared the effects of treatment with atypical antipsychotic drugs on quality of life (QoL) and side effects in 218 patients with schizophrenia attending the ambulatory services of psychiatric in Rio Grande do Norte, Brazil. Socio-economic variables were compared. The five-dimension EuroQoL (EQ-5D) was used to evaluate QoL, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using the χ (2) test and Student's t test, with a significance level of 5 %. Average monthly household incomes in the medication groups were 1.1-2.1 minimum wages ($339-$678). UKU Scale scores showed significant differences in side effects, mainly, clozapine, quetiapine and ziprasidone (p < 0.05). EQ-5D scores showed that all drugs except olanzapine significantly impacted mobility (p < 0.05), and proportions of individuals reporting problems in other dimensions were high: 63.6 % of clozapine users reported mobility problems, 63.7 and 56.3 % of clozapine and ziprasidone users, respectively, had difficulties with usual activities, 68.8 and 54.5 % of ziprasidone and clozapine users, respectively, experienced pain and/or discomfort, and 72.8 % of clozapine users reported anxiety and/or depression. Psychiatric, neurological, and autonomous adverse effects, as well as other side effects, were prevalent in users of atypical antipsychotic drugs, especially clozapine and ziprasidone. Olanzapine had the least side effects. QoL was impacted by side effects and economic conditions in all groups. Thus, the effects of these antipsychotic agents appear to have been masked by aggravating social and economic situations. PMID:24789610
Sohn, Minji; Moga, Daniela C; Blumenschein, Karen; Talbert, Jeffery
The objectives of the study were as follows: to examine the national trend of pediatric atypical antipsychotic (AAP) use in the United States; to identify primary mental disorders associated with AAPs; to estimate the strength of independent associations between patient/provider characteristics and AAP use. Data are from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. First, average AAP prescription rates among 4 and 18-year-old patients between 1993 and 2010 were estimated. Second, data from 2007 to 2010 were combined and analyzed to identify primary mental disorders related to AAP prescription. Third, a multivariate logistic regression model was developed having the presence of AAP prescription as the dependent variable and patient/provider characteristics as explanatory variables. Adjusted odds ratios (AORs) with associated 95% confidence intervals (CIs) were estimated. Outpatient visits including an AAP prescription among 4 to 18-year-old patients significantly increased between 1993 and 2010 in the United States, and over 65% of those visits did not have diagnoses for US Food and Drug Administration-approved AAP indications. During 2007 to 2010, the most common mental disorder was attention-deficit hyperactivity disorder, accounting for 24% of total pediatric AAP visits. Among visits with attention-deficit hyperactivity disorder diagnosis, those with Medicaid as payer (AOR 1.66, 95% CI 1.01-2.75), comorbid mental disorders (e.g., psychoses AOR 3.34, 95% CI 1.35-8.26), and multiple prescriptions (4 or more prescriptions AOR 4.48, 95% CI 2.08-9.64) were more likely to have an AAP prescription. The off-label use of AAPs in children and adolescents is prevalent in the United States. Our study raises questions about the potential misuse of AAPs in the population. PMID:27281081
H. K. Sushma
Conclusions: Schizophrenia is mostly seen in males, middle age group and unemployed people. The present study showed that combination therapy is preferred for the treatment of Schizophrenia. Despite several side-effects, typical antipsychotics, especially trifluoperazine was the most commonly used drug, followed by chlorpromazine either alone or in combination. Among atypical antipsychotics, risperidone was commonly used followed by quetiapine and asenapine. Most of the patients received trihexyphenidyl, an anticholinergic drug along with antipsychotics to reduce extra pyramidal side-effects. [Int J Basic Clin Pharmacol 2015; 4(1.000: 134-138
Full Text Available Peter M Haddad,1,2 Cecilia Brain,3,4 Jan Scott5,6 1Neuroscience and Psychiatry Unit, University of Manchester, Manchester, 2Greater Manchester West Mental Health NHS Foundation Trust, Salford, UK; 3Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, 4Nå Ut-teamet, Psychosis Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Academic Psychiatry, Institute of Neuroscience, Newcastle University, 6Centre for Affective Disorders, Institute of Psychiatry, London, UK Abstract: Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders
Hyun, Hyo Jin; Chung, Un Sun; Chun, Bo Young
We report a case of early resolution of convergence spasms following the addition of antipsychotic medications and present it as a possible alternative to the conventional treatment for convergence spasms. The cessation of atropinization of the eyes and the use of reading glasses was achieved after only 2 months following the initiation of antipsychotic medications for childhood emotional disorder.
Changes in dopamine receptor subtype binding in different brain regions were examined after 28 days treatment of rats with haloperidol, raclopride, clozapine or SCH23390 using in vitro receptor autoradiography. [3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin binding to dopamine D3 receptors was not changed in any brain region by any of the drug treatments. [3H]SCH23390 was only increased by chronic SCH23390 treatment. Haloperidol significantly increased [3H]nemonapride and [3H]spiperone binding to dopamine D2-like receptors in the caudate-putamen. In contrast, haloperidol caused a small, significant increase in [3H]raclopride binding in the lateral caudate-putamen only. Raclopride also elevated, but to a lesser extent [3H]nemonapride and [3H]spiperone binding in caudate-putamen, whereas it did not affect [3H]raclopride binding. Clozapine did not significantly change D2-like striatal binding of [3H]nemonapride, [3H]spiperone or [3H]raclopride. The differences in radioligand binding suggest that [3H]nemonapride and [3H]spiperone may be binding to additional subsets of dopamine D2-like receptors (including D4-like receptors) that are not recognized by [3H]raclopride, which has high affinity for D2 and D3 receptors only.Quantification of [3H]nemonapride or [3H]spiperone binding in the presence of 300 nM raclopride (to block D2 and D3 receptors) revealed that haloperidol, raclopride and clozapine up-regulated D4-like receptors in the caudate-putamen using either radioligand. These results suggest that D4-like receptors may be a common site of action of both typical and atypical antipsychotics. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)
Lee, Jong Il
Objective Atypical antipsychotic (AAP) treatment is associated with weight gain and metabolic disturbances such as dyslipidemia and dysglycemia. The metabolic disturbances are usually considered to develop secondary to weight gain. We performed the comparison of metabolic disturbances of three AAP group with different risk of metabolic side effect after adjusting for body mass to investigate whether any metabolic disturbances develop independently from body mass index (BMI). Methods This cross-sectional study included 174 subjects with schizophrenia who were on 1) monotherapy with clozapine (CL), olanzapine (OL), or quetiapine (QT) (n=61), 2) monotherapy with risperidone (RSP) (n=89), or 3) monotherapy with aripiprizole (ARP), or ziprasidone (ZPS) (n=24) more than 1 year. Association between the prevalence of metabolic disturbances and groups were analysed using logistic regression after adjusting confounding variables including BMI. Analysese of covariance were used to compare the AAP groups in terms of the levels of metabolic parameters. Results There were significant differences among groups in terms of the prevalence of hypertriglyceridemia (p=0.015), low HDL-cholesterol (p=0.017), and hyperglycemia (p=0.022) after adjusting for BMI. Triglyceride level (p=0.014) and the ratio of triglyceride to HDL-cholesterol (p=0.004) were significantly different among groups after adjusting for BMI. Conclusion In conclusion, metabolic disturbances are significantly different in AAP groups even after adjusting BMI. AAPs may have direct effect on metabolic parameters. Blood lipid and glucose levels should be monitored regularly regardless of whether patients tend to gain weight. PMID:25866526
Felipe Filardi da Rocha
Full Text Available CONTEXTO: Os estudos a respeito da ação dos antipsicóticos atípicos no comportamento suicida são controversos e pouco explorados. OBJETIVOS: Análise discursiva da ação dos antipsicóticos atípicos no comportamento suicida de pacientes esquizofrênicos ou esquizoafetivos. MÉTODOS: Revisão de artigos nas bases de dados MEDLINE, LILACS e da Biblioteca Cochrane, entre o período de 1964 e 2009, usando as palavras-chave: "suicidal behavior" e/ou "suicide" e "atypical antipsychotics" e/ou "antipsychotics" e/ou "clozapine". RESULTADOS: As únicas evidências significativas positivas apontam para a clozapina, que apresenta uma relevância superior aos outros antipsicóticos de segunda geração na redução das taxas de autoextermínio. CONCLUSÕES: A clozapina é o único fármaco que pode alterar o comportamento suicida. Esse efeito não está associado à melhora clínica dos pacientes. Ela é a única droga aprovada pelo Food and Drug Administration (FDA para prevenir suicídio em pacientes esquizofrênicos, mas os critérios para esse fim são incertos.BACKGROUND: The literature concerning the net effect of atypical antipsychotic medication on suicidality is not consistent. OBJECTIVES: The empirical literature relating to the efficacy of pharmacological intervention with atypical antipsychotics in esquizophrenic or schizo-affective patients is comprehensively reviewed. METHODS: MEDLINE, LILACS and Cochrane Library were used to search for articles from 1964 to 2009 using these key-words: "suicidal behavior" e/ou "suicide" e "atypical antipsychotics" e/ou "antipsychotics" e/ou "clozapine". RESULTS: The strongest and perhaps unique evidence has been shown for clozapine, which seems to have a clinically relevant advantage over other second-generation antipsychotics for reducing suicidality temptation. DISCUSSION: Clozapine is the unique medication that modulates suicidal behavior. Its action is unknown but is not related do clinical
Pasternak, Björn; Svanström, Henrik; Ranthe, Mattis F;
risperidone (n = 14,134). The primary outcome was any major cardiovascular event (composite of cardiovascular mortality, acute coronary syndrome, or ischemic stroke) within 1 year following treatment initiation. Cox regression was used to estimate hazard ratios (HRs) while on current antipsychotic monotherapy......BACKGROUND: A number of serious cardiovascular safety concerns related to the use of atypical antipsychotics, compared with no use, have emerged, but nearly all reports are from studies of older patients. We aimed to compare the risk of cardiovascular events between the three most commonly used...... in the outpatient setting, adjusting for an outcome-specific disease risk score. RESULTS: The crude rate of any major cardiovascular event was 5.3 per 1,000 person-years among olanzapine users, 3.4 in quetiapine users, and 5.2 in risperidone users. Compared with risperidone, the risk of any major cardiovascular...
Votaw, J. R.; Ritchie, J.; Howell, L. L.
Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design. [18F]fallypride positron emission tomography scans were obtained on four different doses of risperidone and paliperidone (the 9-OH metabolite of risperidone) and compared with multiple off-drug scans in each animal. The half-life of the two drugs in these monkeys was determined to be between 3 and 4 h, and drug was administered by a constant infusion through an intragastric catheter. The D2R occupancy of antipsychotic was determined in the caudate, putamen, ventral striatum, and four prefrontal and temporal cortical regions and was related to serum and cerebrospinal fluid drug levels. Repeated 2-week treatment with risperidone or paliperidone did not produce lasting changes in D2R binding potential in any region examined. As expected, D2R binding potential was highest in the caudate and putamen and was approximately one-third that level in the ventral striatum and 2% of that level in the cortical regions. We found dose-dependent D2R occupancy for both risperidone and paliperidone in both basal ganglia and cortical regions of interest. We could not find evidence of regional variation in D2R occupancy of either drug. Comparison of D2R occupancy and serum drug levels supports a target of 40 to 80 ng/ml active drug for these two atypical antipsychotics. PMID:22214649
Larsen, J. T.; Fagerquist, M.; Holdrup, M.;
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...... population of patients with schizophrenia spectrum disorders, metabolic syndrome remains underdiagnosed and undertreated....... the psychiatrists' choice of recommendations for follow-up interventions based on the patients' laboratory results. Method: This was a cross-sectional, observational multi-center study in Denmark and Sweden, in consecutively screened in- and outpatients with schizophrenia spectrum disorders and continuously treated...
Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.
Vancampfort, Davy; Probst, Michel; Daenen, Anne; Damme, Tine Van; De Hert, Marc; Rosenbaum, Simon; Bruyninckx, David
Antipsychotics are used increasingly in adolescents for a range of psychiatric disorders. The aim of the current study was to investigate whether physical activity levels and physical fitness of adolescent inpatients treated with antipsychotic medication, differs from either (i) antipsychotic naïve adolescents with mental health problems and, (ii) healthy controls. All participants completed the Physical Activity Questionnaire for Adolescents, the Positive-and-Negative-Affect-Schedule and performed the Eurofit test battery. Adolescents with mental health problems (irrespective of antipsychotic medication) were significantly (Prunning speed and cardiovascular endurance compared to healthy controls (n=15, 8♂, 15.9±1.3 years). Adolescents treated with antipsychotic medication (n=15, 8♂, 15.5±1.3 years) were less physically active and had an impaired whole body balance compared with antipsychotic naïve adolescents (n=15, 8♂, 15.7±1.4 years). Given the overwhelming deleterious impact of physical inactivity and low physical fitness on physical and mental health outcomes, interventions specifically targeting physical activity and physical fitness among adolescents experiencing mental illness, both treated with, and not treated with antipsychotic medication are warranted as a priority. Antipsychotic medication should be considered as a risk factor for physical inactivity and poor physical fitness. PMID:27288738
Gasse, Christiane; Jacobsen, Jacob; Pedersen, Lars;
STUDY OBJECTIVE: To examine the association of atypical and conventional antipsychotics with the risk of hospitalization for acute pancreatitis. DESIGN: Population-based, case-control study. DATA SOURCE: Health care databases of Northern Denmark. PATIENTS: A total of 3083 adults hospitalized with...... acute pancreatitis (case patients) and 30,830 control subjects. MEASUREMENTS AND MAIN RESULTS: Controls were selected from the general population by using risk-set sampling and were matched to case patients by age and sex. The date of the case patients' admission for acute pancreatitis was used as the...... index date for the matched control subjects. Conditional logistic regression analysis was used to estimate rate ratios (RRs) for hospitalization due to acute pancreatitis in current users (0-90 days before admission or index date) and former users (> 90 days before admission or index date) of atypical...
Gregoor, Jochem G.; van der Weide, Jan; Mulder, Hans; Cohen, Dan; van Megen, Harold J. G. M.; Egberts, Antoine C. G.; Heerdink, Eibert R.
Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/ A polymorphism are associated with
Freeman, Marlene P; Sosinsky, Alexandra Z; Moustafa, Danna; Viguera, Adele C; Cohen, Lee S
Women of reproductive age commonly use integrative treatments. However, the reproductive safety for most complementary products lacks systematic study. We aimed to study the use of supplements by women in a prospective pregnancy registry. The Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics was established to evaluate the reproductive safety of atypical antipsychotics. Exposed and control participants were systematically queried about the use of vitamins and supplements. Slightly greater than half (53.2 %) of the participants eligible for analysis (N = 534) were using at least one vitamin or supplement at the time of enrollment, not including prenatal vitamins or folic acid. The most common supplements used were omega-3 fatty acids (38.0 %), vitamin D (11.0 %), calcium (8.2 %), and iron (4.7 %). Probiotics and melatonin were used by 2.6 and 0.9 %, respectively. In this prospective pregnancy registry, we found that over half of the participants were taking supplements or vitamins other than prenatal vitamins and folic acid. These findings underscore the need for active query on the part of health care providers about the use of supplements during pregnancy, and the need to obtain rigorous reproductive safety and efficacy data for supplements used by pregnant women and reproductive aged women. PMID:26472040
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
Sárvári, Anitta K., E-mail: email@example.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: firstname.lastname@example.org [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: email@example.com [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: firstname.lastname@example.org [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: email@example.com [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)
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
Reis Helton J
Full Text Available Abstract Background Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D2. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC: Neuronal Calcium Sensor-1 (NCS-1 and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D2 internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT and PC12 cells stably overexpressing NCS-1 (PC12 Clone with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment. Results We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol or atypical (Clozapine and Risperidone antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments. Conclusions Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.
Zedková, I.; Dudová, I.; Urbánek, Tomáš; Hrdlička, M.
Roč. 32, č. 5 (2011), s. 667-670. ISSN 0172-780X Institutional research plan: CEZ:AV0Z70250504 Keywords : schizophrenia * antipsychotics * onset of action Subject RIV: AN - Psychology Impact factor: 1.296, year: 2011
Murray-Thomas, Tarita; Jones, Meghan E; Patel, Deven; Brunner, Elizabeth; Shatapathy, Chetan C; Motsko, Stephen; Van Staa, Tjeerd P
Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64-1.87); cardiac mortality 1.72 (95% CI: 1.42-2.07); SCD primary definition 5.76 (95% CI: 2.90-11.45); SCD secondary definition 2.15 (95% CI: 1.64-2.81); CHD 1.16 (95% CI: 0.94-1.44); and VA 1.16 (95% CI: 1.02-1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80-0.85); cardiac mortality 0.89 (95% CI: 0.82-0.97); and SCD secondary definition 0.76 (95% CI: 0.55-1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort. PMID:24455199
Full Text Available Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD, all-cause mortality (excluding suicide, coronary heart disease (CHD, and ventricular arrhythmias (VA. Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical, 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64–1.87; cardiac mortality 1.72 (95% CI: 1.42–2.07; SCD primary definition 5.76 (95% CI: 2.90–11.45; SCD secondary definition 2.15 (95% CI: 1.64–2.81; CHD 1.16 (95% CI: 0.94–1.44; and VA 1.16 (95% CI: 1.02–1.31. aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80–0.85; cardiac mortality 0.89 (95% CI: 0.82–0.97; and SCD secondary definition 0.76 (95% CI: 0.55–1.04. Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.
Crespo Facorro, Benedicto; Prieto Sánchez, Carlos; Sainz Maza, Jesús Vicente
BACKGROUND: Despite the widespread use of antipsychotics, little is known of the molecular bases behind the action of antipsychotic drugs. A genome-wide study is needed to characterize the genes that affect the clinical response and their adverse effects. METHODS: Here we show the analysis of the blood transcriptome of 22 schizophrenia patients before and after medication with atypical antipsychotics by next-generation sequencing. RESULTS: We found that 17 genes, among the 21 495 genes analyz...
M S Karthik
Full Text Available Background: Given the paucity of research in this area, this study attempted to assess attitudes toward antipsychotic medications and its correlates among patients with schizophrenia, either on first-generation antipsychotics (FGAs or second-generation antipsychotics (SGAs medications. Materials and Methods: Structured assessments of attitudes to antipsychotics, psychopathology, insight and side-effects were carried out in 120 patients with DSM-IV schizophrenia; 89 of these were on SGAs and 31 on FGAs. Results: Patients had predominantly positive attitudes toward antipsychotics. Severity of side-effects was the principal correlate of attitudes, explaining 19.5% of the variance, followed by greater insight (4.2% of the variance. Other factors such as younger age, male gender, employment, higher family income, urban residence and lower symptom-severity explained only a negligible proportion of the variance (0.2% in attitudes. Patients on SGAs had more positive views of their medications than those on FGAs. They felt more normal on their medications, believed that their thoughts were clearer on medications, felt that good things about their medications outweighed the bad and believed that their medications helped them from falling ill again. In addition, they did not feel as tired and sluggish on their medications and did not believe that medications were unnatural or controlled their bodies. Conclusions: Positive attitudes toward antipsychotics were common among patients with schizophrenia. Attitudes were principally determined by severity of side-effects and insight levels. Patients on SGAs had better attitudes, possibly because of less severe side-effects and greater insight among them. The importance of exploring patients′ attitudes toward their antipsychotics is highlighted by this study.
Nielsen, Mette Ødegaard; Rostrup, Egill; Nørbak, Henrik;
BACKGROUND Disturbances of the brain reward system are suggested to play an important role in the development of central psychopathological symptoms in schizophrenia, and antipsychotic medication partly acts by modulating the reward system. Further, the reward system is known to be central to the...... antipsychotic treatment on the reward system relate to weight gain in patients. METHODS 50 antipsychotic-naïve first-episode patients with schizophrenia and 40 healthy controls were included in the study at baseline. 38 patients and 31 healthy controls were re-examined after six weeks where patients were...... assume that it is related to changes in dopamine transmission. Thus our results suggest that by altering the dopaminergic transmission in putamen, antipsychotic medication might through the influence on reward system affect appetite regulation and thereby, together with other mechanisms, lead to weight...
Ping WANG; Tianmei SI
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.
Kotani, Manato; Enomoto, Takeshi; Murai, Takeshi; Nakako, Tomokazu; Iwamura, Yoshihiro; Kiyoshi, Akihiko; Matsumoto, Kenji; Matsumoto, Atsushi; Ikejiri, Masaru; Nakayama, Tatsuo; Ogi, Yuji; Ikeda, Kazuhito
Antagonism of the dopamine D3 receptor is considered a promising strategy for the treatment of cognitive impairment associated with schizophrenia. We have previously reported that the atypical antipsychotic blonanserin, a dopamine D2/D3 and serotonin 5-HT2A receptor antagonist, highly occupies dopamine D3 receptors at its antipsychotic dose range in rats. In the present study, we evaluated the effects of blonanserin on executive function in common marmosets using the object retrieval with detour (ORD) task. The dopamine D3 receptor-preferring agonist (+)-PD-128907 at 1mg/kg decreased success rate in the difficult trial, but not in the easy trial. Since the difference between the two trials is only cognitive demand, our findings indicate that excess activation of dopamine D3 receptors impairs executive function in common marmosets. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by (+)-PD-128907 in the difficult trial. This finding indicates that blonanserin has beneficial effect on executive function deficit induced by activation of the dopamine D3 receptor in common marmosets. Next, and based on the glutamatergic hypothesis of schizophrenia, the common marmosets were treated with the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine. Ketamine at sub-anesthetic doses decreased success rate in the difficult trial, but not in the easy trial. Blonanserin at 0.1mg/kg reversed the decrease in success rate induced by ketamine in the difficult trial. The findings of this study suggest that blonanserin might have beneficial effect on executive dysfunction in patients with schizophrenia. PMID:26970575
Full Text Available Abstract Background This study compared 1-year risk of psychiatric hospitalization and treatment costs in commercially insured patients with bipolar disorder, treated with aripiprazole, ziprasidone, olanzapine, quetiapine or risperidone. Methods This was a retrospective propensity score-matched cohort study using the Ingenix Lab/Rx integrated insurance claims dataset. Patients with bipolar disorder and 180 days of pre-index enrollment without antipsychotic exposure who received atypical antipsychotic agents were followed for up to 12 months following the initial antipsychotic prescription. The primary analysis used Cox proportional hazards regression to evaluate time-dependent risk of hospitalization, adjusting for age, sex and pre-index hospitalization. Generalized gamma regression compared post-index costs between treatment groups. Results Compared to aripiprazole, ziprasidone, olanzapine and quetiapine had higher risks for hospitalization (hazard ratio 1.96, 1.55 and 1.56, respectively; p Conclusions In commercially insured adults with bipolar disorder followed for 1 year after initiation of atypical antipsychotics, treatment with aripiprazole was associated with a lower risk of psychiatric hospitalization than ziprasidone, quetiapine, olanzapine and risperidone, although this did not reach significance with the latter. Aripiprazole was also associated with significantly lower total healthcare costs than quetiapine, but not the other comparators.
Unremitting Impulsive Aggression in a Child with Childhood Onset Schizophrenia and Pervasive Development Disorder-Not Otherwise Specified: The Role of Stimulants, Atypical Antipsychotics and Mood Stabilizers
Taşkıran, Sarper; Coffey, Barbara J.
Advanced Pediatric Psychopharmacology Unremitting Impulsive Aggression in a Child with Childhood Onset Schizophrenia and Pervasive Development Disorder-Not Otherwise Specified: The Role of Stimulants, Atypical Antipsychotics and Mood Stabilizers Presenter: Sarper Taskiran, MD1 Discussant: Barbara J. Coffey, MD, MS2 Chief Complaint and Presenting Problem C. is a 7 ½-year-old, right-handed, elementary school student in a special education class, who carries a...
As the clinical application of universal, atypical antipsychotics have not just as the treatment of schizophrenia, in bipolar disorder treatment, its application is becoming more and more attention by clinical workers. Atypical antipsychotics for bipolar mania and depression phase in the acute phase of treatment, curative effect and adverse reaction of rare, safety tolerance. This paper mainly introduces the atypical antipsychotic drugs in the treatment of bipolar disorder, provide reference for clinical rational drug use.%随着临床应用的普遍，非典型抗精神病药物已不单纯作为精神分裂症的治疗，在双相障碍治疗中，其应用也越来越受到临床工作者的关注。非典型抗精神病药物对于双相障碍躁狂相和抑郁相的急性发作期的治疗，疗效肯定，不良反应少见，安全耐受。本文主要介绍非典型抗精神病药物在双相障碍治疗中的应用，为临床合理用药提供参考。
Bapu V Ravindranath
Full Text Available Background: To review evidence of chronic antipsychotic medication and the association with metabolic syndrome in mentally ill patients. This evidence was used to analyse a cohort of patients with severe mental illness and to deduce a correlation between the prevalence of metabolic syndrome and their dose regimens. Materials and Methods: Twenty-four male patients undergoing Psychiatric rehabilitation underwent a review of current medication and assessment of risk factors for metabolic syndrome. Assessment criteria was based upon National Cholesterol Education Programme expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III (NCEP ATP III criteria, incorporating waist circumference, raised triglycerides, reduced high density lipoprotein, raised blood pressure and fasting blood glucose. PubMed, Nature and Science Direct databases have been used to compile the medical and scientific background on metabolic syndrome and antipsychotic medication and the effect on patients particularly on high dose. Results: Out of 24 patients, 10 patients (41.7% were receiving high dose antipsychotics (HDA and four were on maximum dosage limits of 100%. 8.3% (2/24 patients were receiving only one first generation antipsychotics (FGA, 37.5% (9/24 patients were receiving only one second generation antipsychotic (SGA, 45.8% patients (11/24 were receiving two or more SGA only, and only one patient was receiving two or more FGA. One patient was receiving a combination of FGA and SGA. PRN ("as needed" therapy was not included in this study as their usage was limited. Clozapine was mostly prescribed in these patients (10/24, 41.6%. Four out of the 24 patients refused blood tests therefore were excluded from the following results. In the patients evaluated, 55% (11/20 had confirmed metabolic syndrome. In these patients with metabolic syndrome, 45.4% (5/11 were on HDA and 27.3% (3/11 were on maximum British National
Full Text Available Quetiapine (Que, a commonly used atypical antipsychotic drug (APD, can prevent myelin from breakdown without immune attack. Multiple sclerosis (MS, an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells. In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE, a mouse model for MS. Que treatment was initiated on the onset of MOG(35-55 peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4(+/CD8(+ populations and the proliferation of effector T cells (CD4(+CD25(- in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4(+/CD8(+ T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4(+/CD8(+ T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG(35-55 or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4(+CD25(- isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.
Carty, N C; Xu, J; Kurup, P; Brouillette, J; Goebel-Goody, S M; Austin, D R; Yuan, P; Chen, G; Correa, P R; Haroutunian, V; Pittenger, C; Lombroso, P J
Glutamatergic signaling through N-methyl-D-aspartate receptors (NMDARs) is required for synaptic plasticity. Disruptions in glutamatergic signaling are proposed to contribute to the behavioral and cognitive deficits observed in schizophrenia (SZ). One possible source of compromised glutamatergic function in SZ is decreased surface expression of GluN2B-containing NMDARs. STEP(61) is a brain-enriched protein tyrosine phosphatase that dephosphorylates a regulatory tyrosine on GluN2B, thereby promoting its internalization. Here, we report that STEP(61) levels are significantly higher in the postmortem anterior cingulate cortex and dorsolateral prefrontal cortex of SZ patients, as well as in mice treated with the psychotomimetics MK-801 and phencyclidine (PCP). Accumulation of STEP(61) after MK-801 treatment is due to a disruption in the ubiquitin proteasome system that normally degrades STEP(61). STEP knockout mice are less sensitive to both the locomotor and cognitive effects of acute and chronic administration of PCP, supporting the functional relevance of increased STEP(61) levels in SZ. In addition, chronic treatment of mice with both typical and atypical antipsychotic medications results in a protein kinase A-mediated phosphorylation and inactivation of STEP(61) and, consequently, increased surface expression of GluN1/GluN2B receptors. Taken together, our findings suggest that STEP(61) accumulation may contribute to the pathophysiology of SZ. Moreover, we show a mechanistic link between neuroleptic treatment, STEP(61) inactivation and increased surface expression of NMDARs, consistent with the glutamate hypothesis of SZ. PMID:22781170
Smolen Lee J
Full Text Available Abstract Background Schizophrenia is often a persistent and costly illness that requires continued treatment with antipsychotics. Differences among antipsychotics on efficacy, safety, tolerability, adherence, and cost have cost-effectiveness implications for treating schizophrenia. This study compares the cost-effectiveness of oral olanzapine, oral risperidone (at generic cost, primary comparator, quetiapine, ziprasidone, and aripiprazole in the treatment of patients with schizophrenia from the perspective of third-party payers in the U.S. health care system. Methods A 1-year microsimulation economic decision model, with quarterly cycles, was developed to simulate the dynamic nature of usual care of schizophrenia patients who switch, continue, discontinue, and restart their medications. The model captures clinical and cost parameters including adherence levels, relapse with and without hospitalization, quality-adjusted life years (QALYs, treatment discontinuation by reason, treatment-emergent adverse events, suicide, health care resource utilization, and direct medical care costs. Published medical literature and a clinical expert panel were used to develop baseline model assumptions. Key model outcomes included mean annual total direct cost per treatment, cost per stable patient, and incremental cost-effectiveness values per QALY gained. Results The results of the microsimulation model indicated that olanzapine had the lowest mean annual direct health care cost ($8,544 followed by generic risperidone ($9,080. In addition, olanzapine resulted in more QALYs than risperidone (0.733 vs. 0.719. The base case and multiple sensitivity analyses found olanzapine to be the dominant choice in terms of incremental cost-effectiveness per QALY gained. Conclusion The utilization of olanzapine is predicted in this model to result in better clinical outcomes and lower total direct health care costs compared to generic risperidone, quetiapine, ziprasidone, and
Huang, Mei; Li, Zhu; Ichikawa, Junji; Dai, Jin; Meltzer, Herbert Y
Mood stabilizers (e.g., valproic acid) and antipsychotic drugs (APDs) are commonly co-administered in the treatment of bipolar disorder and schizophrenia. The basis for any synergism between these classes of drugs in either group of disorders has been little studied. Previous studies have shown that atypical APDs (e.g., clozapine) preferentially increases dopamine (DA) and acetylcholine (ACh) efflux in rat medial prefrontal cortex (mPFC) and hippocampus (HIP), both of which have been suggested to contribute to their ability to improve cognition in patients with schizophrenia. We have recently reported that the anticonvulsant mood stabilizers (AMS), valproic acid, carbamazepine, and zonisamide, but not lithium, also preferentially increase DA efflux in the rat mPFC, and that, at subthreshold doses, the AMS also augment the ability of the atypical APDs clozapine and risperidone to increase DA but not ACh efflux in the mPFC. The present study examined the ability of divalproex (DVX), which is chemically related to valproic acid, to enhance DA and ACh efflux in the HIP and to augment the effect of atypical APDs on ACh efflux in the HIP and mPFC. DVX, 500 mg/kg, significantly increased DA and ACh efflux in the HIP, and DA, but not ACh, efflux in the mPFC, whereas a lower dose of DVX, 50 mg/kg, had no effect on DA or ACh in either region. However, DVX, 50 mg/kg, combined with the atypical APDs olanzapine (1.0 mg/kg) or aripiprazole (0.3 mg/kg) significantly potentiated the effect of both APDs on DA, but not ACh efflux in the HIP and mPFC. Pretreatment of olanzapine or aripiprazole with the selective serotonin 5-HT(1A) antagonist, WAY100635 (1.0 mg/kg) partially but significantly blocked the effect of the combination of DVX, 50 mg/kg, and olanzapine or aripiprazole, on DA efflux in both the HIP and mPFC. WAY100635 did not affect the ability of the combination of olanzapine or aripiprazole and DVX to enhance ACh efflux in the HIP or mPFC. Subchronic administration of the
Mishra Biswaranjan; Mishra Baikunthanath; Sahoo Saddichha; Arora Manu; Khess C.R.J
Neuroleptic malignant syndrome (NMS) is the most serious of acute neurological side effects produced by antipsychotic medication, characterized by hyperthermia, rigidity, altered consciousness and autonomic dysfunction, the prevalence of which varies from 0.4-1.4%. NMS is usually seen in treatment with high potency typical antipsychotics and very rarely with atypical antipsychotics. However, NMS cases have been reported with risperidone, clozapine, olanzapine and quetiapine. The presen...
Singh, K P; Singh, Manoj K; Gautam, Shrikant
For clinical management of different forms of psychosis, both classical and atypical anti-psychotic drugs (APDs) are available. These drugs are widely prescribed, even during pregnancy considering their minimal extra-pyramidal side effects and teratogenic potential compared to classical APDs. Among AAPDs, risperidone (RIS) is a first-line drug of choice by physicians. The molecular weight of RIS is 410.49 g/mol; hence, it can easily cross the placental barrier and enter the foetal bloodstream. It is not known whether or not AAPDs like RIS may affect the developing placenta and foetus adversely. Reports on this issue are limited and sketchy. Therefore, this study has evaluated the effects of maternal exposure to equivalent therapeutic doses of RIS on placental growth, histopathological and cytoarchitectural changes, and to establish a relationship between placental dysfunction and foetal outcomes. Pregnant rats (n = 24) were exposed to selected doses (0.8, 1.0 and 2.0 mg/kg) of RIS from gestation days 6-21. These dams were sacrificed; their placentas and foetuses were collected, morphometrically examined and further processed for histopathological examination. This study revealed that in utero exposure to equivalent therapeutic doses of RIS during organogenesis-induced placental dystrophy (size and weight), disturbed cytoarchitectural organization (thickness of different placental layers), histopathological lesions (necrosis in trophoblast with disruption of trophoblastic septa and rupturing of maternal-foetal interface) and intrauterine growth restriction of the foetuses. It may be concluded that multifactorial mechanisms might be involved in the dysregulation of structure and function of the placenta and of poor foetal growth and development. PMID:27256515
Full Text Available Background: Antipsychotic monotherapy or polypharmacy (concurrent use of two or more antipsychotics are used for treating patients with psychiatric disorders (PDs. Usually, antipsychotic monotherapy has a lower cost than polypharmacy. This study aimed to predict the cost of antipsychotic medications (AM of psychiatric patients in Iran. Materials and Methods: For this purpose, 790 patients with PDs who were discharged between June and September 2010 were selected from Razi Psychiatric Hospital, Tehran, Iran. For cost prediction of AM of PD, neural network (NN and multiple linear regression (MLR models were used. Analysis of data was performed with R 2.15.1 software. Results: Mean ± standard deviation (SD of the duration of hospitalization (days in patients who were on monotherapy and polypharmacy was 31.19 ± 15.55 and 36.69 ± 15.93, respectively (P < 0.001. Mean and median costs of medication for monotherapy (n = 507 were $8.25 and $6.23 and for polypharmacy (n =192 were $13.30 and $9.48, respectively (P = 0.001. The important variables for cost prediction of AM were duration of hospitalization, type of treatment, and type of psychiatric ward in the MLR model, and duration of hospitalization, type of diagnosed disorder, type of treatment, age, Chlorpromazine dosage, and duration of disorder in the NN model. Conclusion: Our findings showed that the artificial NN (ANN model can be used as a flexible model for cost prediction of AM.
Full Text Available Haya Ascher-Svanum, Alan JM Brnabic, Anthony H Lawson, Bruce J Kinon, Virginia L Stauffer, Peter D Feldman, Katarina KelinLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USAAbstract: It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients’ clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0–14 days prior and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%. Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions–Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient’s worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians’ stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research
Full Text Available Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999-2001 at the age of 33-35 years. A follow-up was conducted 9 years later during 2008-2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain. The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain. In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.
Veijola, Juha; Guo, Joyce Y.; Moilanen, Jani S.; Jääskeläinen, Erika; Miettunen, Jouko; Kyllönen, Merja; Haapea, Marianne; Huhtaniska, Sanna; Alaräisänen, Antti; Mäki, Pirjo; Kiviniemi, Vesa; Nikkinen, Juha; Starck, Tuomo; Remes, Jukka J.; Tanskanen, Päivikki; Tervonen, Osmo; Wink, Alle-Meije; Kehagia, Angie; Suckling, John; Kobayashi, Hiroyuki; Barnett, Jennifer H.; Barnes, Anna; Koponen, Hannu J.; Jones, Peter B.; Isohanni, Matti; Murray, Graham K.
Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions. PMID:25036617
Wium-Andersen, Marie Kim; Ørsted, David Dynnes; Nordestgaard, Børge Grønne
BACKGROUND: Tobacco smoking is more common among patients with schizophrenia and depression than among healthy individuals. We tested the hypothesis that high tobacco smoking intensity is causally associated with antipsychotic medication use, schizophrenia, antidepressant medication use and....../or depression in the general population, and compared results with those for chronic obstructive pulmonary disease. METHODS: We used self-reported smoking intensity in cigarettes/day and a polymorphism in the CHRNA3 gene cluster (rs1051730) associated with smoking intensity, on 63,296 20-100-year...... compared with non-carriers (CC). Furthermore, in ever-smokers homozygotes had increased risk of antipsychotic medication with an odds ratio (OR) of 1.16 [95% confidence interval (CI) 1.02-1.31] compared with non-carriers, whereas in never-smokers the corresponding OR was 1.07 (0.87-1.31) (P-interaction: 0...
Muly, E.C.; Votaw, J. R.; Ritchie, J.; Howell, L.L.
Blockade of D2 family dopamine receptors (D2Rs) is a fundamental property of antipsychotics, and the degree of striatal D2R occupancy has been related to antipsychotic and motor effects of these drugs. Recent studies suggest the D2R occupancy of antipsychotics may differ in extrastriatal regions compared with the dorsal striatum. We studied this issue in macaque monkeys by using a within-subjects design. [18F]fallypride positron emission tomography scans were obtained on four different doses ...
Ryan P. Balzan
Full Text Available Background: Psychotherapies for psychosis typically aim to develop an awareness of the implausible content of a delusion or target the underlying cognitive biases (i.e., problematic thinking styles, such as hasty decisions and illusory control that foster and maintain delusional beliefs. A recently designed individual-based treatment entitled metacognitive therapy (MCT+ combines these two approaches. Emerging evidence suggests individualised MCT+, when used concurrently with antipsychotic medication, may be an effective psychological treatment for reducing delusional symptoms. However, it remains to be tested whether MCT+ can be effective in patients with active delusions who are not currently receiving psychotropic drugs. Method: We present two cases (one patient with schizophrenia and the other with delusional disorder experiencing active delusions who underwent four-weeks of intensive MCT+, without concurrent antipsychotic medication (minimum 6-months unmedicated. Baseline and 6-week follow-up data are presented on a variety of measures assessing delusion symptom severity (i.e., PANSS, PSYRATS, SAPS, clinical insight, and cognitive bias propensity. Results: After 4-weeks of MCT+, both patients showed substantial reduction in delusional symptoms, reported improved clinical insight, and were less prone to making illusory correlations. Conclusions: The presented case studies provide preliminary evidence for the feasibility of MCT+ in treating patients not taking, or resistant to, antipsychotic medication.
Pakpoor, Jina; Agius, Mark
Since the introduction of antipsychotic medication for the treatment of psychosis, a wide range of different types of antipsychotic drugs have been developed while their side effects have become evident. The side effects of both the typical and atypical generation of antipsychotics have important consequences for the quality of life of recipients, stigma experienced and also the level of care of patients. It is well acknowledged that the side effects of antipsychotics reduce compliance with the medication. In this review the data for an association between typical and atypical antipsychotics and the main side effects that are well-supported in the literature was explored: weight gain and associated metabolic effects; extrapyramidal symptoms and tardive dyskinesia; prolactin elevation and associated sexual effects; QTc elongation; and a group of miscellaneous side effects. It has been demonstrated that the production of adverse effects following the use of antipsychotic medication differs widely both between atypical and typical drugs but also within these subgroups. Considering the wide range of antipsychotics available amongst both groups and the differing effects they have on patients in terms of side effects, there is reason to believe that a more personalised approach to antipsychotic treatment should be considered. Additionally, screening for risk factors, screening for the appearance of side effects, as well as good communication with patients about the side effects and other options available are important tasks for clinicians in order to optimise concordance with medication. PMID:25413553
Full Text Available BACKGROUND: It is important to develop novel antipsychotics that can effectively treat schizophrenia with minor side-effects. The aim of our work is to develop novel antipsychotics that act on dopamine D(2 and D(3, serotonin 5-HT(1A and 5-HT(2A receptors with low affinity for the serotonin 5-HT(2C and H(1 receptors, which can effectively cure positive symptoms, negative symptoms and cognitive impairment without the weight gain side-effect. METHODOLOGY/PRINCIPAL FINDINGS: A series of 2-substituted-5-thiopropylpiperazine (piperidine -1,3,4-oxadiazoles derivatives have been synthesized and the target compounds were evaluated for binding affinities to D(2, 5-HT(1A and 5-HT(2A receptors. Preliminary results indicated that compounds 14, 16 and 22 exhibited high affinities to D(2, 5-HT(1A and 5-HT(2A receptors among these compounds. Further binding tests showed that compound 22 had high affinity for D(3 receptor, and low affinity for serotonin 5-HT(2C and H(1 receptors. In addition, compound 22 inhibited apomorphine-induced climbing behavior and MK-801-induced hyperactivity with no extrapyramidal symptoms liability in mice. Moreover, compound 22 exhibited acceptable pharmacokinetic properties. CONCLUSIONS/SIGNIFICANCE: Compound 22 showed an atypical antipsychotic activity without liability for extrapyramidal symptoms. We anticipate compound 22 to be useful for developing a novel class of drug for the treatment of schizophrenia.
Furiak Nicolas M
Full Text Available Abstract The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms. A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill. Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT and once-monthly risperidone long-acting injection (RIS-LAI with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total and are estimated for LFA therapies given at three, six, and nine month intervals. The one-year results show that LFA therapy every 3 months (LFA-3 ($6,088 is less costly than either RIS-SOT ($10,721 or RIS-LAI ($9,450 with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41. Extending the interval to six (LFA-6 and nine (LFA-9 months resulted in further reductions in relapse and costs. Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health
Ruiz, Lisa M; Damron, Mackenzie; Jones, Kyle B; Weedon, Dean; Carbone, Paul S; Bakian, Amanda V; Bilder, Deborah A
This study describes antipsychotic use and metabolic monitoring rates among individuals with developmental disabilities enrolled in a subspecialty medical home (N = 826). Four hundred ninety-nine participants (60.4 %) were taking antipsychotics, which was associated with male gender (p = 0.01), intellectual disability with and without autism spectrum disorder (p = 0.001 and p = 0.04, respectively), and inversely associated with the youngest and oldest age categories (p = 0.001 and p = 0.04, respectively). Among those taking antipsychotics, annual metabolic monitoring rates ranged from 89 % (lipids) to 99 % (weight). Age was positively associated with glucose (p < 0.001) and lipid monitoring (p < 0.001). Adult participants with dyslipidemia (p < 0.01), prediabetes/diabetes (p = 0.04), and hypertension (p = 0.02) were significantly more likely to obtain lipid monitoring. These values exceeded previously reported rates suggesting the importance of an integrated care model. PMID:26818535
Gonçalves, Pedro; Araújo, João Ricardo; Martel, Fátima
The use of antipsychotic drugs for the treatment of mood disorders and psychosis has increased dramatically over the last decade. Despite its consumption being associated with beneficial neuropsychiatric effects in patients, atypical antipsychotics (which are the most frequently prescribed antipsychotics) use is accompanied by some secondary adverse metabolic effects such as weight gain, dyslipidemia and glucose intolerance. The molecular mechanisms underlying these adverse effects are not fully understood but have been suggested to involve a dysregulation of adipose tissue homeostasis. As such, the aim of this paper is to review and discuss the role of adipose tissue in the development of secondary adverse metabolic effects induced by atypical antipsychotics. Data analyzed in this article suggest that atypical antipsychotics may increase adipose tissue (particularly visceral adipose tissue) lipogenesis, differentiation/hyperplasia, pro-inflammatory mediator secretion and insulin resistance and decrease adipose tissue lipolysis. Consequently, patients receiving antipsychotic medication could be at risk of developing obesity, type 2 diabetes and cardiovascular disease. A better knowledge of the impact of these drugs on adipose tissue homeostasis may unveil strategies to develop novel antipsychotic drugs with less adverse metabolic effects and to develop adjuvant therapies (e.g. behavioral and nutritional therapies) to neuropsychiatric patients receiving antipsychotic medication. PMID:25523882
Hrdlička, M.; Zedková, I.; Blatný, Marek; Urbánek, Tomáš
Roč. 30, č. 2 (2009), s. 256-261. ISSN 0172-780X Institutional research plan: CEZ:AV0Z70250504 Keywords : schizophrenia * antipsychotics * weight gain Subject RIV: AN - Psychology Impact factor: 1.047, year: 2009
Woo, Young Sup; Park, Joo Eon; Kim, Do-Hoon; Sohn, Inki; Hwang, Tae-Yeon; Park, Young-Min; Jon, Duk-In; Jeong, Jong-Hyun
Objective The purpose of this study was to investigate the efficacy and tolerability of atypical antipsychotics (AAPs) with augmentation by blonanserin in schizophrenic patients. Methods aA total of 100 patients with schizophrenia who were partially or completely unresponsive to treatment with an AAP were recruited in this 12-week, open-label, non-comparative, multicenter study. Blonanserin was added to their existing AAP regimen, which was maintained during the study period. Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at weeks 2, 4, 8, and 12. Predictors for PANSS response (≥20% reduction) were investigated. Results The PANSS total score was significantly decreased at 12 weeks of blonanserin augmentation (-21.0±18.1, F=105.849, pschizophrenia who were partially or completely unresponsive to treatment with an AAP.
Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.
Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…
Guo, Joyce Y.; Huhtaniska, Sanna; Miettunen, Jouko; Jääskeläinen, Erika; Kiviniemi, Vesa; Nikkinen, Juha; Moilanen, Jani; Haapea, Marianne; Mäki, Pirjo; Jones, Peter B.; Veijola, Juha; Isohanni, Matti; Murray, Graham K.
Background Progressive brain volume loss in schizophrenia has been reported in previous studies but its cause and regional distribution remains unclear. We investigated progressive regional brain reductions in schizophrenia and correlations with potential mediators. Method Participants were drawn from the Northern Finland Birth Cohort 1966. A total of 33 schizophrenia individuals and 71 controls were MRI scanned at baseline (mean age = 34.7, SD = 0.77) and at follow-up (mean age = 43.4, SD = 0.44). Regional brain change differences and associations with clinical mediators were examined using FSL voxelwise SIENA. Results Schizophrenia cases exhibited greater progressive brain reductions than controls, mainly in the frontal and temporal lobes. The degree of periventricular brain volume reductions were predicted by antipsychotic medication exposure at the fourth ventricular edge and by the number of days in hospital between the scans (a proxy measure of relapse duration) at the thalamic ventricular border. Decline in social and occupational functioning was associated with right supramarginal gyrus reduction. Conclusion Our findings are consistent with the possibility that antipsychotic medication exposure and time spent in relapse partially explain progressive brain reductions in schizophrenia. However, residual confounding could also account for the findings and caution must be applied before drawing causal inferences from associations demonstrated in observational studies of modest size. Less progressive brain volume loss in schizophrenia may indicate better preserved social and occupational functions. PMID:26189075
Liemburg, Edith J.; Knegtering, Henderikus; Klein, Hans C.; Kortekaas, Rudie; Aleman, Andre
Decreased prefrontal activation (hypofrontality) in schizophrenia is thought to underlie negative symptoms and cognitive impairments, and may contribute to poor social outcome. Hypofrontality does not always improve during treatment with antipsychotics. We hypothesized that antipsychotics, which sha
Full Text Available Abstract Background Rabbit syndrome is a movement disorder that is associated with long-term exposure to neuroleptic medications. Of particular interest and importance is the risk of rabbit syndrome with exposure to the newer atypical antipsychotics. Our recent experience with such a case brought to light the importance of exploring this risk. Methods MEDLINE and PubMed (1972–2006 databases were searched for English language articles using the keywords rabbit syndrome, tardive dyskinesia, antipsychotic, extrapyramidal symptoms and side effects. A recent case study is used to expand upon the literature available on newer antipsychotics and rabbit syndrome. Results We reviewed papers that addressed the following aspects of rabbit syndrome 1 the clinical manifestations 2 prevalence and risk factors, 3 etiopathogenesis 4 older antipsychotics and rabbit syndrome 5 newer antipsychotics, 6 treatment options. Moreover, we report a case of RS in a 50 year old white female, diagnosed with bipolar I disorder, that, after the discontinuation of risperidone, developed involuntary movements of the mouth that were fine, rhythmic and rapid, along the vertical axis, and without involvement of the tongue. After the re-introduction of risperidone, the symptoms decreased in a few hours and disappeared after 3 days. Conclusion Eleven cases of rabbit syndrome have been documented since the implementation of newer antipsychotics. Future research is needed to better understand the etiopathogenesis of rabbit syndrome in psychiatric populations treated with the atypical antipsychotics. Understanding the differences and similarities of rabbit syndrome and tardive dyskinesia is crucial to the creation of a successful treatment paradigm.
Full Text Available Gabriel Kaplan,1,2 Julio Casoy,3 Jacqueline Zummo3 1Behavioral Health Services, Bergen Regional Medical Center, Paramus, NJ, USA; 2Department of Psychiatry, Rutgers New Jersey Medical School, Newark, NJ, USA; 3Medical Affairs, Alkermes, Inc., Waltham, MA, USA Abstract: Schizophrenia is a debilitating chronic disease that requires lifelong medical care and supervision. Even with treatment, the majority of patients relapse within 5 years, and suicide may occur in up to 10% of patients. Poor adherence to oral antipsychotics is the most common cause of relapse. The discontinuation rate for oral antipsychotics in schizophrenia ranges from 26% to 44%, and as many as two-thirds of patients are at least partially nonadherent, resulting in increased risk of hospitalization. A very helpful approach to improve adherence in schizophrenia is the use of long-acting injectable (LAI antipsychotics, although only a minority of patients receive these. Reasons for underutilization may include negative attitudes, perceptions, and beliefs of both patients and health care professionals. Research shows, however, significant improvements in adherence with LAIs compared with oral drugs, and this is accompanied by lower rates of discontinuation, relapse, and hospitalization. In addition, LAIs are associated with better functioning, quality of life, and patient satisfaction. A need exists to encourage broader LAI use, especially among patients with a history of nonadherence with oral antipsychotics. This paper reviews the impact of nonadherence with antipsychotic drug therapy overall, as well as specific outcomes of the schizophrenia patient, and highlights the potential benefits of LAIs. Keywords: adherence, long-acting injectable, antipsychotics, schizophrenia, discontinuation, relapse
Wang, Liang-Jen; Lee, Sheng-Yu; Yuan, Shin-Sheng; Yang, Kang-Chung; Yang, Chun-Ju; Lee, Tung-Liang; Shyu, Yu-Chiau
In this nationwide population-based study, we examined whether haloperidol exposure is associated with a higher risk of mortality than are other antipsychotic medications. Patients who newly received monotherapy with chlorpromazine (n = 2133), haloperidol (n = 4454), quetiapine (n = 1513), and risperidone (n = 1046) between January 1, 2001, and December 31, 2011, were selected from a random sample of the 1 million enrollees of the Taiwan National Health Insurance Research Database. The association between antipsychotic prescription and mortality was estimated through Cox proportional hazard regression. To examine the mortality rates of antipsychotics at different exposure durations, we compared the differences among short-term (≤30 days), midterm (31-90 days), and long-term (>90 days) antipsychotic use. The mortality rates during the follow-up among the chlorpromazine, haloperidol, quetiapine, and risperidone groups were 17.4%, 45.5%, 26.8%, and 25.9%, respectively. The mortality risk among patients receiving haloperidol was the highest within 30 days of the prescription, after which the risk reduced rapidly. Compared with the patients receiving chlorpromazine, the mortality risk was higher in short-term (adjusted hazard ratio, 2.11; 95% confidence interval, 1.87-2.39) and midterm haloperidol users (1.86; 1.54-2.25) than in long-term users (0.99; 0.61-1.61). In conclusion, haloperidol use is associated with higher mortality risk than other antipsychotic medications. The mortality risk varies according to the duration of drug exposure. Underlying characteristics and medical conditions may influence the estimation of the mortality risk. Clinicians should pay attention to the mortality risk when prescribing antipsychotic medications, particularly for the elderly and critically ill patients. PMID:26658260
McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Hahn, Chang-Gyu; Richtand, Neil M; Stanford, Kevin E
Previous studies have observed significant abnormalities in the fatty acid composition of peripheral tissues from drug-naïve first-episode schizophrenic (SZ) patients relative to normal controls, including deficits in omega-3 and omega-6 polyunsaturated fatty acids, which are partially normalized following chronic antipsychotic treatment. We hypothesized that postmortem cortical tissue from patients with SZ would also exhibit deficits in cortical docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA; 20:4n-6) relative to normal controls, and that these deficits would be greater in drug-free SZ patients. We determined the total fatty acid composition of postmortem orbitofrontal cortex (OFC) (Brodmann area 10) from drug-free and antipsychotic-treated SZ patients (n=21) and age-matched normal controls (n=26) by gas chromatography. After correction for multiple comparisons, significantly lower DHA (-20%) concentrations, and significantly greater vaccenic acid (VA) (+12.5) concentrations, were found in the OFC of SZ patients relative to normal controls. Relative to age-matched same-gender controls, OFC DHA deficits, and elevated AA:DHA, oleic acid:DHA and docosapentaenoic acid (22:5n-6):DHA ratios, were found in male but not female SZ patients. SZ patients that died of cardiovascular-related disease exhibited lower DHA (-31%) and AA (-19%) concentrations, and greater OA (+20%) and VA (+17%) concentrations, relative to normal controls that also died of cardiovascular-related disease. OFC DHA and AA deficits, and elevations in oleic acid and vaccenic acid, were numerically greater in drug-free SZ patients and were partially normalized in SZ patients treated with antipsychotic medications (atypical>typical). Fatty acid abnormalities could not be wholly attributed to lifestyle or postmortem tissue variables. These findings add to a growing body of evidence implicating omega-3 fatty acid deficiency as well as the OFC in the pathoaetiology of SZ, and suggest that
Strošek in učinkovitost zdravljenja shizofrenije z atipičnimi antipsihotiki v Sloveniji: a cost effectiveness study: raziskava stroškovne učinkovitosti: The cost and effects of atypical antipsychotic agents in patients with schizophrenia in Slovenia:
Petrica, Demetrij; Štuhec, Matej; Toni, Janez
Background: Treatment with atypical antipsychotics is the most important treatment for patients with acute schizophrenia and represents a significant cost. In Slovenia there is lack of studies of cost-effectiveness that can be used in clinical practice. Objective: The primary purpose of the study was to compare the costs and effectiveness of five atypical antipsychotic with the largest market share in 2011 in Slovenia. The study included aripiprazole, quetiapine, paliperidone, risperidone and...
Baandrup, Lone; Kruse, Marie
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...... polypharmacy (HR 1.38; 95 % CI 1.32-1.45), whereas antipsychotic discontinuation was associated with decreased hospitalization risk in most off-label conditions. CONCLUSIONS: The brief duration of most antipsychotic prescriptions suggests that antipsychotics are prescribed more liberally than recommended. As a...
Full Text Available Abstract Background There is a negative association between the use of antipsychotics and cognitive functioning in bipolar patients, which may be mediated by altered dopamine signaling in selected brain areas, and moderation thereof by genetic sequence variation such as COMT Val108/158Met. The interaction between antipsychotic drug use and the COMT Val108/158Met genotype on two-year cognitive functioning in bipolar patients was examined. Methods Interaction between the COMT Val108/158Met and antipsychotics on a composite cognitive measure was examined in 51 bipolar patients who were assessed 12 times at two-monthly intervals over a period of two years (379 observations. Results There was a significant negative effect of the interaction between antipsychotic medications and Val allele load on the composite cognitive measure in bipolar patients (p Conclusions The negative effects of antipsychotics on cognitive functioning in bipolar disorder may be moderated by the COMT Val 108/158 Met genotype, with a negative effect of Val allele load. If replicated, the results may be indicative of pharmacogenetic interactions in bipolar disorder.
Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P; Seiner, Stephen J; Xiang, Yu-Tao
This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (pECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4-11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2-5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. PMID:27285996
Stojanović, Radan; Damjanović, Aleksandar; Prostran, Milica
Psychotic symptoms are present in up to 50% of patients with Parkinson's disease. These symptoms have detrimental effects on patients' and caregivers' quality of life and may predict mortality. The pathogenesis of psychotic symptoms in Parkinson's disease is complex, but the use of dopaminergic medications is one of the risk factors. The treatment of psychotic symptoms in Parkinson's disease is complicated due to the ability of antipsychotic medications to worsen motor symptoms. The efficacy of clozapine in the treatment of psychosis in patients with Parkinson's disease has been confirmed in several clinical trials; however, the adverse effects and the necessity of blood count monitoring are the reasons why the use of this drug is challenging. The studies on safety and efficacy of other antipsychotics conflicting results. The use of antipsychotics in these patients is also associated with increased mortality. Psychotic symptoms in Parkinson's disease per se are also proven predictors of mortality. Thus it is necessary to treat psychotic symptoms but the choice of an antipsychotic should be based on careful risk/benefit assessment. Pimavanserin as a novel therapeutic option with more favorable adverse effects profile is now available for this indication, but careful postmarketing monitoring is necessary to establish the true picture of this drug's long-term safety and efficacy. PMID:27504054
Tarita Murray-Thomas; Jones, Meghan E; Deven Patel; Elizabeth Brunner; Shatapathy, Chetan C.; Stephen Motsko; van Staa, Tjeerd P
Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart diseas...
Peng, Ming; Liu, Jin; Lu, Dan; Yang, Yong-Jian
Blonanserin is a novel atypical antipsychotic agent for the treatment of schizophrenia. Ethyl alcohol, isopropyl alcohol and toluene are utilized in the synthesis route of this bulk drug. A new validated gas chromatographic (GC) method for the simultaneous determination of residual solvents in blonanserin is described in this paper. Blonanserin was dissolved in N, N-dimethylformamide to make a sample solution that was directly injected into a DB-624 column. A postrun oven temperature at 240°C for approximately 2 h after the analysis cycle was performed to wash out blonanserin residue in the GC column. Quantitation was performed by external standard analyses and the validation was carried out according to International Conference on Harmonization validation guidelines Q2A and Q2B. The method was shown to be specific (no interference in the blank solution), linear (correlation coefficients ≥0.99998, n = 10), accurate (average recoveries between 94.1 and 101.7%), precise (intra-day and inter-day precision ≤2.6%), sensitive (limit of detection ≤0.2 ng, and limit of quantitation ≤0.7 ng), robust (small variations of carrier gas flow, initial oven temperature, temperature ramping rate, injector and detector temperatures did not significantly affect the system suitability test parameters and peak areas) and stable (reference standard and sample solutions were stable over 48 h). This extensively validated method is ready to be used for the quality control of blonanserin. PMID:22595261
Sravanti L. Sanivarapu
Full Text Available Risperidone is an atypical antipsychotic agent used primarily to treat schizophrenia. It is a dopamine antagonist with antiserotonergic, antihistaminergic and antiadrenergic properties. Antipsychotic discontinuation symptoms have been described in the literature following abrupt or rapid reduction in the dose. This unusual case demonstrates that sudden withdrawal of even a modest dose of risperidone may cause significant discontinuation symptoms in susceptible individuals. Hence, there is a need for caution while taking a patient off antipsychotic medications in view of the vulnerable subgroup. [Int J Basic Clin Pharmacol 2014; 3(1.000: 233-234
Hall, Ian; Shah, Amar
Adherence with antipsychotic monitoring guidelines is notoriously low nationally. Without active monitoring and measures to improve metabolic abnormalities, more patients may develop related morbidity and mortality. An audit highlighted antipsychotic monitoring in this learning disability service in London did not match guideline recommendations. People with intellectual disability also experience health inequalities. Psychiatrists are well placed to provide advice and assistance that is suit...
Meenan, Richard T; Stumbo, Scott P; Yarborough, Micah T; Leo, Michael C; Yarborough, Bobbi Jo H; Green, Carla A
Individuals with serious mental illnesses suffer from obesity and cardiometabolic diseases at high rates, and antipsychotic medications exacerbate these conditions. While studies have shown weight loss and lifestyle interventions can be effective in this population, few have assessed intervention cost-effectiveness. We present results from a 12-month randomized controlled trial that reduced weight, fasting glucose, and medical hospitalizations in intervention participants. Costs per participant ranged from $4365 to $5687. Costs to reduce weight by one kilogram ranged from $1623 to $2114; costs to reduce fasting glucose by 1 mg/dL ranged from $467 to $608. Medical hospitalization costs were reduced by $137,500. PMID:26149243
Vacheron-Trystram, M-N; Braitman, A; Cheref, S; Auffray, L
This article is a review of the various treatments that are currently available, in particular in France, for the treatment of bipolar disorders. This article specifically addresses the use of novel antipsychotic agents as alternative therapy to a lithium therapy and/or the use of conventional antipsychotics. The prevalence of bipolar disorder over a lifetime is around 1% of the general population. Bipolar disorder consists of alternating depressive and manic episodes. It mainly affects younger subjects, and is often associated with alcohol and drug addictions. There are two main subtypes of bipolar disorder. According to the DSM IV-R, type 1 of bipolar disorder is characterised when at least one manic episode (or a mixed episode) has been diagnosed. Type 2 of bipolar disorder is related to patients enduring recurrent depressive episodes but no manic episode. Type 2 affects women more frequently as opposed to type 1 affecting individuals of both sexes. Manic-depressive disorder (or cyclo-thymic disorder) appears in relation to patients who has never suffered manic episode, mixed episode or severe depressive episode but have undergone numerous periods with some symptoms of depression and hypomanic symptoms over a two-year period during which any asymptomatic periods last no longer than two months. The average age of the person going through a first episode (often a depressive one) is 20 years-old. Untreated bipolar patients may endure more than ten manic or depressive episodes. Finally, in relation to 10 to 20% of patients, the bipolar disorder will turn into a fast cycle form, either spontaneously or as a result of certain medical treatments. Psychiatrists are now able to initiate various treating strategies which are most likely to be effective as a result of the identification of clinical subtypes of the bipolar disorder. Lithium therapy has been effectively and acutely used for patients with pure or elated mania and its prophylaxis. However, lithium medication
García, Saínza; Martínez-Cengotitabengoa, Mónica; López-Zurbano, Saioa; Zorrilla, Iñaki; López, Purificación; Vieta, Eduard; González-Pinto, Ana
Antipsychotics are the drugs prescribed to treat psychotic disorders; however, patients often fail to adhere to their treatment, and this has a severe negative effect on prognosis in these kinds of illnesses. Among the wide range of risk factors for treatment nonadherence, this systematic review covers those that are most important from the point of view of clinicians and patients and proposes guidelines for addressing them. Analyzing 38 studies conducted in a total of 51,796 patients, including patients with schizophrenia spectrum disorders and bipolar disorder, we found that younger age, substance abuse, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliance, experience of barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status are the main risk factors for medication nonadherence in both types of disorder. In the future, prospective studies should be conducted on the use of personalized patient-tailored treatments, taking into account risk factors that may affect each individual, to assess the ability of such approaches to improve adherence and hence prognosis in these patients. PMID:27307187
Full Text Available This meta-analysis of randomized controlled trials (RCTs examined the efficacy and safety of the combination of electroconvulsive therapy (ECT and antipsychotic medication (except for clozapine versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS. Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD, risk ratio (RR ±95% confidence intervals (CIs, number needed to treat (NNT, and number needed to harm (NNH were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1 symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I(2 = 62%, separating the two groups as early as weeks 1-2 with an SMD of -0.58 (p<0.00001; I(2 = 0%; (2 study-defined response (RR = 1.48, p<0.0001 with an NNT of 6 (CI = 4-9 and remission rate (RR = 2.18, p = 0.0002 with an NNT of 8 (CI = 6-16; (3 PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009. Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3 studies. The ECT-antipsychotic combination caused more headache (p = 0.02 with an NNH of 6 (CI = 4-11 and memory impairment (p = 0.001 with an NNH of 3 (CI = 2-5. The use of ECT to augment antipsychotic treatment (clozapine excepted can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache.
Albert, Umberto; Carmassi, Claudia; Cosci, Fiammetta; De Cori, David; Di Nicola, Marco; Ferrari, Silvia; Poloni, Nicola; Tarricone, Ilaria; Fiorillo, Andrea
Atypical antipsychotics (AAs) may play a role in the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), and trauma-related disorders. No reviews on their differential use in these different disorders have been performed recently. The aim of this systematized review was to obtain data on efficacy and comparative effectiveness of AAs as a treatment of anxiety disorders, OCD, and trauma-related disorders to provide guidance for clinicians on when and which AA to use. We searched on PubMed, Psychnet, and Cochrane Libraries from inception to July 2015. Search results were limited to randomized, placebo-controlled trials of adult patients. Evidence of efficacy was considered the presence of positive results in two or more double-blind placebo-controlled studies. Our systematized search identified 1298 papers, of which 191 were subjected to a full-text review and 56 were included. Quetiapine extended-release showed a role in both acute and maintenance treatment of uncomplicated generalized anxiety disorder, whereas more studies are needed before drawing practical recommendations on the use of olanzapine and risperidone; aripiprazole and risperidone are effective in resistant OCD as augmentation treatments. Risperidone and olanzapine add-on may have a role in resistant or chronic post-traumatic stress disorder patients, although only risperidone addition can be recommended on the basis of the criterion of two or more positive placebo-controlled trials. This systematized review supports the evidence that only a few AAs are effective in only a minority of the off-label conditions in which they are currently used and confirms that AAs are not all the same. Their use should be on the basis of a balance between efficacy and side effects, and the characteristics as well as the preference of the patient. PMID:26974213
Suheyla Dogan Bulut
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
Peter J Siekmeier
Full Text Available A large number of cellular level abnormalities have been identified in the hippocampus of schizophrenic subjects. Nonetheless, it remains uncertain how these pathologies interact at a system level to create clinical symptoms, and this has hindered the development of more effective antipsychotic medications. Using a 72-processor supercomputer, we created a tissue level hippocampal simulation, featuring multicompartmental neuron models with multiple ion channel subtypes and synaptic channels with realistic temporal dynamics. As an index of the schizophrenic phenotype, we used the specific inability of the model to attune to 40 Hz (gamma band stimulation, a well-characterized abnormality in schizophrenia. We examined several possible combinations of putatively schizophrenogenic cellular lesions by systematically varying model parameters representing NMDA channel function, dendritic spine density, and GABA system integrity, conducting 910 trials in total. Two discrete "clusters" of neuropathological changes were identified. The most robust was characterized by co-occurring modest reductions in NMDA system function (-30% and dendritic spine density (-30%. Another set of lesions had greater NMDA hypofunction along with low level GABA system dysregulation. To the schizophrenic model, we applied the effects of 1,500 virtual medications, which were implemented by varying five model parameters, independently, in a graded manner; the effects of known drugs were also applied. The simulation accurately distinguished agents that are known to lack clinical efficacy, and identified novel mechanisms (e.g., decrease in AMPA conductance decay time constant, increase in projection strength of calretinin-positive interneurons and combinations of mechanisms that could re-equilibrate model behavior. These findings shed light on the mechanistic links between schizophrenic neuropathology and the gamma band oscillatory abnormalities observed in the illness. As such, they
Ružić, Klementina; Dadić-Hero, Elizabeta; Knez, Rajna; Medved, Paola; Graovac, Mirjana
Patients' non-compliance in treatments, such as irregular taking of medication, represents an enormous problem with psychiatric patients in general. This difficulty occurs especially in patients suffering from chronic mental illnesses such as schizophrenia. There are not any significant differences in the efficacy of reducing the positive symptoms in schizophrenia between the conventional and the atypical antipsychotics. However, the effects which are manifested in negative schizophr...
Atypical antipsychotic drug treatment for 6 months restores N-acetylaspartate in left prefrontal cortex and left thalamus of first-episode patients with early onset schizophrenia: A magnetic resonance spectroscopy study.
Gan, Jing-Li; Cheng, Zheng-Xiang; Duan, Hui-Feng; Yang, Jia-Ming; Zhu, Xi-Quan; Gao, Cun-You
Early onset schizophrenia (EOS) is often associated with poorer outcomes, including lack of school education, higher risk of mental disability and resistance to treatment. But the knowledge of the neurobiological mechanism of EOS is limited. Here, using proton magnetic resonance spectroscopy, we investigated the possible neurochemical abnormalities in prefrontal cortex (PFC) and thalamus of first-episode drug-naïve patients with EOS, and followed up the effects of atypical antipsychotic treatment for 6 months on neurochemical metabolites and clinical symptoms. We measured the ratios of N-acetylaspartate (NAA), choline (Cho) to creatine (Cr) in 41 adolescents with first episode of EOS and in 28 healthy controls matched for age, gender, and years of education. The EOS patients presented with abnormally low NAA/Cr values in the left PFC and left thalamus with a reduced tendency in the right PFC compared with healthy controls. No significant differences were detected between groups for Cho/Cr in PFC and thalamus in any hemisphere. After atypical antipsychotic treatment for 6 months, the reduced NAA/Cr in the left PFC and left thalamus in EOS patients was elevated to the normal level in healthy controls, without any alteration in Cho/Cr. We also found that there was no significant correlation between the neurochemical metabolite ratios in the PFC and thalamus in patients with EOS, and clinical characteristics. Our results suggest that there was neurochemical metabolite abnormalities in PFC and thalamus in EOS patients, atypical antipsychotic treatment can effectively relieve the symptoms and restore the reduced NAA in PFC and thalamus. PMID:24831926
Ramdour, S; Duxbury, J A; Becket, G; Wilson, S
Delays in effective treatment of a first episode psychosis can result in more severe symptoms, a longer time to achieve symptom control and a poorer quality of life; yet around 40% do not take antipsychotic medication as prescribed. There is evidence that patients and staff have different perceptions of what affects adherence with medication. Research in adults suggests healthcare professionals and patients understand the importance of good insight in promoting adherence with medication for schizophrenia; however, healthcare staff may overestimate the impact of side effects and underestimate the importance of medication effectiveness. There is also some evidence to suggest that motivations to take prescribed medication may differ in first and multi-episode psychosis. This research therefore sought views of staff working with adolescents diagnosed with first episode psychosis about what factors affected adherence with antipsychotic medication. Staff responding to the survey felt that young people were more likely to take medication if they felt it would make them better, prevent relapse and if they had a positive rapport with staff. As in an adult population, side effects, particularly weight gain, sedation and muscular side effects, were expressed as a common reason for poor adherence. Doctors and nurses assigned differing importance to parameters such as family views of medication, fear of admission and a preference for cannabis over medication suggesting that views may differ between professional groups Views of young people will be obtained in the next phase of the research study to enable comparison with staff views and consideration of staff interventions to better promote medication adherence. Antipsychotic medication is an effective treatment for first episode psychosis; yet 40% of patients do not take medication as prescribed. Previous research in adults with schizophrenia comparing healthcare professional and patient views suggests that while healthcare
Prescripción de antipsicóticos atípicos en pacientes hospitalizados de la Clínica Psiquiátrica Universitaria Prescription of atypical antipsychotic drugs for inpatients at a university psychiatric clinic
Rodrigo Nieto R
Psychiatric Clinic between May and September 2005. We registered every antipsychotic drug used and its dosagefor every diagnosis, including whether it was prescribed as permanent or as PRN. Results: During this period there were 246 hospital discharges and some kind of antipsychotic drug was used in 80% of cases. The main diagnoses associated with the use of antipsychotic drugs were schizophrenia, exogenous psychosis and bipolar disorder, but they were also used frequently in other diseases such as eating disorders, personality disorders, and unipolar depression. Atypical antipsychotic drugs were the most frequently used, whether alone or in PRN combination with a neuroleptic drug. Among atypical antipsychotics, the most frequently prescribed were risperidone (41% and quetiapine (34%. The dosage used was widely different depending on the diagnosis. Conclusión: Antipsychotic drugs, particularly atypical ones, are broadly used in the treatment of inpatients with several psychiatric disorders
To examine the underlying mechanisms of intracerebral or clinical actions of the atypical antipsychotic, risperidone (RIS), the effects of RIS on absolute regional cerebral blood flows (rCBFs) measured with 99mTc-HMPAO SPECT and correlations between the rCBFs and psychotic symptoms assessed with positive and negative syndrome scale (PANSS) were investigated in 10 drug-naive and unmedicated schizophrenic patients with acute hallucinatory and delusional state. Both the SPECT and PANSS were repeated before and after oral 2-week administration of RIS 3 mg/day in all of the 10 patients and after subsequent 2-week administration of RIS 4-6 mg/day in half of the patients. The rCBF values were significantly decreased in the left precentral gyrus alone after the low dose of RIS 3 mg/day in comparison with before the RIS dose. The rCBF values were significantly decreased in the right cingulate, postcentral, inferior parietal gyri and the left inferior temporal gyrus after the high dose of RIS 4-6 mg/day in comparison with before the low dose of RIS 3 mg/day. The psychiatric assessment with PANSS showed an improvement of positive and negative symptoms after the low RIS dose and still more after the high RIS dose. Statistical analyses on relationships between the rCBF values and PANSS scores before and after the low RIS dose showed a positive correlation between the rCBF values in the right middle temporal gyrus and hallucinations (mainly auditory hallucination). These results suggest that chronic RIS administration dose-dependently produces a decrease of rCBF in the cerebral cortex in the manner that the low dose decreases rCBF in a few restricted cortical regions, while the high dose induces the rCBF reduction in more widespread cortical regions. The RIS-induced rCBF decrease in the cerebral cortex is considered to be attributable to a secondary inactivation in the cerebral cortex due to D2 dopamine receptor blockade of RIS in the striatum through the cortico
Full Text Available Jose Manuel Olivares,1 Manickam Thirunavukarasu,2 Jayashri Kulkarni,3 Hong Yan Zhang,4 Mingyuan Zhang,5 Fan Zhang61Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario de Vigo, Vigo, Spain; 2Department of Psychiatry, SRM Medical College Hospital and Research Center, Tamil Nadu, India; 3Department of Psychiatry, Monash University and the Alfred Hospital, Prahran, Vic, Australia; 4Department of Psychiatry, Peking University Institute of Mental Health, Beijing, People's Republic of China; 5Department of Psychiatry, Shanghai Mental Health Center, Shanghai, People's Republic of China; 6Medical Affairs, Xian Janssen Pharmaceutical, Beijing, People's Republic of ChinaBackground: Nonadherence is a well-known problem among schizophrenia patients, among whom relapse is fivefold more likely, adversely affecting health, employment, and social functioning. The Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES survey was developed to determine the scope and causes of medication nonadherence in schizophrenia.Methods: The 20-question ADHES survey was distributed to 19,370 psychiatrists in 13 Asia–Pacific countries in January–April 2012, to ascertain psychiatrists' perceptions of antipsychotic medication adherence levels among their schizophrenia patients, reasons for partial/nonadherence, their preferred methods of assessing adherence, and strategies to improve adherence. Responses are reported as mean and range across countries.Results: Four thousand, six hundred sixty one psychiatrists (24% of recipients completed the survey (highest contributors: People's Republic of China, 1854; India, 1616. Psychiatrists perceived that 56% (range, 30%-71% of schizophrenia patients were non- or partially adherent to medication. Patients discontinue medication primarily due to lack of insight into their condition (mean, 37%; 1%–65% and because patients consider medication unnecessary when feeling better (mean, 27%; 15%–68%. Over
McNamara, Robert K.; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W
Polyunsaturated fatty acids (PUFA), a lipid family comprised of omega-3 (n-3) and n-6 fatty acids, are a critical component of cellular membranes, and recent in vitro studies have found that antipsychotic medications up-regulate genes responsible for PUFA biosynthesis. To evaluate this effect in vivo, rats were treated with risperidone (1.5, 3, 6 mg/kg/d), paliperidone (1.5, 3, 6 mg/kg/d), olanzapine (2.5, 5, 10 mg/kg/d), quetiapine (5, 10, 20 mg/kg/d), haloperidol (1, 3 mg/kg/d) or vehicle t...
蔡亦蕴; 徐理; 吴彦
Atypical antipsychotic agents in the treatment of bipolar disorder remain a hot issue in clinic. Their efifcacy in acute manic and depression episodes has been veriifed. However, the long-term preventive efifcacy has not yet been demonstrated. This paper reviews the application of atypical antipsychotic agents in the treatment of bipolar disorder so as to provide a guideline for pharmacotherapy in clinic.%非典型抗精神病药物在双相情感障碍治疗中的应用备受关注。非典型抗精神病药物用于双相情感障碍躁狂相和抑郁相的急性发作期治疗有较为肯定的疗效，但用于稳定期维持治疗的疗效不确定。本文介绍非典型抗精神病药物在双相情感障碍治疗中的应用，为临床合理用药提供参考。
Nielsen, Mette Ødegaard; Rostrup, Egill; Nørbak-Emig, Henrik;
mechanisms, lead to weight gain. . Reference List (1) Mathews J, Newcomer JW, Mathews JR et al. Neural correlates of weight gain with olanzapine. Arch Gen Psychiatry 2012;69:1226-1237. (2) Nielsen MO, Rostrup E, Wulff S et al. Improvement of brain reward abnormalities by antipsychotic monotherapy...
Olivares, Jose Manuel; Thirunavukarasu, Manickam; Kulkarni, Jayashri; Zhang, Hong Yan; Zhang, Mingyuan; Zhang, Fan
Background Nonadherence is a well-known problem among schizophrenia patients, among whom relapse is fivefold more likely, adversely affecting health, employment, and social functioning. The Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES) survey was developed to determine the scope and causes of medication nonadherence in schizophrenia. Methods The 20-question ADHES survey was distributed to 19,370 psychiatrists in 13 Asia–Pacific countries in January–April 2012, to ascertain psychiatrists’ perceptions of antipsychotic medication adherence levels among their schizophrenia patients, reasons for partial/nonadherence, their preferred methods of assessing adherence, and strategies to improve adherence. Responses are reported as mean and range across countries. Results Four thousand, six hundred sixty one psychiatrists (24% of recipients) completed the survey (highest contributors: People’s Republic of China, 1854; India, 1616). Psychiatrists perceived that 56% (range, 30%–71%) of schizophrenia patients were non- or partially adherent to medication. Patients discontinue medication primarily due to lack of insight into their condition (mean, 37%; 1%–65%) and because patients consider medication unnecessary when feeling better (mean, 27%; 15%–68%). Over half of psychiatrists (mean, 55%; 42%–99%) assess medication adherence at every visit, almost exclusively (81%) by asking their patients, versus quantitative measures. One in three psychiatrists expressed their preference to switch to or add a long-acting antipsychotic to improve adherence (15%–82%). Conclusions The substantial prevalence of partial/nonadherence to medication demonstrates that more proactive management of patients with schizophrenia is needed to improve adherence and thereby treatment outcomes. Registration Registration of this study was not required. PMID:23976858
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 99mTc-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)
Zheng, Wei; Cao, Xiao-Lan; Ungvari, Gabor S.; Xiang, Ying-Qiang; Guo, Tong; Liu, Zheng-Rong; Wang, Yuan-Yuan; Forester, Brent P.; Seiner, Stephen J.; Xiang, Yu-Tao
This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of the combination of electroconvulsive therapy (ECT) and antipsychotic medication (except for clozapine) versus the same antipsychotic monotherapy for treatment-resistant schizophrenia (TRS). Two independent investigators extracted data for a random effects meta-analysis and pre-specified subgroup and meta-regression analyses. Weighted and standard mean difference (WMD/SMD), risk ratio (RR) ±95% confidence intervals (CIs), number needed to treat (NNT), and number needed to harm (NNH) were calculated. Eleven studies (n = 818, duration = 10.2±5.5 weeks) were identified for meta-analysis. Adjunctive ECT was superior to antipsychotic monotherapy regarding (1) symptomatic improvement at last-observation endpoint with an SMD of -0.67 (p<0.00001; I2 = 62%), separating the two groups as early as weeks 1–2 with an SMD of -0.58 (p<0.00001; I2 = 0%); (2) study-defined response (RR = 1.48, p<0.0001) with an NNT of 6 (CI = 4–9) and remission rate (RR = 2.18, p = 0.0002) with an NNT of 8 (CI = 6–16); (3) PANSS positive and general symptom sub-scores at endpoint with a WMD between -3.48 to -1.32 (P = 0.01 to 0.009). Subgroup analyses were conducted comparing double blind/rater-masked vs. open RCTs, those with and without randomization details, and high quality (Jadad≥adadup analyses were Jadad<3) studies. The ECT-antipsychotic combination caused more headache (p = 0.02) with an NNH of 6 (CI = 4–11) and memory impairment (p = 0.001) with an NNH of 3 (CI = 2–5). The use of ECT to augment antipsychotic treatment (clozapine excepted) can be an effective treatment option for TRS, with increased frequency of self-reported memory impairment and headache. Trial registration CRD42014006689 (PROSPERO). PMID:27285996
Hall, Ian; Shah, Amar
Adherence with antipsychotic monitoring guidelines is notoriously low nationally. Without active monitoring and measures to improve metabolic abnormalities, more patients may develop related morbidity and mortality. An audit highlighted antipsychotic monitoring in this learning disability service in London did not match guideline recommendations. People with intellectual disability also experience health inequalities. Psychiatrists are well placed to provide advice and assistance that is suitable for those with complex communication, behaviour, and social needs. The QI team tested ideas to increase rates of antipsychotic reviews. The focus was the follow up monitoring of all universal measures recommended by NICE 2014, collected at 2-weekly intervals. We trialled interventions in four broad categories; Intervention 1: to make monitoring more structured and planned; Intervention 2: to increase staff and patient awareness of healthy eating and exercise programs; Intervention 3: to increase the collection of diet and exercise histories from patients; Intervention 4: to improve the uptake of blood tests. The interventions created an improvement in monitoring. There are lessons in the methodology for others carrying out similar projects.
Hall, Ian; Shah, Amar
Adherence with antipsychotic monitoring guidelines is notoriously low nationally. Without active monitoring and measures to improve metabolic abnormalities, more patients may develop related morbidity and mortality. An audit highlighted antipsychotic monitoring in this learning disability service in London did not match guideline recommendations. People with intellectual disability also experience health inequalities. Psychiatrists are well placed to provide advice and assistance that is suitable for those with complex communication, behaviour, and social needs. The QI team tested ideas to increase rates of antipsychotic reviews. The focus was the follow up monitoring of all universal measures recommended by NICE 2014, collected at 2-weekly intervals. We trialled interventions in four broad categories; Intervention 1: to make monitoring more structured and planned; Intervention 2: to increase staff and patient awareness of healthy eating and exercise programs; Intervention 3: to increase the collection of diet and exercise histories from patients; Intervention 4: to improve the uptake of blood tests. The interventions created an improvement in monitoring. There are lessons in the methodology for others carrying out similar projects. PMID:27335645
Rijcken, C.A.W.; Knegtering, H; Bruggeman, R; Tobi, H; de Jong-van den Berg, Lolkje Theodora Wilhelmina
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 co
Deurell, Maria; Weischer, Merete; Pagsberg, Anne Katrine;
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...
Full Text Available Introduction. Extrapyramidal syndromes are significant side effects of antipsychotic therapy due to their severity, frequent occurrence and complications. This paper gives a brief summary of the literature with the emphasis on epidemiology, etiology, diagnosis and differential diagnosis, as well as the treatment of extrapyramidal disorders induced by antipsychotics. Dystonia. Sustained muscle contractions cause twisting and repetitive movements or abnormal postures. It may appear either as an acute or delayed, i.e. tardive sign. The incidence of dystonia is 2-3% among the patients treated with antipsychotics, and 50% among the ones cured with conventional antipsychotics. Akathisia. The main feature of this curious adverse effect is the psychomotor restlessness and the inability to remain motionless. Although akathisia is not very frequent, its incidence and prevalence ranges from 5 to 50% among the treated patients. It is most probably a result of the blockage of dopaminergic receptors. Parkinsonism. The most frequent secondary Parkinsonism is the one caused by drugs. The characteristic parkinsonian signs regress 4 to 16 weeks after the discontinuation of antipsychotic therapy. In the era of atypical antipsychotics this adverse effect appears less frequently. Tardive dyskinesia. Involuntary choreatic movements may appear days and months after the introduction of continuous use of antipsychotics. The individual susceptibility may play the major role in the development of this side effect. Conclusion. Numerous studies have compared conventional and atypical antipsychotics as well as atypical ones with one another in order to decrease the risk of development of extrapyramical side effects as well as to prevent their occurrence and improve their treatment.
Demler, Tammie Lee; Trigoboff, Eileen
Clozapine is an atypical antipsychotic agent used for refractory schizophrenia. It has a relatively low affinity for D2 receptors and thus is associated with a lower incidence of extrapyramidal side effects when compared with typical antipsychotics. Clozapine as monotherapy can induce a rare, but serious, blood dyscrasia called agranulocytosis; however, some concomitant medications may contribute to the risk. Examples of these medications are mood-stabilizing antiepileptic drugs, such as carb...
Michele Fornaro; Brendon Stubbs; Domenico De Berardis; Giampaolo Perna; Alessandro Valchera; Nicola Veronese; Marco Solmi; Licínia Ganança
Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label...
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.
Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical
Burghardt, Kyle J.; Kristen N. Gardner; Johnson, Joshua W.; Ellingrod, Vicki L.
Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to de...
Xiang, Y-T; Ungvari, G S; Correll, C U; Chiu, H F K; Shinfuku, N
To date, antipsychotics remain the mainstay of treatment for schizophrenia and related disorders although other psychotropic medications and non-pharmaceutical interventions have been used adjunctively in some patients and settings. Regular surveys on access to and prescription patterns of psychotropic medications in clinical practice are an important and efficient way of examining the use and time trends of treatments in a given population and region. Unlike developed Western countries, Asian countries have not fully undergone deinstitutionalisation of the severely and chronically mentally ill, and community-based mental health services are still under-developed. As a result, a large number of psychiatric patients still receive treatments in psychiatric hospitals. Moreover, there have been very limited studies examining access to and prescription patterns of psychotropic medications for schizophrenia patients in Asian countries. In this paper, we focus on the only international project on the use of psychotropic medications in schizophrenia patients in selected East and Southeast Asian countries/territories summarising its major findings. Most of the first- and second-generation antipsychotics (FGAs and SGAs) are available in Asian countries, but the access to psychotropic medications is largely affected by socio-cultural and historical contexts, health insurance schemes, health care policy, medication cost and consumers' preference across different countries/territories. Overall, the proportional use of FGAs, high dose antipsychotic treatment and antipsychotic polypharmacy have decreased, while the use of SGAs and antidepressants have increased and the utilisation of benzodiazepines and mood stabilisers has remained relatively stable over time. However, within these general trends, there is great inter-country variation regarding the psychotropic prescribing patterns and trends in Asian schizophrenia patients that also seems to differ from data in many Western
Quirk, Alan; Chaplin, Rob; Lelliott, Paul; Seale, Clive
The professional identity of psychiatry depends on it being regarded as one amongst many medical specialties and sharing ideals of good practice with other specialties, an important marker of which is the achievement of shared decision-making and avoiding a reputation for being purely agents of social control. Yet the interactions involved in trying to achieve shared decision-making are relatively unexplored in psychiatry. This study analyses audiotapes of 92 outpatient consultations involving nine consultant psychiatrists focusing on how pressure is applied in shared decisions about antipsychotic medication. Detailed conversation analysis reveals that some shared decisions are considerably more pressured than others. At one end of a spectrum of pressure are pressured shared decisions, characterised by an escalating cycle of pressure and resistance from which it is difficult to exit without someone losing face. In the middle are directed decisions, where the patient cooperates with being diplomatically steered by the psychiatrist. At the other extreme are open decisions where the patient is allowed to decide, with the psychiatrist exerting little or no pressure. Directed and open decisions occurred most frequently; pressured decisions were rarer. Patient risk did not appear to influence the degree of pressure applied in these outpatient consultations. PMID:21812791
Ponizovsky, Alexander M.; Marom, Eli; Ben-Laish, Michal; Barash, Igor; Weizman, Abraham; Schwartzberg, Eyal
Background Although serious mental illneses are treated with both typical and atypical antipsychotic grugs, trends in their use in psychiatric inpatient population in Israel are unrecognized. The aim of this study was to detect trends in the use of typical and atypical antipsychotic drugs in the Israeli inpatient psychiatric population throughout the last decade. Methods Data regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the ele...
Moreno, Ricardo Alberto; Moreno, Doris Hupfeld; Soares, Márcia Britto de Macedo; Ratzke, Roberto
Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam) and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are effective in acute manic episodes. Lamotrigine has been shown to reduce cycling and effective in depressive episodes. Based on the available data, olanzapine was found to be the most appropriate atypical antipsychotic agent for the treatment of manic bipolar patients, although there are also studies suggesting the efficacy of risperidone, aripiprazole and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. There is no consistent information supporting the prophylactic use of newer antipsychotics. PMID:15597138
Full Text Available Abstract Background How long an antipsychotic is effective in maintaining response is important in choosing the correct treatment for people with schizophrenia. This post-hoc analysis describes maintenance of response over 24 or 28 weeks in people treated for schizophrenia with olanzapine, risperidone, quetiapine, ziprasidone, or aripiprazole. Methods This was a post-hoc analysis using data from 5 double-blind, randomized, comparative trials of 24 or 28 weeks duration in which olanzapine was compared to risperidone (1 study; N = 339, quetiapine (1 study; N = 346, ziprasidone (2 studies; N = 548 and 394 or aripiprazole (1 study; N = 566 for treatment of schizophrenia. For each study, time to loss of response in patients who met criteria for response at Week 8 and the proportion of patients who lost response following Week 8 were compared by treatment group. The number needed to treat (NNT with olanzapine rather than comparator to avoid loss of one additional responder over 24 or 28 weeks of treatment was calculated for each study. Results Time maintained in response was significantly longer (p Conclusion During 24 and 28 weeks of treatment, the antipsychotics studied differed in the time that treated patients with schizophrenia remained in response and the proportion of patients who lost response. Olanzapine treatment resulted in a consistent and statistically significant advantage in maintenance of response compared to treatment with risperidone, quetiapine and ziprasidone; but not compared to treatment with aripiprazole.
Discovery of novel heteroarylazole N-phenylpiperazine prototypes candidates to atypic antipsychotic drugs [Descoberta de novos protótipos N-fenilpiperazínicos heteroarilazólicos candidatos a fármacos antipsicóticos atípicos
Andresa H. Betti
Full Text Available This work describes the discovery of new N-phenylpiperazine prototypes belonging to pyrazole series,i.e. LASSBio-579 (10a, or to 1,2,3-triazole series, represented by LASSBio-581 (10c, which were designed fromthe structural simplification of the atypical antipsychotic drug clozapine (8. The evaluation of the affinity andintrinsic activity profiles of LASSBio-579 and LASSBio-581 indicate its ability to bind dopamine receptors fromD2-like family, acting as pre-synaptic agonists. Additionally, the investigation of the antipsychotic properties ofthese two prototypes in behavioral models has confirmed its effectiveness, which is also dependent on themodulation of serotoninergic receptors 5-HT2A and 5-HT1A. The pronounced antipsychotic effect evidenced forthese N-phenylpiperazine derivatives through in vivo pharmacological assays confirmed their importance asnew neuroactive drug-candidate prototypes for the treatment of schizophrenia.
Anant D. Patil
Full Text Available Although many atypical antipsychotics are available, there is a need of an atypical antipsychotic effective in all symptom domains of schizophrenia and well tolerated especially for side effects like extrapyramidal side effects, weight gain and blood prolactin elevation. Blonanserin is an atypical antipsychotic which blocks dopamine D2 and serotonin 5HT2A receptors. Its efficacy and safety has been studied in patients with schizophrenia and delirium. Blonanserin is found to be effective and well tolerated in both conditions. This article has reviewed efficacy and tolerability of blonanserin in these two psychiatry diseases. [Int J Basic Clin Pharmacol 2013; 2(6.000: 689-692
Acioly LT Lacerda
disorder, especially in the acute manic phase. Recently new alternatives have become available with the development of newer atypical antipsychotic agents. A comprehensive Medline search was conducted, and all available literature concerning the role of atypical antipsychotics in the treatment of bipolar patients was retrieved. Olanzapine showed to be quite effective in the treatment of acute mania, and it was found that an average of 63.5% of the patients had a significant improvement in double blind controlled studies, with weight gain as the major side effect. Data was less robust for clozapine and risperidone, mainly due to methodological limitations of the few available studies. It was also found a considerable interest in future investigating the efficacy of these pharmacological agents in refractory cases and in the treatment of the disorder's depressive phase. Additionally, there has been extensive interest in evaluating their potential action as mood stabilizers, for which there will be a need of longer-term longitudinal studies.
Full Text Available Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined.Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of 'good' adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period.Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention; the adjusted costs difference was £598 (95% CI -£4,533, £5,730. The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8,020, £14,000. The extra cost per patient of achieving 'good' adherence was £2,950 (CI -£19,400, £27,800. Probability of cost-effectiveness exceeded 97.5% at willingness-to-pay values of £14,000 for a 20% increase in adherence and £27,800 for good adherence.Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive are unlikely to be increased by this intervention.ISRCTN.com 77769281.
Alphs L; Bossie CA; Sliwa JK; Fu DJ; Ma YW; Hulihan J
Larry Alphs,1 Cynthia A Bossie,1 Jennifer Kern Sliwa,2 Dong-Jing Fu,1 Yi-Wen Ma,3 Joseph Hulihan11CNS Medical Affairs, 2Medical Information, Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 3Biostatistics, B&P, Janssen Research & Development LLC, Titusville, NJ, USABackground: This post hoc subgroup analysis of a randomized, double-blind trial evaluated the response to treatment with two long-acting injectable atypical antipsychotics, ie, paliperidone palmitate and risper...
Full Text Available Evidence supporting the use of second generation antipsychotics (SGAs in the treatment of acute depression with mixed features (MFs associated with bipolar disorder (BD is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo- controlled trials (RCTs or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI. Six RCTs and one open-label placebo-controlled studies (including post-hoc reports representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS (SMD −0.74, 95% CI −1.20 to −0.28, n SGA = 907, control = 652. Meta-analysis demonstrated that participants in receipt of SGA (n = 979 experienced a large improvement in the Montgomery–Åsberg Depression Rating Scale (MADRS scores (SMD −1.08, 95% CI −1.35 to −0.81, p < 0.001 vs. placebo (n = 678. Publication and measurement biases and relative paucity of studies. Overall, SGAs appear to offer favorable improvements in MADRS and YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable
Fornaro, Michele; Stubbs, Brendon; De Berardis, Domenico; Perna, Giampaolo; Valchera, Alessandro; Veronese, Nicola; Solmi, Marco; Ganança, Licínia
Evidence supporting the use of second generation antipsychotics (SGAs) in the treatment of acute depression with mixed features (MFs) associated with bipolar disorder (BD) is scarce and equivocal. Therefore, we conducted a systematic review and preliminary meta-analysis investigating SGAs in the treatment of acute BD depression with MFs. Two authors independently searched major electronic databases from 1990 until September 2015 for randomized (placebo-) controlled trials (RCTs) or open-label clinical trials investigating the efficacy of SGAs in the treatment of acute bipolar depression with MFs. A random-effect meta-analysis calculating the standardized mean difference (SMD) between SGA and placebo for the mean baseline to endpoint change in depression as well as manic symptoms score was computed based on 95% confidence intervals (CI). Six RCTs and one open-label placebo-controlled studies (including post-hoc reports) representing 1023 patients were included. Participants received either ziprasidone, olanzapine, lurasidone, quetiapine or asenapine for an average of 6.5 weeks across the included studies. Meta-analysis with Duval and Tweedie adjustment for publication bias demonstrated that SGA resulted in significant improvements of (hypo-)manic symptoms of bipolar mixed depression as assessed by the means of the total scores of the Young Mania Rating Scale (YMRS) (SMD -0.74, 95% CI -1.20 to -0.28, n SGA = 907, control = 652). Meta-analysis demonstrated that participants in receipt of SGA (n = 979) experienced a large improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS) scores (SMD -1.08, 95% CI -1.35 to -0.81, p YMRS scores vs. placebo. Nevertheless, given the preliminary nature of the present report, additional original studies are required to allow more reliable and clinically definitive conclusions. PMID:26891297
van der Weide, Jan; Hinrichs, John WJ
Since the identification of all the major drug-metabolising cytochrome P450 (CYP) enzymes and their major gene variants, pharmacogenetics has had a major impact on psychotherapeutic drug therapy. CYP enzymes are responsible for the metabolism of most clinically used drugs. Individual variability in CYP activity is an important reason for drug therapy failure. Variability in CYP activity may be caused by various factors, including endogenous factors such as age, gender and morbidity as well as exogenous factors such as co-medication, food components and smoking habit. However, polymorphisms, present in most CYP genes, are responsible for a substantial part of this variability. Although CYP genotyping has been shown to predict the majority of aberrant phenotypes, it is currently rarely performed in clinical practice. PMID:16886044
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
Yu-Xi Wang; Yu-Tao Xian; Yun-Ai Su; Qian Li; Liang Shu; Chee H Ng; Gabor S Ungvari
Background:Optimizing treatment outcomes for depression requires understanding of how evidence-based treatments are utilized in clinical practice.Antipsychotic medications concurrent with antidepressant treatment are frequently used in major depression,but few studies have investigated trends and patterns of their use over time.This study aimed to examine the prescription patterns of antipsychotic medications for major depression in China from 2002 to 2012 and their association with treatment satisfaction and quality of life (QOL).Methods:A total of 3655 subjects with major depression treated in 45 Chinese psychiatric hospitals/centers nationwide were interviewed between 2002 and 2012.Patients' socio-demographic and clinical characteristics including psychopathology,medication side effects,satisfaction with treatment and QOL were recorded using a standardized protocol and data collection.Results:The frequency ofantipsychotic use was 24.9％ in the whole sample;the corresponding figures were 17.1％,20.3％,and 32.8％ in 2002,2006,and 2012,respectively (x2 =90.3,df=2,P ＜ 0.001).Multiple logistic regression analyses revealed that patients on concurrent antipsychotics had significantly more delusions or hallucinations,longer illness duration,greater side effects,and more likely to be treated as inpatients and in major hospitals (i.e.,Levcl-Ⅲ hospital).Antipsychotic use was associated with lower treatment satisfaction while there was no significant difference with respect to physical and mental QOL between the antipsychotic and nonantipsychotic groups.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.
Khan Rashid AM
Full Text Available Abstract Background It has been known for a long time that use of antipsychotics, particularly atypical antipsychotics, is associated with weight gain and increase in risk of metabolic disturbances. In this study we have tried to find out if use of antipsychotics is associated with increase in weight and body mass index (BMI in the Pakistani population. Methods We performed a case note review of all patients who had been prescribed antipsychotic medication at the psychiatry outpatient clinic of a tertiary care university hospital in Pakistan over a 4-year period. Results A total of 50% of patients had a BMI in the overweight or higher range at baseline. Patients showed a mean weight gain of 1.88 kg from baseline in 3 months and 3.29 kg in 6 months. Both of these values were statistically significant. The increase in mean BMI from baseline was 0.74 and 1.3 in 3 months and 6 months, respectively. In patients for whom we had at least one further weight measurement after baseline, 48% (39/81 showed a clinically significant weight gain. Conclusion Pakistani patients are just as likely to put on weight during antipsychotic treatment as patients from other countries. Considering that this population already has a much higher prevalence of diabetes mellitus compared to the Western countries, the consequences of increased weight may be even more serious in terms of increased morbidity and mortality.
Full Text Available Background and Objectives: Metabolic syndrome (visceral obesity, dyslipidaemia, hyperglycaemia, hypertension is a substantial public health problem, especially amongst individuals receiving antipsychotic medication. Methods: We studied routine screening practices for metabolic syndrome amongst psychiatry outpatients receiving injected depot anti-psychotic medication at a clinic in Dublin, Ireland. Results: Our initial audit (n = 64 demonstrated variable levels of documentation of criteria for metabolic syndrome in outpatient files; e.g. weight was recorded in 1.6% of files, serum high density lipoprotein in 12.5%. As our intervention, we introduced a screening check-list comprising risk factors and criteria for metabolic syndrome, based on the definition of the International Diabetes Federation. Re-audit (n = 54 demonstrated significantly improved levels of documentation; e.g. weight was recorded in 61.1% of files. Notwithstanding these improvements, only 11 (20.4% of 54 patient files examined in the re-audit, contained sufficient information to determine whether or not the patient fulfilled criteria for metabolic syndrome; of these, 3 patients (27.3% fulfilled criteria for metabolic syndrome. There was, however, significant additional morbidity in relation to individual criteria (waist circumference, serum triglyceride level, systolic blood pressure and serum fasting glucose. Conclusions: We recommend enhanced attention be paid to metabolic morbidity in this patient group.
Kannisto, Kati Anneli; Adams, Clive E; Koivunen, Marita; Katajisto, Jouko; Välimäki, Maritta
Objectives To explore feedback on tailored SMS reminders to encourage medication adherence and outpatient treatment among patients taking antipsychotic medication, and associations related to the feedback. Design A cross-sectional survey nested within a nationwide randomised clinical trial (“Mobile.Net” ISRCTN27704027). Setting Psychiatric outpatient care in Finland. Participants Between September 2012 and December 2013, 403 of 558 adults with antipsychotic medication responded after 12 months of SMS intervention. Main outcome measure Feedback was gathered with a structured questionnaire based on Technology Acceptance Model theory. Data were analysed by Pearson's χ2 test, binary logistic regression and stepwise multiple regression analyses. Results Almost all participants (98%) found the SMS reminders easy to use and 87% felt that the SMS did not cause harm. About three-quarters (72%) were satisfied with the SMS received, and 61% found it useful. Divorced people were particularly prone to find SMS reminders useful (χ2=13.17, df=6, p=0.04), and people seeking employment were more often ‘fully satisfied’ with the SMS compared with other groups (χ2=10.82, df=4, p=0.029). People who were older at first contact with psychiatric services were more often ‘fully satisfied’ than younger groups (OR=1.02, 95% CI 1.01 to 1.04, p=0.007). Conclusions The feedback of patients taking antipsychotic medication on SMS services was generally positive. Overall, people were quite satisfied despite considerable variation in their sociodemographic background and illness history. Our results endorse that the use of simple easy-to-use existing technology, such as mobile phones and SMS, is acceptable in psychiatric outpatient services. Moreover, people using psychiatric outpatient services are able to use this technology. This acceptable and accessible technology can be easily tailored to each patient's needs and could be customised to the needs of the isolated or jobless
Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics Revisão da eficácia do placebo nos ensaios clínicos que comparam antipsicóticos típicos e atípicos
Irismar Reis de Oliveira
Full Text Available OBJECTIVE: To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD: Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms "amisulpride", "aripiprazole", "clozapine", "olanzapine", "quetiapine", "risperidone", "sertindole", "ziprasidone" and "zotepine". Main efficacy parameters were calculated using the proportion of "events" (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS: The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS: Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.OBJETIVO: Revisar a eficácia do placebo em comparação com a dos antipsicóticos atípicos e típicos no tratamento da esquizofrenia e do transtorno
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
Birnbaum, Michael; Sharif, Zafar
Antipsychotic medications provide the foundation for treatment of acute exacerbations as well as relapse prevention in patients with schizophrenia as demonstrated by rigorous placebo-controlled trials. However, despite their proven effectiveness, poor adherence to prescribed antipsychotic regimens remains the most important driver of suboptimal clinical outcomes in this population. This paper reviews the magnitude of the problem of medication non-adherence in patients with schizophrenia and the various factors that contribute to non-adherence, with particular emphasis on factors related to antipsychotic medications. The profile of the latest atypical antipsychotic, paliperidone extended-release (ER) tablets, is then reviewed and the implications of its unique pharmacokinetic profile for adherence in this patient population are discussed. PMID:19920968
Full Text Available Michael Birnbaum1, Zafar Sharif21St. Luke’s-Roosevelt Hospital Center, 1111 Amsterdam Ave, New York, NY, USA; 2Columbia University College of Physicians and Surgeons, New York, NY, USAAbstract: Antipsychotic medications provide the foundation for treatment of acute exacerbations as well as relapse prevention in patients with schizophrenia as demonstrated by rigorous placebo-controlled trials. However, despite their proven effectiveness, poor adherence to prescribed antipsychotic regimens remains the most important driver of suboptimal clinical outcomes in this population. This paper reviews the magnitude of the problem of medication non-adherence in patients with schizophrenia and the various factors that contribute to nonadherence, with particular emphasis on factors related to antipsychotic medications. The profile of the latest atypical antipsychotic, paliperidone extended-release (ER tablets, is then reviewed and the implications of its unique pharmacokinetic profile for adherence in this patient population are discussed.Keywords: schizophrenia, adherence, paliperidone, pharmacokinetics
Lindenmayer, Jean-Pierre; Kaur, Amandeep
Schizoaffective disorder (SAD) is an incapacitating illness that presents clinicians with challenges in terms of both its diagnosis and its psychopharmacological management. Most studies conducted on the psychopharmacological treatment of SAD also include patients with schizophrenia or other psychotic illnesses, thereby providing an unspecific view to the clinician as to the best way of treating patients with SAD. The objective of this article is to review studies on evidence-based treatment of patients with SAD. We conducted a systematic literature search in MEDLINE/PubMed for full-text studies in the English language using the terms 'Schizoaffective and treatment' or 'antipsychotic schizoaffective'. Our review found relatively few studies with either an active comparator or placebo that examined the efficacy of antipsychotics for patients with SAD without an admixture of patients with schizophrenia. Only oral paliperidone extended release (ER), paliperidone long-acting injection (LAI), and risperidone have been shown to be effective and safe in reducing psychotic as well as affective components in acutely ill SAD patients in controlled studies. Paliperidone ER and LAI have also been shown to be efficacious in the maintenance treatment phase of SAD patients. While no supportive data exist, it is possible that other atypical antipsychotics may have similar efficacy to the two mentioned above. We conclude with a number of research recommendations for the study of treatment options for patients with SAD. First, there is a need for studies with patients specifically diagnosed with SAD for both the acute and the maintenance phase. The sample size needs to be adequate to allow a primary analysis of efficacy and to allow for analysis of the SAD subtypes: depressed and bipolar. Another recommendation is the need for studies of patients with SAD stratified into patients with and without mood stabilizers or antidepressants to allow the examination of the adjunctive role of
Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe;
Dopamine D(3) antagonism combined with serotonin 5-HT(1A) and 5-HT(2A) receptor occupancy may represent a novel paradigm for developing innovative antipsychotics. The unique pharmacological features of 5i are a high affinity for dopamine D(3), serotonin 5-HT(1A) and 5-HT(2A) receptors, together w...
Kapur, Shitij; Mamo, David
A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology. PMID:14642968
Kato, Yamato; Umetsu, Ryogo; Abe, Junko; Ueda, Natsumi; NAKAYAMA, Yoko; Kinosada, Yasutomi; NAKAMURA, MITSUHIRO
Background Antipsychotics are potent dopamine antagonists used to treat schizophrenia and bipolar disorder. The aim of this study was to evaluate the relationship between antipsychotic drugs and adverse hyperglycemic events using the FDA Adverse Event Reporting System (FAERS) database. In particular, we focused on adverse hyperglycemic events associated with atypical antipsychotic use, which are major concerns. Findings We analyzed reports of adverse hyperglycemic events associated with 26 an...
Andrade, Chittaranjan; Radhakrishnan, Rajiv
Background: Antipsychotic drugs are commonly used in the treatment of the behavioral and psychological symptoms of dementia (BPSD). Materials and Methods: We present a qualitative review of the data on the efficacy and safety of antipsychotic drugs for BPSD. We more specifically examine safety issues with an especial focus on recent research. We examine two safety studies in detail to provide readers with a critical perspective. Results: Typical and atypical antipsychotic drugs both attenuate...
Honey, Garry D; Bullmore, Edward T.; Soni, William; Varatheesan, Malini; Williams, Steve C R; Sharma, Tonmoy
Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal...
Calcium Signaling Pathway Is Associated with the Long-Term Clinical Response to Selective Serotonin Reuptake Inhibitors (SSRI) and SSRI with Antipsychotics in Patients with Obsessive-Compulsive Disorder
Umehara, Hidehiro; Numata, Shusuke; Tajima, Atsushi; Nishi, Akira; Nakataki, Masahito; Imoto, Issei; Sumitani, Satsuki; Ohmori, Tetsuro
Background Selective serotonin reuptake inhibitors (SSRI) are established first-line pharmacological treatments for obsessive-compulsive disorder (OCD), while antipsychotics are used as an augmentation strategy for SSRI in OCD patients who have either no response or a partial response to SSRI treatment. The goal of the present study was to identify genetic variants and pathways that are associated with the long-term clinical response of OCD patients to SSRI or SSRI with antipsychotics. Methods We first performed a genome-wide association study of 96 OCD patients to examine genetic variants contributing to the response to SSRI or SSRI with antipsychotics. Subsequently, we conducted pathway-based analyses by using Improved Gene Set Enrichment Analysis for Genome-wide Association Study (i-GSEA4GWAS) to examine the combined effects of genetic variants on the clinical response in OCD. Results While we failed to detect specific genetic variants associated with clinical responses to SSRI or to SSRI with an atypical antipsychotic at genome-wide levels of significance, we identified 8 enriched pathways for the SSRI treatment response and 5 enriched pathways for the treatment response to SSRI with an antipsychotic medication. Notably, the calcium signaling pathway was identified in both treatment responses. Conclusions Our results provide novel insight into the molecular mechanisms underlying the variability in clinical response to SSRI and SSRI with antipsychotics in OCD patients. PMID:27281126
Gareri, Pietro; De Fazio, Pasquale; Manfredi, Valeria Graziella Laura; De Sarro, Giovambattista
In recent years, the use of antipsychotics has been widely debated for reasons concerning their safety in elderly patients affected with dementia. To update the use of antipsychotics in elderly demented people, a MEDLINE search was conducted using the following terms: elderly, conventional and atypical antipsychotics, adverse events, dementia, and behavioral and psychotic symptoms in dementia (BPSD). Owing to the large amounts of studies on antipsychotics, we mostly restricted the field of research to the last 10 years. Conventional antipsychotics have been widely used for BPSD; some studies showed they have an efficacy superior to placebo only at high doses, but they are associated with several and severe adverse effects. Atypical antipsychotics showed an efficacy superior to placebo in randomized studies in BPSD treatment, with a better tolerability profile versus conventional drugs. However, in 2002, trials with risperidone and olanzapine in elderly patients affected with dementia-related psychoses suggested the possible increase in cerebrovascular adverse events. Drug regulatory agencies issued specific recommendations for underlining that treatment of BPSD with atypical antipsychotics is "off-label." Conventional antipsychotics showed the same likelihood to increase the risk of death in the elderly as atypical agents, and they should not replace the atypical agents discontinued by Food and Drug Administration warnings. Before prescribing an antipsychotic drug, the following are factors to be seriously considered: the presence of cardiovascular diseases, QTc interval on electrocardiogram, electrolytic imbalances, familiar history for torsades des pointes, concomitant treatments, and use of drugs able to lengthen QTc. Use of antipsychotics in dementia needs a careful case-by-case assessment, together with the possible drug-drug, drug-disease, and drug-food interactions. PMID:24158020
The aim of this audit was to review current practice within a rural mental health service area on the monitoring and documentation of side effects of antipsychotic depot medication. Following a review of the literature on best practice internationally, an evidence based audit tool was adapted. A sample of 60 case files, care plans and prescriptions were audited between January and May 2010. This represented 31% of the total number of service users receiving depot injections in the mental health service region (n=181). The audit results revealed that most service users had an annual documented medical review and a documented prescription. However, only 5 (8%) case notes examined had documentation recorded describing the condition of the injection site and alternation of the injection site was recorded in only 28 (47%) case notes. No case notes examined had written consent to commence treatment recorded, and only 3 (5%) of case notes had documented that information on the depot injection and side effects was given. In 57 (95%) of case notes no documentation of recorded information on the depot and on side effects was given. Documentation of physical observations and tests revealed that 58% of cases had full blood count, liver function tests, thyroid function tests and fasting lipids recorded. All other tests (i.e. temperature, pulse, respirations, blood pressure, ECG) were recorded in less than 50% of cases. Prolactin levels were not recorded in any case. The lack of written consent was partly attributed to lack of recording of consent. The failure to monitor and record some\\r\
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.
Mattson, Margaret E; Albright, Victoria A; Yoon, Joanna; Council, Carol L
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. PMID:26056465
Polcwiartek, Christoffer; Sørensen, Kristian Dahl Kragholm; Schjerning, Ole; Graff, Claus; Nielsen, Jimmi
cardiovascular risk factors. Areas covered: This clinical overview summarizes the cardiovascular safety of antipsychotics by focusing on the wide range of associated adverse effects. In addition, we also discuss current guidelines regarding routine electrocardiogram (ECG) monitoring. Expert opinion: As SCD in......, as this may increase risk of Torsades de Pointes and eventually SCD. However, other serious cardiovascular complications of antipsychotics also include Brugada syndrome phenotype, myocardial infarction, and myocarditis. Increased awareness of the cardiovascular safety of antipsychotics can allow...
Lim, Chor Hong; Zainal, Nor Zuraida; Kanagasundram, Sharmilla; Zain, Shamsul Mohd; Mohamed, Zahurin
Although major progress has been achieved in research and development of antipsychotic medications for bipolar disorder (BPD), knowledge of the molecular mechanisms underlying this disorder and the action of atypical antipsychotics remains incomplete. The levels of microRNAs (miRNAs)-small non-coding RNA molecules that regulate gene expression, including genes involved in neuronal function and plasticity-are frequently altered in psychiatric disorders. This study aimed to examine changes in miRNA expression in bipolar mania patients after treatment with asenapine and risperidone. Using a miRNA microarray, we analyzed miRNA expression in the blood of 10 bipolar mania patients following 12 weeks of treatment with asenapine or risperidone. Selected miRNAs were validated by using real-time PCR. A total of 16 miRNAs were differentially expressed after treatment in the asenapine group, 14 of which were significantly upregulated and the other two significantly downregulated. However, all three differentially expressed miRNAs in the risperidone group were downregulated. MiRNA target gene prediction and gene ontology analysis revealed significant enrichment for pathways associated with immune system response and regulation of programmed cell death and transcription. Our results suggest that candidate miRNAs may be involved in the mechanism of action of both antipsychotics in bipolar mania. © 2016 Wiley Periodicals, Inc. PMID:27177356
Full Text Available Long-acting injectable antipsychotics constitute a valuable alternative for the treatment of psychotic disorders, mainly schizophrenia. They assure a more stable drug level, improve treatment compliance, and increase the chances for favorable and long-lasting improvement. Additionally, the long-acting second-generation antipsychotics combine the values of long-acting injectable drugs with the values of atypical antipsychotics. Four second generation long-acting antipsychotics have been described: risperidone, olanzapine, aripiprazole and paliperidone. The indications for their use, treatment strategy, tolerance, and potential interactions are discussed.
Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318
Melissa Guarieiro Ramos
Full Text Available OBJETIVO: O emprego de antipsicóticos atípicos (AA no tratamento de sintomas psicológicos e comportamentais das demências (SPCD tem sido alvo de discussão em relação à eficácia e à segurança. O objetivo deste artigo é propiciar atualização sobre o tema. MÉTODOS: Revisão da literatura publicada nos últimos dez anos com ênfase em metanálises e ensaios clínicos randomizados (ECR controlados com placebo. RESULTADOS: Três metanálises e nove ensaios clínicos foram analisados. Há evidências de eficácia clínica para risperidona (1mg/dia, olanzapina (5 a 10mg/dia e aripiprazol (2 a 15mg/dia no tratamento de agressividade e/ou SPCD em geral, e para risperidona (1mg/dia no tratamento de sintomas psicóticos associados à demência. Os eventos adversos comuns com o uso de AA foram sonolência, sintomas extrapiramidais (SEP, incontinência ou infecção do trato urinário e alterações de marcha. O tratamento com AA associou-se a maior risco de eventos cerebrovasculares e de mortalidade em idosos com demência. CONCLUSÃO: Baixas dosagens de risperidona, olanzapina e aripiprazol são eficazes na redução de agressividade e/ou SPCD globais; risperidona é eficaz na redução de sintomas psicóticos associados à demência. Em virtude de esses tratamentos associarem-se a pequeno aumento no risco de eventos cerebrovasculares e mortalidade, seu uso deve ser reservado para sintomatologia moderada/grave.OBJECTIVE: Concerns have been raised about efficacy and adverse events of atypical antipsychotics in the treatment of behavioural and psychological symptoms of dementia (BPSD. This paper is an update on current evidence of this theme. METHODS: Review of published meta-analysis and randomized placebo-controlled trials (RCTs in the last ten years. RESULTS: Three meta-analysis and nine RCTs were evaluated. Evidence suggests that risperidone (1mg/day, olanzapine (5 to 10mg/day, and aripiprazole (2 to 15mg/day are effective in treating
Full Text Available Atypical depression is defined as a specifier of major depressive disorder. Columbia criteria for atypical depression are commonly used to make a diagnosis. Female sex, onset at early age, chronic course, and higher rate of comorbidity (especially anxiety disorder and bipolar disorder is noteworthy in atypical depression. Although, the atypical depression seems to support the familial genetic transition, there is not any specific study supporting these data. In the treatment of atypical depression, monoamine oxidase inhibitors are reported to be more effective than tricyclic antidepressants. In recent studies, selective serotonin reuptake inhibitors have also proven to be efficient.
Brindisi, Margherita; Butini, Stefania; Franceschini, Silvia; Brogi, Simone; Trotta, Francesco; Ros, Sindu; Cagnotto, Alfredo; Salmona, Mario; Casagni, Alice; Andreassi, Marco; Saponara, Simona; Gorelli, Beatrice; Weikop, Pia; Mikkelsen, Jens D.; Scheel-Kruger, Jorgen; Sandager-Nielsen, Karin; Novellino, Ettore; Campiani, Giuseppe; Gemma, Sandra
Combination of dopamine D3 antagonism, serotonin 5-HT1A partial agonism, and antagonism at 5-HT2A leads to a novel approach to potent atypical antipsychotics. Exploitation of the original structure-activity relationships resulted in the identification of safe and effective antipsychotics devoid of...
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 re
Vehof, Jelle; Risselada, Arne J.; Al Hadithy, Asmar F. Y.; Burger, Huibert; Snieder, Harold; Wilffert, Bob; Arends, Johan; Wunderink, Lex; Knegtering, Henrikus; Wiersma, Durk; Cohen, Dan; Mulder, Hans; Bruggeman, Richard
Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor ge
J. Vehof (Jelle); A.J. Risselada (Arne); A.F.Y. Al Hadithy (Asmar); H. Burger (Herman); H. Snieder (Harold); B. Wilffert (Bob); J. Arends (Johan); L. Wunderink (Lex); H. Knegtering (Henrikus); D. Wiersma (Durk); D. Cohen (Daniel); H. Mulder (Hans Sipko); R. Bruggeman (Richard)
textabstractRationale: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. Objectives: We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylchol
Full Text Available Over half a century after the discovery of chlorpromazine and haloperidol, antipsychotic drugs showed a true evolutionary revolution. The knowledge of their adverse effects is of outmost importance as it may contribute to the prevention of unwanted sequelae, to the decrease of the duration and cost of hospitalization, it may improve the quality of life of patients, minimize the problems and maximize the therapeutic gain. Aim: The aim of this review was the presentation of the hematologic side-effects of antipsychotic drugs, and most particularly their frequency and association with the different classes of these drugs, their clinical picture and their pathophysiologic mechanisms. Material-method: This paper is a review of the literature (mainly articles from journals, PubMed, as well as books and monographs of the period 1978-2012. Key-words used included antipsychotics, hematologic adverse effects, drug-induced adverse effects. Results: Antipsychotic-drug induced hematologic side-effects are not particularly highly prevalent, while many of them are found in case reports. For this reason they have not drawn much of attention. These hematologic dyscrasias may concern all the blood cell series as well as the coagulation mechanism. Excluded from this rule is the case of clozapine-induced agranulocytosis, which demands increased clinical vigilance. In fact, agranulocytosis was the reason why the drug was drawn away from circulation approximately 35 years ago. Conclusions: In any case the appearance of a hematologic disorder in a patient receiving antipsychotic medications should prompt careful evaluation.
Sørensen, Holger J; Jensen, Signe O W; Nielsen, Jimmi
(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...
Individuals with schizophrenia are at very high risk for drug abuse and addiction. Patients with a coexisting drug problem fare worse than patients who do not use drugs, and are also more difficult to treat. Current hypotheses cannot adequately account for why patients with schizophrenia so often have a co-morbid drug problem. I present here a complementary hypothesis based on evidence showing that chronic exposure to antipsychotic medications can induce supersensitivity within the brain's dopamine systems, and that this in turn can enhance the rewarding and incentive motivational effects of drugs and reward cues. At the neurobiological level, these effects of antipsychotics are potentially linked to antipsychotic-induced increases in the striatal levels of dopamine D2 receptors and D2 receptors in a high-affinity state for dopamine, particularly at postsynaptic sites. Antipsychotic-induced dopamine supersensitivity and enhanced reward function are not inevitable consequences of prolonged antipsychotic treatment. At least two parameters appear to promote these effects; the use of antipsychotics of the typical class, and continuous rather than intermittent antipsychotic exposure, such that silencing of dopaminergic neurotransmission via D2/3 receptors is unremitting. Thus, by inducing forms of neural plasticity that facilitate the ability of drugs and reward cues to gain control over behaviour, some currently used treatment strategies with typical antipsychotics might contribute to compulsive drug seeking and drug taking behaviours in vulnerable schizophrenia patients. PMID:23793001
Choi, Ho-Dong; Kim, Kyoung-Keun; Koo, Bon-Hoon
Several studies have reported on catatonia caused by the use of antipsychotic drugs and on the association between catatonia and neuroleptic malignant syndrome (NMS), but none has reported such a case in Korea. Here, we report the case of a 20-year-old woman whose catatonia and NMS appeared associated with the administration of an atypical antipsychotic drug. We discuss the association between NMS and catatonia due to neuroleptic use.
Sanivarapu, Sravanti L.; Krishnamurthy CN
Risperidone is an atypical antipsychotic agent used primarily to treat schizophrenia. It is a dopamine antagonist with antiserotonergic, antihistaminergic and antiadrenergic properties. Antipsychotic discontinuation symptoms have been described in the literature following abrupt or rapid reduction in the dose. This unusual case demonstrates that sudden withdrawal of even a modest dose of risperidone may cause significant discontinuation symptoms in susceptible individuals. Hence, there is a n...
Jeste, Dilip V.; Blazer, Dan; Casey, Daniel; Meeks, Thomas; Salzman, Carl; Schneider, Lon; Tariot, Pierre; Yaffe, Kristine
In elderly persons, antipsychotic drugs are clinically prescribed off-label for a number of disorders outside of their Food and Drug Administration (FDA)-approved indications (schizophrenia and bipolar disorder). The largest number of antipsychotic prescriptions in older adults is for behavioral disturbances associated with dementia. In April 2005, the FDA, based on a meta-analysis of 17 double-blind randomized placebo-controlled trials among elderly people with dementia, determined that atyp...
de Bartolomeis, Andrea; Marmo, Federica; Buonaguro, Elisabetta F; Latte, Gianmarco; Tomasetti, Carmine; Iasevoli, Felice
The postsynaptic density (PSD) has been regarded as a functional switchboard at the crossroads of a dopamine-glutamate interaction, and it is putatively involved in the pathophysiology of psychosis. Indeed, it has been demonstrated that antipsychotics may modulate several PSD transcripts, such as PSD-95, Shank, and Homer. Despite switching antipsychotics is a frequent strategy to counteract lack of efficacy and/or side effect onset in clinical practice, no information is available on the effects of sequential treatments with different antipsychotics on PSD molecules. The aim of this study was to evaluate whether a previous exposure to a typical antipsychotic and a switch to an atypical one may affect the expression of PSD transcripts, in order to evaluate potential neurobiological correlates of this common clinical practice, with specific regards to putative synaptic plasticity processes. We treated male Sprague-Dawley rats intraperitoneally for 15days with haloperidol or vehicle, then from the sixteenth day we switched the animals to amisulpride or continued to treat them with vehicle or haloperidol for 15 additional days. In this way we got six first treatment/second treatment groups: vehicle/vehicle, vehicle/haloperidol, vehicle/amisulpride, haloperidol/vehicle, haloperidol/haloperidol, haloperidol/amisulpride. In this paradigm, we evaluated the expression of brain transcripts belonging to relevant and interacting PSD proteins, both of the Immediate-Early Gene (Homer1a, Arc) and the constitutive classes (Homer1b/c and PSD-95). The major finding was the differential effect of amisulpride on gene transcripts when administered in naïve vs. antipsychotic-pretreated rats, with modifications of the ratio between Homer1a/Homer1b transcripts and differential effects in cortex and striatum. These results suggest that the neurobiological effects on PSD transcripts of amisulpride, and possibly of other antipsychotics, may be greatly affected by prior antipsychotic
García-Ruiz, Antonio J; Pérez-Costillas, Lucía; Montesinos, Ana C.; Alcalde, Javier; Oyagüez, Itziar; Casado, Miguel A
Background: Schizophrenia is a severe form of mental illness which is associated with significant and long-lasting health, social and financial burdens. The aim of this project is to assess the efficiency of the antipsychotics used in Spain in reducing schizophrenia relapses under the Spanish Health System perspective. Material and methods: A decision-analytic model was developed to explore the relative cost-effectiveness of five antipsychotic medications, amisulpride, aripiprazole, olanzapin...
Dibben, Claire R. M.; Khandaker, Golam M.; Underwood, Benjamin R.; O'Loughlin, Christopher; Keep, Catherine; Mann, Louisa; Jones, Peter B.
Aims and method To identify training needs of the next generation of psychiatrists and barriers in prescribing first-generation antipsychotics (FGAs). We have surveyed psychiatry trainees in East Anglia with regard to their training experience, knowledge and attitudes to the use of oral FGAs as regular medication. Results Two-thirds of trainees were aware that first- and second-generation antipsychotics (SGAs) have similar efficacy, and a similar proportion perceived the older drugs to have m...
Pani, Luca; Pira, Luigi; Marchese, Giorgio
Clinically important differences exist between antipsychotic agents and formulations in terms of safety and tolerability. Features of the biochemical interaction between the antipsychotic and the D2-receptor may underlie these differences. This article reviews current information on the relationship between antipsychotic receptor occupancy and clinical response. A literature search was performed using the keywords 'antipsychotic or neuroleptic', 'receptor' and 'occupancy' and 'dopamine' and 'D2' supplemented by the authors' knowledge of the literature. Imaging and clinical data have generally supported the hypotheses that optimal D2-receptor occupancy in the striatum lies in a 'therapeutic window' between approximately 65 and approximately 80%, however, pharmacokinetic and pharmacodynamic properties of a drug should also be taken into account to fully evaluate its therapeutic effects. Additional research, perhaps in preclinical models, is needed to establish D2-receptor occupancy in various regions of the brain and the optimal duration of D2-receptor blockade in order to maximise efficacy and tolerability profiles of atypical antipsychotics and thereby improve treatment outcomes for patients with schizophrenia. PMID:17419008
Roberts, Rona Jeannie; Lohano, Kavita K; El-Mallakh, Rif S
Three second-generation antipsychotic (SGA) agents have received FDA approval for adjunctive treatment, to antidepressant, of major depressive disorder: quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone have been approved for the treatment of bipolar depression. There are data suggesting that quetiapine is effective for major depressive disorder as monotherapy. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all SGA will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e., produce a depression-like clinical picture). The antidepressant effect appears to be unique to some agents, with direct evidence of insignificant antidepressant action for ziprasidone. Three general principles can guide the use of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects; (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic doses are to be used; and (iii) SGAs do not have a general antidepressant effect, rather, this appears to be unique to quetiapine and aripiprazole, and possibly lurasidone. PMID:25963405
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
Sahlholm, Kristoffer; Zeberg, Hugo; Nilsson, Johanna; Ögren, Sven Ove; Fuxe, Kjell; Århem, Peter
Newer, "atypical" antipsychotics carry a lower risk of motor side-effects than older, "typical" compounds. It has been proposed that a ~100-fold faster dissociation from the dopamine D2 receptor (D2R) distinguishes atypical from typical antipsychotics. Furthermore, differing antipsychotic D2R affinities have been suggested to reflect differences in dissociation rate constants (koff), while association rate constants (kon) were assumed to be similar. However, it was recently demonstrated that lipophilic accumulation of ligand in the cell interior and/or membrane can cause underestimation of koff, and as high-affinity D2R antagonists are frequently lipophilic, this may have been a confounding factor in previous studies. In the present work, a functional electrophysiology assay was used to measure the recovery of dopamine-mediated D2R responsivity from antipsychotic antagonism, using elevated concentrations of dopamine to prevent the potential bias of re-binding of lipophilic ligands. The variability of antipsychotic kon was also reexamined, capitalizing on the temporal resolution of the assay. kon was estimated from the experimental recordings using a simple mathematical model assumed to describe the binding process. The time course of recovery from haloperidol (typical antipsychotic) was only 6.4- to 2.5-fold slower than that of the atypical antipsychotics, amisulpride, clozapine, and quetiapine, while antipsychotic kons were found to vary more widely than previously suggested. Finally, affinities calculated using our kon and koff estimates correlated well with functional potency and with affinities reported from radioligand binding studies. In light of these findings, it appears unlikely that typical and atypical antipsychotics are primarily distinguished by their D2R binding kinetics. PMID:26811292
Fernandes, B S; Steiner, J; Bernstein, H-G; Dodd, S; Pasco, J A; Dean, O M; Nardin, P; Gonçalves, C-A; Berk, M
The inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85 000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, Pbody mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they
Full Text Available Abstract Background Anti-psychotics, prescribed to people with dementia, are associated with approximately 1,800 excess annual deaths in the UK. A key public health objective is to limit such prescribing of anti-psychotics. Methods This project was conducted within primary care in Medway Primary Care Trust (PCT in the UK. There were 2 stages for the intervention. First, primary care information systems including the dementia register were searched by a pharmacy technician to identify people with dementia prescribed anti-psychotics. Second, a trained specialist pharmacist conducted targeted clinical medication reviews in people with dementia initiated on anti-psychotics by primary care, identified by the data search. Results Data were collected from 59 practices. One hundred and sixty-one (15.3% of 1051 people on the dementia register were receiving low-dose anti-psychotics. People with dementia living in residential homes were nearly 3.5 times more likely to receive an anti-psychotic [25.5% of care home residents (118/462 vs. 7.3% of people living at home (43/589] than people living in their own homes (p Of the 161 people with dementia prescribed low-dose anti-psychotics, 91 were receiving on-going treatment from local secondary care mental health services or Learning Disability Teams. Of the remaining 70 patients the anti-psychotic was either withdrawn, or the dosage was reduced, in 43 instances (61.4% following the pharmacy-led medication review. Conclusions In total 15.3% of people on the dementia register were receiving a low-dose anti-psychotic. However, such data, including the recent national audit may under-estimate the usage of anti-psychotics in people with dementia. Anti-psychotics were used more commonly within care home settings. The pharmacist-led medication review successfully limited the prescribing of anti-psychotics to people with dementia.
Positive predictive value of a case definition for diabetes mellitus using automated administrative health data in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid study
Bobo William V
Full Text Available Abstract Background We developed and validated an automated database case definition for diabetes in children and youth to facilitate pharmacoepidemiologic investigations of medications and the risk of diabetes. Methods The present study was part of an in-progress retrospective cohort study of antipsychotics and diabetes in Tennessee Medicaid enrollees aged 6–24 years. Diabetes was identified from diabetes-related medical care encounters: hospitalizations, outpatient visits, and filled prescriptions. The definition required either a primary inpatient diagnosis or at least two other encounters of different types, most commonly an outpatient diagnosis with a prescription. Type 1 diabetes was defined by insulin prescriptions with at most one oral hypoglycemic prescription; other cases were considered type 2 diabetes. The definition was validated for cohort members in the 15 county region geographically proximate to the investigators. Medical records were reviewed and adjudicated for cases that met the automated database definition as well as for a sample of persons with other diabetes-related medical care encounters. Results The study included 64 cases that met the automated database definition. Records were adjudicated for 46 (71.9%, of which 41 (89.1% met clinical criteria for newly diagnosed diabetes. The positive predictive value for type 1 diabetes was 80.0%. For type 2 and unspecified diabetes combined, the positive predictive value was 83.9%. The estimated sensitivity of the definition, based on adjudication for a sample of 30 cases not meeting the automated database definition, was 64.8%. Conclusion These results suggest that the automated database case definition for diabetes may be useful for pharmacoepidemiologic studies of medications and diabetes.
Geerts, Paul; Martinez, Guadalupe; Schreiner, Andreas
Background Discontinuation of antipsychotic treatment for schizophrenia can interrupt improvement and exacerbate the illness. Reasons for discontinuing treatment are multifactorial and include adherence, efficacy and tolerability issues. Poor adherence may be addressed through non-pharmacological approaches as well as through pharmacological ones, ie ensured delivery of medication, such as that achieved with long-acting injectable (LAI) antipsychotics. However, attitudes of healthcare profess...
Protopapas, Athanasios; Sotiropoulou, Maria; Athanasiou, Stavros; Loutradis, Dimitrios
Atypical polypoid adenomyomas (APAMs) are rare uterine tumors that occur predominantly in premenopausal women, with less than 250 cases reported so far, worldwide. They may recur after treatment, and they may coexist with, or precede development of an endometrial adenocarcinoma. For this reason cases managed with conservative surgery or medical therapies require long-term follow-up. We report the case of a 41 years old nulliparous patient who during a diagnostic hysteroscopy was found with an endocervical atypical polypoid adenomyoma (APAM). The patient was desirous of a pregnancy, reported menometrorrhagia, and had a coexistent 5 cm, grade 2, submucous myoma, 3 endometrial polyps, and diffuse adenomyosis. She was treated with hysteroscopic resection of the APAM and polyps, plus laparoscopic myomectomy and wedge resection of adenomyosis. She is on an IVF list and after 4 months she is symptoms-free. PMID:26304721
V. P. Volkov
Full Text Available Aim. To study the morphological and functional heart disorders in patients with different duration of antipsychotic treatment. Material and methods. Medical documents of 78 deceased schizophrenic patients treated with antipsychotic drugs were studied. The patients were split into 4 groups depending on duration of neuroleptic treatment: group 1 — <10 years, group 2 — 11-20 years; group 3 — 21-30 years, group 4 — >30 years. ECG-disorders and left ventricular morphometric data were analyzed. Сorrelation analysis of myocardium morphological changes and electrophysiological disorders was performed. Results. The dependence of morphometric myocardium changes on the treatment duration was found: increase in stromal-parenchymal ratio (from 9.9±4.1% to 80.0±10.1% in groups 1 and 4, respectively, in specific volume of atrophied cardiomyocytes (from 8.0±3.8% to 45.1±12.6% in groups 1 and 4, respectively, in specific volume of degenerative cardiomyocytes (from 5.2±3.1% to 35.2±12.1% in groups 1 and 4, respectively. Increased incidence of extrasystole detection (from 2.2% to 11.2% in groups 1 and 2, respectively, as well as left anterior fascicular block (from 1.1% to 25.9% in groups 1 and 2, respectively and left ventricle hypertrophy (from 2.2% to 18.5% in groups 1 and 4, respectively were found. A strong positive correlation (r=0.88–0.99 was revealed between antipsychotic treatment duration and ECG disorders, as well as between morphological myocardium state and ECG disorders. Conclusion. Awareness about the neuroleptic-depended ECG changes is necessary for early diagnosis, secondary prevention and correction of existing heart disorders due to cardiotoxic side effects of antipsychotic drugs.
Seibt, Kelly Juliana; Oliveira, Renata da Luz; Bogo, Mauricio Reis; Senger, Mario Roberto; Bonan, Carla Denise
Antipsychotic agents are used for the treatment of psychotic symptoms in patients with several brain disorders, such as schizophrenia. Atypical and typical antipsychotics differ regarding their clinical and side-effects profile. Haloperidol is a representative typical antipsychotic drug and has potent dopamine receptor antagonistic functions; however, atypical antipsychotics have been developed and characterized an important advance in the treatment of schizophrenia and other psychotic disorders. Purine nucleotides and nucleosides, such as ATP and adenosine, constitute a ubiquitous class of extracellular signaling molecules crucial for normal functioning of the nervous system. Indirect findings suggest that changes in the purinergic system, more specifically in adenosinergic activity, could be involved in the pathophysiology of schizophrenia. We investigated the effects of typical and atypical antipsychotics on ectonucleotidase and adenosine deaminase (ADA) activities, followed by an analysis of gene expression patterns in zebrafish brain. Haloperidol treatment (9 µM) was able to decrease ATP hydrolysis (35%), whereas there were no changes in hydrolysis of ADP and AMP in brain membranes after antipsychotic exposure. Adenosine deamination in membrane fractions was inhibited (38%) after haloperidol treatment when compared to the control; however, no changes were observed in ADA soluble fractions after haloperidol exposure. Sulpiride (250 µM) and olanzapine (100 µM) did not alter ectonucleotidase and ADA activities. Haloperidol also led to a decrease in entpd2_mq, entpd3 and adal mRNA transcripts. These findings demonstrate that haloperidol is an inhibitor of NTPDase and ADA activities in zebrafish brain, suggesting that purinergic signaling may also be a target of pharmacological effects promoted by this drug. PMID:26156500
Full Text Available Larry Alphs,1 Cynthia A Bossie,1 Jennifer Kern Sliwa,2 Dong-Jing Fu,1 Yi-Wen Ma,3 Joseph Hulihan11CNS Medical Affairs, 2Medical Information, Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 3Biostatistics, B&P, Janssen Research & Development LLC, Titusville, NJ, USABackground: This post hoc subgroup analysis of a randomized, double-blind trial evaluated the response to treatment with two long-acting injectable atypical antipsychotics, ie, paliperidone palmitate and risperidone long-acting injectable (RLAI, in subjects with schizophrenia experiencing clinically significant symptoms despite recent treatment with oral risperidone only or other oral antipsychotics.Methods: Adult subjects were eligible for the 13-week, double-blind, double-dummy trial (NCT00589914 if they had an established diagnosis of schizophrenia for at least one year and a Positive and Negative Syndrome Scale (PANSS total score of 60–120 inclusive at screening. Subjects received either paliperidone palmitate (234 mg, day 1; 156 mg, day 8; then once-monthly flexible dosing or RLAI (25–50 mg biweekly, with oral risperidone supplementation on days 1–28, plus matched placebo injections/tablets.Results: This post hoc analysis reports data on 747 subjects who, within 2 weeks of starting double-blind study medication, had reportedly received oral risperidone only (paliperidone palmitate group, n = 126; RLAI group, n = 107, other oral antipsychotics (paliperidone palmitate group, n = 199; RLAI group, n = 203, or no antipsychotic (paliperidone palmitate group, n = 56; RLAI group, n = 56. Mean PANSS total scores improved significantly at end point across all subgroups (mean change from baseline ranged from −17.5 to −19.5, all P < 0.0001. Clinical Global Impression-Severity and Personal and Social Performance scale measures also significantly improved from baseline (all P < 0.0001.Conclusion: Treatment with paliperidone palmitate or RLAI resulted in a significant reduction
Olivares, José Manuel; Alptekin, Köksal; Azorin, Jean-Michel; Cañas, Fernando; Dubois, Vincent; Emsley, Robin; Gorwood, Philip; Haddad, Peter M; Naber, Dieter; Papageorgiou, George; Roca, Miquel; Thomas, Pierre; Martinez, Guadalupe; Schreiner, Andreas
Background Nonadherence is common among patients with schizophrenia, although the rates vary according to means of assessment and patient population. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes, including increasing the risk of relapse and rehospitalization. Understanding psychiatrists’ perception of the causes and consequences of nonadherence is crucial to addressing adherence problems effectively. Methods The Europe, the Middle East, and Africa (EMEA) Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES) survey was conducted by questionnaire during January–March 2010 among psychiatrists treating patients with schizophrenia in 36 countries. The survey comprised 20 questions. In addition to recording the demographic details of the 4722 respondents (~12% response rate), it canvassed their preferred methods of assessing adherence, their perceptions of adherence rates, reasons for nonadherence, and strategies to improve adherence. Results Psychiatrists estimated that 53% of their patients with schizophrenia were partially/nonadherent during the previous month. They estimated only one-third of patients who deteriorated after stopping medication were able to attribute this to nonadherence. Psychiatrists assessed adherence most often by patient interview. Lack of insight was viewed as the most important cause of medication discontinuation, followed by patients feeling better and thinking their medication unnecessary, and experiencing undesirable side effects. Considerably fewer psychiatrists viewed insufficient efficacy, cognitive impairment, or drug/alcohol abuse as the most important reasons for their patients stopping medication. Conclusion Psychiatrists throughout EMEA recognize the impact of partial/nonadherence to medication, with patient enquiry being the most commonly used means of assessment. There remains a need for more proactive management of patients with schizophrenia, particularly in
Kyra-Verena Sendt; Giovanni Giaroli; Tracy, Derek K.
The dopamine hypothesis of schizophrenia remains the primary theoretical framework for the pharmacological treatment of the disorder. Despite various lines of evidence of dopaminergic abnormalities and reasonable efficacy of current antipsychotic medication, a significant proportion of patients show suboptimal treatment responses, poor tolerability, and a subsequent lack of treatment concordance. In recent decades, intriguing evidence for the critical involvement of other neurotransmitter sys...
... Ask for other treatments, such as talk therapy (psychotherapy). • If you try an antipsychotic, ask for a ... the marketing of the prescription drug Neurontin. This brief should not be viewed as a substitute for ...
The introduction of antipsychotic medications in the clinical practice of psychiatric pharmacotherapy that took place half a century ago was a real revolution. Antipsychotic medications reorientated the organic basis of mental disease and gave a clear therapeutic choice in the treatment of psychotic patients. The gradual application of their use made possible the de-institutionalization of patients as well as the 4th revolution of psychiatry, that is community and social psychiatry.Αntipsycho...
Full Text Available José Manuel Olivares,1 Köksal Alptekin,2 Jean-Michel Azorin,3 Fernando Cañas,4 Vincent Dubois,5 Robin Emsley,6 Philip Gorwood,7 Peter M Haddad,8 Dieter Naber,9 George Papageorgiou,10 Miquel Roca,11 Pierre Thomas,12 Guadalupe Martinez,13 Andreas Schreiner141Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario de Vigo, Vigo, Spain; 2Department of Psychiatry, Dokuz Eylül University School of Medicine, Izmir, Turkey; 3Department of Psychiatry, Sainte Marguerite Hospital, Marseille, France; 4Department of Psychiatry, Hospital Dr R Lafora, Madrid, Spain; 5Cliniques Universitaires St-Luc, Bruxelles, Belgium; 6Department of Psychiatry, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa; 7Sainte-Anne Hospital, Paris Descartes University and INSERM U894, Paris, France; 8Greater Manchester West Mental Health National Health Service Foundation Trust and Department of Psychiatry, University of Manchester, Manchester, UK; 9Universitätsklinikum Hamburg-Eppendorf, Klinik für Psychiatrie und Psychotherapie, Hamburg, Germany; 10Department of Psychiatry, Evangelismos General Hospital, Athens, Greece; 11Unidad de Psiquiatría, Hospital Juan March, Institut Universitari d’Investigació en Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain; 12Department of Psychiatry, Fontan Hospital CHRU Lille, UDSL, University North of France, Lille, France; 13Medical Affairs, Janssen, Madrid, Spain; 14Medical Affairs, Janssen, Neuss, GermanyBackground: Nonadherence is common among patients with schizophrenia, although the rates vary according to means of assessment and patient population. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes, including increasing the risk of relapse and rehospitalization. Understanding psychiatrists’ perception of the causes and consequences of nonadherence is crucial to addressing adherence problems
Despite US Food and Drug Administration black box warning, antipsychotics are frequently used for behavioral and psychological symptoms of dementia (BPSD) of Alzheimer's disease (AD). A 24-weeks prospective cohort study of 10,079 Japanese AD patients in. 357 medical sites was done. The mortality rates in the whole exposed group did not differ from those in the non-user control group. However, further analysis disclosed that the exposed group with shorter treatment periods had higher mortality risk. The results confirmed the mortality associated with antipsychotics suggesting that new use of antipsychotics should be avoided. Patients having been maintained on the drugs for long periods may be at less risk. PMID:27025097
JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identifi...
Ricardo Alberto Moreno
Full Text Available O transtorno bipolar é uma condição médica complexa e até o momento não há um tratamento único comprovadamente eficaz no controle de todos aspectos da doença. Foram revisadas a literatura disponível sobre o uso de anticonvulsivantes (valproato, carbamazepina, oxcarbazepina, lamotrigina, gabapentina, topiramato, clonazepam e antipsicóticos atípicos (clozapina, risperidona, olanzapina, quetiapina, ziprasidona e aripiprazole no tratamento agudo e profilático do transtorno bipolar. Existe um acúmulo de evidências acerca da eficácia do lítio na profilaxia e de ser melhor no tratamento da mania aguda do que nos episódios depressivos. Outros dados indicam que a carbamazepina e o valproato são eficazes na mania aguda. A lamotrigina parece reduzir ciclagem e ser eficaz em episódios depressivos. Baseado nas informações disponíveis, as evidências apontam a olanzapina como o antipsicótico atípico mais apropriado no tratamento de pacientes bipolares em mania, embora existam estudos sugerindo a eficácia da risperidona, aripiprazol e da clozapina. Resultados preliminares avaliando a eficácia de ziprasidona e quetiapina no transtorno bipolar ainda são bastante limitadas. Não há dados consistentes apoiando o uso profilático dos novos antipsicóticos.Bipolar disorder is a complex medical condition, and up to the date there is no single treatment with proven efficacy in the control of all aspects of the illness. The available literature on the use of anticonvulsants (valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin, topiramate, clonazepam and atypical antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole for acute and prophylactic treatment of bipolar disorder was reviewed. There is a large amount of evidence that lithium is efficacious in the prophylaxis of episodes and better for acute mania than for depressive episodes. Other data show that carbamazepine and valproate are
Full Text Available Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO and neurotrophic factors when they are activated in response to immunological stimuli. Recent reports show that pathophysiology of schizophrenia is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling, which is mainly controlled by the endoplasmic reticulum (ER, is important for microglial functions such as release of NO and cytokines, migration, ramification and deramification. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of schizophrenia, while it remains unclear how typical or atypical antipsychotics affect intracellular Ca2+ mobilization in microglial cells. This mini-review article summarizes recent findings on cellular mechanisms underlying the characteristic differences in the actions of antipsychotics on microglial intracellular Ca2+ signaling and reinforces the importance of the ER of microglial cells as a target of antipsychotics for the treatment of schizophrenia.