Sample records for antipsychotics zyprexa olanzapine

  1. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    JP Lindenmayer


    Full Text Available 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 identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS. While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of

  2. Olanzapine

    ... depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) in adults and teenagers 13 years of age and older. Olanzapine is in a class of medications called atypical antipsychotics. It works by ...

  3. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

    Ye W


    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

  4. Olanzapine-high potency antipsychotic drug inducing significant weight gain: A case report

    Marić Nađa P.


    Full Text Available INTRODUCTION Olanzapine is a second generation antipsychotic (SGA with a high level of therapeutic effectiveness in schizophrenia and other psychotic disorders. Along with the positive therapeutic effects, an increase of the body weight frequently occurs. According to the literature, the average weight gain is about 6-7 kg during several months of treatment. This could be valued as a moderate weight increase. CASE OUTLINE This article presents a case of a young female with schizophrenia, without clinical improvement with several antipsychotics (clozapine, risperidone, haloperidol and with the occurrence of significant neurological side effects. The treatment started with olanzapine (baseline was associated with good initial response (PANSS reduction 20% in the first two weeks and the improvement was maintained further on (PANSS reduction 50% after 16 weeks. Significant increase (20 kg, 40% in weight appeared during the following 16 weeks (BMI at baseline 17.9 kg/m2; BMI 16 weeks later 25.1 kg/m2. CONCLUSION High effectiveness of olanzapine in schizophrenia symptoms reduction was accompanied by a significant weight gain. However, this drug leads to impaired glucoregulation, dyslipidaemia etc. It also increases the risk of diabetes and cardio-vascular diseases, i.e. the main causes of mortality in schizophrenia after a suicide. Therefore, clinicians are suggested to focus on possible predictors of weight gain during olanzapine therapy, and act accordingly in order to prevent serious health consequences.

  5. The predictive value of early treatment response in antipsychotic-naive patients with first-episode psychosis: Haloperidol versus olanzapine.

    Rasmussen, Sean A; Rosebush, Patricia I; Anglin, Rebecca E; Mazurek, Michael F


    Early antipsychotic response predicts outcomes for psychotic patients, but recent evidence suggests that this may not be true for patients treated with olanzapine. In this study, we assessed the predictive value of early response to olanzapine or haloperidol in 75 antipsychotic-naive, first-episode psychosis inpatients. Patients were assessed weekly using the Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Young Mania Rating Scale (YMRS). Regression analyses were used to determine whether improvement at week 2 or week 3 predicted improvement at hospital discharge. The majority of patients in both groups experienced a decrease in symptom severity of ≥50% at week 2. In the haloperidol group, week 2 improvement predicted improvement at discharge for all measures except the HAM-A. In the olanzapine group, week 2 improvement only predicted improvement at discharge for HAM-D scores. However, week 3 improvement in the olanzapine group predicted improvement at discharge for all measures except the HAM-A. Olanzapine non-responders at week 3 (but not week 2) benefited from having olanzapine switched to another antipsychotic. These results suggest that a 2 week trial of haloperidol is sufficient to predict treatment outcomes, while a 3 week trial is required for olanzapine. PMID:27156027

  6. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    JP Lindenmayer


    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...

  7. Antipsychotic-induced metabolic effects in the female rat: Direct comparison between long-acting injections of risperidone and olanzapine.

    Ersland, Kari M; Skrede, Silje; Røst, Therese H; Berge, Rolf K; Steen, Vidar M


    Several antipsychotics have well-known adverse metabolic effects. Studies uncovering molecular mechanisms of such drugs in patients are challenging due to high dropout rates, previous use of antipsychotics and restricted availability of biological samples. Rat experiments, where previously unexposed animals are treated with antipsychotics, allow for direct comparison of different drugs, but have been hampered by the short half-life of antipsychotics in rodents. The use of long-acting formulations of antipsychotics could significantly increase the value of rodent models in the molecular characterization of therapeutic and adverse effects of these agents. However, as long-acting formulations have rarely been used in rodents, there is a need to characterize the basic metabolic phenotype of different antipsychotics. Using long-acting olanzapine injections as a positive control, the metabolic effects of intramuscular long-acting risperidone in female rats were investigated for the first time. Like olanzapine, risperidone induced rapid, significant hyperphagia and weight gain, with concomitant increase in several plasma lipid species. Both drugs also induced weight-independent upregulation of several genes encoding enzymes involved in lipogenesis, but this activation was not confirmed at the protein level. Our findings shed light on the role of drug administration, drug dose and nutritional status in the development of rodent models for adverse metabolic effects of antipsychotic agents. PMID:26378122

  8. Antipsychotic monotherapy among outpatients with schizophrenia treated with olanzapine or risperidone in Japan: a health care database analysis

    Takahashi M


    Full Text Available Wenyu Ye,1 Haya Ascher-Svanum,2 Yuka Tanji,3 Jennifer A Flynn,3 Michihiro Takahashi,3,4 Robert R Conley21Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai, People’s Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan KK, Kobe, Japan; 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Antipsychotic monotherapy is often recommended over antipsychotic polypharmacy because of fewer adverse events, reduced treatment complexity, and lower medication cost. This study compared the rate and the duration of antipsychotic monotherapy following initiation of olanzapine or risperidone in the treatment of outpatients with schizophrenia in Japan.Methods: Outpatients diagnosed with schizophrenia in the Japan Medical Data Center database were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision, diagnosis codes. Patients were between 20 and 65 years old, initiated on olanzapine or risperidone therapy between August 2003 and July 2008, and continuously enrolled during the 6 months prior to and the 12 months following the initiation date. Antipsychotic polypharmacy was defined as concurrent use of two or more antipsychotics. The probability of monotherapy during the 12-month follow-up period was assessed using a propensity score-adjusted generalized estimating equation model. Duration of monotherapy was contrasted using a propensity score-adjusted bootstrapping model.Results: After applying all inclusion and exclusion criteria, the final analytic sample consisted of 332 olanzapine- and 496 risperidone-treated outpatients. At treatment initiation, 61.5% of the olanzapine-treated patients and 45.6% of the risperidone-treated patients received antipsychotic monotherapy (P < 0.001. After correcting for background differences, monotherapy was more common among olanzapine-treated patients (P = 0.001. In addition, olanzapine was used as

  9. Change in level of productivity in the treatment of schizophrenia with olanzapine or other antipsychotics

    Osuntokun Olawale


    Full Text Available Abstract Background When treating schizophrenia, improving patients' productivity level is a major goal considering schizophrenia is a leading cause of functional disability. Productivity level has been identified as the most preferred treatment outcome by patients with schizophrenia. However, little has been done to systematically investigate productivity levels in schizophrenia. We set out to better understand the change in productivity level among chronically ill patients with schizophrenia treated with olanzapine compared with other antipsychotic medications. We also assessed the links between productivity level and other clinical outcomes. Methods This post hoc analysis used data from 6 randomized, double-blind clinical trials of patients with schizophrenia or schizoaffective disorder, with each trial being of approximately 6 months duration. Change in productivity level was compared between olanzapine-treated patients (HGBG, n = 172; HGHJ, n = 277; HGJB, n = 171; HGLB, n = 281; HGGN, n = 159; HGDH, n = 131 and patients treated with other antipsychotic medications (separately vs. haloperidol [HGGN, n = 97; HGDH, n = 132], risperidone [HGBG, n = 167; HGGN, n = 158], quetiapine [HGJB, n = 175], ziprasidone [HGHJ, n = 271] and aripiprazole [HGLB, n = 285]. Productivity was defined as functional activities/work including working for pay, studying, housekeeping and volunteer work. Productivity level in the prior 3 months was assessed on a 5-point scale ranging from no useful functioning to functional activity/work 75% to 100% of the time. Results Chronically ill patients treated with olanzapine (OLZ experienced significantly greater improvement in productivity when compared to patients treated with risperidone (RISP (OLZ = 0.22 ± 1.19, RISP = -0.03 ± 1.17, p = 0.033 or ziprasidone (ZIP (OLZ = 0.50 ± 1.38, ZIP = 0.25 ± 1.27, p = 0.026, but did not significantly differ from the quetiapine, aripiprazole or haloperidol treatment groups. Among

  10. Cost-effectiveness model comparing olanzapine and other oral atypical antipsychotics in the treatment of schizophrenia in the United States

    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

  11. Olanzapine induced hyperprolactinemia

    Veena Nayak; Virupaksha Devaramane; Deepak Mallya; Panambur V Bhandary


    Olanzapine, a second generation antipsychotic is widely used for the treatment of schizophrenia and bipolar disorders. Though olanzapine is an efficacious antipsychotic it has been associated with many adverse effects like weight gain, hyperlipidemia, diabetes mellitus, etc necessitating its discontinuation. Here, we present two cases of hyperprolactinemia induced by olanzapine. [Int J Basic Clin Pharmacol 2013; 2(6.000): 836-837

  12. Atypical antipsychotics olanzapine, quetiapine, and risperidone and risk of acute major cardiovascular events in young and middle-aged adults

    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...

  13. Olanzapine induced hyperprolactinemia

    Veena Nayak


    Full Text Available Olanzapine, a second generation antipsychotic is widely used for the treatment of schizophrenia and bipolar disorders. Though olanzapine is an efficacious antipsychotic it has been associated with many adverse effects like weight gain, hyperlipidemia, diabetes mellitus, etc necessitating its discontinuation. Here, we present two cases of hyperprolactinemia induced by olanzapine. [Int J Basic Clin Pharmacol 2013; 2(6.000: 836-837

  14. Antipsychotic Medicines for Schizophrenia and Bipolar Disorder: What You Should Know

    ... these four as Consumer Reports Best Buy Drugs: Clozapine (generic) Olanzapine (Zyprexa) Perphenazine (generic) Risperidone (generic) For bipolar disorder: Lithium is the standard treat- ment for bipolar disorder. Carbamazepine and valproic acid are also widely used. An ...

  15. Electrochemical Studies for the Determination of Quetiapine Fumarate and Olanzapine Antipsychotic Drugs

    El-Shal, Manal A


    Purpose: Cyclic voltammetry and differential pulse voltammetry were used to explore the diffusion behavior of two antipsychotic drugs at a glassy carbon electrode. A well-defined oxidation peak was obtained in Britton-Robinson (BR) buffer (pH 2.0). The response was evaluated as a function of some variables such as the scan rate, and pH. Methods: A simple, precise, inexpensive and sensitive voltammetric method has been developed for the determination of the cited drugs Olanza...


    Ravindra Waykar et al


    Full Text Available Generic drugs are lower-cost versions of patent-expired original brand-name medications. According to guidelines of regulatory agencies of the Canada, US and European Union, a generic drug must be “identical, or bioequivalent to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use”. Bioequivalence is decreed when the ratio of the generic to the reference compound for the area-under-the-curve and maximum plasma concentration (Cmax fall within a 0.80–1.25 range. The present study was to develop Olanzapine Tablets and compare pharmacokinetic profile of Zyprexa 10 mg film-coated tablets, Zyprexa Velotabs 10 mg orodispersible tablets and Olanzapine 10mg tablets. Multi media dissolution studies in 0.1N HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer were carried out for Reference (Zyprexa Velotab 10 mg and Zyprexa 10 mg and test product (i.e. Olanzapine 10 mg. A single centre, open-label, single-dose, randomised, 3-way crossover bioequivalence study, performed under fasting conditions. Based on the results obtained, it can be concluded that the test olanzapine (Treatment A is bioequivalent to both references Zyprexa Velotab (Treatment B and Zyprexa (Treatment C following a 10 mg dose under fasting conditions. All formulations were well tolerated, with no major side effects and no relevant differences in safety profiles were observed between the preparations, particularly with respect to the number and pattern of adverse event.

  17. A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania

    R.A. Moreno; Hanna, M M; Tavares, S. M.; Y. P. Wang


    The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean ± SD final dosage: 5.8 ± 3.8 mg) or olanzapine (mean ± SD final dosage: 13.6 ± 6.9 mg) in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopatholo...

  18. A double-blind comparison of the effect of the antipsychotics haloperidol and olanzapine on sleep in mania

    R.A. Moreno


    Full Text Available The effects of haloperidol and olanzapine on polysomnographic measures made in bipolar patients during manic episodes were compared. Twelve DSM-IV mania patients were randomly assigned to receive either haloperidol (mean ± SD final dosage: 5.8 ± 3.8 mg or olanzapine (mean ± SD final dosage: 13.6 ± 6.9 mg in a 6-week, double-blind, randomized, controlled clinical trial. One-night polysomnographic evaluation was performed before and after the haloperidol or olanzapine treatment. Psychopathology and illness severity were rated respectively with the Young Mania Rating Scale (YMRS and the Clinical Global Impressions - Bipolar version (CGI-BP. There was a significant improvement in the YMRS and CGI-BP scores at the end of the study for both groups. Mixed ANOVA used to compare the polysomnographic measures of both drugs demonstrated significant improvement in sleep measures with olanzapine. In the olanzapine group, statistically significant time-drug interaction effects on sleep continuity measures were observed: sleep efficiency (mean ± SEM pre-treatment value: 6.7 ± 20.3%; after-treatment: 85.7 ± 10.9%, total wake time (pre-treatment: 140.0 ± 92.5 min; after-treatment: 55.2 ± 44.2 min, and wake time after sleep onset (pre-treatment: 109.7 ± 70.8 min; after-treatment: 32.2 ± 20.7 min. Conversely, improvement of polysomnographic measures was not observed for the haloperidol group (P > 0.05. These results suggest that olanzapine is more effective than haloperidol in terms of sleep-promoting effects, although olanzapine is comparatively as effective as haloperidol in treating mania. Polysomnography records should provide useful information on how manic states can be affected by psychopharmacological agents.

  19. Olanzapine-induced hyperventilation: case report

    Sattar, S. Pirzada; Gastfriend, David R.


    Although olanzapine therapy has been associated with fewer extrapyramidal side effects than the traditional antipsychotic medications, reported side effects include dystonia, tardive dyskinesia, hypotension, diabetes mellitus, seizures and neuroleptic malignant syndrome. There are no previous published reports of hyperventilation associated with olanzapine therapy, but we present the case of a male patient who developed dyspnea and hyperventilation while taking olanzapine.

  20. Antipsychotic monotherapy among outpatients with schizophrenia treated with olanzapine or risperidone in Japan: a health care database analysis

    Ye, Wenyu


    Wenyu Ye,1 Haya Ascher-Svanum,2 Yuka Tanji,3 Jennifer A Flynn,3 Michihiro Takahashi,3,4 Robert R Conley21Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai, People’s Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan KK, Kobe, Japan; 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Antipsychotic monotherapy is often recommended over antipsychotic polypharmacy because of fewer adverse events, reduced treatment...

  1. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

    Ye W; Ascher-Svanum H; Flynn JA; Tanji Y; Takahashi M


    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 ...

  2. Priapism Associated with Olanzapine

    S.H. Hosseini; A.K. Polonowita


    Priapism is a rare but serious adverse effect of psychotropic drugs where antipsychotic agents were implicated in 15 to 26% of priapism associated with medications. Among atypical antipsychotic, clozapine, risperidone and olanzapine have been reported to be associated with the condition. The patient was a 24 years old male referred to the OPD Clinic at Zare Psychiatry Hospital in 2007 with symptoms of delusion of control, delusion of persecution, delusion of somatic and auditory hallucination...

  3. The Underlying Mechanisms for Olanzapine-induced Hypertriglyceridemia

    Adachi, Hiroki; Yanai, Hidekatsu; Hirowatari, Yuji


    Olanzapine is an efficacious antipsychotic drug often used in the treatment for schizophrenia or bipolar disorder, however, sometimes induces metabolic disorders. We will introduce a patient with bipolar disorder, who has been treated by olanzapine and showed severe hypertriglyceridemia. As a result of measurements of parameters associated with lipid metabolism, very-low density lipoprotein was most important lipoprotein for olanzapin-induced hypertriglyceridemia. The cessation of olanzapine ...

  4. Olanzapine Discontinuation Emergent Recurrence in Bipolar Disorder

    Manu Arora; Samir Kumar Praharaj


    Objective: The efficacy of atypical antipsychotics including olanzapine in acute treatment of manic episode has been established, whereas its role in maintenance treatment is not clear. Materials and Methods: Thirteen patients of bipolar disorder who were on regular treatment with mood stabilizer and subsequently relapsed into mania or depressive episode after discontinuation of olanzapine were studied for various socio-demographic and clinical factors using retrospective chart review. Result...

  5. Delirium Associated with Olanzapine Therapy in an Elderly Male with Bipolar Affective Disorder

    Sharma, Ravi C.; Aggarwal, Ashish


    Atypical antipsychotic medications are commonly used to treat symptoms of delirium. Olanzapine has been successfully used in the treatment of delirium. However, there have been few case reports of delirium associated with olanzapine. We hereby report a case of delirium associated with olanzapine therapy. Possible risk factors and underlying pathogenesis is discussed.

  6. Evaluation of bioequivalence of two oral formulations of olanzapine

    R Singhal; Thakkar, V.; A Srivastava


    Olanzapine is an atypical antipsychotic drug, used for the management of schizophrenia and for the treatment of moderate to severe mania associated with bipolar disorder. The objective of the present randomised, crossover study was to compare the bioavailability of olanzapine 10 mg/5 ml powder for oral suspension with olanzapine 10 mg orally disintegrating tablet. Eighteen healthy male volunteers were randomly assigned to crossover, single-dose treatment regimens. Serial blood samples were co...

  7. Olanzapine Injection

    ... of interest in life, and strong or inappropriate emotions). Olanzapine injection is used to treat episodes of ... this medication affects should know that alcohol can add to the drowsiness caused by this ...

  8. Serum prolactin level in patients taking olanzapine

    Diganta Das


    Full Text Available Introduction: Olanzapine is a commonly used antipsychotic. Prolactin elevation is a common adverse effect of anstipsychotics, and serum prolactin elevation is seen in about 30% patients treated with olanzapine. There are confounding results about dose dependency of olanzapine and prolactin elevation, and also the duration of treatment. Method: Fifty six patients, 36 male and 20 female, who were taking olanzapine for any condition for more than a month at a constant dose were enrolled in the study. Patients’ age, weight, body mass index (BMI, serum prolactin levels, and some biochemical values were recorded. Patients were taken from the review outpatient department (OPD after due consent. Results: Five each in male and female groups showed elevation of serum prolactin (estimated to be high if >20 ng/dl for males, and >25 ng/dl for females. In females, the elevation was found at lesser dose of olanzapine (13 mg/day, in males 18 mg/day and early in the treatment (2.4 months vs. 9.7 months in males. Males tended to show raised prolactin with higher doses of olanzapine (mean 18 mg/day. Females (26.31% also showed higher prevalence of prolactin elevation compared to males (13.51%. No other parameter was found to modify the prolactin levels. Conclusion: Olanzapine causes elevation of serum prolactin, though lesser degree than some other antipsychotics. Females are more prone to have raised serum prolactin with olanzapine compared to males. However, the elevation seems to be transient. Higher doses of olanzapine tend to cause elevation of serum prolactin. Serum prolactin estimation in patients taking olanzapine may be undertaken to maintain quality life, particularly in females.

  9. Pharmacokinetic Variability of Olanzapine : A Study Based on Therapeutic Drug Monitoring Data


    Olanzapine is one of the most commonly used antipsychotic drugs in treatment of schizophrenia and bipolar disorder. The interindividual variability in pharmacokinetics of olanzapine is extensive, with a 10-20-fold difference in serum concentration despite equivalent dosing. The aim of this thesis was to identify and evaluate factors that influence the pharmacokinetics of olanzapine, and thereby provide knowledge that can be applied in order to individualize treatment with olanzapine. Ther...

  10. Atypicality in presentation of neuroleptic malignant syndrome caused by olanzapine

    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...

  11. [Lichenoid drug eruption induced by olanzapine].

    Fernández-Torres, R; Almagro, M; del Pozo, J; Robles, O; Martínez-González, C; Mazaira, M; Fonseca, E


    Lichenoid drug eruptions can mimic idiopathic lichen planus and other dermatoses. The list of drugs that can cause them is long and growing steadily. Although cutaneous side effects of antipsychotics are rare, various cutaneous manifestations have been reported in association with olanzapine. We present the case of a patient who developed an atypical lichenoid eruption due to olanzapine. A review of the literature in Medline from 1951 to 2007 and in the Indice Médico Español (Spanish Medical Index) revealed no previous cases of lichenoid eruptions associated with the use of this drug. PMID:18358199

  12. Olanzapine discontinuation emergent recurrence in bipolar disorder

    Manu Arora


    Full Text Available Objective: The efficacy of atypical antipsychotics including olanzapine in acute treatment of manic episode has been established, whereas its role in maintenance treatment is not clear. Materials and Methods: Thirteen patients of bipolar disorder who were on regular treatment with mood stabilizer and subsequently relapsed into mania or depressive episode after discontinuation of olanzapine were studied for various socio-demographic and clinical factors using retrospective chart review. Results: There was no correlation found between the period of tapering olanzapine, time to recurrence of episode after discontinuation, and the dosage of olanzapine at the time of discontinuation. The predominant early signs of relapse after discontinuation of olanzapine included sleep disturbance (72.7%, lack of insight for change in behavior (72.7%, irritability (54.5%, and elevated mood (45.5%. Conclusion: Mood stabilizer alone as a maintenance therapy of bipolar disorder may be inadequate for long-term management. A low dose of olanzapine along with mood stabilizers might be useful for prevention of recurrence in bipolar disorder.

  13. Effect of olanzapine treatment on INR of a patient receiving warfarin therapy

    Derya Arslan


    Full Text Available Olanzapine is an atypical antipsychotic drug, commonly used in the management of psychotic symptoms in patients with schizoprenia and bipolar affective disorder. Deep venous thrombosis is a manifestation of venous thromboembolism. It is very well known that use of antipsychotic drugs increase the risk of thrombosis in a patient with schizophrenia. It has been reported in many studies the effects of olanzapine on thrombosis but there isn't any report about the effect of olanzapine on international normalized ratio (INR. in the medical literature. In this paper, a patient with schizophrenia and also family history of deep venous thrombosis who emerged deep venous thrombosis after being started on olanzapine treatment and effect of olanzapine treatment on INR has been reported. [Cukurova Med J 2016; 41(2.000: 370-373

  14. Olanzapine-induced tender pitting pre-tibial edema

    Kaliaperumal Mathan; Venkatesan Muthukrishnan; Vikas Menon


    Antipsychotic-induced edema is uncommonly encountered in clinical practice. We report a case of tender pitting pre-tibial edema with olanzapine in a woman with no medical comorbidities. The peculiar distribution of edema resulted in diagnostic confusion necessitating specific investigations. Eventually, the edema resolved following complete stoppage of the drug, but caused distress to the patient and the caregiver.

  15. Olanzapine-induced tender pitting pre-tibial edema

    Kaliaperumal Mathan


    Full Text Available Antipsychotic-induced edema is uncommonly encountered in clinical practice. We report a case of tender pitting pre-tibial edema with olanzapine in a woman with no medical comorbidities. The peculiar distribution of edema resulted in diagnostic confusion necessitating specific investigations. Eventually, the edema resolved following complete stoppage of the drug, but caused distress to the patient and the caregiver.

  16. Olanzapine-induced neuroleptic malignant syndrome in a patient with bipolar affective disorder: Does quetiapine holds the solution?

    Praveen Tripathi; Hemika Agrawal; Priyanka Goyal; Sujita Kumar Kar


    Neuroleptic Malignant Syndrome (NMS) is a rare, severe and life threatening condition induced by antipsychotic medications. It is commonly encountered with the use of first generation antipsychotics, however cases of NMS have been reported with the use of second generation antipsychotics like Olanzapine, Risperidone, Paliperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine and Clozapine, though the incidence of such reports is rare. Due to decreased use of first generation antipsychot...

  17. Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1

    Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila;


    -HT7 receptors. In the C-terminus of the 5-HT7 receptor, we identified two YXXΦ motifs, LR residues, and a palmitoylated cysteine anchor as potential sites involved in receptor trafficking to lysosomes followed by receptor degradation. Mutating either of these sites inhibited clozapine- and olanzapine...

  18. Trends in Scientific Literature on Atypical Antipsychotics in South Korea: A Bibliometric Study

    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...

  19. [Antipsychotics in bipolar disorders].

    Vacheron-Trystram, M-N; Braitman, A; Cheref, S; Auffray, L


    may worsen depressive symptoms when used for a long term maintenance therapy. Additionally, mixed mania, rapid cycling type patients and bipolar disorder associated with substance abuse do not respond well to lithium therapy. In addition to the lithium therapy or in place of a lithium therapy, one can report the frequent use of antipsychotic agents in respect of patients with bipolar disorder during both the acute and maintenance phases of treatment. Antipsychotic agents have been used for almost forty years and may be used in combination with a lithium therapy. Conventional antipsychotics are effective but they may induce late dyskinesia, weight gain, sedation, sexual dysfunction and depression. These adverse side effects often lead to non compliance in particular in circumstances where antipsychotic agents are combined with a lithium therapy. A number of alternative somatic treatment approaches have been reported for patients who do not respond well or who are intolerant to lithium therapy. As such, valproate has received regulatory approval for the acute treatment of mania and carbamazepine has been indicated for this condition in a number of countries. Divalproex (Depakote) has recently obtained the authorization to market in France and may be prescribed for manic states or hypomanic states that do not tolerate lithium therapy or for which lithium therapy is contraindicated. A number of other anticonvulsants (lamotrigine, gabapentin and topiramate) are currently being tested. Because of the side effects of the conventional antipsychotic agents, atypical antipsychotic agents are currently on trial and appear to be of interest in the treatment of bipolar disorders. Currently, a number of prospective studies are available with clozapine, risperidone and olanzapine in the treatment of bipolar disorder. Most are short-term studies. Recent randomised, double-blind, placebo-controlled studies have shown clozapine, risperidone and olanzapine to be effective with antimanic

  20. Effect of fosamprenavir/ritonavir on the pharmacokinetics of single-dose olanzapine in healthy volunteers.

    Jacobs, Birgit S; Colbers, Angela P H; Velthoven-Graafland, Kirsten; Schouwenberg, Bas J J W; Burger, David M


    Psychosis and other mental illnesses are common in HIV-infected patients. Olanzapine is one of the preferred antipsychotic agents for the treatment of schizophrenia. Olanzapine is primarily metabolised by CYP1A2 and uridine diphosphate glucuronosyltransferase (UGT). High-dose ritonavir has been shown to increase olanzapine elimination through induction of CYP1A2 and/or UGT, but the effect of low-dose ritonavir on olanzapine pharmacokinetics is unknown. Fosamprenavir is an HIV protease inhibitor that is boosted by low-dose ritonavir. To compensate for the induction of olanzapine metabolism by fosamprenavir/ritonavir, we hypothesised that a dose increase of olanzapine to 15 mg with fosamprenavir/ritonavir would lead to a similar area under the concentration-time curve (AUC) compared with olanzapine 10 mg alone. An open-label, randomised, two-period, cross-over, single-centre trial was conducted in 24 healthy volunteers. Subjects were randomised to one of the following treatments: (A) fosamprenavir/ritonavir 700/100 mg twice daily (b.i.d.) for 16 days with a single dose of olanzapine 15 mg on Day 13, a wash-out period of 31 days and a single dose of olanzapine 10 mg on Day 48; or (B) the same medication in reverse order. Twenty subjects completed the trial. The geometric mean ratios (90% CI) of olanzapine AUClast, maximum drug concentration (C(max)) and apparent elimination half-life (t(1/2)) when taken with fosamprenavir/ritonavir versus olanzapine alone were 1.00 (0.93-1.08), 1.32 (1.18-1.47) and 0.68 (0.63-0.74), respectively. Fosamprenavir/ritonavir 700/100 mg b.i.d. appeared to induce olanzapine metabolism. We therefore propose a 50% dosage increase of olanzapine when combining with a ritonavir-boosted protease inhibitor. PMID:24929949

  1. Intramuscular Olanzapine – a UK case series of early cases

    Taylor Mark


    Full Text Available Abstract Background Clinical trials assessing efficacy and safety of Intramuscular (IM Olanzapine in acute schizophrenia and acute mania have previously been undertaken in studies required for drug registration in patients who were required to give informed consent. These patients may have less severe forms of psychosis than patients treated in routine practice. Data derived from naturalistic practice following the launch of IM olanzapine may be helpful for clinicians in assessing efficacy and safety of IM olanzapine. The PANSS-EC scale used in the clinical studies may represent a tool that could be used in routine clinical practice. Case presentation We report on an early unselected case series of 7 patients who received IM olanzapine in routine clinical practice settings in the UK. In this case series, olanzapine IM was generally effective, and no adverse events were reported. Adjunctive benzodiazepines were given concomitantly in 1 of the 7 subjects. This is relevant as concomitant benzodiazepines are not recommended for a minimum of 1 hour post IM olanzapine administration. PANSS-EC data was collected in 2 of the 7 subjects. Conclusion Although patients had greater severity of psychosis than clinical trial patients there were no unexpected findings. In addition the PANSS-EC scale is a scale that may be useful in assessing the efficacy of IM antipsychotics in routine clinical practice.

  2. Evaluation of bioequivalence of two oral formulations of olanzapine

    R Singhal


    Full Text Available Olanzapine is an atypical antipsychotic drug, used for the management of schizophrenia and for the treatment of moderate to severe mania associated with bipolar disorder. The objective of the present randomised, crossover study was to compare the bioavailability of olanzapine 10 mg/5 ml powder for oral suspension with olanzapine 10 mg orally disintegrating tablet. Eighteen healthy male volunteers were randomly assigned to crossover, single-dose treatment regimens. Serial blood samples were collected, and plasma concentrations of olanzapine were analysed using the LC-MS/MS technique. Pharmacokinetic parameters and bioequivalence limits were calculated using non-compartmental methods. Average C max following administration of the single 10 mg disintegrating tablet formulation and 10 mg/5 ml suspension were 14.47±4.25 ng/ml and 13.56±3.99 ng/ml respectively. Corresponding median T max were 5.0 h and 6.0 h, respectively. The average AUC 0-t values and AUC 0-inf values were similar following each of the olanzapine preparations. Overall, the 90% Confidence Interval for the intra-individual ratios of the log-transformed C max and AUC values of the two formulations were within the bioequivalence interval of 80-125%. The study has demonstrated the bioequivalence of the 10 mg tablet and the 10 mg/5 ml oral suspension of olanzapine.

  3. Antipsychotics as antidepressants.

    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

  4. Olanzapine-induced weight gain: lessons learned from developing rat models

    Zwaal, E.M. van der


    Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying mechanisms. Therefore, this thesis describes the development of a number of rat models that were designed to determine the effects of olanzapine on different aspects of energy balance. In both short- a...

  5. Olanzapine-induced neuroleptic malignant syndrome in a patient with bipolar affective disorder: Does quetiapine holds the solution?

    Praveen Tripathi


    Full Text Available Neuroleptic Malignant Syndrome (NMS is a rare, severe and life threatening condition induced by antipsychotic medications. It is commonly encountered with the use of first generation antipsychotics, however cases of NMS have been reported with the use of second generation antipsychotics like Olanzapine, Risperidone, Paliperidone, Aripiprazole, Ziprasidone, Amisulpride, Quetiapine and Clozapine, though the incidence of such reports is rare. Due to decreased use of first generation antipsychotics, NMS is reported less frequently now a days. In this case report- we highlight the management issues of a patient suffering from bipolar affective disorder, who had developed NMS following intramuscular injection of haloperidol, which was withdrawn and olanzapine was given later on. The patient had again developed NMS with olanzapine. Finally the patient was managed with modified electroconvulsive therapy and discharged on Lithium carbonate and Quetiapine.

  6. Evaluation of proximal therapeutic effect and distal social function restoration of olanzapine on schizophrenia patients%奥氮平对精神分裂症患者近期疗效及远期社会功能恢复效果评价

    王长虹; 赵峥; 李晏; 潘苗; 刘旭


    Objective To evaluate the efficacy and prognosis of olanzapine in treatment of the schizophrenia. Methods A randomized controlled clinical study was performed to compare the efficacy and prognosis of olanzapine to that of chlorpromazine. 60 patients with schizophrenia were divided two groups. 32cases were treated with olanzapine. 28 cases were treated with chlorpromazine .Results The significant effect rate and effective rate on olanzapine group were 63% and 82% respectively ; which in chlorpromazine group were 32% and 50% .There were less side effects, and less recurrent rate in olanzapine. Conclusion Olanzapine is one of the safe and effective atypical antipsychotic for schizophrenia with significantly fewer side effects.

  7. Cognitive Function and Depression in Symptom Resolution in Schizophrenia Patients Treated with an Atypical Antipsychotic

    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…

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

    Correll Christoph


    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

  9. Cost-effectiveness analysis of antipsychotics in reducing schizophrenia relapses

    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...

  10. Olanzapine induced de-novo obsessive compulsive disorder in a patient with schizophrenia

    Gajanan Kulkarni


    Full Text Available There are reports of de novo development or exacerbation of obsessive-compulsive symptoms in patients with schizophrenia treated with atypical antipsychotics, although this is widely debated. We report one such case where a patient with a primary diagnosis of schizophrenia, treated with olanzapine, developed de novo obsessive-compulsive disorder, with convincing evidence for its causality due to the drug.

  11. Olanzapine-induced weight gain: lessons learned from developing rat models

    van der Zwaal, E.M.


    Olanzapine is an effective and commonly prescribed antipsychotic drug, used for the treatment of schizophrenia and bipolar disorder. Unfortunately significant weight gain is a common side effect. In order to effectively address this side effect, it is crucial to gain insight into the underlying mech

  12. Sexual dysfunction and hormonal changes in first episode psychosis patients on olanzapine or risperidone

    M. van Bruggen; T. van Amelsvoort; L. Wouters; P. Dingemans; L. de Haan; D. Linszen


    Atypical antipsychotics interfere with central and peripheral neurotransmitter systems and with hormonal production. In this study we compared the effect of olanzapine and risperidone on hormonal state and sexual function (by using the Questionnaire for Sexual Dysfunction, QSD) in 40 patients with a

  13. [Antipsychotic agents and stimulants: a judicious combination?].

    de Jong, M H; Eussen, M L J M; van Gool, A R


    A 31-year-old male, diagnosed with schizophrenia and receiving maintenance treatment with olanzapine, was prescribed methylphenidate for comorbid attention deficit hyperactivity disorder (adhd). The adhd symptoms diminished and there were hardly any side-effects. No increase in psychotic symptoms occurred. The patient used far fewer amphetamines and benzodiazepines. In theory, stimulants and antipsychotics produce opposite effects. Relevant literature on the subject is discussed. PMID:20054798

  14. A Case Report: Anti-Psychotic Agents Related Ocular Toxicity.

    Choy, Bonnie Nga Kwan; Ng, Alex Lap Ki; Shum, Jennifer Wei Huen; Fan, Michelle Ching Yim; Lai, Jimmy Shiu Ming


    Chlorpromazine is known to cause ocular pigmentary deposits. However, delayed presentation after cessation of chlorpromazine has not been reported. There are also no reports on whether newer generation of anti-psychotic agents contribute to ocular toxicity. We describe a case of ocular toxicity related to anti-psychotic agents. To the best of our knowledge, this is the first reported case of anterior segment pigmentary deposits associated with olanzapine use, 2 years after the cessation of chlorpromazine.We report a case of ocular toxicity in a patient with history of chlorpromazine usage of 100 mg per day for 13 years and subsequently switched to olanzapine 5 mg for 2 years. There were no signs of ocular toxicity while the patient was on chlorpromazine. However, when the patient switched to olanzapine, she developed the ocular side effect as described for chlorpromazine-induced ocular toxicity, with pigmentary depositions on both corneas and the anterior lens surface and decrease in vision.Olanzapine, a newer anti-psychotic agent, may play a role in the ocular pigmentary deposition, either directly causing pigmentary deposition itself or accentuating the effect of chlorpromazine as the 2 drugs act on the same receptors, although further studies are required to support this hypothesis. As patients with psychiatric conditions may not voluntarily complain of visual symptoms, ocular screening could be considered in these patients receiving chronic anti-psychotic treatment, so that any ocular toxicity could be diagnosed in a timely manner. PMID:27082594

  15. Spontaneous Ejaculations in an Adolescent With Olanzapine Use: Case Report.

    Yektaş, Çiğdem; Tufan, Ali Evren


    Olanzapine (OLZ) is a second-generation atypical antipsychotic (AAP) frequently used in acute and maintenance treatment of children and adolescents with psychotic disorders. Most commonly reported sexual problems caused by AAPs are decreases in libido or arousal, erectile dysfunctions, reduced/abnormal ejaculations, and problems in achieving or maintaining orgasm. Olanzapine is less commonly implicated for those adverse effects, which may reflect its more selective affinity to dopaminergic receptors or more transient effects on prolactin levels. Sexual dysfunction with AAPs, including OLZ, is reported predominantly in adult patients and adverse sexual effects in prepubertal/peripubertal patients with psychosis received scant attention. Studies and reports of sexual adverse effects of AAPs in this special population may benefit clinicians. Therefore, in this study, we report an adolescent male patient with psychosis who developed spontaneous ejaculations with OLZ and whose complaints remitted with change in treatment. PMID:26882319

  16. Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties

    Montgomery W


    Full Text Available William Montgomery1, Tamas Treuer2, Jamie Karagianis3, Haya Ascher-Svanum4, Gavan Harrison51Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 2Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 5Asia-Pacific Medical Communications, Eli Lilly and Company, Sydney, AustraliaAbstract: Orally disintegrating olanzapine (ODO is a rapid-dissolving formulation of olanzapine which disintegrates in saliva almost immediately, developed as a convenient and adherence-enhancing alternative to the standard olanzapine-coated tablet (SOT. Clinical studies, which form the basis of this review, have shown ODO and SOT to have similar efficacy and tolerability profiles. However, ODO appears to have a number of advantages over SOT in terms of adherence, patient preference, and reduction in nursing burden. Overall, the existing clinical data suggests that compared to SOT, ODO is not only well-suited for difficult-to-treat, agitated, and/or nonadherent patients but, due to its potential ability to improve adherence and greater patient preference, may also be an appropriate formulation for the majority of patients for which olanzapine is the antipsychotic of choice.Keywords: orodispersible formulation, orally disintegrating, olanzapine, atypical antipsychotics, patient adherence, preference, schizophrenia, bipolar disorder

  17. Metabolic side effects of antipsychotic agents: a prospective study in a teaching hospital.

    Ankesh Barnwal


    Full Text Available Background: Antipsychotic drugs have propensity to produce side effects like extrapyramidal syndrome, hyperglycemia, lipid abnormalities and weight gain. As data from India related to this aspect are scarce, this study was carried out.Aims and Objectives: To study metabolic effects of antipsychotic drugs using biochemical parameters and to compare metabolic effects of different antipsychotic agents.Materials and methods: This was a prospective study of patients attending the psychiatry outpatient department from September 2007 to May 2008. Each patient enrolled was followed up for 12weeks or less till the antipsychotics were prescribed. Body weight,fasting blood glucose, fasting lipid profile were recorded at baseline and at subsequent visits.Results: Out of 45 patients, 33 completed the study. Bipolar disorder (31% was the most frequent diagnosis followed by brief psychotic disorder (22%, schizophrenia (20% and others.Olanzapine was the most frequently prescribed antipsychotic drug (56% followed by risperidone (24% and haloperidol (20%. 84% received single antipsychotic drug. After 12weeks of therapy all antipsychotics caused significant weight gain (p<0.001, olanzapine caused significant rise in fasting blood glucose (p<0.001 and serum cholesterol (p<0.001. All antipsychotics caused significant rise in serum triglyceride level (p<0.01 Conclusion: All antipsychotics can cause significant abnormalities in carbohydrate and lipid metabolism. Selection of antipsychotics, particularly the newer ones requires consideration of co morbidities like obesity, diabetes mellitus and dyslipidemias. During antipsychotic drug therapy periodic monitoring for metabolic abnormalities is advisable.

  18. Use of antipsychotics in the treatment of depressive disorders

    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.

  19. Effects of typical and atypical antipsychotic drugs on gene expression profiles in the liver of schizophrenia subjects

    Song Jonathan


    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.

  20. Determination of olanzapine in whole blood using simple protein precipitation and liquid chromatography-tandem mass spectrometry

    Nielsen, Marie Katrine Klose; Johansen, Sys Stybe


    A simple, sensitive, and reproducible liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of the antipsychotic drug olanzapine in whole blood using dibenzepine as internal standard (IS). After acidic methanol-induced protein precipitation of...

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

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


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

  2. Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling of the Dopamine D-2 Receptor Occupancy of Olanzapine in Rats

    Johnson, Martin; Kozielska, Magdalena; Reddy, Venkatesh Pilla; Vermeulen, An; Li, Cheryl; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.


    A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol

  3. A pooled analysis of injection site-related adverse events in patients with schizophrenia treated with olanzapine long-acting injection

    Atkins, Susan; Detke, Holland C; McDonnell, David P; Case, Michael G; Wang, Shufang


    Background Depot antipsychotic injections are an important tool for the management of patients with schizophrenia who have difficulty with adherence to oral medication. However, pain and discomfort at the injection site can be a potential impediment to the use of these long-acting formulations. We report here the results of a pooled analysis of injection site-related adverse events (AEs) collected during treatment with the olanzapine long-acting injection (olanzapine LAI). Methods Unsolicited...

  4. Comparision of the Efficacy of Two Combinations;Sodium Valproate with Lithium & Sodium Valproate with Olanzapine in Treatment of Acute Mania

    S Amanat; M Nuri; HR Rouh Afza; Afshar, H.


    Introduction: Acute mania is a psychiatric emergency state that often requires rapid management. There are many different therapeutic protocols for this emergent situation. One of them is combination of moodstabilizers and antipsychotics. Olanzapine which is now available in our country can be used for this purpose. Methods and Materials: In this study, we compared the effectiveness, rapidity of response and side effects of sodium valproate plus olanzapine (group I) with sodium valproate plus...

  5. Guidelines for the use of second-generation long-acting antipsychotics

    Marek Jarema


    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.

  6. Hematological Side Effects of Atypical Antipsychotic Drugs

    Serap Erdogan


    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

  7. Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and ziprasidone: a pragmatic, randomized trial

    Løberg Else-Marie; Kroken Rune A; Jørgensen Hugo A; Kjelby Eirik; Johnsen Erik


    Abstract Background Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patient...

  8. Olanzapine is superior to lamotrigine in the prevention of bipolar depression: a naturalistic observational study

    Pan,Pei-Yin; Lee, Meei-Shyuan; Lo, Miao-Chi; Yang, En-Lin; Yeh, Chin-Bin


    Background Bipolar disorder is a highly recurrent disease and has great impact on the function of patients. Depressive symptoms consist of more than 50% of life time during the illness and may lead to self harm or suicidal behaviors. Little is known about the antidepressant effects of olanzapine, an atypical antipsychotic, as monotherapy despite its indication for preventing manic episodes. In contrast, lamotrigine, a mood stabilizer, has been proven to be effective in preventing depression i...

  9. Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

    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

  10. Acute camptocormia induced by olanzapine: a case report

    Boyer Stéphane


    Full Text Available Abstract Introduction Camptocormia refers to an abnormal posture with flexion of the thoraco-lumbar spine which increases during walking and resolves in supine position. This symptom is an increasingly recognized feature of parkinsonian and dystonic disorders, but may also be caused by neuromuscular diseases. There is recent evidence that both central and peripheral mechanisms may be involved in the pathogenesis of camptocormia. We report a case of acute onset of camptocormia, a rare side effect induced by olanzapine, a second-generation atypical anti-psychotic drug with fewer extra-pyramidal side-effects, increasingly used as first line therapy for schizophrenia, delusional disorders and bipolar disorder. Case presentation A 73-year-old Caucasian woman with no history of neuromuscular disorder, treated for chronic delusional disorder for the last ten years, received two injections of long-acting haloperidol. She was then referred for fatigue. Physical examination showed a frank parkinsonism without other abnormalities. Routine laboratory tests showed normal results, notably concerning creatine kinase level. Fatigue was attributed to haloperidol which was substituted for olanzapine. Our patient left the hospital after five days without complaint. She was admitted again three days later with acute back pain. Examination showed camptocormia and tenderness in paraspinal muscles. Creatine kinase level was elevated (2986 UI/L. Magnetic resonance imaging showed necrosis and edema in paraspinal muscles. Olanzapine was discontinued. Pain resolved quickly and muscle enzymes were normalized within ten days. Risperidone was later introduced without significant side-effect. The camptocormic posture had disappeared when the patient was seen as an out-patient one year later. Conclusions Camptocormia is a heterogeneous syndrome of various causes. We believe that our case illustrates the need to search for paraspinal muscle damage, including drug

  11. Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia

    Zhao Zhongyun; Stensland Michael; Ascher-Svanum Haya; Kinon Bruce J


    Abstract Background Previous research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol). ...

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

    Rayees Ahmad Wani


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

  13. Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice

    Song, Jae Chun; Seo, Mi Kyoung; Park, Sung Woo; Lee, Jung Goo; Kim, Young Hoon


    Objective We investigated the differential effects of the antipsychotic drugs olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis in mice. Methods MK-801 (0.1 mg/kg) was administered 20 minutes prior to behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment, either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40 minutes prior to MK-801 for the final 4 days. Spatial memory performance was measured using a Morris water maze (MWM) test for 9 days (four trials/day). Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn cells labeled in tissue sections from the dentate gyrus of the hippocampus. Results MK-801 administration over 9 days significantly impaired memory performance in the MWM test compared to untreated controls (p<0.05) and these deficits were blocked by treatment with olanzapine (p<0.05) but not haloperidol. The administration of MK-801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p<0.01), which was prevented by treatment with olanzapine (p<0.05) but not haloperidol. Conclusion These results suggest that olanzapine has a protective effect against cognitive impairments induced by MK-801 in mice via the stimulating effects of neurogenesis. PMID:27489382

  14. Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management.

    Fang, Fang; Sun, Hongwei; Wang, Zuowei; Ren, Ming; Calabrese, Joseph R; Gao, Keming


    Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to

  15. Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia

    Swartz Marvin


    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

  16. Off-label indications for atypical antipsychotics: A systematic review

    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...

  17. Could Reward-disturbances caused by antipsychotic medication lead to weight gain?

    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...

  18. Ziprasidone Vs Olanzapine in Recent-Onset Schizophrenia and Schizoaffective Disorder : Results of an 8-Week Double-Blind Randomized Controlled Trial

    Grootens, K. P.; van Veelen, N. M. J.; Peuskens, J.; Sabbe, B. G. C.; Thys, E.; Buitelaar, J. K.; Verkes, R. J.; Kahn, R. S.


    Introduction: Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions. The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia. Methods: The study was an 8-week

  19. Cognitive and psychomotor effects of adjunctive aripiprazole or paliperidone in patients of schizophrenia receiving olanzapine: a double blind placebo controlled clinical study

    Mayur M. Mayabhate


    Conclusions: The best augmenting strategy with for olanzapine nonresponsive patients will be D2 receptor partial agonist like aripiprazole rather than D2 antagonist like paliperidone and other atypical antipsychotic agents for better improvement in cognition and psychomotor domains. [Int J Basic Clin Pharmacol 2014; 3(1.000: 130-138

  20. Olanzapine-induced eosinophilic pleuritis

    Matthew Evison


    Eosinophilic pleural fluid is not a marker of non-malignant aetiology and eosinophilic pleural effusions require a careful and systematic diagnostic work-up. This is the second case report to identify olanzapine as a causative agent in eosinophilic pleural effusion.

  1. Interactions between antiepileptic and antipsychotic drugs.

    Besag, Frank M C; Berry, David


    Antiepileptic and antipsychotic drugs are often prescribed together. Interactions between the drugs may affect both efficacy and toxicity. This is a review of human clinical data on the interactions between the antiepileptic drugs carbamazepine, valproic acid (sodium valproate), vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine, levetiracetam, pregabalin, felbamate, zonisamide, phenobarbital and phenytoin with the antipsychotic drugs risperidone, olanzapine, quetiapine, clozapine, amisulpride, sulpiride, ziprasidone, aripiprazole, haloperidol and chlorpromazine; the limited information on interactions between antiepileptic drugs and zuclopenthixol, periciazine, fluphenazine, flupenthixol and pimozide is also presented. Many of the interactions depend on the induction or inhibition of the cytochrome P450 isoenzymes, but other important mechanisms involve the uridine diphosphate glucuronosyltransferase isoenzymes and protein binding. There is some evidence for the following effects. Carbamazepine decreases the plasma concentrations of both risperidone and its active metabolite. It also decreases concentrations of olanzapine, clozapine, ziprasidone, haloperidol, zuclopenthixol, flupenthixol and probably chlorpromazine and fluphenazine. Quetiapine increases the ratio of carbamazepine epoxide to carbamazepine and this may lead to toxicity. The data on valproic acid are conflicting; it may either increase or decrease clozapine concentrations, and it appears to decrease aripiprazole concentrations. Chlorpromazine possibly increases valproic acid concentrations. Lamotrigine possibly increases clozapine concentrations. Phenobarbital decreases clozapine, haloperidol and chlorpromazine concentrations. Phenytoin decreases quetiapine, clozapine, haloperidol and possibly chlorpromazine concentrations. There are major gaps in the data. In many cases there are no published clinical data on interactions that would be predicted on theoretical grounds. PMID

  2. Fracture Risk among Nursing Home Residents Initiating Antipsychotic Medications

    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

  3. Efficacy, tolerability and cost effectiveness of zotepine versus olanzapine in patients of acute schizophrenia

    Saroj Kothari


    Full Text Available Background: Schizophrenia is a functional psychosis with severe personality changes and thought disorders without cerebral damage. No reports are available in literature regarding efficacy and tolerability of atypical antipsychotic drug zotepine over olanzapine a preferred drug worldwide for the treatment of schizophrenia. Therefore, present study is undertaken to evaluate efficacy, tolerability and cost effectiveness of zotepine over olanzapine in patients suffering from schizophrenia. Methods: A prospective, randomized, single blind, parallel, 6 weeks clinical study was conducted on a total of 112 patients, of schizophrenia attending psychiatry outpatient department at G. R. Medical College, Gwalior, India randomized into two groups (56 in each. Patients received either olanzapine (10-20mg or zotepine (75-150mg per day for a period of 6 week. Efficacy was measured by Positive and Negative Syndrome Scale (PANSS and Clinical Global Impression (CGI scale whereas tolerability was measured by dropout rate and frequency of adverse effects. Cost effectiveness was calculated in terms of cost incurred for improvement at the end of treatment period. Results: Both the drugs showed significant (P.0.05. Olanzapine showed significantly better (P0.05 between the two groups. Incidence of akathisia and drop out (16% and 23% with zotepine were significant (P<0.05 as compared to olanzapine (2% and 11% respectively. Conclusions: Though the efficacy of both the drugs is comparable, olanzapine appears to have better tolerability and cost effectiveness than zotepine in patients of schizophrenia. [Int J Basic Clin Pharmacol 2013; 2(5.000: 577-582

  4. Olanzapine approved for the acute treatment of schizophrenia or manic/mixed episodes associated with bipolar I disorder in adolescent patients

    Ann E Maloney


    Full Text Available Ann E Maloney1,2, Linmarie Sikich31Maine Medical Center Research Institute, Scarborough, ME, USA; 2Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA; 3Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USABackground: Severe and persistent mental illnesses in children and adolescents, such as early-onset schizophrenia spectrum (EOSS disorders and pediatric bipolar disorder (pedBP, are increasingly recognized. Few treatments have demonstrated efficacy in rigorous clinical trials. Enduring response to current medications appears limited. Recently, olanzapine was approved for the treatment of adolescents with schizophrenia or acute manic/mixed episodes in pedBP.Methods: PubMed searches were conducted for olanzapine combined with pharmacology, schizophrenia, or bipolar disorder. Searches related to schizophrenia and bipolar disorder were limited to children and adolescents. The bibliographies of the retrieved articles were hand-checked for additional relevant studies. The epidemiology, phenomenology, and treatment of EOSS and pedBP, and olanzapine’s pharmacology are reviewed. Studies of olanzapine treatment in youth with EOSS and pedBP are examined.Results: Olanzapine is efficacious for EOSS and pedBP. However, olanzapine is not more efficacious than risperidone, molindone, or haloperidol in EOSS and is less efficacious than clozapine in treatment-resistant EOSS. No comparative trials have been done in pedBP. Olanzapine is associated with weight gain, dyslipidemia, and transaminase elevations in youth. Extrapyramidal symptoms, neuroleptic malignant syndrome, and blood dyscrasias have also been reported but appear rare.Conclusions: The authors conclude that olanzapine should be considered a second-line agent in EOSS and pedBP due to its risks for significant weight gain and lipid dysregulation. Awareness of the consistent weight and metabolic changes observed in olanzapine

  5. Olanzapine in Chinese patients with schizophrenia or bipolar disorder: a systematic literature review

    Xue HBH


    Full Text Available Hai Bo Haber Xue,1 Li Liu,1 Hena Zhang,2 William Montgomery,3 Tamás Treuer41Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, Shanghai, 2China Pharmaceutical University, Nanjing, People’s Republic of China; 3Eli Lilly Australia Pty Ltd, West Ryde, Australia; 4Eli Lilly & Co, Budapest, HungaryBackground: Despite the burden of schizophrenia and bipolar disorder in the Chinese population, country-specific data to guide practitioners regarding antipsychotic therapy are lacking. The primary aim of this systematic review was to examine evidence of the efficacy, effectiveness, and safety of olanzapine in Chinese populations.Methods: A systematic literature search was conducted using databases covering international and Chinese core journals using search terms related to schizophrenia and bipolar disorder, specified countries (People’s Republic of China, Hong Kong, Taiwan, and olanzapine treatment. Following initial screening, inclusion and exclusion criteria were applied to the search results to identify relevant studies from which data were extracted.Results: A total of 489 publications were retrieved and 61 studies were identified for inclusion. Most studies were related to schizophrenia (n=54, with six studies related to bipolar disorder and one study related to both conditions. The quality of study methods and reporting in international journals was noticeably better than in Chinese language journals. Most studies included relatively small patient populations and were of short duration. The efficacy of olanzapine in Chinese populations was confirmed by multiple comparative and noncomparative studies that found statistically significant reductions in symptom measures in studies conducted for ≥6 weeks (schizophrenia or ≥3 weeks (bipolar disorder. Findings related to effectiveness (treatment discontinuation, quality of life, and neurocognitive improvements were generally consistent with those observed in non-Chinese populations. No new

  6. Efficacy and safety of atypical antipsychotic drug treatment for dementia: a systematic review and meta-analysis

    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, ...

  7. Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications.

    Lian, Jiamei; Huang, Xu-Feng; Pai, Nagesh; Deng, Chao


    Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapine-induced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental

  8. Emphysematous pancreatitis predisposed by Olanzapine

    Sukhen Samanta


    Full Text Available A 32-year-old male presented to our intensive care unit with severe abdominal pain and was diagnosed as acute pancreatitis after 2 months of olanzapine therapy for bipolar disorder. His serum lipase was 900 u/L, serum triglyceride 560 mg/dL, and blood sugar, fasting and postprandial were 230 and 478 mg/dL, respectively on admission. Contrast enhanced computed tomography (CECT of abdomen was suggestive of acute pancreatitis. Repeat CECT showed gas inside pancreas and collection in peripancreatic area and patient underwent percutaneous drainage and antibiotics irrigation through the drain into pancreas. We describe the rare case of emphysematous pancreatitis due to development of diabetes, hypertriglyceridemia and immunosuppression predisposed by short duration olanzapine therapy.

  9. Antipsychotic polypharmacy in clozapine resistant schizophrenia: a randomized controlled trial of tapering antipsychotic co-treatment

    Jari Tiihonen


    Full Text Available There is a considerable disparity between clinical practice and recommendations based on meta-analyses of antipsychotic polypharmacy in clozapine resistant schizophrenia. For this reason, we investigated the clinical response to reducing the use olanzapine that had been previously added on clozapine treatment among seriously ill hospitalized patients. In a randomized controlled trial with crossover design, we studied volunteer patients (N = 15 who had olanzapine added on to clozapine in a state mental hospital. Clozapine monotherapy was just as effective as clozapine-olanzapine therapy, according to results from Clinical Global Impression Scale and Global Assessment of Functioning as primary outcome measures. Polypharmacy is widely used in treating schizophrenia, and usually, add-on medications are started because of worsening of the clinical state. A major confounding feature of these add-ons is whether observed improvements are caused by the medication or explained by the natural fluctuating course of the disorder. The present study, in spite of its small size, indicates the necessity of reconsidering the value of polypharmacy in treating schizophrenia.

  10. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases

    Stefaniak Victoria J


    Full Text Available Abstract Background An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI. During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI. Methods Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors. Results Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients. Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness. However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified. Conclusions Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post

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

    Oytun Erbaş


    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

  12. A suspected case of olanzapine induced hyponatremia

    Ajay Kumar Bakhla


    Full Text Available Here we report a case of a 63-year-old male diagnosed with recurrent depressive disorder and current episode of severe depression with psychotic symptoms, developed hyponatremia soon after addition of olanzapine and increasing the dose of escitalopram. A possible causality association was established with olanzapine, and the possible etiological reasons of this clinically significant risk were discussed.

  13. [Anticonvulsants and antipsychotics in the treatment of bipolar disorder].

    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

  14. Incident users of antipsychotics

    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...

  15. Deep venous thrombosis and atypical antipsychotics: three cases report

    Sheikhmoonesi Fatemeh


    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.

  16. Different antipsychotics elicit different effects on magnocellular oxytocinergic and vasopressinergic neurons as revealed by Fos immunohistochemistry

    Kiss, A; Bundzikova, J; Pirnik, Z;


    autonomic, neuroendocrine, and behavioral processes. This study was focused to reveal the responsiveness of hypothalamic OXY- and AVP- producing magnocellular neurons, in terms of quantitative and topographical distinctions, to antipsychotics displaying different pharmacological profiles. Naive male Wistar...... accessory (ACS) cell groups, and 4 distinct PVN subdivisions using a computerized light microscope. Most apparent activation of single Fos, Fos/OXY, and Fos/AVP cells was induced by clozapine and olanzapine; effects of risperidone and haloperidol were substantially lower; no colocalizations were revealed in...... naive or vehicle treated control rats. The data indicate the existence of a substantial diversity in the stimulatory effect of the selected antipsychotics on quantity of Fos, Fos/OXY, and Fos/AVP immunostainings with the preferential action of the atypicals clozapine over olanzapine and little effects...

  17. Determination of olanzapine and N-desmethyl-olanzapine in plasma using a reversed-phase HPLC coupled with coulochemical detection: correlation of olanzapine or N-desmethyl-olanzapine concentration with metabolic parameters.

    Mong-Liang Lu

    Full Text Available BACKGROUND: Olanzapine (OLZ is one of the most prescribed atypical antipsychotic drugs but its use is associated with unfavorable metabolic abnormalities. N-desmethyl-olanzapine (DMO, one of the OLZ metabolites by CYP1A2, has been reported to have a normalizing action on metabolic abnormalities, but this remains unclear. Our aim was to explore the correlation between the concentrations of OLZ or DMO with various metabolic parameters in schizophrenic patients. METHODS: The chromatographic analysis was carried out with a solvent delivery system coupled to a Coulochem III coulometric detector to determine OLZ and DMO simultaneously in OLZ-treated patients. The correlation between the concentration of OLZ or DMO and the metabolic parameters was analyzed by the Spearman rank order correlation method (r s. PRINCIPAL FINDINGS: The established analytical method met proper standards for accuracy and reliability and the lower limitation of quantification for each injection of DMO or OLZ was 0.02 ng. The method was successfully used for the analysis of samples from nonsmoking patients (n = 48 treated with OLZ in the dosage range of 5-20 mg per day. There was no correlation between OLZ concentrations and tested metabolic parameters. DMO concentrations were negatively correlated with glucose (r s = -0.45 and DMO concentrations normalized by doses were also negatively correlated with insulin levels (r s = -0.39; however, there was a marginally positive correlation between DMO and homocysteine levels (r s = +0.38. CONCLUSIONS: The observed negative correlations between levels of DMO and glucose or insulin suggest a metabolic normalization role for DMO regardless of its positive correlation with a known cardiovascular risk factor, homocysteine. Additional studies of the mechanisms underlying DMO's metabolic effects are warranted.

  18. A Systemic Review and Experts’ Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder

    Chou, Yuan Hwa; Chu, Po-Chung; Wu, Szu-Wei; Lee, Jen-Chin; Lee, Yi-Hsuan; Sun, I-Wen; Chang, Chen-Lin; Huang, Chien-Liang; Liu, I-Chao; Tsai, Chia-Fen; Yen, Yung-Chieh


    Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician’s clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms. PMID:26243837

  19. Eosinophilic myocarditis during treatment with olanzapine

    Vang, Torkel; Rosenzweig, Mary; Bruhn, Christina Hedegaard; Polcwiartek, Christoffer; Kanters, Jørgen Kim; Nielsen, Jimmi


    BACKGROUND: Drug-induced eosinophilic myocarditis is a life-threatening and frequently overlooked condition. The prevalence of myocarditis in clozapine-treated patients may be as high as 3 %. An association between olanzapine and myocarditis has not previously been described, but given the chemical...... fatal cases of eosinophilic myocarditis associated with the use of olanzapine. CASE PRESENTATION: Case 1 was a 39-year-old Caucasian man with known substance abuse and schizophrenia. He was found dead in his home. Olanzapine was prescribed at day -54, and dose at time of death was 40 mg/day. Post......-mortem toxicological examination demonstrated presence of olanzapine, morphine, venlafaxine and oxazepam. Syringes indicating substance abuse were found in his home. Case 2 was a 36-year-old Caucasian man diagnosed with schizophrenia was found dead unexpectedly. There was no history of substance abuse. Current...

  20. Evaluation of striatal dopamine transporter density using ({sup 123}I)-{beta}-CIT SPECT in schizophrenic patients treated with olanzapine: pilot study

    Kim, Chul Eung; Moon, Hey Won; Choe, Won Sick; Kim, Chang Ho; Chi, Dae Yoon [Inha Univ., Incheon (Korea, Republic of)


    This pilot study was performed to understand the pharmacological effect of olanzapine, an atypical antipsychotic agent, on dopamine transporter in schizophrenic patients. Six patients (3 male, 3 female) with schizophrenia, who had not taken any psychotropic drugs for at least four weeks, were studied. Nuclear imaging using ({sup 123}I)-{beta}-CIT SPECT was obtained before and after 4-week treatment with olanzapine. Analysis of ROI on the striatum, caudate nucleus, and putamen was performed. Post-treatment uptake was significantly increased in all the ROIs compared with pre-treatment uptake. This preliminary study with the small number of schizophrenic patients suggested an increase in uptake of dopamine transporter in the striatum, caudate nucleus, and putamen after 4-week treatment with olanzapine, which warrants a large-scaled controlled study to confirm the current findings.

  1. Delirium with anticholinergic symptoms after a combination of paliperidone and olanzapine pamoate in a patient known to smoke cannabis: an unfortunate coincidence.

    Kokalj, Anja; Rijavec, Nikolina; Tavčar, Rok


    We report a case of delirium with anticholinergic symptoms in a 19-year-old female patient with schizophrenia. On the day the symptoms emerged, the patient received olanzapine long-acting injection and a higher dose of paliperidone. We observed symptoms ranging from confusion to delirium as well as some anticholinergic symptoms. The delirium lasted 24 hours and was managed by intravenous fluid substitution and oral benzodiazepines. Olanzapine pamoate, paliperidone and cannabis are central nervous system (CNS) depressants, and their combination can increase the risks of CNS depression. In this case report, we review the symptoms of delirium in a case of antipsychotic overdose and provide general guidelines for managing these symptoms. We also review possible complications in combined use of cannabis, olanzapine and paliperidone. PMID:27335358

  2. Design and in-vitro evaluation of mouth dissolving tablets of olanzapine

    Manjunatha Kattalagere Maheswarappa


    Full Text Available The aim of the present investigation was to formulate mouth dissolving tablets of olanzapine, an anti-psychotic drug. Mouth dissolving tablets (MDT of Olanzapine were prepared with the addition of different superdisintegrants, namely, crospovidone, croscarmellose sodium, and sodium starch glycolate. Each of these superdisintegrants was used in concentrations of 2% w/w, 4% w/w, 6% w/w, and 8% w/w. Formulation with 4% w/w crospovidone showed minimum disintegration time (<30 seconds. Furthermore, increasing the concentration of the superdisintegrants did not decrease the disintegration time (DT significantly, so the same formulation was selected to incorporate the effervescent agent to reduce the disintegration time further. The formulation was optimized successfully with sodium bicarbonate and citric acid (monohydrate as the effervescent agent, with 4% of crospovidone, thereby reducing the disintegration time to 10 seconds. The prepared batches were evaluated for organoleptic properties, hardness, friability, weight variation, in-vitro disintegration time, in-vitro dispersion time, wetting time, in-vitro drug release studies, and stability studies. The drug-excipient interaction was studied by Fourier transform infrared spectroscopy (FTIR studies. The optimized formulation showed minimum disintegration time (10 seconds and an almost complete release of the drug within five minutes. Finally it was concluded that the MDT of Olanzapine could be successfully formulated by adding superdisintegrants and an effervescent agent, with improved patient compliance.

  3. A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Betahistine to Counteract Olanzapine-Associated Weight Gain.

    Barak, Nir; Beck, Yaffa; Albeck, Joseph H


    Patients with schizophrenia experience higher rates of obesity and related morbidity and mortality than the general population does. Given preclinical studies revealing the role of histamine H1 receptor in human eating behavior, and the potential of olanzapine to block with this system, we hypothesized that histamine H1 receptor agonists may be beneficial in reducing antipsychotic-associated weight gain. In the present study, 36 patients with a diagnosis of schizophrenia or schizoaffective disorder and treated with olanzapine were randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study outcomes were change in body weight from baseline and effect on antipsychotic efficacy of olanzapine. The patients in the betahistine group had less weight gain (-1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg, respectively). Positive and Negative Syndrome Scale Questionnaire showed improvement within each group and that subjects treated with betahistine enjoyed an improvement (reduction) by a mean of 35.7 points, higher when compared with placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal amount of subjects in both groups experienced adverse effects during the course of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects). Overall, there were no clinically marked differences in safety signals between both groups. A larger study addressing the weaknesses of this pilot study is warranted. PMID:27028981

  4. Frequency of sexual dysfunction and other reproductive side-effects in patients with schizophrenia treated with risperidone, olanzapine, quetiapine, or haloperidol: the results of the EIRE study.

    Bobes, J; Garc A-Portilla, M P; Rejas, J; Hern Ndez, G; Garcia-Garcia, M; Rico-Villademoros, F; Porras, A


    Atypical antipsychotics seem to differ mainly in their tolerability profile. The aim of this cross-sectional study, the Estudio de Investigaci n de Resultados en Esquizofrenia (Outcomes Research Study in Schizophrenia; EIRE study), was to assess in a clinical setting the frequency of several side-effects related to haloperidol, risperidone, olanzapine, and quetiapine. This article addresses sexual dysfunction and other reproductive side-effects (gynecomastia, menorrhage, amenorrhea, and galactorrhea). We recruited outpatients diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994) criteria and who had received a single antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) for at least 4 weeks. During a single visit, we collected data, including demographic and clinical characteristics, current antipsychotic and concomitant treatment, and adverse effects listed in a modified version of the UKU Scale. We used a Chi-squared test to determine pairs comparisons of the frequency of adverse reactions between treatments. To estimate risk of a given adverse reaction with a given treatment, we used a logistic regression method. We assessed 636 evaluable patients out of 669 recruited. Frequency of sexual dysfunction was high with haloperidol (38.1%) and also with olanzapine (35.3%), quetiapine (18.2%), and risperidone (43.2%). We found the frequency of other reproductive side-effects to be relatively low with all four drugs: haloperidol (6.9%), olanzapine (6.4%), quetiapine (2.7%), and risperidone (11.7%). Sexual dysfunction appeared to be dose-related with haloperidol, risperidone, and olanzapine. Risperidone and olanzapine showed a higher risk of sexual dysfunction and other reproductive sideeffects than haloperidol. Quetiapine showed a lower risk of sexual dysfunction during short-term treatment ( 12 weeks) are lacking. Our results suggest that none of the atypical

  5. Clozapine and olanzapine are better antioxidants than haloperidol, quetiapine, risperidone and ziprasidone in in vitro models.

    Brinholi, Francis Fregonesi; Farias, Carine Coneglian de; Bonifácio, Kamila Landucci; Higachi, Luciana; Casagrande, Rúbia; Moreira, Estefânia Gastaldello; Barbosa, Décio Sabbatini


    Although the etiopathogenic mechanisms of schizophrenia (SCZ) are unknown, evidences suggest that excessive free radical production or oxidative stress may be involved in the pathophysiology of SCZ. Antipsychotics are the drugs used in the treatment of SCZ but it remains controversial the impact that typical vs. atypical antipsychotics has on the oxidative stress status in SCZ patients. In vitro, the antioxidant capacity of six antipsychotics was assessed by their ability to: decrease or scavenge reactive oxygen species in the neutrophil respiratory burst; donate hydrogen and stabilize the free radical 2,2-diphenyl-1-picryl-hydrazyl (DPPH); and scavenge 2,2'-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS(+)). This study demonstrated that both clozapine and olanzapine have antioxidant effects, in vitro, by scavenging superoxide anion on the respiratory burst, donating electron in the ABTS(+) assay and stabilizing the radical DPPH. Ziprasidone significantly scavenged ABTS(+) and stabilized the radical DPPH whereas risperidone significantly reduced the respiratory burst. Haloperidol and quetiapine lacked antioxidant effects. The chemical structure-related antioxidant capacity suggests a possible neuroprotective mechanism of these drugs on the top of their antipsychotic mechanism of action. PMID:27261620

  6. The use of olanzapine in Huntington disease accompanied by psychotic symptoms

    Cafer Alhan


    Full Text Available Huntington's disease is an autosomal dominant neurodegenerative disease. The disease begins between the ages of 30-50, including motor symptoms, psychiatric symptoms and is characterized by progressive dementia. Common psychiatric disorders of Huntington’s disease include mood and anxiety disorders, behavior and personality changes. Psychosis is relatively rare. Here, a patient is present, who has Huntington’s disease, which is associated with psychotic symptoms. 61-year-old male patient who were followed for Huntington disease for 25 years was admitted for complaints of thinking of poisoning and refuse to eat something. Patient was started on olanzapine at dose of 5 mg/day. In follow up psychotic symptoms disappeared. Emerging psychotic symptoms in Huntington disease is created a need for antipsychotic treatment. Atypical antipsychotic agents should be preferred in the treatment and as in the case olanzapine may be used as a treatment option should be kept in mind to control both involuntary movements and psychotic symptoms in Huntington's disease with psychotic features. J Clin Exp Invest 2014; 5 (2: 326-328

  7. Patient perspectives on antipsychotic treatments and their association with clinical outcomes

    Hong Liu-Seifert


    Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

  8. Antipsychotic polypharmacy in a regional health service: a population-based study

    Bernardo Miguel


    Full Text Available Abstract Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain, focusing on the use of clozapine and long-acting injections (LAI. Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA from the Anatomical Therapeutic Chemical classification (ATC code N05A (except lithium were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9% corresponded to an antipsychotic combination, 47,386 (66.7% to monotherapy and 13,763 (19.4% to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1% and oral risperidone (36.4% were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8% revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%. Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%. A total of 3.800 patients (5.4% were given LAI antipsychotics, and 2.662 of these (70.1% were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine.

  9. Cardiovascular safety of antipsychotics

    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...

  10. Olanzapine versus haloperidol: Which can control stuttering better?

    Vahid Shaygannejad


    Conclusions: It seems that olanzapine does have better impact in controlling stuttering, and it may be recommended to prescribe olanzapine for stutters as the first choice to control the stuttering under a careful follow-up.

  11. Diabetic control and atypical antipsychotics: a case report

    Gaston Romina


    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.

  12. Atypical antipsychotics in the treatment of early-onset schizophrenia

    Hrdlicka M


    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

  13. A double blind, placebo-controlled, randomized crossover study of the acute metabolic effects of olanzapine in healthy volunteers.

    Vance L Albaugh

    Full Text Available Atypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral glucose tolerance (oGTT along with reduced plasma free fatty acids (FFA and leptin in animal models. It is unclear whether the same acute effects occur in humans.A double blind, randomized, placebo-controlled crossover trial was conducted to examine the potential metabolic effects of olanzapine in healthy volunteers. Participants included male (8 and female (7 subjects [18-30 years old, BMI 18.5-25]. Subjects received placebo or olanzapine (10 mg/day for three days prior to oGTT testing. Primary endpoints included measurement of plasma leptin, oral glucose tolerance, and plasma free fatty acids (FFA. Secondary metabolic endpoints included: triglycerides, total cholesterol, high- and low-density lipoprotein cholesterol, heart rate, blood pressure, body weight and BMI. Olanzapine increased glucose Area Under the Curve (AUC by 42% (2808±474 vs. 3984±444 mg/dl·min; P = 0.0105 during an oGTT. Fasting plasma leptin and triglycerides were elevated 24% (Leptin: 6.8±1.3 vs. 8.4±1.7 ng/ml; P = 0.0203 and 22% (Triglycerides: 88.9±10.1 vs. 108.2±11.6 mg/dl; P = 0.0170, whereas FFA and HDL declined by 32% (FFA: 0.38±0.06 vs. 0.26±0.04 mM; P = 0.0166 and 11% (54.2±4.7 vs. 48.9±4.3 mg/dl; P = 0.0184, respectively after olanzapine. Other measures were unchanged.Olanzapine exerts some but not all of the early endocrine/metabolic changes observed in rodent models of the metabolic side effects, and this suggest that antipsychotic effects are not limited to perturbations in glucose metabolism alone. Future prospective clinical studies should focus on identifying which reliable metabolic alterations might be useful as potential screening tools in assessing patient susceptibility to weight gain and diabetes caused by atypical NCT00741026.

  14. Use and safety of antipsychotics in behavioral disorders in elderly people with dementia.

    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

  15. Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics: rat profile and implications for behavioral and psychological symptoms of dementia.

    Kołaczkowski, Marcin; Mierzejewski, Paweł; Bienkowski, Przemyslaw; Wesołowska, Anna; Newman-Tancredi, Adrian


    Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD. PMID:24599316

  16. Long-term cost-effectiveness of atypical antipsychotics in the treatment of adults with schizophrenia in the US

    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 ...

  17. Antipsychotic-induced Hyperprolactinemia

    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

  18. Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia

    Zhao Zhongyun


    Full Text Available Abstract Background Previous research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol. Methods Data were drawn from the acute phase (first 6-weeks of a double-blind randomized clinical trial of olanzapine versus haloperidol in the treatment of 1296 men and 700 women with schizophrenia-spectrum disorders. The associations between weight change and change in core schizophrenia symptoms, depressive symptoms, and functional status were examined post-hoc for men and women and for each medication group. Core schizophrenia symptoms (positive and negative were measured with the Brief Psychiatric Rating Scale (BPRS, depressive symptoms with the BPRS Anxiety/Depression Scale and the Montgomery-Asberg Depression Rating Scale, and functional status with the mental and physical component scores on the Medical Outcome Survey-Short Form 36. Statistical analysis included methods that controlled for treatment duration. Results Weight gain during 6-week treatment with olanzapine and haloperidol was significantly associated with improvements in core schizophrenia symptoms, depressive symptoms, mental functioning, and physical functioning for men and women alike. The conditional probability of clinical response (20% reduction in core schizophrenia symptom, given a clinically significant weight gain (at least 7% of baseline weight, showed that about half of the patients who lost weight responded to treatment, whereas three-quarters of the patients who had a clinically significant weight gain responded to treatment. The positive associations between therapeutic

  19. Schizophrenia, antipsychotics and risk of hip fracture

    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...

  20. Olanzapine and Betamethasone Are Effective for the Treatment of Nausea and Vomiting due to Metastatic Brain Tumors of Rectal Cancer

    M. Suzuki


    Full Text Available Brain lesions originating from metastasis of colorectal cancer represent 3-5% of all brain metastases and are relatively rare. Of all distant metastases of colorectal cancer, those to the liver are detected in 22-29% of cases, while those to the lungs are detected in 8-18% of cases. In contrast, brain metastasis is quite rare, with a reported incidence ranging from 0.4 to 1.8%. Treatments for metastatic brain tumors include surgery, radiotherapy, chemotherapy and supportive care with steroids, etc. Untreated patients exhibit a median survival of only approximately 1 month. The choice of treatment for brain metastasis depends on the number of lesions, the patient's general condition, nerve findings and presence of other metastatic lesions. We herein report the case of a 78-year-old male who presented with brain metastases originating from rectal carcinoma. He suffered from nausea, vomiting, anorexia and vertigo during body movement. He received antiemetics, glycerol and whole brain radiation therapy; however, these treatments proved ineffective. Olanzapine therapy was started at a dose of 1.25 mg every night. The persistent nausea disappeared the next day, and the frequency of vomiting subsequently decreased. The patient was able to consume solid food. Olanzapine is an antipsychotic that has recently been used as palliative therapy for refractory nausea and vomiting in patients receiving chemotherapy. We consider that olanzapine was helpful as a means of supportive care for the treatment of nausea and vomiting due to brain metastasis.

  1. One-year risk of psychiatric hospitalization and associated treatment costs in bipolar disorder treated with atypical antipsychotics: a retrospective claims database analysis

    Pikalov Andrei


    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.

  2. Long-term treatment with olanzapine in hospital conditions: Prevalence and predictors of the metabolic syndrome

    Popović Irena


    Full Text Available Introduction. The risk of metabolic abnormalities is greatly increased in schizophrenic patients started on an atypical antipsychotic medication. Patients with psychiatric disorders exceed mortality ranges resulting from, among others, increased risk of cardiovascular events. Other factors contributing to the development of metabolic syndrome include prolonged duration of illness, increasing age, female sex and lifestyle factors. Objective. This cross-sectional study was taken up to assess the prevalence of the metabolic syndrome (MetS in schizophrenic patients receiving olanzapine monotherapy for at least six months and to determine the most important risk factors associated with metabolic syndrome presence in these patients. Methods. A total of 93 long term hospitalized schizophrenic patients (71 men, 22 women, had a screening of the following: case-history data, psychiatric scales, anthropometric measures, blood (fasting glucose, lipid status, C-reactive protein - CRP and urine samples (microalbuminuria. Results. Prevalence of MetS according to International Diabetes Federation criteria in our study was 34.4%. The multivariate analysis distinguished the following significant predictors of MetS presence (in order of appearance: data about diabetes mellitus in family history (p=0.002, body mass index >25 kg/m2 (p=0.002, hyperlipidemia in family history (p=0.008, and elevated CRP value (p=0.042. Conclusion. High rate of MetS in patients treated with olanzapine in this study exceeds MetS prevalence in general population. Among observed parameters, our study pointed to several “high risk” predictors associated with MetS presence. Regular monitoring of cardiometabolic risk factors is highly recommended. Positive heredity distress mentioned above may direct a psychiatrist to prescribe some other drug than olanzapine in the long term treatment of schizophrenia.

  3. Long-term cost-effectiveness of atypical antipsychotics in the treatment of adults with schizophrenia in the US

    O'Day K


    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

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

    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

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

    Sárvári, Anitta K., E-mail: [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Veréb, Zoltán, E-mail: [Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Uray, Iván P., E-mail: [Clinical Cancer Prevention Department, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Fésüs, László, E-mail: [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: [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

  6. Simultaneous Estimation of Fluoxetine HCl and Olanzapine in Bulk Drug and Pharmaceutical Formulation by Using UV-Visible Spectroscopy Method

    Rubesh kumar S


    Full Text Available Present work is to carry out an analytical method development and validation of Fluoxetine HCl (FLU and Olanzapine (OLZ in bulk drug and pharmaceutical dosage form. The developed method is based upon simultaneous equations (Vierodt’s method by using UV/Visible spectroscopy. Both drugs come in the categories of anti- depressant and anti-psychotic agent. The developed method can be used for the simultaneous estimation of FLU and OLZ in pharmaceutical dosage form without separating from each other or from the excipients. Primarily the λ max of Fluoxetine HCl (FLU and Olanzapine (OLZ was determined as 226 and 258 nm respectively. The suggested method is validated by using ICH validation parameters like accuracy, precession, linearity and LOD and LOQ respectively. Accuracy study showed percentage recovery in the range of 97-102% w/w respectively. Precision studies were carried out for 6 successive absorbance and studied for their percentage relative standard deviation (%RSD was < 2%, LOD and LOQ was studied and the limit of detection and limit of quantification were found to be was 1-100 µg/ml for Olanzapine and Fluoxetine HCl, the slope of interception Y=0.23x6+0.054 (R2 0.993 and Y=0.222x6-0.014 (R 2 0.995 respectively. Relative standard deviation for Fluoxetine hydrochloride and Olanzapine were 0.4904 and 0.53969, the co-relation coefficient were 0.997 and 0.825 respectively. This procedure was applied successfully for the analysis of FLU and OLZ in bulk drug and Pharmaceutical preparations.

  7. Effects of quetiapine and olanzapine in patients with psychosis and violent behavior: a pilot randomized, open-label, comparative study

    Gobbi G


    Full Text Available Gabriella Gobbi,1,2 Stefano Comai,1 Guy Debonnel1,2,† 1Neurobiological Psychiatric Unit, Department of Psychiatry, McGill University and McGill University Health Center, 2Institut Philippe Pinel, Department of Psychiatry, Université de Montréal, Montréal, QC, Canada †Guy Debonnel passed away on November 4, 2006 Objective: Patients suffering from psychosis are more likely than the general population to commit aggressive acts, but the therapeutics of aggressive behavior are still a matter of debate. Methods: This pilot randomized, open-label study compared the efficacy of quetiapine versus olanzapine in reducing impulsive and aggressive behaviors (primary endpoints and psychotic symptoms (secondary endpoints from baseline to days 1, 7, 14, 28, 42, 56, and 70, in 15 violent schizophrenic patients hospitalized in a maximum-security psychiatric hospital. Results: Quetiapine (525±45 mg and olanzapine (18.5±4.8 mg were both efficacious in reducing Impulsivity Rating Scale from baseline to day 70. In addition, both treatments reduced the Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale scores at day 70 compared to baseline, and no differences were observed between treatments. Moreover, quetiapine, but not olanzapine, yielded an improvement of depressive symptoms in the items “depression” in Brief Psychiatric Rating Scale and “blunted affect” in Positive and Negative Syndrome Scale. Modified Overt Aggression Scale scores were also decreased from baseline to the endpoint, but due to the limited number of patients, it was not possible to detect a significant difference. Conclusion: In this pilot study, quetiapine and olanzapine equally decreased impulsive and psychotic symptoms after 8 weeks of treatment. Double-blind, large studies are needed to confirm the validity of these two treatments in highly aggressive and violent schizophrenic patients. Keywords: schizophrenia, aggression

  8. Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis

    Wang, Bo; Franklin, Jessica M.; Eddings, Wesley; Landon, Joan; Kesselheim, Aaron S.


    Background Following Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved (“off-label”) uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children. Methods Retrospective, segmented time-series analysis using new prescription claims during 2003–2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone. Results During the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79). Conclusions The FDA’s sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency’s expert judgments to clinical practice. PMID:27032095

  9. Maintenance of response with atypical antipsychotics in the treatment of schizophrenia: a post-hoc analysis of 5 double-blind, randomized clinical trials

    Liu Lin


    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.

  10. Immunosuppressant-Associated Neurotoxicity Responding to Olanzapine

    James A. Bourgeois


    Full Text Available Immunosuppressants, particularly tacrolimus, can induce neurotoxicity in solid organ transplantation cases. A lower clinical threshold to switch from tacrolimus to another immunosuppressant agent has been a common approach to reverse this neurotoxicity. However, immunosuppressant switch may place the graft at risk, and, in some cases, continuation of the same treatment protocol may be necessary. We report a case of immunosuppressant-associated neurotoxicity with prominent neuropsychiatric manifestation and describe psychiatric intervention with olanzapine that led to clinical improvement while continuing tacrolimus maintenance.

  11. Evaluation of the efficacy and safety of olanzapine as an adjunctive treatment for anorexia nervosa in adolescent females: a randomized, double-blind, placebo-controlled trial

    Moher David


    Full Text Available Abstract Background Anorexia Nervosa (AN is a serious, debilitating condition that causes significant physical, emotional, and functional impairment. The condition is characterized by destructive weight loss behaviours and a refusal to maintain body weight at or above a minimally normal weight for age and height. AN often develops in adolescence and is a predominantly female disorder. Treatment for AN typically involves medical, nutritional and psychological interventions. Pharmacotherapy is also often used; however, the literature on the effectiveness of these drugs in a pediatric population is very limited. Olanzapine, which is an 'atypical' antipsychotic, is becoming more widespread in the treatment of AN. Olanzapine is hypothesized to facilitate weight gain, while decreasing levels of agitation and decreasing resistance to treatment in young women with AN. This randomized, double-blind placebo-controlled trial seeks to examine the effectiveness and safety of olanzapine in female youth with AN. Methods/Design Adolescent females between the ages of 12 and 17 diagnosed with AN (either restricting or binge/purge type or Eating Disorder Not Otherwise Specified with a Body Mass Index of less than or equal to 17.5, will be offered inclusion in the study. Patients will be randomly assigned to receive either olanzapine or placebo. Patients assigned to receive olanzapine will start at a low dose of 1.25 mg/day for three days, followed by 2.5 mg/day for four days, 5 mg/day for one week, then 7.5 mg/day (the target dose chosen for 10 weeks. After 10 weeks at 7.5 mg the medication will be tapered and discontinued over a period of two weeks. The effectiveness of olanzapine versus placebo will be determined by investigating the change from baseline on measures of eating attitudes and behaviors, depression and anxiety, and change in Body Mass Index at week 12, and after a follow-up period at week 40. It is anticipated that 67 participants will be recruited

  12. New users of antipsychotic medication

    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...

  13. Effectiveness of second generation antipsychotics: A systematic review of randomized trials

    Jørgensen Hugo A


    Full Text Available Abstract Background Systematic reviews based on efficacy trials are inconclusive about which second generation antipsychotic drug (SGA should be preferred in normal clinical practice, and studies with longer duration and more pragmatic designs are called for. Effectiveness studies, also known as naturalistic, pragmatic, practical or real life studies, adhere to these principles as they aim to mimic daily clinical practice and have longer follow-up. Objective To review the head-to-head effectiveness of SGAs in the domains of global outcomes, symptoms of disease, and tolerability. Methods Searches were made in Embase, PubMED, and the Cochrane central register of controlled trials for effectiveness studies published from 1980 to 2008, week 1. Different combinations of the keywords antipsychotic*, neuroleptic* AND open, pragmatic, practical, naturalistic, real life, effectiveness, side effect*, unwanted effect*, tolera* AND compar* AND random* were used. Results Sixteen different reports of randomized head-to-head comparisons of SGA effectiveness were located. There were differences regarding sample sizes, inclusion criteria and follow-up periods, as well as sources of financial sponsorship. In acute-phase and first-episode patients no differences between the SGAs were disclosed regarding alleviating symptoms of disease. Olanzapine was associated with more weight gain and adverse effects on serum lipids. In the chronic phase patients olanzapine groups had longer time to discontinuation of treatment and better treatment adherence compared to other SGAs. The majority of studies found no differences between the SGAs in alleviating symptoms of psychosis in chronically ill patients. Olanzapine was associated with more metabolic adverse effects compared to the others SGAs. There were surprisingly few between-drug differences regarding side effects. First generation antipsychotics were associated with lower total mental health care costs in 2 of 3 studies

  14. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets

    Vidarsdottir, Solrun; Roelfsema, Ferdinand; Streefland, Trea; Holst, Jens J; Rehfeld, Jens F; Pijl, Hanno


    , might cause less weight gain than olanzapine standard oral tablets (OST). DESIGN AND METHODS: Ten healthy men received olanzapine ODT (10 mg o.d., 8 days), olanzapine OST (10 mg o.d., 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, blood samples were taken for...... measurement of pancreatic polypeptide, peptide YY, glucagon-like peptide-1, total glucagon, total ghrelin, and cholecystokinin (CCK) concentrations. RESULTS: With the exception of pre- and postprandial concentration of ghrelin at dinner and preprandial CCK concentrations at breakfast, which were all slightly...

  15. Sudden cardiac and sudden unexpected death related to antipsychotics: A meta-analysis of observational studies.

    Salvo, F; Pariente, A; Shakir, S; Robinson, P; Arnaud, M; Thomas, Shl; Raschi, E; Fourrier-Réglat, A; Moore, N; Sturkenboom, M; Hazell On Behalf Of Investigators Of The Aritmo Consortium, L


    To estimate the risk of sudden cardiac death (SCD) or sudden unexpected death (SUD) related to individual antipsychotics, a meta-analysis of observational studies was performed. Adjusted odds ratio (OR) of SCD/SUD with 95% confidence intervals (CI) were extracted and pooled; heterogeneity was studied using Q statistic and I(2) index, and its potential causes (e.g., hERG blockade potency) explored using meta-regression. Two cohort (740,306 person-years) and four case-control (2,557 cases; 17,670 controls) studies, investigating nine antipsychotics, were included. Compared with nonusers, the risk was increased for quetiapine (OR = 1.72, 95% CI: 1.33-2.23), olanzapine (OR = 2.04, 1.52-2.74), risperidone (OR = 3.04, 2.39-3.86), haloperidol (OR = 2.97, 1.59-5.54), clozapine (OR = 3.67, 1.94-6.94), and thioridazine (OR = 4.58, 2.09-10.05). Heterogeneity was found (Q = 20.0, P = 0.01; I(2) = 60.0%), and the increasing mean hERG blockade potency (P = 0.01) accounted for 43% of this. The SCD/SUD risk differed between individual antipsychotics, and mean hERG blockade potency could be an explanatory factor. This should be considered when initiating antipsychotic treatment. PMID:26272741

  16. Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study.

    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

  17. Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder

    Azekawa T


    Full Text Available Takaharu Azekawa, Shizuko Ohashi, Akira ItamiShioiri Mental Clinic, Yokosuka-shi, Kanagawa-ken, JapanBackground: Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting.Methods: Using a retrospective cohort study design, we screened all outpatients (n = 7936 who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703 diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic.Results: Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant.Conclusion: Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.Keywords: retrospective study, second-generation antipsychotics, effectiveness, treatment continuation, schizophrenia, aripiprazole

  18. Olanzapine Administration Shortened the Laying Interval in Pigeon (Columba livia

    Jin-Guo Liu


    Full Text Available About 120 pairs of American king pigeon were used to investigate the effect of olanzapine on laying interval. Olanzapine was added to the basal diet of 720 days old pigeon breeders at the level of 0, 0.5, 0.75 and 1.25 mg kg-1, respectively. During 60 days of treatment, laying interval of 0.75 and 1.25% group decreased significantly by 37.46 and 29.83% (p<0.05, respectively. This change was accompanied by significantly elevated plasma FSH and progesterone levels whereas declined PRL levels and diminished Prolactin Receptor (PRLR mRNA expression in liver of olanzapine-treated pigeons. The results provided evidence that olanzapine shorten the laying intervals accompanying with changes in the secretion of hormones and expression of PRLR gene.

  19. Investigation into effects of antipsychotics on ectonucleotidase and adenosine deaminase in zebrafish brain.

    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

  20. Intramuscular Olanzapine – a UK case series of early cases

    Taylor Mark; Bushe Chris J; Mathew Mathew


    Abstract Background Clinical trials assessing efficacy and safety of Intramuscular (IM) Olanzapine in acute schizophrenia and acute mania have previously been undertaken in studies required for drug registration in patients who were required to give informed consent. These patients may have less severe forms of psychosis than patients treated in routine practice. Data derived from naturalistic practice following the launch of IM olanzapine may be helpful for clinicians in assessing efficacy a...

  1. A Case Report of Somnambulism Associated With Olanzapine

    Faridhosseini, Farhad; Zamani, Azar


    Somnambulism consists of a group of behaviors leading to unwanted movements during sleep or even sleepwalking. Medications applied for psychiatric disorders could increase the likelihood of somnambulism in adults. The following article is a case report of somnambulism seen in a patient with schizophrenia, which occurred after remission of an acute episode following treatment with olanzapine. When olanzapine dosage was decreased, no previous and similar symptoms were reported after 6 months of...

  2. A case report of somnambulism associated with olanzapine.

    Faridhosseini, Farhad; Zamani, Azar


    Somnambulism consists of a group of behaviors leading to unwanted movements during sleep or even sleepwalking. Medications applied for psychiatric disorders could increase the likelihood of somnambulism in adults. The following article is a case report of somnambulism seen in a patient with schizophrenia, which occurred after remission of an acute episode following treatment with olanzapine. When olanzapine dosage was decreased, no previous and similar symptoms were reported after 6 months of follow up. PMID:24644473

  3. Sertindole, in contrast to clozapine and olanzapine, does not disrupt water maze performance after acute or chronic treatment

    Didriksen, Michael; Kreilgaard, Mads; Arnt, Jørn


    -mediated impairment was enhanced after chronic treatment. Sertindole (2.5 mg/kg, p.o.) had no disruptive effect on performance after either acute or chronic treatment. Exposure measurements confirmed that all three compounds were present in the serum at least at clinically effective concentrations. Thus, the three......Cognitive deficits in schizophrenia are associated with poor functional outcome, and may be further aggravated by treatment with antipsychotics. In the present study the acute and chronic (3 weeks of treatment) effects of clozapine, olanzapine, and sertindole on performance in the Morris water maze...... in rats was compared, using pharmacologically and/or clinically relevant dose regimens. An experimental design consisting of three trials/day over 3 days was used. Performance was expressed as the distance and latency to find a submerged platform, as well as the percentage of "non-finders", i...

  4. Olanzapine treatment in anorexia nervosa: case report.

    Dadić-Hero, Elizabeta; Ruzić, Klementina; Pernar, Mirjana; Kabalin, Milena; Medved, Paola


    A 15 year old patient suffering from psychiatric disturbances looked for psychiatric help but refused hospital admission. Following an ambulatory treatment, the patient was diagnosed with Anorexia nervosa. The patient, a girl, was 175 centimeters tall, weighting only 39 kilos. Within the clinical picture, there were few dominant disorders present; anxiety, depression, low self-esteem, fear of feminization, with recurrent psychotic episodes. By the implementation of an intensive psychotherapeutic treatment, without the use of psychopharmacs, the weight was kept stable. In accordance with the girl's mother, a psychopharmacotherapy was commenced, a combination of olanzapine and paroxetine (the choice of psychopharmacs was lead by the side effects known). At the end of a 24-month period of a psychological treatment which was combined with psychopharmacotherapy, the patient exhibited no symptomatology and a stable clinical remission of the illness was achieved. PMID:19270636


    G N S Sangeetha Lakshmi


    Full Text Available Background: Schizophrenia is a mental disorder characterized by persistent defects in the perception, thinking or the expression of reality. The term “schizophrenia” translates roughly as “shattered mind,” and comes from the Greek (schizo, “to split” or “to divide” and (phrēn, “mind”. Material and Methods: The study was designed to be a prospective control study. Schizophrenic patients taking Olanzapine and Haloperidol were selected and follow up at three weeks and six weeks was done. Results: In this prospective control study, Olanzapine and Haloperidol were associated with an increase in Blood Glucose Levels. The mean changes in Glucose remained within clinically normal range in this six week study. Conclusion: Antipsychotic treatmemt leads to the development of Diabetes mellitus in a significant 10.1% of patients within 6 weeks. Given the serious implications for morbidity and mortality attributable to diabetes mellitus, clinicians need to be aware of these risk factors when treating patients with chronic schizophrenia

  6. Differential Effects of Antipsychotic Medications on Polyunsaturated Fatty Acid Biosynthesis in Rats: Relationship with Liver Delta6-Desaturase Expression

    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...

  7. Adverse Effects of Second-Generation Antipsychotics as Adjuncts to Antidepressants: Are the Risks Worth the Benefits?

    Thase, Michael E


    Over the past decades, several adjunctive therapies have been introduced for treatment-resistant depression (TRD), and these strategies have ebbed and flowed in popularity. Currently, adjunctive therapy with the second-generation antipsychotics (SGAs) is most commonly used by psychiatrists. Four SGAs are FDA approved for indications related to TRD (aripiprazole, brexpiprazole, olanzapine, and quetiapine extended release); some evidence also supports use of risperidone and ziprasidone as adjunctive therapies. This article briefly reviews the role of adjunctive therapy with SGAs in contemporary algorithms for TRD, considering both the evidence of benefit and the adverse effects. PMID:27514300

  8. Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia

    Watson Susan B


    considering olanzapine LAI, as with all antipsychotics, it is important to carefully consider the potential benefits and risks for an individual patient. Trial Registration NCT00088491

  9. Adherence and continuation of treatment with first- and second-generation antipsychotics in schizophrenia

    Nisha Warikoo


    Full Text Available Background: Despite a large body of evidence, the issue of differences in adherence and continuation of treatment with first-generation antipsychotics (FGAs and second-generation antipsychotics (SGAs in schizophrenia remains unresolved. This study compared adherence and continuation of treatment between patients on SGAs and FGAs and examined the influence of several socio-demographic and clinical variables on adherence in the two antipsychotic groups. Materials and Methods: Two groups, one of 40 patients with schizophrenia on SGAs and the other with 30 patients on FGAs, were compared on clinician-rated and patient-rated measures of adherence over 6 months; a 3-month period prior to intake and a 3-month follow-up period. Mean scores on these measures and the proportion of adherent/non-adherent patients was estimated for both groups. Results: The two groups did not differ in the 3-month period prior to intake. Over the subsequent 3 months of follow-up, a-fifth of the patients on FGAs became non-adherent, while about 10% of those on SGAs became more adherent. These differences in continuation rates resulted in patients on SGAs being rated as significantly more adherent at the end of this 3-month follow-up period and over the entire 6 months of the study. Differences in adherence and continuation rates between the two groups were primarily driven by the differences between olanzapine and the FGAs. Supervision of treatment by relatives emerged as the only consistent determinant of adherence, but explained only 8% of the variance. Conclusions: Patients on certain SGAs, notably olanzapine, are more likely to continue with their treatment that those on FGAs.

  10. Depression: Should You Consider Antipsychotics?

    ... 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 ...

  11. Comparative cost-effectiveness of 11 oral antipsychotics for relapse prevention in schizophrenia within Singapore using effectiveness estimates from a network meta-analysis.

    Lin, Liang; Zhao, Ying J; Zhou, Hui J; Khoo, Ai L; Teng, Monica; Soh, Lay B; Lim, Boon P; Sim, Kang


    This study modelled the cost-effectiveness of 11 oral antipsychotics for relapse prevention among patients with remitted schizophrenia in Singapore. A network meta-analysis determined the relative efficacy and tolerability of 11 oral antipsychotics (amisulpride, aripiprazole, chlorpromazine, haloperidol, olanzapine, paliperidone, quetiapine, risperidone, sulpiride, trifluoperazine and ziprasidone). The clinical estimates were applied in a Markov model to estimate lifetime costs and quality-adjusted life-years gained. Quality-of-life data were obtained from published literature. Resource utilization and cost data were retrieved from local hospital databases. The annual direct cost of healthcare services for a patient experiencing a relapse episode was three-fold that of a patient not in relapse of schizophrenia. The most favourable pharmacological treatment for relapse prevention was olanzapine with an annual probability of relapse of 0.24 (0.13-0.38) with placebo as a reference of 0.75 (0.73-0.78). Olanzapine emerged as the dominant treatment with the highest quality-adjusted life-years gained and lowest lifetime costs. Ziprasidone, aripiprazole and paliperidone incurred higher lifetime costs compared with no treatment. Probability and cost of relapse were key drivers of cost-effectiveness in sensitivity analyses. The data can help prescribers in choosing appropriate treatment and payers in allocating resources for the clinical management of this serious psychiatric disorder. PMID:26619182

  12. Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of therapeutic effective plasma levels of antipsychotics

    Olsen, Christina Kurre; Brennum, Lise Tøttrup; Kreilgaard, Mads


    In the rat, selective suppression of conditioned avoidance response has been widely reported as a test with high predictive validity for antipsychotic efficacy. Recent studies have shown that the relationship between dopamine D2 receptor occupancy and the suppression of conditioned avoidance...... receptor occupancy required to suppress conditioned avoidance response behaviour according to EC50 measurements to be sertindole (+dehydrosertindole)=dehydrosertindole=paliperidone (the metabolite of risperidone)=haloperidol=olanzapine>risperidone>clozapine. Overall, a good agreement was observed between...... the rat dopamine D2 receptor occupancy levels providing 50% response in the conditioned avoidance response test and the dopamine D2 receptor occupancy levels reported from responding schizophrenic patients treated with antipsychotics. Predictions of therapeutically effective steady-state levels for...

  13. Extrapyramidal syndromes caused by antipsychotics

    Živanović Olga


    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.

  14. Melanin-concentrating hormone is necessary for olanzapine-inhibited locomotor activity in male mice.

    Chee, Melissa J S; Douris, Nicholas; Forrow, Avery B; Monnard, Arnaud; Lu, Shuangyu; Flaherty, Stephen E; Adams, Andrew C; Maratos-Flier, Eleftheria


    Olanzapine (OLZ), an atypical antipsychotic, can be effective in treating patients with restricting type anorexia nervosa who exercise excessively. Clinical improvements include weight gain and reduced pathological hyperactivity. However the neuronal populations and mechanisms underlying OLZ actions are not known. We studied the effects of OLZ on hyperactivity using male mice lacking the hypothalamic neuropeptide melanin-concentrating hormone (MCHKO) that are lean and hyperactive. We compared the in vivo effects of systemic or intra-accumbens nucleus (Acb) OLZ administration on locomotor activity in WT and MCHKO littermates. Acute systemic OLZ treatment in WT mice significantly reduced locomotor activity, an effect that is substantially attenuated in MCHKO mice. Furthermore, OLZ infusion directly into the Acb of WT mice reduced locomotor activity, but not in MCHKO mice. To identify contributing neuronal mechanisms, we assessed the effect of OLZ treatment on Acb synaptic transmission ex vivo and in vitro. Intraperitoneal OLZ treatment reduced Acb GABAergic activity in WT but not MCHKO neurons. This effect was also seen in vitro by applying OLZ to acute brain slices. OLZ reduced the frequency and amplitude of GABAergic activity that was more robust in WT than MCHKO Acb. These findings indicate that OLZ reduced Acb GABAergic transmission and that MCH is necessary for the hypolocomotor effects of OLZ. PMID:26092201

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

    Bodén R


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

  16. Torsadogenic Risk of Antipsychotics: Combining Adverse Event Reports with Drug Utilization Data across Europe

    Raschi, Emanuel; Poluzzi, Elisabetta; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Bennie, Marion; Barbui, Corrado; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio


    Background Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. Methods FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID). Results Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents was found in several Countries (+3.47 in France): the exposure to olanzapine increased across all Countries (+1.84 in France) and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009). Among Group B drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia). Conclusions This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  17. Torsadogenic risk of antipsychotics: combining adverse event reports with drug utilization data across Europe.

    Emanuel Raschi

    Full Text Available BACKGROUND: Antipsychotics (APs have been associated with risk of torsade de Pointes (TdP. This has important public health implications. Therefore, (a we exploited the public FDA Adverse Event Reporting System (FAERS to characterize their torsadogenic profile; (b we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. METHODS: FAERS data (2004-2010 were analyzed based on the following criteria: (1 ≥ 4 cases of TdP/QT abnormalities; (2 Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers; (3 ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD; (4 Significant ROR for VA/SCD; (5 Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled to group E (unclear/uncertain signal: only 2/5 criteria. Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID. RESULTS: Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone. In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia to 13.99 (France, 2009. Considerable increment of Group A agents was found in several Countries (+3.47 in France: the exposure to olanzapine increased across all Countries (+1.84 in France and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009. Among Group B drugs, levomepromazine peaked 3.78 (Serbia; fluphenazine 1.61 (Slovenia. CONCLUSIONS: This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  18. Late Onset Anorexia Nervosa Treated With Olanzapine: A Case Report

    Paolo Santonastaso


    Full Text Available A case of late onset anorexia nervosa (AN treated with olanzapine is reported. The patient suffered AN onset at the age of 53 and was brought to our attention four years later in a very poor state of health due to extreme starvation and laxative abuse. She presented severe obsessions about food, a very disturbed body image, and “ascetic” rituals of self-punishment. There was no improvement of her symptoms with cognitive behavioural therapy, antidepressant drugs and inpatient nutritional therapy. After the prescription of olanzapine, the patient was more cooperative and able to maintain a stable acceptable weight, although her psychiatric and anorexic symptoms only improved partially.

  19. Current Trends on Antipsychotics: Focus on Asenapine.

    Marazziti, Donatella; Piccinni, Armando; Baroni, Stefano; Mungai, Francesco; Presta, Silvio; Mucci, Federico; Dell'Osso, Liliana


    Over the years, both first- (FGAs) and second-generation antipsychotics (SGAs), continue to gain increasing evidence of being effective in the treatment of psychotic symptoms. Currently, they represent the first-line treatment of schizophrenia and bipolar disorder, although they are widely used in psychotic depression and other clinical conditions, such as agitation and/or behavioural disturbances. Despite representing an indispensable tool for the treatment of severe psychotic disorders, they are widely known to have a number of unwanted side effects that the clinician must be aware of, and handle carefully to provide the patient the best available treatment in the short and long-term. However, even with respect to the long-term use of some of the most effective SGAs, it is imperative for clinicians not to overlook the risk linked to the onset of potentially severe metabolic side effects such as weight gain, dyslipidaemia, insulinresistance and type II diabetes. Asenapine is one of the newest SGAs licenced in Europe for the treatment of manic episodes and in the US for schizophrenia. It belongs to the same class of clozapine, olanzapine and quetiapine, sharing with them a rather complex pharmacological binding profile. In fact, asenapine shows a high affinity for the serotonin (5HT) receptor of the type 2A (5HT2A) and to a lesser extent for the dopamine receptor of the type 2 (D2), similar to other SGAs. Asenapine behaves also as an antagonist at the level of 5HT2C, H1 and α2-receptors. Asenapine has been reported to be effective either in monotherapy or in combination with mood stabilers (lithium and valproate) in the treatment of manic or mixed episodes, with a lower propensity to induce, or being followed by, depressive symptoms, when compared to other SGAs. These unique properties may explain the increasing interest towards the use of this drug in mixed states, besides schizophrenia and acute mania. The aim of this paper was at reviewing current data on

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

    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.

  1. The Effect of Concurrent Administration of Typical or Atypical Antipsychotic Drugs and Lithium on Lithium Ratio in Acute Manic Patients

    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.

  2. Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients.

    Misiak, Błażej; Frydecka, Dorota; Beszłej, Jan A; Moustafa, Ahmed A; Tybura, Piotr; Kucharska-Mazur, Jolanta; Samochowiec, Agnieszka; Bieńkowski, Przemysław; Samochowiec, Jerzy


    We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms. PMID:26836264

  3. Drug: D00454 [KEGG MEDICUS

    Full Text Available D00454 Drug Olanzapine (JAN/USAN/INN); Zyprexa (TN) C17H20N4S 312.1409 312.4325 D00454.gif Antip ... ypical Olanzapine D00454 Olanzapine (JAN/USAN/INN) Bipolar ... Agents Bipolar ... Agents, Other Olanzapine D00454 Ola ...

  4. Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study

    Wani RA


    Full Text Available Rayees Ahmad Wani, Mansoor Ahmad Dar, Rajesh Kumar Chandel, Yasir Hassan Rather, Inaamul Haq, Arshad Hussain, Altaf Ahmad MallaDepartment of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir, IndiaBackground: Patients with schizophrenia suffer high rates of metabolic derangements on some antipsychotic medications that predispose them to cardiovascular diseases. Keeping this fact in mind, we planned this open-label study to see the effect on various metabolic parameters after switching stable schizophrenia subjects, who had developed metabolic syndrome on olanzapine, to aripiprazole.Methods: Sixty-two patients with schizophrenia who were stable on olanzapine and were fulfilling modified National Cholesterol Education Program (NCEP Adult Treatment Panel III (ATP-III criteria for the presence of metabolic syndrome were enrolled on the study. Patients were randomly assigned either to switch to aripiprazole or to stay on olanzapine, on a 1:1 basis. Cross-tapering over a period of 1 month was done while switching patients to aripiprazole. Laboratory assessment for metabolic parameters was done at baseline, 8 weeks, and 24 weeks after enrollment; efficacy assessment was done using the Positive and Negative Syndrome Scale (PANSS at baseline and 24 weeks, the Clinical Global Impressions severity subscale (CGI-S at baseline, and the Clinical Global Impressions improvement subscale (CGI-I at 24 weeks.Results: All parameters of metabolic syndrome (waist circumference, blood pressure, triglyceride level, fasting blood glucose, and high-density lipoprotein cholesterol kept deteriorating in the stay group, compared with a continuous improvement in the switch group over time. At the end of the study, 26 patients (100% from the stay group and 15 patients (42.8% from switch group met the modified NCEP ATP-III criteria for presence of metabolic syndrome (P<0.001. There were no statistically significant differences between groups in

  5. Genetic determinants of antipsychotic drug response

    Gregoor, J.G.


    Since their introduction, the use of antipsychotic drugs has been complicated by adverse effects. While the first generation of antipsychotic agents mainly caused motor side effects, the newer antipsychotic drugs are also associated with metabolic disturbance such as diabetes and obesity. The introd

  6. The Effect of Ranitidine on Olanzapine-Induced Weight Gain

    Fatemeh Ranjbar


    Full Text Available Induced weight gain is a disturbing side effect of Olanzapine that affects the quality of life in psychotic patients. The aim of this study was to assess the efficacy of Ranitidine in attenuating or preventing Olanzapine-induced weight gain. A parallel 2-arm clinical trial was done on 52 patients with schizophrenia, schizoaffective and schizophreniform disorders who received Olanzapine for the first time. All these were first-episode admitted patients. They were randomly allocated to receive either Ranitidine or placebo. The trend of body mass index (BMI was compared between groups over 16-week course of treatment. Mean weight was 62.3 (SD: 9.6 kg at baseline. Thirty-three subjects (63.5% had positive family history of obesity. The average BMI increment was 1.1 for Ranitidine group and 2.4 for the placebo group. The multivariate analysis showed this effect to be independent of sex, family history of obesity, and baseline BMI value. The longitudinal modeling after controlling for baseline values failed to show the whole trend slope to be different. Although the slight change in trend’s slope puts forward a hypothesis that combined use of Ranitidine and Olanzapine may attenuate the weight gain long run, this needs to be retested in future larger scale long-term studies. This trial is registered with 201009112181N5.

  7. QSAR–CoMSIA applied to antipsychotic drugs with their dopamine D2 and serotonine 5HT2A membrane receptors



    Full Text Available Antipsychotic drugs are psychiatric medication primarily used to manage psychosis (e.g., delusions or hallucinations, particularly in schizophrenia and bipolar disorder. First and second generations of antipshychotics tend to block receptors in the brain's dopamine pathways, but antipsychotic drugs encompass a wide range of receptor targets. The inhibition constant, Ki, at the level of membrane receptors is a major determinant of their pharmacokinetic behavior and, consequently, it can affect their antipsychotic activity. Here, predicted inhibition constants, Ki for 71 antipsychotics, already approved for clinical treatment, as well as representative new chemical structures which exhibit antipsychotic activity, were evaluated using 3D-QSAR–CoMSIA models. Significant values of the cross-validated correlation q2 (higher than 0.70 and the fitted correlation r2 (higher than 0.80 revealed that these models have reasonable power to predict the biological affinity of the 15 new risperidone and 12 new olanzapine derivatives in interactions with dopamine D2 and serotonin 5HT2A receptors; these compounds are suggested for further studies.

  8. Anthropometric parameters as indicators of metabolic derangements in schizophrenia patients stabilized on olanzapine in an Indian rural population

    Jayanta Kumar Rout


    Full Text Available Context: For any given body mass, Asian Indians have higher central obesity than Europeans. A periodic measurement of body mass index (BMI and waist hip ratio (WHR is practically more feasible than other parameters of metabolic syndrome by repeated blood collection. However, few studies are available on the relative importance of BMI and WHR as markers of dyslipidemia and insulin resistance in schizophrenia patients stabilized on second generation antipsychotics in Indian population. Aim: We conducted the present study on such patients to examine whether BMI or WHR can better predict dyslipidemia and insulin resistance in these patients in a rural area. Settings and Design: The study was a hospital based case control study under rural settings on 38 schizophrenia patients stabilized on olanzapine and 30 matched controls. Materials and Methods: Fasting concentrations of blood glucose, lipid parameters and serum insulin were assessed. Data for Homeostatic model for assessment of insulin resistance (HOMA-IR, BMI, and WHR were obtained to assess the insulin resistance, overall body fat distribution and abdominal fat dispensation respectively. Statistical analysis used: ′t′ test was performed to assay any difference in corresponding mean values between cases and controls. Dependence of HOMA-IR on key parameters was assessed by analysis of co-variance (ANCOVA study. Results: Cases exhibited significantly higher values for HOMA-IR, serum triglyceride and low density lipoprotein cholesterol (LDLc with a significantly lower high density lipoprotein cholesterol (HDLc level. ANCOVA study reflected that irrespective of age and sex, HOMA-IR was dependent on serum triglyceride level and WHR (F=8.3 and 5.7 respectively, P<0.05, but not on BMI (F<0.001, P=0.997. Conclusions: Central obesity could be more closely associated with the pathogenesis of prediabetic state in our case group. So, WHR is a better anthropometric parameter than BMI for an early

  9. Olanzapine and fluoxetine combination therapy for treatment-resistant depression: review of efficacy, safety, and study design issues

    William V Bobo


    Full Text Available William V Bobo, Richard C SheltonDepartment of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USAAbstract: Treatment-resistant depression (TRD is a common occurrence in clinical practice. Up to 30% of patients with major depression do not respond to conventional antidepressant treatment, while a significantly greater number of patients experience only partial symptom reduction. Numerous strategies may be applied by the practicing clinician to overcome limitations in the effectiveness of antidepressant monotherapy, including combining drug treatment with evidence-supported psychotherapies, combining antidepressants (combination pharmacotherapy, and combining antidepressants with other non-antidepressant psychotropic medications (augmentation treatment. One such augmentation strategy, the combination of the selective serotonin reuptake inhibitor, fluoxetine (FLX, with the atypical antipsychotic drug, olanzapine (OLZ, is supported by the results of four randomized, double-blind, acute phase studies of patients who had responded inadequately to antidepressant monotherapy. In each study, the FLX/OLZ combination caused rapid reduction in Montgomery-Asberg Depression Rating scale scores, with two of the four studies showing significantly greater improvement than antidepressant monotherapy at study endpoint. Effects of the FLX/OLZ combination were strongest in cases where failure to respond to two antidepressants prior to randomization was established during the current depressive episode. The FLX/OLZ combination was well-tolerated; however, body weight gain and increases in prolactin were greater than that of the antidepressant monotherapy groups, and were comparable to that of OLZ monotherapy. While effective during acute-phase treatment, questions remain regarding the long-term efficacy and safety of FLX/OLZ relative to antidepressant monotherapy and other combination strategies. Efforts aimed at determining the placement of

  10. 奥氮平防治化疗相关性呕吐的研究进展%Progression on prevention and treatment of olanzapine in chemotherapy-induced nausea and vomiting

    周冬爱; 易俊(综述); 马进安(审校)


    Chemotherapy⁃induced nausea and vomiting is the most common gastrointestinal reaction of chemotherapy side effects, and also one of the important influential factors in chemotherapy compliance within tumor patients. Olanzapine is a widely⁃used atypical antipsychotics in psychiatric clinical pratice, which also has a ability to block many different antiemetic properties ossociated receptors. In recent years, olanzapine has been approved effectively in the prevention and treatment of chemotherapy⁃induced nausea and vomiting, with little adverse reaction and good tolerance. This paper summarizes the clnical progression on prevention and treatment of olanzapine in chemotherapy induced nausea and vomiting.%化疗所致的恶心呕吐( CINV)是化疗最常见的消化道副作用,也是影响患者化疗依从性的重要原因之一。奥氮平作为一种在精神科已被临床广泛应用的非典型抗精神病药物,具有拮抗多种呕吐相关受体作用,近年被越来越多的研究证实可有效地防治化疗所致的恶心呕吐,且不良反应轻微,耐受性良好。本文综述了近年奥氮平防治CINV的临床研究进展。

  11. Predictors and correlates for weight changes in patients co-treated with olanzapine and weight mitigating agents; a post-hoc analysis

    Heinloth Alexandra N


    Full Text Available Abstract Background This study focuses on exploring the relationship between changes in appetite or eating behaviors and subsequent weight change for adult patients with schizophrenia or bipolar disorder treated with olanzapine and adjunctive potential weight mitigating pharmacotherapy. The aim is not to compare different weight mitigating agents, but to evaluate patients' characteristics and changes in their eating behaviors during treatment. Identification of patient subgroups with different degrees of susceptibility to the effect of weight mitigating agents during olanzapine treatment may aid clinicians in treatment decisions. Methods Data were obtained from 3 randomized, double-blind, placebo-controlled, 16-week clinical trials. Included were 158 patients with schizophrenia or bipolar disorder and a body mass index (BMI ≥ 25 kg/m2 who had received olanzapine treatment in combination with nizatidine (n = 68, sibutramine (n = 42, or amantadine (n = 48. Individual patients were analyzed for categorical weight loss ≥ 2 kg and weight gain ≥ 1 kg. Variables that were evaluated as potential predictors of weight outcomes included baseline patient characteristics, factors of the Eating Inventory, individual items of the Eating Behavior Assessment, and the Visual Analog Scale. Results Predictors/correlates of weight loss ≥ 2 kg included: high baseline BMI, low baseline interest in food, and a decrease from baseline to endpoint in appetite, hunger, or cravings for carbohydrates. Reduced cognitive restraint, increase in hunger, and increased overeating were associated with a higher probability of weight gain ≥ 1 kg. Conclusion The association between weight gain and lack of cognitive restraint in the presence of increased appetite suggests potential benefit of psychoeducational counseling in conjunction with adjunctive pharmacotherapeutic agents in limiting weight gain during antipsychotic drug therapy. Trial Registration This analysis was not

  12. Factors associated with early response to olanzapine and clinical and functional outcomes of early responders treated for schizophrenia in the People’s Republic of China

    Ye W


    Full Text Available Wenyu Ye,1 William Montgomery,2 Zbigniew Kadziola,3 Li Liu,4 Haibo Xue,4 Michael D Stensland,5 Tamas Treuer61Real World Analytics, Eli Lilly and Company, Indianapolis, IN, USA; 2Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Real World Analytics Capabilities, Eli Lilly GmbH, Vienna, Austria; 4Lilly Suzhou Pharmaceutical Co, Ltd, Shanghai Branch, People’s Republic of China; 5Agile Outcomes Research, Inc., Rochester, MN, USA; 6Neuroscience Research, Eli Lilly and Company, Budapest, HungaryBackground: The aims of this analysis were to identify factors associated with early response (at 4 weeks to olanzapine treatment and to assess whether early response is associated with better longer-term outcomes for patients with schizophrenia in the People’s Republic of China.Methods: A post hoc analysis of a multi-country, 6-month, prospective, observational study of outpatients with schizophrenia or bipolar mania who initiated or switched to treatment with oral olanzapine was conducted using data from the Chinese schizophrenia subgroup (n=330. Factors associated with early response were identified using a stepwise logistic regression with baseline clinical characteristics, baseline participation in a weight control program, and adherence with antipsychotics during the first 4 weeks of treatment. Mixed models for repeated measures with baseline covariates were used to compare outcomes over time between early responders and early nonresponders to olanzapine.Results: One hundred and thirty patients (40% achieved an early response. Early response was independently predicted by higher baseline Clinical Global Impressions-Severity score (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.15–1.97, fewer years since first diagnosis (OR 0.94, CI 0.90–0.98, a greater number of social activities (OR 1.22, CI 1.05–1.40, participation in a weight control program (OR 1.81, CI 1.04–3.15, and high adherence


    Ashish Chauhan*, Amit Mittal, Pradeep Kumar Arora


    Full Text Available Mental illness constitutes the second-largest disease burden in the United States. Psychosis is one of the most common and severe mental illnesses. It is an extremely devastating condition characterised by delusions, hallucinations, distortion of thoughts and deteriorating social functioning experiences. Psychosis in all human societies has approximately same incidence of occurrence as in accordance to “anthropo-parity principle.” It has large economic impact on various aspects of cognition, health, and quality of life which has devastated effects on its sufferers and facing them large economic burden. Psychosis (Schizophrenia is associated with an imbalance of the dopaminergic system, entailing hyper-stimulation of dopamine function in the brain, particularly in the mesolimbic pathway. Consequences of antipsychotic treatment are far reaching and expensive. Detrimental extrapyramidal side effects associated with conventional antipsychotics and non-compliance among patients limits long term treatment with conventional antipsychotics. It gives rise to a new class, atypical antipsychotics owning low propensity to cause EPS, efficacy against refractory cases and better control over negative symptoms, better tolerance and compliance along with lower relapse rate and safer adverse effect profile. Atypical antipsychotics have revolutionized the treatment of psychosis, now being the treatment of choice for patients with psychosis. The positive therapeutic experience with the atypical antipsychotics in the treatment of psychosis and their favourable effects outweighs their unfavourable adverse effects. Though atypical antipsychotics are widely prescribed in the treatment of schizophrenia, however not a single atypical antipsychotic drug having any exceptional efficacy and safety profile. Thus, there is still a lot of research needed to be carried out in the development of novel atypical antipsychotics. This review is comprehensive appraisal about

  14. The potential role of appetite in predicting weight changes during treatment with olanzapine

    Case Michael


    Full Text Available Abstract Background Clinically significant weight gain has been reported during treatment with atypical antipsychotics. It has been suggested that weight changes in patients treated with olanzapine may be associated with increased appetite. Methods Data were used from adult patients for whom both appetite and weight data were available from 4 prospective, 12- to 24-week clinical trials. Patients' appetites were assessed with Eating Behavior Assessment (EBA, Study 1, Platypus Appetite Rating Scale (PARS, Study 2, Eating Inventory (EI, Study 3, Food Craving Inventory (FCI, Study 3, and Eating Attitude Scale (EAS, Study 4. Results In Studies 1 (EBA and 4 (EAS, patients who reported overall score increases on appetite scales, indicating an increase in appetite, experienced the greatest overall weight gains. However, in Studies 2 (PARS and 3 (EI, FCI, patients who reported overall score increases on appetite scales did not experience greater weight changes than patients not reporting score increases. Early weight changes (2-4 weeks were more positively correlated with overall weight changes than early or overall score changes on any utilized appetite assessment scale. No additional information was gained by adding early appetite change to early weight change in correlation to overall weight change. Conclusions Early weight changes may be a more useful predictor for long-term weight changes than early score changes on appetite assessment scales. Clinical Trials Registration This report represents secondary analyses of 4 clinical studies. Studies 1, 2, and 3 were registered at, under NCT00190749, NCT00303602, and NCT00401973, respectively. Study 4 predates the registration requirements for observational studies that are not classified as category 1 observational studies.

  15. Hypomania after augmenting venlafaxine and olanzapine with sarcosine in a patient with schizophrenia: a case study

    Strzelecki D


    Full Text Available Dominik Strzelecki, Justyna Szyburska, Magdalena Kotlicka-Antczak, Olga KałużyńskaDepartment of Affective and Psychotic Disorders, Medical University of Lódz, Central Clinical Hospital, Lódz, PolandAbstract: Glutamate is the main excitatory neurotransmitter in the central nervous system. Dysfunction of the glutamatergic system plays an important and well-established role in the pathogenesis of schizophrenia. Agents with glutamatergic properties such as N-methyl-D-aspartate receptor coagonists (ie, glycine, D-cycloserine and glycine transporter type 1 inhibitors (eg, sarcosine, bitopertin are investigated in schizophrenia with special focus on negative and cognitive symptomatology. In this article, we describe a case of a 34-year-old woman with diagnosis of schizophrenia with persistent moderate negative and cognitive symptoms, a participant of the Polish Sarcosine Study (PULSAR treated with olanzapine (25 mg per day and venlafaxine (75 mg per day. During ten weeks of sarcosine administration (2 g per day the patient’s activity and mood improved, but in the following 2 weeks, the patient reported decreased need for sleep, elevated mood, libido and general activity. We diagnosed drug-induced hypomania and recommended decreasing the daily dose of venlafaxine to 37.5 mg per day, which resulted in normalization of mood and activity in about 1 week. After this change, activity and mood remained stable and better than before adding sarcosine, and subsequent depressive symptoms were not noted. We describe here the second case report where sarcosine induced important affect changes when added to antidepressive and antipsychotic treatment, which supports the hypothesis of clinically important glutamate–serotonin interaction.Keywords: MNDA receptor, glutamatergic system, serotoninergic system

  16. Effect of short and long-term treatment with antipsychotics on orexigenic/anorexigenic neuropeptides expression in the rat hypothalamus.

    Rojczyk, Ewa; Pałasz, Artur; Wiaderkiewicz, Ryszard


    Among numerous side effects of antipsychotic drugs (neuroleptics), one of the leading problems is a significant weight gain caused by disturbances in energy homeostasis. The hypothalamus is considered an important target for neuroleptics and contains some neuronal circuits responsible for food intake regulation, so we decided to study which hypothalamic signaling pathways connected with energy balance control are modified by antipsychotic drugs of different generations. We created an expression profile of different neuropeptides after single-dose and chronic neuroleptic administration. Experiments were carried out on adult male Sprague-Dawley rats injected intraperitoneally for 1 day or for 28 days by three neuroleptics: olanzapine, chlorpromazine and haloperidol. Hypothalami were isolated in order to perform PCR reactions and also whole brains were sliced for immunohistochemical analysis. We assessed the expression of orexigenic/anorexigenic neuropeptides and their receptors--neuropeptide Y (NPY), NPY receptor type 1 (Y1R), preproorexin (PPOX), orexin A, orexin receptor type 1 (OX1R) and 2 (OX2R), nucleobindin 2 (NUCB2), nesfatin-1, proopiomelanocortin (POMC), alpha-melanotropin (α-MSH) and melanocortin receptor type 4 (MC4R)--both on the mRNA and protein levels. We have shown that antipsychotics of different generations administered chronically have the ability to upregulate PPOX, orexin A and Y1R expression with little or no effect on orexigenic receptors (OX1R, OX2R) and NPY. Interestingly, antipsychotics also increased the level of some anorexigenic factors (POMC, α-MSH and MC4R), but at the same time strongly downregulated NUCB2 and nesfatin-1 signaling--a newly discovered neuropeptide known as a food-intake inhibiting factor. Our results may contribute to a better understanding of mechanisms responsible for antipsychotics' side effects. They also underline the complex nature of interactions between classical monoamine receptors and hypothalamic peptidergic

  17. Late Onset Anorexia Nervosa Treated With Olanzapine: A Case Report

    Paolo Santonastaso; Arianna Camporese; Lorenza Caregaro; Angela Favaro


    A case of late onset anorexia nervosa (AN) treated with olanzapine is reported. The patient suffered AN onset at the age of 53 and was brought to our attention four years later in a very poor state of health due to extreme starvation and laxative abuse. She presented severe obsessions about food, a very disturbed body image, and “ascetic” rituals of self-punishment. There was no improvement of her symptoms with cognitive behavioural therapy, antidepressant drugs and inpatient nutritional ther...

  18. Olanzapine versus Placebo in Adolescents with Schizophrenia; a 6-Week, Randomized Double-Blind, Placebo-Controlled Trial

    Kryzhanovskaya, Ludmila; Schulz, Charles; McDougle, Christopher; Frazier, Jean; Dittman, Ralf; Robertson-Plouch, Carol; Bauer, Theresa; Xu, Wen; Wang, Wei; Carlson, Janice; Tohen, Mauricio


    The efficacy of olanzapine in treating schizophrenia was tested through a placebo-controlled trial involving one hundred seven inpatient and outpatients adolescents. Patients who took olanzapine experienced significant symptom improvement.

  19. Asenapine in the treatment of borderline personality disorder: an atypical antipsychotic alternative.

    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

  20. Recent evidence and potential mechanisms underlying weight gain and insulin resistance due to atypical antipsychotics

    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.

  1. The reproductive safety profile of mood stabilizers, atypical antipsychotics, and broad-spectrum psychotropics.

    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

  2. Determination of olanzapine by spectrophotometry using permanganate

    Nagaraju Rajendraprasad


    Full Text Available Two new spectrophotometric methods using permanganate as the oxidimetric reagent for the determination of olanzapine (OLP were developed and validated as per the current ICH guidelines. The methods involved the addition of known excess of permanganate to OLP in either acid or alkaline medium followed by the determination of unreacted permanganate at 550 nm (method A or bluish-green color of manganate at 610 nm (method B. The decrease in absorbance in method A or increase in absorbance in method B as a function of concentration of OLP was measured and related to OLP concentration. Under optimized conditions, Beer's law was obeyed over the ranges 2.0 to 20 and 1.0 to 10 μg mL-1 in method A and method B, respectively. The calculated molar absorptivity values were 1.34 x 10(4 and 2.54 x 10(4 l mol-1cm-1 for method A and method B respectively, and the respective Sandell sensitivities were 0.0233 and 0.0123 μg cm-2. The LOD and LOQ for method A were calculated to be 0.37 and 1.13 μg mL-1and the corresponding values for method B were 0.16 and 0.48 μg mL-1. Intermediate precision, expressed as RSD was in the range 0.51 to 2.66 %, and accuracy, expressed as relative error ranged from 0.79 to 2.24 %. The proposed methods were successfully applied to the assay of OLP in commercial tablets with mean percentage recoveries of 102 ±1.59 % (method A and 101 ±1.53 % (method B. The accuracy and reliability of the methods were further confirmed by performing recovery tests via standard addition procedure.Dois métodos espectrofotométricos novos, usando o permanganato como o reagente oxidimétrico para a determinação da olanzapina (OLP foram utilizados e validados de acordo com as diretrizes atuais do ICH. Os métodos envolveram a adição de excesso conhecido de permanganato à OLP em meio ácido ou alcalino, determinando-se o permanganato que não reagiu em 550 nm (método A, ou pela cor verde-azulada do manganato a 610 nm (método B. A diminuição da

  3. Retrospective Study of Olanzapine in Depressive and Anxious States in Primary Care

    Jackson, W. Clay; Manning, J. Sloan; Connor, Pamela D.; Deardorff, O. Greg


    Context: Bipolar spectrum and treatment-resistant unipolar mood disorders are increasingly identified in primary care settings. Olanzapine demonstrates efficacy in the treatment of acute mania and bipolar depression and in bipolar maintenance therapy. Olanzapine-fluoxetine combination therapy shows efficacy in treatment-resistant depression.

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

    Evers, Simon S; van Vliet, André; van Vugt, Barbara; Scheurink, Anton J W; van Dijk, Gertjan


    Second generation antipsychotics, like olanzapine (OLZ), have become the first line drug treatment for patients with schizophrenia. However, OLZ treatment is often associated with body weight (BW) gain and metabolic derangements. Therefore, the search for prospective markers for OLZ's negative side effects as well as adjunctive treatments to inhibit these has been of major interest. The aim of this study was to investigate in healthy male volunteers (age: 36 ± 11 years; BW: 84 ± 12 kg; BMI=25.5 ± 2.5) whether adjunctive topiramate (TPM) administration opposes OLZ-induced weight gain over the course of 14 days treatment. In addition, we investigated behavioral, endocrine and metabolic characteristics as underlying and potentially predictive factors for weight regulation and/or metabolic derangements associated with OLZ and TPM treatment. While adjunctive TPM indeed reduced OLZ-induced weight gain (Phormones revealed that individuals with a low plasma TSH profile were also those that were most sensitive to adjunctive TPM treatment blocking OLZ-induced ΔBW gain. Others have shown that OLZ-induced BW gain is associated with improvement in brief psychiatric rating scores (BPRS); adjunctive TPM treatment may be a solution specifically for those subjects susceptible to OLZ-induced rapid weight gain who-on a therapeutic level-benefit most of OLZ treatment. PMID:26802597

  5. A placebo controlled trial on add-on modafinil on the anti-psychotic treatment emergent hyperglycemia and hyperlipidemia

    Pathapati Lakshmi Prasuna


    Full Text Available Modafinil is non stimulant drug which is marketed for mainly Narcolepsy and daytime drowsiness. The clinical experience and Summary of Product Characteristics (SPC of the drug also mentions Anorexia as one of the side effects. Anorexia can have a direct impact on the carbohydrate and fat intake, which may, in turn, regulate antipsychotic induced dyslipidemia and Hyperglycaemia. Aim: To compare the effects of Modafinil- ADDON with Placebo add on with olanzapine, Clozapine and Risperidone in drug naive subjects and people who were started on the drugs within 15days of assessment. Materials and Methods: Randomized, Double blind, Placebo controlled study, which was conducted at two centres, one at department of Psychiatry, S.V Medical College, Tirupati and the other at Asha hospitals, Hyderabad. Seventy two patient were randomised, sixty three patients have completed the total study period of three months.The dose of Modafinil was 200 mgs constantly as Flexible doses of Olanzapine, Clozapine and Risperidone as per clinical need was given. A baseline, three week and twelve week assessments of Fasting blood Glucose and fasting Serum cholesterol were made and the groups were compared on these parameters. Results: From baseline to week 3 there was a significant raise in Fasting serum cholesterol followed by a fall from week 3 to week 12 in the Modafinil addon group, though it could not be considered a drug for hypercholesteremia like Statins in controlling hyperlipidaemia. The implications of these findings were discussed.

  6. Reversal of evoked gamma oscillation deficits is predictive of antipsychotic activity with a unique profile for clozapine.

    Hudson, M R; Rind, G; O'Brien, T J; Jones, N C


    Recent heuristic models of schizophrenia propose that abnormalities in the gamma frequency cerebral oscillations may be closely tied to the pathophysiology of the disorder, with hypofunction of N-methyl-d-aspartate receptors (NMDAr) implicated as having a crucial role. Prepulse inhibition (PPI) is a behavioural measure of sensorimotor gating that is disrupted in schizophrenia. We tested the ability for antipsychotic drugs with diverse pharmacological actions to (1) ameliorate NMDAr antagonist-induced disruptions to gamma oscillations and (2) attenuate NMDAr antagonist-induced disruptions to PPI. We hypothesized that antipsychotic-mediated improvement of PPI deficits would be accompanied by a normalization of gamma oscillatory activity. Wistar rats were implanted with extradural electrodes to facilitate recording of electroencephalogram during PPI behavioural testing. In each session, the rats were administered haloperidol (0.25 mg kg(-1)), clozapine (5 mg kg(-1)), olanzapine (5 mg kg(-1)), LY379268 (3 mg kg(-1)), NFPS (sarcosine, 1 mg kg(-1)), d-serine (1800 mg kg(-1)) or vehicle, followed by the NMDAr antagonists MK-801(0.16 mg kg(-1)), ketamine (5 mg kg(-1)) or vehicle. Outcome measures were auditory-evoked, as well as ongoing, gamma oscillations and PPI. Although treatment with all the clinically validated antipsychotic drugs reduced ongoing gamma oscillations, clozapine was the only compound that prevented the sensory-evoked gamma deficit produced by ketamine and MK-801. In addition, clozapine was also the only antipsychotic that attenuated the disruption to PPI produced by the NMDAr antagonists. We conclude that disruptions to evoked, but not ongoing, gamma oscillations caused by NMDAr antagonists are functionally relevant, and suggest that compounds, which restore sensory-evoked gamma oscillations may improve sensory processing in patients with schizophrenia. PMID:27093066

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

    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

  8. Profile of olanzapine long-acting injection for the maintenance treatment of adult patients with schizophrenia

    Rosaria Di Lorenzo


    Full Text Available Rosaria Di Lorenzo1, Alice Brogli21Department of Mental Health, AUSL-MODENA, Presidio Psichiatrico di Diagnosi e Cura 1, NOCSAE, Baggiovara, Modena, Italy; 2School of Specialization in Psychiatry, University of Modena e Reggio Emilia, Modena, ItalyAbstract: Olanzapine long-acting injection (OLAI is a crystalline salt composed of olanzapine and pamoic acid, which permits a depot intramuscular formulation of olanzapine. The half-life of olanzapine pamoate is 30 days, and its steady state is reached approximately at 12 weeks. Oral supplementation of olanzapine is not required during OLAI initiation, according to Eli Lilly recommendations, although a study indicated that ≥60% of D2 receptor occupancy was reached only by the fifth injection cycle. To date, a short-term, placebo-controlled study of 8 weeks in acutely ill patients and a long-term, controlled trial of 24 weeks in stabilized patients have been conducted. In both the studies, efficacy and safety were similar to those of oral olanzapine, with the exception of an acute adverse effect, the so-called inadvertent intravascular injection event, which occurred 1–3 hours after the injection with an incidence rate of 0.07% per injection. It consisted of symptoms that are similar to those reported in cases of oral olanzapine overdose. The most significant studies published to date, on the use of olanzapine pamoate in schizophrenia, are reviewed in this article. The pharmacodynamic and pharmacokinetic profile and related side effects of OLAI are reported.Keywords: olanzapine pamoate long-acting injection, efficacy, safety

  9. Metabolic syndrome and obesity among users of second generation antipsychotics: A global challenge for modern psychopharmacology.

    Rojo, Leonel E; Gaspar, Pablo A; Silva, H; Risco, L; Arena, Pamela; Cubillos-Robles, Karen; Jara, Belen


    Second generation antipsychotics (SGAs), such as clozapine, olanzapine, risperidone and quetiapine, are among the most effective therapies to stabilize symptoms schizophrenia (SZ) spectrum disorders. In fact, clozapine, olanzapine and risperidone have improved the quality of life of billions SZ patients worldwide. Based on the broad spectrum of efficacy and low risk of extrapyramidal symptoms displayed by SGAs, some regulatory agencies approved the use of SGAs in non-schizophrenic adults, children and adolescents suffering from a range of neuropsychiatric disorders. However, increasing number of reports have shown that SGAs are strongly associated with accelerated weight gain, insulin resistance, diabetes, dyslipidemia, and increased cardiovascular risk. These metabolic alterations can develop in as short as six months after the initiation of pharmacotherapy, which is now a controversial fact in public disclosure. Although the percentage of schizophrenic patients, the main target group of SGAs, is estimated in only 1% of the population, during the past ten years there was an exponential increase in the number of SGAs users, including millions of non-SZ patients. The scientific bases of SGAs metabolic side effects are not yet elucidated, but the evidence shows that the activation of transcriptional factor SRBP1c, the D1/D2 dopamine, GABA2 and 5HT neurotransmitions are implicated in the SGAs cardiovascular toxicity. Polypharmacological interventions are either non- or modestly effective in maintaining low cardiovascular risk in SGAs users. In this review we critically discuss the clinical and molecular evidence on metabolic alterations induced by SGAs, the evidence on the efficacy of classical antidiabetic drugs and the emerging concept of antidiabetic polyphenols as potential coadjutants in SGA-induced metabolic disorders. PMID:26218604

  10. Quality of life in patients with schizophrenia: the impact of socio-economic factors and adverse effects of atypical antipsychotics drugs.

    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

  11. Developments in antipsychotic drugs - an update.

    Reynolds, G P


    Antipsychotic drug research has recently made much progress. Over the past two years several new drugs have been introduced for the treatment of schizophrenia and more compounds are shortly to be released. Pharmacological studies, improved behavioural models and modern imaging techniques have all contributed to a better understanding of the mechanisms of antipsychotic drug action. Some of the developments that have been made over the past year are reviewed here. PMID:15991957

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

    Vik-Mo Audun O


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

  13. Microtitrimetric determination of a drug content of pharmaceuticals containing olanzapine in non-aqueous medium



    Two simple, rapid, reliable and cost-effective methods based on titrimetry in non-aqueous medium are described for the determination of olanzapine in pharmaceuticals. In these methods, the drug dissolved in the glacial acetic acid was titrated with the acetous perchloric acid with visual and potentiometric end point detection, crystal violet being used as the indicator for visual titration. The methods are applicable over 1-15 mg range of olanzapine. The procedures were applied to determine o...

  14. Quality of Life and Hormonal, Biochemical, and Anthropometric Profile Between Olanzapine and Risperidone Users.

    de Araújo, Aurigena Antunes; Ribeiro, Susana Barbosa; Dos Santos, Ana Cely Souza; Lemos, Telma Maria Araújo Moura; Medeiros, Caroline Addison Xavier; Guerra, Gerlane Coelho Bernardo; de Araújo Júnior, Raimundo Fernandes; Serrano-Blanco, Antoni; Rubio-Valera, Maria


    This cross-sectional study compared quality of life and side effects in 108 users of olanzapine or risperidone suffering schizophrenia and being attended at psychiatric ambulatory services in Rio Grande do Norte, Brazil. Economic, socio-demographic, anthropometric, biochemical, and hormonal variables were compared. The EuroQoL Five-Dimension Scale (EQ-5D) was used to evaluate quality of life, 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 %.The household incomes of approximately 80 % of patients were <2.0 minimum wages ($678). Anthropometric variables (waist circumference, hip circumference, weight, waist-to-hip ratio) and systolic and diastolic blood pressure were noted among male olanzapine users (all p < 0.05). EQ-5D scores showed that olanzapine use significantly impacted self-help ability (p < 0.001). Risperidone users had a mean quality-adjusted life year value of 1. Mean total Simpson-Angus Scale scores was 0.38 for olanzapine users and 0.11 for risperidone users (p < 0.02). Significant differences in UKU were observed for the following items: asthenia/lassitude/fatigue (higher among olanzapine users, p = 0.02), dystonia (higher among olanzapine users, p = 0.01), tremors (higher among olanzapine users, p = 0.03), gynecomastia (higher among risperidone users, p < 0.02), and ejaculatory dysfunction (higher among risperidone users, p < 0.02). Olanzapine users had impaired quality of life, which can be explained in part by adverse motor, biochemical, and hormonal effects characteristic of metabolic syndrome. PMID:26220635

  15. Effect of Early Intervention with Omega-3 on Insulin Resistance in Patients Initiated on Olanzapine with either Sodium Valproate or Lithium: A randomized, Double-blind, Placebo-Controlled Trial

    Vandad Sharifi


    Full Text Available "n  "n  "n  "n "n "nObjective: Metabolic side effects of the second generation (atypical antipsychotics have been a forefront of attention since their availability. One common concern is the development of hyperglycemia and insulin resistance. The aim of this study was to evaluate the effect of early initiation of omega-3 fatty acids supplementation on glucose-insulin homeostasis in a group of psychiatric patients under treatment with olanzapine and sodium valproate or lithium combination. "nMethod: In a double-blind design, eligible participants with schizophrenia, bipolar I, and schizoaffective disorders who were initiated on olanzapine combination with sodium valproate or lithium were randomly assigned to receive omega-3 or identical placebo capsules for 6 weeks. Fasting blood sugar (FBS, insulin and HbA1c were measured at the baseline and at the end of the 6th week. Homeostatic model assessment of insulin resistance (HOMA-IR, as a measure of insulin resistance, was also determined at the same times. "nResults: At the end of the study, no significant difference was observed between the two arms in terms of FBS, fasting insulin, HbA1c and HOMA-IR. However, trends toward decreasing both fasting insulin levels (p= 0.06 and HOMA-IR (p= 0.07 were noted in the group receiving omega-3. No significant changes in the outcome variables were observed from the baseline to the final measurements in both groups. "nConclusion: This study noted that adding omega-3 fatty acids at the commencement of olanzapine combination therapy with valproate or lithium could not favorably influence glucose-insulin homeostasis. However, trends toward a decrease in insulin levels (p= 0.06 and HOMA-IR (p= 0.07 observed in patients receiving omega-3 suggest a possible beneficial role of this supplement in this population and, therefore, warrant further evaluation.

  16. Comparision of the Efficacy of Two Combinations;Sodium Valproate with Lithium & Sodium Valproate with Olanzapine in Treatment of Acute Mania

    S Amanat


    Full Text Available Introduction: Acute mania is a psychiatric emergency state that often requires rapid management. There are many different therapeutic protocols for this emergent situation. One of them is combination of moodstabilizers and antipsychotics. Olanzapine which is now available in our country can be used for this purpose. Methods and Materials: In this study, we compared the effectiveness, rapidity of response and side effects of sodium valproate plus olanzapine (group I with sodium valproate plus lithium (group II in acutely manic or mixed bipolar patients. In this randomized, double blind, parallel group study, 44 acutely manic or mixed patients according to DSM IV-TR criteria were randomly assigned to receive combinations of sodium valproate (20mg/kg per day with either olanzapine (5-15mg/day or lithium (900mg/day during a ten-day course. Efficacy was measured with Young Mania Rating Scale (YMRS. Effectiveness measures included YMRS response (YMRS reduction ³ 50% and YMRS remission (YMRS<=12. Data was entered in SPSS11 software program and analyzed by Mann-Whitney, Fisher exact test and Wilcoxon tests (P-values < 0.05 were significant. Results: Total number of patients were 44 (mean age 27.18±7.34, 21 in group I and 23 in group II. Response rate was 85.7% (18 patients and 73.9% (17 patients in group I and II, respectively; with no significant differences between the two groups(P=0.33. Remission rate was 42.9 %(9 patients and 43.5% (10 patients in group I and II, respectively; with no significant differences between two groups(P=0.97. The reduction in total scores in YMRS on the 2nd, 7th and 10th days of study were significant in both groups (P<0.05, but the rapidity of response was similar. The rates of adverse effects between two groups were not statistically significant. Conclusion: Both combinations of drugs were effective in acutely manic or mixed patients. Both treatments were safe and well tolerated

  17. Betahistine decreases olanzapine-induced weight gain and somnolence in humans.

    Barak, Nir; Beck, Yaffa; Albeck, Joseph H


    Olanzapine's efficacy in schizophrenia is attributed to antagonism of dopamine and serotonin receptors. Olanzapine is also a potent histamine-H1 antagonist that results in weight gain and somnolence. Betahistine is a centrally acting histamine-H1 agonist, and therefore may reduce olanzapine's effect on histamine receptors in the brain. Olanzapine's high affinity for the histamine-H1 receptor warrants the use of high doses of betahistine. Forty-eight healthy women were recruited and randomized to receive either betahistine 144 mg/day or matching placebo for 4 weeks. Due to the high dose of betahistine, olanzapine was started only on the second week and titrated up to 10 mg/day, and co-administration continued for an additional 2 weeks. Only nominal differences in adverse events were noted between the treatment groups. Betahistine caused a 37% reduction in mean weight gain (1.24 kg in the betahistine arm vs. 1.93 kg in the placebo arm; p=.049) and 60% reduction in the mean increase in daytime Epworth sleepiness scores (1.82 units in the betahistine group vs. 3.57 units in the placebo group; p=.042). The present study suggests that betahistine-olanzapine co-administration, in healthy female subjects, yields an acceptable safety profile with mitigation of weight gain and somnolence. This should be further tested in a patient cohort. PMID:26839321

  18. An In Vitro Analysis of Disintegration Times of Different Formulations of Olanzapine Orodispersible Tablet: A Preliminary Report

    Hobbs, David; Karagianis, Jamie; Treuer, Tamas; Raskin, Joel


    Background Orodispersible tablets (ODTs) are tablet or wafer forms of medication that disintegrate in the mouth, aided only by saliva. ODTs rely on different fast dissolve/disintegration manufacturing technologies. Objectives Disintegration time differences for several olanzapine ODT forms were investigated. Risperdal M-Tab® was included as a non-olanzapine ODT comparator. Research Design and Methods Eleven olanzapine ODT examples and orodispersible risperidone strengths were evaluated in vit...

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

    Tomiki eSumiyoshi


    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.

  20. First Episode Schizophrenia Regional Cerebral Blood Flow Assessment after Atypical Antipsychotics

    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)

  1. Anticonvulsivantes e antipsicóticos no tratamento do transtorno bipolar Anticonvulsants and antipsychotics in the treatment of Bipolar Disorder

    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

  2. Newer antipsychotics and the rabbit syndrome

    Masalehdan Azadeh


    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.

  3. Antipsychotic drug-induced hematologic disorders

    Theocharis Kyziridis


    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.

  4. A fatal intoxication related to MDPV and pentedrone combined with antipsychotic and antidepressant substances in Cyprus.

    Liveri, Katerina; Constantinou, Maria A; Afxentiou, Maria; Kanari, Popi


    This is a case report of a fatal intoxication in Cyprus related to 3,4-methylenedioxypyrovalerone (MDPV) and 2-(methylamino)-1-phenylpentan-1-one (pentedrone) intake combined with antipsychotic and antidepressant substances. A 42- year old man with a history of serious psychiatric illness was found unresponsive in his bed. Seized materials were also found close to his body. The forensic autopsy reported myocardial infarction due to multidrug intoxication. Toxicology screening in blood and urine was applied. Biological specimens were analysed by enzyme immunoassay procedure and GC/MS. MDPV, pentedrone and etizolam detected and quantitated in blood and urine. Other drugs quantitated in blood were also olanzapine, mirtazapine, and ephedrine. This was the first fatal case reported in Cyprus associated with new psychoactive substances. Additionally, this was the first case reported to Early Warning System of the European Monitoring Center of Drugs and Drug Abuse (EMCDDA), related to multidrug intoxication, attributed to the consumption of cathinones, designer benzodiazepines, and other drugs. PMID:26930452

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

    Alkhadhari S


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

  6. Stability-indicating simultaneous HPTLC method for olanzapine and fluoxetine in combined tablet dosage form

    Shah C


    Full Text Available A rapid, selective and stability-indicating high performance thin layer chromatographic method was developed and validated for the simultaneous estimation of olanzapine and fluoxetine in combined tablet dosage form. Olanzapine and fluoxetine were chromatographed on silica gel 60 F 254 TLC plate using methanol:toluene (4:2 v/v as the mobile phase and spectrodensitometric scanning-integration was performed at a wavelength of 233 nm using a Camag TLC Scanner III. This system was found to give compact spots for both olanzapine (R f value of 0.63±0.01 and fluoxetine (R f value of 0.31±0.01. The polynomial regression data for the calibration plots showed good linear relationship with r 2 =0.9995 in the concentration range of 100-800 ng/spot for olanzapine and 1000-8000 ng/spot for fluoxetine with r 2 =0.9991. The method was validated in terms of linearity, accuracy, precision, recovery and specificity. The limit of detection and the limit of quantification for the olanzapine were found to be 30 and 100 ng/spot, respectively and for fluoxetine 300 and 1000 ng/spot, respectively. Olanzapine and fluoxetine were degraded under acidic, basic and oxidation degradation conditions which showed all the peaks of degraded product were well resolved from the active pharmaceutical ingredient. Both drugs were not further degraded after thermal and photochemical degradation. The method was found to be reproducible and selective for the simultaneous estimation of olanzapine and fluoxetine. As the method could effectively separate the drugs from their degradation products, it can be employed as a stability-indicating method.

  7. Commentary on strategies for switching antipsychotics

    Leucht Stefan


    Full Text Available Abstract Both the new generation of antipsychotics and the more traditional antipsychotic drugs produce an important and meaningful improvement in patients with schizophrenia, but most patients are neither cured nor free of symptoms. As a consequence, it is common to switch from one drug to another in the hope of obtaining a better response. All antipsychotic drugs produce some side effects, so switching can also be a tolerance issue. There are reports in the literature on the tactics of switching: abrupt discontinuation, cross tapering, starting a patient on a new drug while continuing with the old drug until the new drug has reached a steady state, or some variation on these tactics. In this issue, Ganguli et al. have carried out a randomized switching study, the data from which indicates the tactics that might be optimal. We put this paper into context, provide a critique and describe indications for switching.

  8. Benzisoxazole derivatives as Atypical Antipsychotic drugs: A Review

    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.

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

    Montemagni C


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

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

    Pouzet, B; Mow, T; Kreilgaard, Mads; Velschow, S


    Several clinical reports have demonstrated that most antipsychotics of the new generation, but not the typical antipsychotic haloperidol, induce weight gain in schizophrenic patients. Since weight gain induces serious health complications in humans, it is crucial to test upcoming antipsychotic co...

  11. Antipsychotic Potentials of Ocimum sanctum Leaves

    Renu Kadian


    Full Text Available The present study was undertaken to evaluate the antipsychotic potential of Ocimum sanctum in experimental animal models. Male Wistar rats (180-220 g and albino mice (25-30 g were used for the study. The antipsychotic effect of the Ocimum sanctum was evaluated on haloperidol induced catalepsy, cooks pole climbing apparatus, locomotor activity on actophotometer, ketamine induced stereotype behavior. Different groups of rats were fed orally with a specially prepared diet containing various concentrations (2% w/w, 4% w/w and 8% w/w of Ocimum sanctum leaves paste (OCLP for 15 consecutive days. Further, the biochemical estimations were done by estimating brain dopamine levels. The OCLP produced significant dose dependent potentiation of haloperidol (1mg/kg, i.p. induced catalepsy in rats, significantly increased the time taken by the rat to climb the pole in dose dependent manner, significantly decreased the locomotor activity. The OCLP significantly decreased ketamine (50 mg/kg, i.p. induced stereotyped behavior in a dose dependent manner. Ocimum sanctum leaves paste (OCLP significantly decreased the brain dopamine levels. The results suggest that OCLP posse’s antipsychotic activity. Further neurochemical investigation can explore the mechanism of action of the plant drug with respect to anti-dopaminergic functions and help to establish the plant as an antipsychotic agent.

  12. [Therapy of dementia with antipsychotics and antidepressives].

    Frölich, L; Hausner, L


    In dementia depressive symptoms, anxiety, hallucinations and delusions often occur and are accompanied by unspecific behavioral changes. A targeted pharmacotherapy is complicated by the underlying cognitive impairment and physical comorbidities. The current review focusses on recent evidence on the use of antidepressives and antipsychotics for psychotic disturbances, agitation and depression in dementia and analyzes currently published randomized controlled clinical trials and meta-analyses. The evidence on the use of antipsychotics for different indications favors risperidone, with lower evidence levels for quetiapine and aripiprazole, whereas haloperidol should be avoided. Increased mortality and the risk of cerebrovascular events due to antipsychotics are of major concern. With respect to antidepressives, the benefit of antidepressive pharmacotherapy in dementia is critically discussed because of limited efficacy and increased side effects; however, selective serotonin reuptake inhibitors (SSRI), such as citalopram and sertraline have demonstrated efficacy on neuropsychiatric behavioral symptoms in general. These conclusions on the risk-benefit ratio of antidepressives and antipsychotics in dementia are in accordance with the recommendations of the German Society of Neurology and German Association for Psychiatry, Psychotherapy and Psychosomatics (DGN/DGPPN) S3 guidelines on the treatment of dementia. PMID:25787724

  13. The Survey and the Analysis of the Antipsychotic Drug Use in A Hospital during 2011~2013%某院2011~2013年抗精神病药使用调查分析

    黎伟金; 黄焕麟; 吴海峰


    Objietive:To understand the development trend and clinical drug use of antipsychotic drugs in A hospital for formulating the basic drug list and promoting clinical rational drug use. Methods:With the retrospective method,we analyzed the antipsychotic drug sales in A hospital during 2011~2013 by Defined Daily Dose(DDDs) and Defined Daily Dose Consumption(DDDc). Results:The Institute of the antipsychotic drug sales amount and the frequency of drug use overall shows ascendant trend. The typical antipsychotic DDDs overall decreased year by year.The atypical antipsychotic DDDs increased year by year. Risperidone and Olanzapine were more than 65%of the amount of the antipsychotic drug sales. Typical antipsychotics such as Perphenazine and Sulpiride had patients welcome.Conclusions:The cost of drugs in A hospital grows steadily and the clinical use of antipsychotic is reasonable.%目的:了解本院抗精神病药的使用情况及临床用药的发展趋势,为制订基本用药目录,促进临床合理用药提供参考。方法:采用回顾性方法,对本院2011~2013年度抗精神病药的销售金额、用药频度(DDDs)和日均费用(DDDc)等情况进行统计分析。结果:本院抗精神病药销售金额和用药频率整体呈逐年上升趋势,典型抗精神病药用药频度整体逐年下降。非典型抗精神病药用药频度整体逐年上升。其中利培酮和奥氮平占抗精神病药销售金额的65%以上,典型抗精神病药奋乃静、舒必利仍受到患者的欢迎。结论:我院药品费用增长平稳,临床抗精神病药使用合理。

  14. Microtitrimetric determination of a drug content of pharmaceuticals containing olanzapine in non-aqueous medium



    Full Text Available Two simple, rapid, reliable and cost-effective methods based on titrimetry in non-aqueous medium are described for the determination of olanzapine in pharmaceuticals. In these methods, the drug dissolved in the glacial acetic acid was titrated with the acetous perchloric acid with visual and potentiometric end point detection, crystal violet being used as the indicator for visual titration. The methods are applicable over 1-15 mg range of olanzapine. The procedures were applied to determine olanzapine in pharmaceutical products and the results were found to be in a good agreement with those obtained by the reference method. Associated pharmaceutical materials did not interfere. The precision results, expressed by inter-day and intra-day relative standard deviation values, were satisfactory, higher than 2%. The accuracy was satisfactory as well. The methods proved to be suitable for the analysis of olanzapine in bulk drug and in tablets. The accuracy and reliability of the methods were further ascertained by recovery studies via a standard addition technique with percent recoveries in the range 97.51-103.7% with a standard deviation of less than 2%.

  15. Translation of randomised controlled trial findings into clinical practice: comparison of olanzapine and valproate in the EMBLEM study

    Novick, D; Gonzalez-Pinto, A; Haro, J M;


    Medication) was a 2-year, prospective, observational study of health outcomes associated with the treatment of mania. Severity of mania and depression were assessed at baseline and 6 weeks using the YMRS and the 5-item version of the HAMD, respectively. RESULTS: 621 patients were analysed (n=107 valproate, n......=514 olanzapine). Both groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with greater mean improvements in the olanzapine compared with the valproate group. Olanzapine was associated with more weight gain and less gastrointestinal difficulties than valproate. DISCUSSION...


    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.


    Ružić, Klementina; Dadić-Hero, Elizabeta; Grahovac, Tanja; Sabljić, Vladimir; Kosec, Tanja; Knez, Rajna


    Depression is a disorder held responsible for high morbidity in the overall population. Causes of depression vary, but lifestyle and stress can greatly contribute to its morbidity. Consumption of antidepressants is showing a trend in the economically developed countries. Apart from antidepressants, the treatment of depression can consist of other psychopharmaca. Depending on the severity of a disorder, that is - of psychotic symptoms, antipsychotics can be introduced in the treatment...

  18. Review of antipsychotics in children and adolescents.

    Kapetanovic, Suad; Simpson, George M


    The use of antipsychotics in children and adolescents in the clinical setting is increasing. This article reviews 77 clinical trials published in the last 10 years, investigating their efficacy, effectiveness, safety and pharmacokinetic data in paediatric populations. The diagnostic categories in which the antipsychotics are commonly used (schizophrenia, pervasive developmental disorders, Tourette's disorder, mental retardation/subaverage intelligence, mood disorders and disruptive behaviour disorders) were used in order to review the evidence and effectiveness. All randomised, double-blind, placebo-controlled trials from the past decade are also summarised. This review refers to recent relevant practice parameters, guidelines and reviews throughout the text. Consistent with previous reviews, it is concluded that the recent trend of increased use of antipsychotics in children and adolescents is not adequately supported by evidence. Specific suggestions have been provided on how to incorporate the existing evidence base into clinical decision making. The review ends with the authors' opinion on the clinical and research implications for the field and future directions. PMID:17020414

  19. Schizophrenia Gene Expression Profile Reverted to Normal Levels by Antipsychotics

    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...

  20. Antipsychotics and Sexual Dysfunction: Sexual Dysfunction - Part III

    Anil Kumar Mysore Nagaraj


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

  1. Efeitos adversos metabólicos de antipsicóticos e estabilizadores de humor Metabolic side effects of antipsychotics and mood stabilizers

    Paulo José Ribeiro Teixeira


    use of lithium and valproic acid once again directed the attention to their metabolic effects. This study aims to review the medical literature with regard to metabolic side effects associated with the use of antipsychotics and mood stabilizers. METHOD: Research was carried out at MEDLINE and LILACS through October 2005. CONCLUSION: Metabolic side effects remain a major concern for psychopharmacology. Clinically relevant weight gain occurs frequently in patients taking antipsychotics and mood stabilizers, particularly clozapine, olanzapine, lithium, and valproic acid. Clozapine and olanzapine are also associated with higher incidence of diabetes mellitus and dyslipidemias, either due to weight gain or because of a direct deleterious action on glucose metabolism. Incidence of obesity and other metabolic disorders is lower with risperidone when compared to olanzapine or clozapine. Carbamazepine is associated with lower weight gain when compared to lithium or valproic acid. Drugs such as haloperidol, ziprasidone, aripiprazole and lamotrigine are not associated with significant weight gain or with higher incidence of diabetes mellitus. They are alternatives for patients more likely to develop these adverse effects.

  2. Post-Injection Delirium/Sedation Syndrome after Olanzapine Long-Acting Intramuscular Injection - Who is at Risk?

    Łukasik-Głębocka, Magdalena; Sommerfeld, Karina; Teżyk, Artur; Panieński, Paweł; Żaba, Czesław; Zielińska-Psuja, Barbara


    The post-injection olanzapine delirium/sedation syndrome (PDSS) was observed in a 60-year-old Caucasian, schizophrenic, non-smoker and underweight [body mass index (BMI), 18.2 kg/m(2) ] women after the fourth intramuscular injection of 405 mg olanzapine pamoate. Clinical symptoms of PDSS were similar to those of acute oral olanzapine intoxication. The patient received supportive treatment and recovered fully. High olanzapine concentrations in serum, with maximum level of 698 ng/mL, were confirmed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The authors wonder whether a low BMI and advanced age may predispose patients to PDSS occurrence. PMID:25703610

  3. Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

    Schirmbeck, Frederike; Mier, Daniela; Esslinger, Christine; Rausch, Franziska; Englisch, Susanne; Eifler, Sarah; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias


    Background Patients with schizophrenia have an approximately 10-fold higher risk for obsessive–compulsive symptoms (OCS) than the general population. A large subgroup seems to experience OCS as a consequence of second-generation antipsychotic agents (SGA), such as clozapine. So far little is known about underlying neural mechanisms. Methods To investigate the role of SGA treatment on neural processing related to OCS in patients with schizophrenia, we stratified patients according to their monotherapy into 2 groups (group I: clozapine or olanzapine; group II: amisulpride or aripiprazole). We used an fMRI approach, applying a go/no-go task assessing inhibitory control and an n-back task measuring working memory. Results We enrolled 21 patients in group I and 19 patients in group II. Groups did not differ regarding age, sex, education or severity of psychotic symptoms. Frequency and severity of OCS were significantly higher in group I and were associated with pronounced deficits in specific cognitive abilities. Whereas brain activation patterns did not differ during working memory, group I showed significantly increased activation in the orbitofrontal cortex (OFC) during response inhibition. Alterations in OFC activation were associated with the severity of obsessions and mediated the association between SGA treatment and co-occurring OCS on a trend level. Limitations The main limitation of this study is its cross-sectional design. Conclusion To our knowledge, this is the first imaging study conducted to elucidate SGA effects on neural systems related to OCS. We propose that alterations in brain functioning reflect a pathogenic mechanism in the development of SGA-induced OCS in patients with schizophrenia. Longitudinal studies and randomized interventions are needed to prove the suggested causal interrelations. PMID:25268790

  4. Metabolic Disturbances Independent of Body Mass in Patients with Schizophrenia Taking Atypical Antipsychotics

    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

  5. Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics.

    Spina, Edoardo; Pisani, Francesco; de Leon, Jose


    Antiepileptic drugs (AEDs) are frequently co-prescribed with new antidepressants (ADs) or new antipsychotics (APs). A PubMed search with no time limit was used to update the review of the clinically significant pharmacokinetic (PK) drug interactions DIs (DIs) between AEDs with new ADs and APs. Our best interpretation of what to expect regarding dosing changes in the average patient after combining AEDs with new ADs or new APs is summarized on updated tables that integrate the information on in vitro metabolism studies, therapeutic drug monitoring (TDM) studies, case report/series and prospective studies. There will be a need to periodically update these dose correction factors as new knowledge becomes available. These tables will provide some orientation to clinicians with no TDM access and may also encourage clinicians to further study TDM. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone on new ADs and new APs and the inhibitory properties of valproic acid and some new ADs, are relatively well understood. On the other hand, PK DI studies combining new AEDs with weak inductive properties (particularly oxcarbazepine doses≥1200mg/day), topiramate doses≥400mg/day, clobazam, eslicarbazepine, and rufinamide), with new ADs and new APs are needed. Valproic acid may be 1) an inhibitor and/or inducer of clozapine and olanzapine with potential for clinically relevant DIs, 2) an inhibitor of paliperidone, and 3) a weak inducer of aripiprazole. Fluoxetine and fluvoxamine are relevant inhibitors of phenytoin and valproic acid and possibly of clobazam, lacosamide, phenobarbital, or primidone. PMID:26896788

  6. A naturalistic comparison of the efficacy and safety of intramuscular olanzapine and intramuscular levomepromazine in agitated elderly patients with schizophrenia

    Suzuki H; Gen K


    Hidenobu Suzuki,1 Keishi Gen2 1Department of Psychiatry, Suzuki Clinic, Tokyo, Japan; 2Department of Psychiatry, Seimo Hospital, Gunma, Japan Background: There have not been any reports in Japan clarifying the efficacy and safety of intramuscular (IM) olanzapine and IM levomepromazine in agitated elderly patients with schizophrenia. This study was a comparative investigation of the clinical efficacy and safety of IM olanzapine and IM levomepromazine in agitated elderly patients with schizoph...

  7. Corrected QT changes during antipsychotic treatment of children and adolescents

    Jensen, Karsten Gjessing; Juul, Klaus; Fink-Jensen, Anders;


    OBJECTIVE: To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth. METHOD: We searched PubMed ( for randomized or open clinical trials of antipsychotics in youth <18 years with QTc data, meta-analyzing the results. Meta-regression a...

  8. Can antipsychotic treatment contribute to drug addiction in schizophrenia?

    Samaha, Anne-Noël


    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

  9. Volumetric changes in the Basal Ganglia after antipsychotic monotherapy

    Ebdrup, B H; Nørbak, H; Borgwardt, S; Glenthøj, B


    studies. Results: We identified 13 studies published in the period from 1996 to 2011. Overall six compounds (two classified as FGAs and four as SGAs) have been investigated: haloperidol, zuclophentixol, risperidone, olanzapine, clozapine, and quetiapine. The follow-up period ranged from 3-24 months...

  10. Effects of divalproex and atypical antipsychotic drugs on dopamine and acetylcholine efflux in rat hippocampus and prefrontal cortex.

    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

  11. Benzo- and thienobenzo- diazepines: multi-target drugs for CNS disorders.

    Mendonça Júnior, F J B; Scotti, L; Ishiki, H; Botelho, S P S; Da Silva, M S; Scotti, M T


    Benzodiazepines (BZ or BZD) are a class of gabaminergic psychoactive chemicals used in hypnotics, sedation, in the treatment of anxiety, and in other CNS disorders. These drugs include alprazolam (Xanax), diazepam (Valium), clonazepam (Klonopin), and others. There are two distinct types of pharmacological binding sites for benzodiazepines in the brain (BZ1 and BZ2), these sites are on GABA-A receptors, and are classified as short, intermediate, or long-acting. From the thienobenzodiazepine class (TBZ), Olanzapine (2-methyl-4-(4-methyl-l-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine) (Zyprexa) was used as an example to demonstrate the antagonism of this class of compounds for multiples receptors including: dopamine D1-D5, α-adrenoreceptor, histamine H1, muscarinic M1-M5 and 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3 and 5-HT6 receptors. Olanzapine is an atypical antipsychotic agent, structurally related to clozapine, and extensively used for the treatment of schizophrenia, bipolar disorder-associated mania, and the behavioral symptoms of Alzheimer's disease. The functional blockade of these multiple receptors contributes to the wide range of its pharmacologic and therapeutic activities, having relatively few side effects when compared to other antipsychotics agents. Thienobenzodiazepines (such as Olanzapine) are characterized as multi- receptor- targeted- acting- agents. This mini-review discusses these 2 drug classes that act on the central nervous system, the main active compounds used, and the various receptors with which they interact. In addition, we propose 12 olanzapine analogues, and generated Random Forest models, from a data set obtained from the ChEMBL database, to classify the structures as active or inactive against 5 dopamine receptors (D1, D2, D3, D4, D5 and D6), and dopamine transporter. PMID:25694077

  12. Simultaneous determination of olanzapine and fluoxetine hydrochloride in capsules by spectrophotometry, TLC-spectrodensitometry and HPLC

    Tantawy, Mahmoud A.; Hassan, Nagiba Y.; Elragehy, Nariman A.; Mohamed Abdelkawy


    This paper describes sensitive, accurate and precise spectrophotometric, TLC-spectrodensitometric and high performance liquid chromatographic (HPLC) methods for simultaneous determination of olanzapine and fluoxetine HCl. Two spectrophotometric methods were developed, namely; first derivative (D1) and derivative ratio (DD1) methods. The TLC method employed aluminum TLC plates precoated with silica gel GF254 as the stationary phase and methanol:toluene:ammonia (7:3:0.1, by volume) as the mobil...

  13. The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR study (NCT00237913

    Pans Miranda


    Full Text Available Abstract Background The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC, which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]. Method This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone in patients with schizophrenia (DSM-IV-TR criteria. The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ at Week 26. The outcome research variables included the Arizona Sexual Experience scale (ASEX. This along with the data collected on serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this paper. Results A total of 555 patients were randomised to receive aripiprazole (n = 284 or SOC (n = 271. Both treatment groups experienced improvements in sexual function from baseline ASEX assessments. However at 8 weeks the aripiprazole treatment group reported significantly greater improvement compared with the SOC group (p = 0.007; OC. Although baseline mean serum prolactin levels were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group and 42.3 mg/dL in the SOC group, p = NS at Week 26 OC, mean decreases in serum prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in the SOC group (p Conclusion The study findings suggest that aripiprazole has the potential to reduce sexual dysfunction, which in turn might improve patient compliance.

  14. A rare case of neuroleptic malignant syndrome presenting with serious hyperthermia treated with a non-invasive cooling device: a case report

    Storm Christian


    Full Text Available Abstract Introduction A rare side effect of antipsychotic medication is neuroleptic malignant syndrome, mainly characterized by hyperthermia, altered mental state, haemodynamic dysregulation, elevated serum creatine kinase and rigor. There may be multi-organ dysfunction including renal and hepatic failure as well as serious rhabdomyolysis, acute respiratory distress syndrome and disseminated intravascular coagulation. The prevalence of neuroleptic malignant syndrome is between 0.02% and 2.44% for patients taking neuroleptics and it is not necessary to fulfil all cardinal features characterizing the syndrome to be diagnosed with neuroleptic malignant syndrome. Because of other different life-threatening diseases matching the various clinical findings, the correct diagnosis can sometimes be hard to make. A special problem of intensive care treatment is the management of severe hyperthermia. Lowering of body temperature, however, may be a major clinical problem because hyperthermia in neuroleptic malignant syndrome is typically unresponsive to antipyretic agents while manual cooling proves difficult due to peripheral vasoconstriction. Case presentation A 22-year-old Caucasian man was admitted unconscious with a body temperature of 42°C, elevated serum creatine phosphokinase, tachycardia and hypotonic blood pressure. In addition to intensive care standard therapy for coma and shock, a non-invasive cooling device (Arctic Sun 2000®, Medivance Inc., USA, originally designed to induce mild therapeutic hypothermia in patients after cardiopulmonary resuscitation, was used to lower body temperature. After successful treatment it became possible to obtain information from the patient about his recent ambulant treatment with Olanzapin (Zyprexa® for schizophrenia. Conclusion Numerous case reports have been published about patients who developed neuroleptic malignant syndrome due to Olanzapin (Zyprexa® medication. Frequently hyperthermia has been observed

  15. Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

    Jakovcevski, Igor


    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

  16. Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, trauma-related, and somatic symptom disorders: a systematized review.

    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

  17. Antipsychotic Management of Schizoaffective Disorder: A Review.

    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

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

    Nielsen, René Ernst; Nielsen, Jimmi


      The cornerstone in treatment of psychosis is antipsychotic drugs. Treatment options have increased over the years; newer antipsychotic drugs with a proposed efficacy regarding negative and cognitive symptoms, but also a shift in side-effects from neurological side-effects to metabolic side-effe...... treatment. The clinically relevant aspects of antipsychotic drug treatment are reviewed; mechanism of antipsychotic drug action, clinical considerations in treatment, switching antipsychotic drugs, polypharmacy, safety and patient preference.  ...

  19. Efficacy and safety of blonanserin versus other antipsychotics: a review

    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

  20. Switching antipsychotics: Imaging the differential effect on the topography of postsynaptic density transcripts in antipsychotic-naïve vs. antipsychotic-exposed rats.

    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

  1. Pedal edema associated with atypical antipsychotics

    Santanu Munshi


    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.

  2. Olanzapine-induced hepatopathy in albino rats: A newer model for screening putative hepatoprotective agents, namely silymarin

    Sengupta Parama


    Full Text Available Backgrounds: This study was conducted to establish olanzapine-induced hepatopathy in Wistar albino rats as a newer model to screen putative hepatoprotective agents namely silymarin. Materials and Methods: Albino rats were divided into three groups, namely vehicle control group (CG, olanzapine-treated group (OZ, and olanzapine plus silymarin (OZS treated groups. Both the OZ and OZS groups were treated with the same dose of intraperitoneal olanzapine for 6 weeks and group OZS additionally received oral silymarin. Baseline and terminal hepatic enzymes (SGOT, SGPT, and ALP were measured in all three groups. Results: Histopathological examination of livers of both OZ and OZS groups showed degenerative changes, whereas those of control group showed normal architecture. Liver enzyme levels showed statistically significant rise in comparison to the control group as well as the respective base line values in both the test groups, but the differences in the rise of liver enzymes between the two test groups were not statistically significant. Conclusion: Olanzapine-induced hepatopathy in rats can be used as a model for screening putative hepatoprotective agents and in our setting silymarin has failed to provide any hepatoprotection.

  3. New atypical antipsychotics for schizophrenia: iloperidone

    Silvio Caccia


    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

  4. Improvement of Brain Reward Abnormalities by Antipsychotic Monotherapy in Schizophrenia

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne;


    CONTEXT Schizophrenic symptoms are linked to a dysfunction of dopamine neurotransmission and the brain reward system. However, it remains unclear whether antipsychotic treatment, which blocks dopamine transmission, improves, alters, or even worsens the reward-related abnormalities. OBJECTIVE To....... Antipsychotic treatment tends to normalize the response of the reward system; this was especially seen in the patients with the most pronounced treatment effect on the positive symptoms. TRIAL REGISTRATION Identifier: NCT01154829....... investigate changes in reward-related brain activations in schizophrenia before and after antipsychotic monotherapy with a dopamine D2/D3 antagonist. DESIGN Longitudinal cohort study. SETTING Psychiatric inpatients and outpatients in the Capital Region of Denmark. PARTICIPANTS Twenty-three antipsychotic...

  5. Metabolic Complications of Antipsychotic Therapy for Tourette Syndrome

    J Gordon Millichap


    Seventy-three children with Tourette syndrome treated with antipsychotics were monitored for metabolic and neurologic side effects every six months in a study at University of Calgary, Alberta, Canada.

  6. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Rosenbloom ArlanL


    Full Text Available There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  7. Hyperprolactinemia with Antipsychotic Drugs in Children and Adolescents

    Arlan L. Rosenbloom


    Full Text Available There is increasing use of antipsychotic drugs in pediatric and psychiatry practice for a wide range of behavioral and affective disorders. These drugs have prominent side effects of interest to pediatric endocrinologists, including weight gain and associated metabolic risk factors and hyperprolactinemia. The drugs block dopamine action, thus disinhibiting prolactin secretion. Hyperprolactinemia is especially prominent with first-generation antipsychotics such as haloperidol and the second-generation drugs, most commonly risperidone, with some patients developing gynecomastia or galactorrhea or, as a result of prolactin inhibition of gonadotropin releasing hormone from the hypothalamus, amenorrhea. With concern about the long-term effects of antipsychotics on bone mass and pituitary tumor formation, it is prudent to monitor serum prolactin levels in antipsychotic drug-treated pediatric patients and consider treatment with an agent less likely to induce hyperprolactinemia.

  8. Time Trends in Antipsychotic Drug Use in Patients with Dementia

    Nørgaard, Ane; Jensen-Dahm, Christina; Gasse, Christiane; Hansen, Hanne Vibe; Waldemar, Gunhild


    BACKGROUND: Antipsychotics are often used to treat neuropsychiatric symptoms in dementia, but the evidence for effect is limited. Antipsychotics have been associated with increased risk of adverse events and mortality in patients with dementia, leading to safety regulations worldwide. OBJECTIVE: To...... investigate time trends in use of antipsychotics and other psychotropic drugs in dementia care. METHODS: The study included longitudinal data on all Danish residents ≥65 years. The study population was defined on January 1 of each year from 2000-2012. Data included prescriptions, discharge diagnoses, and...... somatic and psychiatric comorbidities. Multivariate time trend analyses of psychotropic drug use in patients with dementia within 4-year age bands were performed. RESULTS: Overall, among patients with dementia the prevalence of antipsychotic drug use decreased from 31.3% in 2000 to 20.4% in 2012. The...

  9. Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

    Bordia, Tanuja; McIntosh, J. Michael; Quik, Maryka


    Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce ...

  10. First-generation antipsychotics: not gone but forgotten

    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...