Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olanzapine (Zyprexa) is an atypical neuroleptic used in adult and pediatric patients for the management of schizophrenia. Common side effects include increased appetite and weight gain. An uncommon but severe adverse effect is the development of diabetic ketoacidosis, reported until now only in adults. We report a case of acute onset diabetic ketoacidosis presenting in a 16-year-old girl during olanzapine therapy.
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PMID:Diabetic ketoacidosis associated with olanzapine in an adolescent patient. 1139 46

This randomized double-blind trial was conducted to test the efficacy and safety of olanzapine in Japanese patients with schizophrenia. Importantly, this study also represents the first large clinical trial of olanzapine conducted in an Asian population. Patients (n = 182) were randomly assigned to treatment with olanzapine or haloperidol over a period of 8 weeks. The primary analyses included: (i) a test of non-inferiority of olanzapine compared with haloperidol in efficacy using the Final Global Improvement Rating (FGIR); and (ii) comparison between the treatment groups in extrapyramidal symptom severity using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Olanzapine was comparable to haloperidol in efficacy in treating positive symptoms and significantly superior in treating negative symptoms. Extrapyramidal symptom severity was significantly improved for olanzapine-treated patients versus haloperidol-treated patients. Olanzapine was shown to be more effective and better tolerated than haloperidol in the treatment of Japanese patients suffering from chronic schizophrenia.
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PMID:Olanzapine versus haloperidol in the treatment of patients with chronic schizophrenia: results of the Japan multicenter, double-blind olanzapine trial. 1144 93

The Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS) programme was an international series of naturalistic studies designed to evaluate drug use patterns and outcomes. RODOS consisted of retrospective chart reviews performed in patients who had been admitted to hospital and treated in 61 centres in nine countries. The analysed population consisted of 1901 patients with diagnoses of schizophrenia or schizoaffective disorder. The mean (SD) daily doses of risperidone and olanzapine were 5.3 (2.6) mg/day and 14.5 (5.1) mg/day, respectively. Patients treated with risperidone stayed an average of 3.8 days less in hospital compared to those receiving olanzapine (time to discharge was 43.6 days versus 47.4 days, respectively; P = 0.004). Risperidone was rated as effective in significantly more patients than olanzapine (84% versus 79%; P = 0.01). The time to onset of efficacy was significantly shorter with risperidone than with olanzapine (P < 0.001). The numbers of adverse events in the two treatment groups were not significantly different (13% risperidone, 11% olanzapine; P = 0.1). Correcting for small but statistically significant baseline differences between the two treatment groups did not produce a substantive change in the magnitude or significance of any outcome parameter. In conclusion, the clinical outcomes reported by RODOS suggest that risperidone may be more effective as a first-line therapy drug for schizophrenia than olanzapine.
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PMID:Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): efficacy and tolerability results of an international naturalistic study. 1145 31

We report the health economic data from the Risperidone Olanzapine Drug Outcomes studies in Schizophrenia (RODOS) programme. Details of the efficacy and tolerability data from RODOS are available in a companion paper. The population analysed during RODOS consisted of 1901 patients with diagnoses of schizophrenia or schizoaffective disorder. The mean +/- SD daily dose of olanzapine treatment was 14.5 +/- 5.1 mg compared to 5.3 +/- 2.6 mg for risperidone. Use of concomitant neuroleptics (risperidone, 65%; olanzapine, 62%; P = 0.2) and other concomitant drugs (risperidone, 76%; olanzapine, 73%; P = 0.2) was similar in both groups. The mean +/- SD total costs of all inpatient drugs was significantly (P < 0.001) higher for olanzapine (US$ 297.5 +/- 305.1) than risperidone (US$159.9 +/- 183.3). Although this difference in the average total costs in part reflects the longer treatment duration for olanzapine compared to risperidone (34 days versus 31 days), the cost difference remained when looking at costs on a daily basis. The mean +/- SD daily cost of all inpatient drugs was also significantly (P < 0.001) higher for olanzapine (US$7.7 +/- 4.0) than for risperidone (US$ 4.6 +/- 2.9). These findings were very consistent across all nine countries. The results from RODOS suggest that treatment costs are significantly higher with olanzapine than with risperidone without any clinical benefit to offset this.
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PMID:Risperidone olanzapine drug outcomes studies in schizophrenia (RODOS): health economic results of an international naturalistic study. 1145 32

(1) Olanzapine, a neuroleptic, has obtained European marketing authorisation for the treatment of schizophrenia. (2) The clinical file is satisfactory, but in the absence of relevant trials it has not yet been demonstrated that olanzapine has a specific activity on the positive or negative symptoms of schizophrenia. (3) The global efficacy of olanzapine was not significantly different from that of haloperidol in two of the three comparative trials published to date. (4) The only relevant comparative trial fails to demonstrate the superiority of olanzapine over risperidone. (5) Olanzapine has fewer adverse neurological effects than haloperidol, but there is no evidence that it differs from other recent neuroleptics in this respect. (6) Olanzapine can have anticholinergic adverse effects and frequently causes weight gain. (7) Active pharmacovigilance is required, as subclinical cases of elevated transaminase levels, increased blood pressure and QT prolongation were observed in clinical trials (2,500 patients treated).
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PMID:Olanzapine: new preparation. Keep an eye on this neuroleptic. 1150 36

A comprehensive evaluation of atypical antipsychotics for the treatment of schizophrenia involves documentation of clinical effectiveness, quality of life and medical cost outcomes. The results of pharmacoeconomic studies assist psychiatrists, and other healthcare decision-makers, in identifying pharmacotherapies that provide the greatest benefit to patients at the most acceptable cost. The cost-effectiveness of the newer atypical antipsychotics has been examined using clinical decision-modeling studies and randomized clinical trials. The research evidence suggests that clozapine is a cost-effective treatment for neuroleptic refractory schizophrenia. Olanzapine and risperidone may be cost-neutral or, at best, slightly cost-saving compared with conventional antipsychotics, although they do improve clinical symptoms and quality of life outcomes. There is insufficient published data on pharmacoeconomic outcomes for sertindole, quetiapine and ziprasidone to make any conclusions about their cost-effectiveness in treating schizophrenia.
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PMID:Cost effectiveness of the newer atypical antipsychotics: a review of the pharmacoeconomic research evidence. 1152 2

The aim of this study was to compare in vivo striatal D2 dopamine receptor occupancy induced by olanzapine and haloperidol in schizophrenic patients using a baseline-endpoint [(123)I]IBZM single photon computed emission tomography (SPECT) design. The relationships of striatal D2 receptor occupancy with clinical efficacy and extrapyramidal symptoms (EPS) were also assessed. Twenty-seven inpatients with schizophrenia or schizophreniform disorder were included in a 4-week prospective, randomized, double-blind, parallel and comparative clinical trial. Thirteen patients were treated with haloperidol (10 mg/day) and 14 with olanzapine (10 mg/day). Ratings of clinical status and EPS were obtained weekly. The percentage of D2 receptor occupancy was estimated by using basal ganglia (striatum)/frontal cortex IBZM uptake ratios obtained from each patient before and after 4 weeks of maintained antipsychotic treatment. Olanzapine led to a mean striatal D2 receptor occupancy of 49% (range 28-69%), which was significantly lower than that induced by haloperidol (mean 64%, range 46-90%). The baseline-endpoint SPECT design used in this study revealed lower antipsychotic D2 occupancy percentage values than those reported in the literature, using other approaches. The degree of striatal D2 receptor occupancy correlated to the EPS, which predominantly appeared in patients on haloperidol. No relationship was found between the striatal D2 receptor occupancy and clinical improvement. Olanzapine induced a lower striatal D2 occupancy than haloperidol. This low striatal D2 occupancy, together with the lower incidence of EPS in olanzapine-treated patients, contributed to confirm the atypical behavior of this new antipsychotic drug. Nevertheless, conclusions based on SPECT-estimated percentages of antipsychotic D2 occupancy should be cautious, since the SPECT design could influence the results. In this regard, SPECT studies including baseline and endpoint examinations should be encouraged.
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PMID:Double-blind olanzapine vs. haloperidol D2 dopamine receptor blockade in schizophrenic patients: a baseline-endpoint. 1153 Feb 75

The mechanism of action of both typical antipsychotics and the atypical antipsychotic, clozapine, may be related to the (changing) interaction of dopamine and serotonin in schizophrenia. This study examined the effect of olanzapine in schizophrenic patients on cerebrospinal fluid (CSF) metabolites of dopamine (homovanillic acid, HVA) and serotonin (5-hydroxyindoleacetic acid, 5-HIAA). Twenty-three male schizophrenic patients, who were drug-free for at least 2 weeks (mean drug-free period of 35 days +/- 43; median 16 days), underwent a lumbar puncture (LP). Patients were subsequently treated with olanzapine 10 mg/day for 6 weeks, after which the LP was repeated. CSF was assayed for HVA and 5-HIAA concentrations. Psychiatric symptoms were rated once a week. Olanzapine significantly increased HVA concentrations and the HVA/5-HIAA ratio while 5-HIAA concentrations were not altered. These changes did not significantly correlate with treatment response. A negative correlation was found between HVA concentrations and negative symptoms after olanzapine treatment. In conclusion, olanzapine treatment increases HVA concentrations and the HVA/5-HIAA ratio in CSF of schizophrenic patients, but these changes are unrelated to its clinical efficacy.
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PMID:The effect of olanzapine treatment on monoamine metabolite concentrations in the cerebrospinal fluid of schizophrenic patients. 1155 60

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.
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PMID:Tissue distribution of olanzapine in a postmortem case. 1156 38

The aim of this study was to estimate the long-term effectiveness of olanzapine as adjunctive therapy in patients with bipolar disorder who exhibited an inadequate response to mood stabilizers. Twenty-three Research Diagnostic Criteria (RDC) patients with bipolar I and II were assessed by means of the Schedule for Affective Disorders and Schizophrenia and entered if they gave their consent to participate. All of them had experienced frequent relapses, residual subsyndromal symptoms, and inadequate responses to other drugs, such as lithium, valproate, or carbamazepine. While maintaining other drugs, they all received open-label, increasing doses of olanzapine, until achieving clinical response. Other drugs were maintained. The patients were assessed several consecutive times from baseline to the endpoint with the Clinical Global Impressions (CGI) scale for use in bipolar illness. Records of recurrences, hospitalizations, and side effects were also collected. The last-observation-carried-forward analysis showed that there was a significant reduction of CGI scores after the introduction of olanzapine, either in manic symptoms (p = 0.0015), depressive symptoms (p = 0.0063), or global symptoms (p = 0.0003). The most frequent adverse events were somnolence (17%) and weight gain (13%). The mean dose of olanzapine at the end of the 43-week follow-up was 8.1 mg/day. Olanzapine may be a useful medication for the long-term adjunctive treatment of patients with bipolar disorder who exhibit a poor response to mood stabilizers, such as lithium, valproate, or carbamazepine. These results suggest mood-stablizing properties of olanzapine.
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PMID:Olanzapine as long-term adjunctive therapy in treatment-resistant bipolar disorder. 1159 70


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