UMLS:C0036341 - FACTA Search

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Query: UMLS:C0036341 (schizophrenia)
60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Issues to consider when evaluating maintenance drug therapy for patients with schizophrenia are discussed; these include potential adverse effects of antipsychotic therapy, such as weight gain, diabetes mellitus, extrapyramidal symptoms, sexual dysfunction, cognitive dysfunction, and cardiac effects, as well as quality of life. Patients with schizophrenia are more likely to be overweight than the general population. Olanzapine and clozapine have been associated with the greatest weight gain of the newer antipsychotics. While patients with schizophrenia are at increased risk of developing diabetes mellitus independent of antipsychotic therapy, diabetes may be more prevalent in patients taking the newer agents. Acute extrapyramidal symptoms occur in 75-90% of patients receiving first-generation antipsychotics like thioridazine and haloperidol. The probability of tardive dyskinesia (TD) occurring with second- and third-generation agents is less than 1% per year, compared with about 5% per year for the traditional antipsychotics. When patients are switched from a traditional antipsychotic to clozapine or olanzapine, TDs usually abate somewhat. Thioridazine causes a pronounced prolongation of the QTc interval, which can lead to ventricular arrhythmias. The slight increase in QTc interval caused by ziprasidone most likely will not be a problem in healthy individuals. Newer antipsychotics are associated with improved neurocognitive functioning and most cause less prolactin elevation, compared with traditional agents. The newer antipsychotic agents are not devoid of adverse effects, but those that do occur can be managed. Once issues related to adherence are resolved, rehabilitation of patients with schizophrenia will be a high priority.
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PMID:Clinical issues associated with maintenance treatment of patients with schizophrenia. 1222 83

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metabolite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% ( < 0.01) increase of olanzapine from 31 +/- SD 15 ng/mL (week 0) to 56 +/- 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed ( > 0.05). Fluvoxamine concentrations were 48 +/- 26 ng/mL on week 1 and 83 +/- 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications.
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PMID:Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects. 1235 74

Hyperprolactinaemia has been associated with a variety of side effects including amenorrhoea, galactorrhoea, sexual dysfunction, breast engorgement and osteoporosis. Since the mid-1970s, the impact of antipsychotics on human prolactin (hPrl) levels has been investigated. Baseline levels of hPrl were found to be similar in healthy controls and patients who were diagnosed as having schizophrenia. Short-term acute studies done after single parenteral or oral doses of phenothiazines found rapid two- to tenfold increases in hPrl. Similar increases were found in longer term studies that reported increases of three times in both men and women after 3 days that doubled again after several weeks of treatment. A study of longer term injectable fluphenazine enanthate found that elevation induced by a single injection lasted up to 28 days. The same results with significant increases have been reported with the butyrophenone, haloperidol. Substantial increases are found after single injections (up to nine times) and after weeks of treatment (up to three times sustained). Thus, early literature believed that there might be an association between these induced changes and response to therapy. However, prolactin is secreted by the anterior pituitary and is under inhibitory control of dopamine released from the tuberoinfundibular neurones. Thus, increases in prolactin are due to antipsychotic impact on tuberoinfundibular tract, one of four dopamine-related tracts. With the application of clozapine and other atypical antipsychotics, it was found that medications can successfully treat psychosis without increasing hPrl. In fact, early single-dose trails found clozapine to reduce hPrl by 16%. Later studies replicated this result and also found that up to 6 weeks of administration led to reductions in hPrl of up to 80%. Risperidone, however, has been found to persistently elevate hPrl in studies, despite its impact on other receptor sites. Olanzapine, quetiapine and ziprasidone have all been found to have little effect or produce decreases in hPrl. Most recently, aripiprazole, in early studies, appears to produce significant reductions in hPrl while maintaining therapeutic efficacy for psychosis.
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PMID:Antipsychotics: impact on prolactin levels. 1238 84

DMP 406 is a clozapine analogue developed by Dupont-Pharma for the treatment of schizophrenia. Unfortunately it caused agranulocytosis in dogs during preclinical studies. Clozapine also causes agranulocytosis and this is believed to be due to a reactive nitrenium ion metabolite produced by neutrophils. We studied the oxidation of DMP 406 by activated neutrophils and found that the major reactive species that is produced is not a nitrenium ion but rather an imine. This metabolite is similar to the reactive metabolite that has been proposed to be responsible for mianserin-induced agranulocytosis. Therefore we also studied the oxidation of mianserin by activated neutrophils and found that, although the major species is an iminium ion, it also bears a lactam moiety in the piperazine ring resulting from further oxidation. We usually find that HOCl is a good model system for the production of reactive metabolites of drugs that are formed by activated neutrophils, but in the case of both DMP 406 and mianserin, the products produced were significantly different than those formed by activated neutrophils. In contrast, the combination of horseradish peroxidase and hydrogen peroxide (HRP/H(2)O(2)) formed a very similar pattern of products, and this system was used to produce sufficient quantities of metabolites to allow for identification. The reactive metabolites of both DMP 406 and mianserin reacted with a range of nucleophiles, but in many cases the reaction was reversible. The best nucleophile for trapping these reactive metabolites was cyanide. It has been demonstrated that the products of clozapine oxidation by HRP/H(2)O(2), presumably the nitrenium ion, induced apoptosis in neutrophils at therapeutic concentrations of clozapine. It has been suggested that this process is involved in the mechanism of clozapine-induced agranulocytosis. We tested DMP 406 and mianserin in this system to see if the ability of a reactive metabolite of a drug to cause apoptosis could predict the ability of that drug to cause agranulocytosis. We used clozapine as a positive control and we also tested olanzapine, a drug that forms a reactive metabolite similar to that of clozapine but is given at a lower dose and does not cause agranulocytosis. We found that DMP 406 did not increase apoptosis at concentrations below 50 microM, and although mianserin did increase apoptosis at 10 microM this is above the therapeutic concentration. Olanzapine caused an increase in apoptosis at the same concentration as clozapine (1 microM), but because its therapeutic concentration is lower, this concentration was above the pharmacological range. There was no increase in apoptosis with any drug in the absence of HRP/H(2)O(2). These results indicate that this assay is unable to reliably predict the ability of different types of drugs to cause agranulocytosis. This is not a surprising result given that different drugs may induce agranulocytosis by different mechanisms.
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PMID:Predicting drug-induced agranulocytosis: characterizing neutrophil-generated metabolites of a model compound, DMP 406, and assessing the relevance of an in vitro apoptosis assay for identifying drugs that may cause agranulocytosis. 1239 62

The aim of the study was to compare the effect of olanzapine versus fluphenazine treatment on cognitive functioning. Eighteen schizophrenic outpatients, aged 25 - 61 (average 37 years), all meeting DSM-IV diagnostic criteria for schizophrenia, were included in the study. They were randomly assigned to 22 weeks of either olanzapine or fluphenazine treatment. Certain subscales of the Wechsler Adult Intelligence Scale, the Stroop Neuropsychological Screening Test and the Wisconsin Card Sorting Test were performed. Olanzapine treatment proved to have a beneficial effect on digit-symbol performance and some aspects of executive function. In comparison to the fluphenazine treatment, the olanzapine treatment only showed a beneficial effect in increased percentage of conceptual level responses. Although the results are preliminary, they could implicate that the benefit of olanzapine treatment is primarily related to certain aspects of executive function, i.e. frontal lobe functioning. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:A preliminary study of the comparative effects of olanzapine and fluphenazine on cognition in schizophrenic patients. 1240 20

This double-blind, randomized, multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia. Patients (n = 249) who met DSM-IV criteria for schizophrenia were randomly assigned to receive olanzapine monotherapy, risperidone monotherapy, divalproex plus olanzapine, or divalproex plus risperidone for 28 days. Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day. Olanzapine and risperidone, were, respectively, initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and 6 mg/day. Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in the two combination therapy and the two antipsychotic monotherapy groups, with statistically significant treatment differences favoring combination therapy as soon as day 3 for Positive and Negative Syndrome Scale (PANSS) total score, derived Brief Psychiatric Rating Scale (BPRSd) total score, as well as PANSS and BPRSd subscales. These findings were confirmed in post hoc repeated-measures analyses of variance in which treatment differences favoring combination therapy were observed for PANSS total (p = 0.020) and PANSS positive scale scores (p = 0.002). Both combination therapy and antipsychotic monotherapy were well tolerated. Treatment with divalproex in combination with an atypical antipsychotic agent resulted in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia. Further evaluation is warranted to confirm these findings.
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PMID:Effect of divalproex combined with olanzapine or risperidone in patients with an acute exacerbation of schizophrenia. 1497 33

To date there is no common or adequate therapeutic strategy for treatment of refractory schizophrenic patients. Increasing antipsychotics' doses in treatment-resistant schizophrenic patients is the most common intervention used by clinicians. Olanzapine is an atypical antipsychotic, which in a number of double-blind, placebo-controlled studies has been found to be more effective than haloperidol for the treatment of positive and negative symptoms of schizophrenia. During the last few years there have been several reports of successful results in prescribing olanzapine at dosages of more than 25 mg/day for treatment-resistant schizophrenic and schizoaffective patients. This report presents the results from the treatment of three resistant schizophrenic patients treated successfully with high dosages of olanzapine (35, 40, and 60 mg/day). None of the patients had any side effects, including abnormal laboratory levels and weight gain. The results and literature data suggest that in clinical practice some schizophrenic patients resistant to conventional neuroleptic treatment and not responding to olanzapine at recommended dosages as high as 20 mg/day may respond to higher dosages such as 40 or 60 mg/day, and these dosages are well tolerated. Further prospective clinical studies are needed.
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PMID:High-dose olanzapine for treatment-refractory schizophrenia. 1267 23

Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease. Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need. We report a multicenter, double-blind, parallel, 30-week study designed to compare the efficacy, safety, and associated resource use for olanzapine and risperidone in Australia and New Zealand. The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia, schizoaffective disorder, or schizophreniform disorder. Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale (PANSS) total, Brief Psychiatric Rating Scale (BPRS) total, and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients. Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20% or greater improvement in their PANSS total score compared to risperidone-treated patients. Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale (CGI-S) at endpoint. Using generic and disease-specific measures of quality of life, olanzapine-treated patients showed significant within-group improvement in most measures, and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale (QLS) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument (SF-36) Role Functioning Limitations-Emotional subscale scores. Despite the relatively small sample size, our study suggests that olanzapine has a superior risk:benefit profile compared to risperidone.
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PMID:Olanzapine vs risperidone in the management of schizophrenia: a randomized double-blind trial in Australia and New Zealand. 1272 82

Atypical antipsychotics generally have milder side-effects than conventional antipsychotics, but also differ among themselves in this respect. This study aimed to compare the impact of different side-effect profiles of individual atypical antipsychotics on non-compliance, relapse and cost in schizophrenia. A state-transition model was built using literature data supplemented by expert opinion. The model found that quetiapine and ziprasidone were similar in estimated non-compliance and relapse rates. Olanzapine and risperidone had higher estimated non-compliance and relapse rates, and incremental, 1-year, per-patient direct costs, using US-based cost data, of approximately $530 (95% confidence interval [CI] approximately $275, $800), and approximately $485 (95% CI approximately $235, $800), respectively, compared with quetiapine. Incremental costs attributable to different side-effect profiles were highly significant. This study shows that differing side-effect profiles of the newer antipsychotic agents are likely to lead to different compliance rates, and consequent variation in relapse rates. The cost implications of these heterogenous clinical outcomes are substantial.
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PMID:Impact of side-effects of atypical antipsychotics on non-compliance, relapse and cost. 1287 Mar 71

Potential weight gain must be taken into account in the patient's comprehensive treatment approach when initiating antipsychotic treatment with Olanzapine. There are effective preventive and therapeutic pharmacological interventions to control this adverse effect. Not addressing this eventual treatment aspect of Olanzapine treatment may compromise the patient's health and his/her compliance with the pharmacological treatment indicated in serious psychiatric conditions. The decision to use a molecule must be made taking into account its efficacy, efficiency and adverse effect profile. In this study, concomitant administration of Ranitidine prevented or corrected weight gain in 59.6% of cases. Patients followed by 16 weeks had shown the following results: Olanzapine without Ranitidine, exhibited an average weight gain of 3.4 kilograms, ranging between -2.5 and +16 kg. This implies an average increase of 1.19 in BMI for this group. Patients treated additionally with Ranitidine at doses of 300 mg, a 0.9 kilogram weight gain ranging between -4 and +10.6 kg was observed, implying an average BMI change of 0.34. In patients treated with Ranitidine at doses of 600 mg, the weight gain curve trended toward normalization with a 1.6 kilogram decrease, ranging between -15 and +7 kilograms, accounting for a decrease of 0.6 points in BMI. While more extensive studies are required, our interest with this study is to demonstrate that we can count on a potentially simple and useful response for the treatment of weight gain associated with Olanzapine use. The risk/benefit ratio is a paradigm in the practice of medicine. In the case of Olanzapine, the scale clearly tips in favor of the latter, making it the drug of choice in the treatment of schizophrenia and other psychotic disorders.
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PMID:[Randomized, open label study on the use of ranitidine at different doses for the management of weight gain associated with olanzapine administration]. 1288 89

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