Clozapine, Olanzapine, Risperidone, and Haloperidol in the Treatment of Patients With Chronic Schizophrenia and Schizoaffective Disorder

Volavka, Jan; Czobor, Pál; Sheitman, Brian; Lindenmayer, Jean-Pierre; Citrome, Leslie; McEvoy, Joseph P.; Cooper, Thomas B.; Chakos, Miranda; Lieberman, Jeffrey A.

doi:10.1176/foc.2.1.59

Cited by 101 publications

(149 citation statements)

References 12 publications

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“…These changes are putatively related to increased risk of diabetes and atherosclerotic cardiovascular disease. Although recent studies have suggested that olanzapine and clozapine may be more effective than other antipsychotics in treatment of schizophrenia, 12,13 especially partially responsive or treatment-resistant schizophrenia, [14][15][16] the effects of these two drugs on weight gain and their metabolic effects on glucose and lipids may limit their overall utility because of risk/benefit ratios. If we could identify characteristics of patients who would be more or less likely to develop increases in lipids with specific types of antipsychotics, this could help inform clinicians' evaluation of risk/benefit propensity and aid in drug selection.…”

Section: Discussionmentioning

confidence: 99%

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia

et al. 2007

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Schizophrenic patients who are treated with antipsychotics, especially second generation antipsychotics, such as clozapine and olanzapine, manifest an increase in cholesterol and triglycerides as well as other changes associated with diabetes or the metabolic syndrome. Previous studies have shown that polymorphisms in several genes that regulate lipid metabolism can influence the levels of these lipids and response to drug treatment. We have investigated in an exploratory study whether polymorphisms in the apolipoprotein C-III (ApoC3), apolipoprotein A-V gene (ApoA5) and lipoprotein lipase genes influence differential lipid response to treatment with three second generation antipsychotics-olanzapine, clozapine and risperidone-or treatment with a first generation antipsychotic. A total of 189 patients with schizophrenia or schizoaffective disorder who were being treated with a single antipsychotic were studied in a cross-sectional study design in which fasting serum cholesterol and triglycerides and selected single-nucleotide polymorphosms (SNPs) in the three lipid metabolism genes were assessed. The treatment with antipsychotic monotherapy makes drug haplotype ascertainment less complex. Our analyses showed several nominally significant drug Â gene and drug Â haplotype interactions. The rarer C allele or the ApoA5_1131 (T/C) SNP was associated with higher cholesterol levels in patients treated with first generation antipsychotics and lower cholesterol levels in patients treated with olanzapine or clozapine. The rarer C allele of the ApoA5_SW19 (G/C) SNP was associated with higher cholesterol in risperidone-treated patients. An ApoA5 CG haplotype was associated with decreased cholesterol in olanzapine-or clozapine-treated patients and higher cholesterol in patients treated with first generation antipsychotics. The presence of the rarer T allele of the ApoC3_1100 (C/T) SNP or the presence of the ApoC3 TG haplotype was associated with decreased triglyceride levels in patients treated with olanzapine or clozapine and a nonsignificant trend for increased triglycerides in patients treated with first generation antipsychotics. The presence of the ApoC3 CC haplotype was associated with increased triglycerides in patients treated with olanzapine or clozapine. The overall magnitude of the effects was not large. These results provide a potential initial step toward a pharmacogenetic approach to selection of antipsychotic treatment which may help minimize the side effect of increases in serum lipids.

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Section: Discussionmentioning

confidence: 99%

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia

et al. 2007

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“…Of 52 subjects randomized, 15 dropped out of the study before week 4. The number of subjects lost to follow-up is not uncommon for such studies (Martin et al, 2002;Meyer-Lindenberg et al, 1997;Purdon et al, 2001;Volavka et al, 2002;Santarlasci and Messori, 2003) and there was no indication of selective attrition in one group, which might have biased the results.…”

Section: Cognitive Improvement In Schizophrenic Patientsmentioning

confidence: 99%

Cognitive Improvement in Schizophrenic Patients does not Require a Serotonergic Mechanism: Randomized Controlled Trial of Olanzapine vs Amisulpride

Wagner

Quednow

Westheide

et al. 2004

Neuropsychopharmacol

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Combined serotonin-2A (5-HT 2A ) and dopamine-2 (D 2 ) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D 2 /D 3 receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10-20 mg/day) or amisulpride (400-800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT 2A /D 2 receptor blockade is probably not necessary for cognitive improvement by SGAs.

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“…[1][2][3] These newer AAPDs produce fewer side-effects than did the initial AAPDs, especially clozapine, 4 but are not without side-effects. The most commonly reported sideeffect, possibly related to patient noncompliance, 5 is weight gain.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic drug-induced weight gain: development of an animal model

et al. 2005

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OBJECTIVE: Weight gain is a prominent effect of most atypical antipsychotic drugs (AAPDs); yet, the mechanisms are not fully understood and no well-established mouse models exist for investigating the mechanisms. Thus, we developed a mouse model to evaluate the effects of AAPDs on eating, body weight (BW), and body composition. METHODS: Female C57BL/6J mice were used to test olanzapine, quetiapine, ziprasidone, and risperidone. Mice were acclimated to individual housing, given ad libitum access to chow and water, dosed with placebo peanut butter pills for 1 week, and then dosed daily with AAPD-laced peanut butter pills for 4 weeks. Weekly food intakes and BWs were measured, and body compositions were determined at the end of each experiment. RESULTS: After 4 weeks of treatment, olanzapine, quetiapine, ziprasidone, and risperidone caused significant weight increases, but only olanzapine and quetiapine were associated with significantly increased food intake. Body composition data revealed that olanzapine-treated mice had more relative fat mass and risperidone-treated mice had more relative lean mass than did control mice. Quetiapine and ziprasidone did not significantly affect relative body composition even though BW was increased. CONCLUSIONS: Oral AAPD administration causes increased BW in female mice. Our mouse model of AAPD-induced weight gain resembles the human response to these medications and will be used to investigate the mechanisms for weight gain and fat accumulation.

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Clozapine, Olanzapine, Risperidone, and Haloperidol in the Treatment of Patients With Chronic Schizophrenia and Schizoaffective Disorder

Cited by 101 publications

References 12 publications

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia

Cognitive Improvement in Schizophrenic Patients does not Require a Serotonergic Mechanism: Randomized Controlled Trial of Olanzapine vs Amisulpride

Antipsychotic drug-induced weight gain: development of an animal model

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