Comparative Effectiveness of Antipsychotic Drugs: A Commentary on Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1) and Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)

ArticleinArchives of General Psychiatry 63(10):1069-72 · November 2006with10 Reads
DOI: 10.1001/archpsyc.63.10.1069 · Source: PubMed
    • "The second-generation (''atypical'') antipsychotic drug olanzapine is commonly prescribed as a first-line treatment for schizophrenia, bipolar disorder, and other psychotic disorders. Since their introduction in the 1990s, olanzapine and other atypical antipsychotics have come into widespread clinical use because they are efficacious and usually lack the extrapyramidal adverse drug reactions associated with older, ''typical'' antipsychotics like haloperidol [1, 2]. However, atypical antipsychotics can induce dramatic weight gain: 11–17 kg in a systematic review of treatment-naï ve adults [3] and 7–9 kg in adolescents over short-term treatment [4]. "
    [Show abstract] [Hide abstract] ABSTRACT: The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.
    Full-text · Article · Dec 2014
    • "We tested the replicability of our findings in the MGS study by carrying out the same analyses of the genotypic and phenotypic architecture of schizophrenia in the CATIE (19, 22, 23) and Portuguese Island (19, 21) samples. A total of 1,303 SNPs were shared between the selected SNPs in the MGS (see the Data Cleaning section in the online data supplement) and CATIE samples, and 1,234 SNPs between the MGS and Portuguese Island samples. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: The authors sought to demonstrate that schizophrenia is a heterogeneous group of heritable disorders caused by different genotypic networks that cause distinct clinical syndromes. Method: In a large genome-wide association study of cases with schizophrenia and controls, the authors first identified sets of interacting single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (SNP sets) regardless of clinical status. Second, they examined the risk of schizophrenia for each SNP set and tested replicability in two independent samples. Third, they identified genotypic networks composed of SNP sets sharing SNPs or subjects. Fourth, they identified sets of distinct clinical features that cluster in particular cases (phenotypic sets or clinical syndromes) without regard for their genetic background. Fifth, they tested whether SNP sets were associated with distinct phenotypic sets in a replicable manner across the three studies. Results: The authors identified 42 SNP sets associated with a 70% or greater risk of schizophrenia, and confirmed 34 (81%) or more with similar high risk of schizophrenia in two independent samples. Seventeen networks of SNP sets did not share any SNP or subject. These disjoint genotypic networks were associated with distinct gene products and clinical syndromes (i.e., the schizophrenias) varying in symptoms and severity. Associations between genotypic networks and clinical syndromes were complex, showing multifinality and equifinality. The interactive networks explained the risk of schizophrenia more than the average effects of all SNPs (24%). Conclusions: Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.
    Full-text · Article · Sep 2014
    • "Perazine is a phenothiazine derivative widely used in some European countries, including Germany and Poland, and it is thought to exert potent antipsychotic and sedative effects, as well as a relatively low risk of extrapyramidal side effects (Leucht et al., 2014; Adamowski and Kiejna, 2012). Interestingly, recent naturalistic studies have demonstrated that the effectiveness of some typical and atypical antipsychotics did not differ in clinical settings (Lieberman, 2006; Lewis and Lieberman, 2008; Stahl, 2008; Leucht et al., 2009; Naber and Lambert, 2009). At the time of study conception, perazine and olanzapine were the two most widely used antipsychotic drugs at both recruiting centers and ziprasidone had just been introduced to the Polish market. "
    [Show abstract] [Hide abstract] ABSTRACT: The primary aim of the present study was to assess the possible associations between dopaminergic, serotonergic, and glutamatergic system-related genes and adverse events after antipsychotic treatment in paranoid schizophrenia patients. The second aim of the study was to compare the intensity of these symptoms between atypical (ziprasidone and olanzapine) and typical (perazine) antipsychotic drugs. One-hundred and ninety-one Polish patients suffering from paranoid schizophrenia were genotyped for polymorphisms of DRD2, DAT1, COMT, MAOA, SERT, 5HT2A, and GRIK3. The patients were randomized to treatment with perazine, olanzapine or ziprasidone monotherapy for 3 months. The intensity of side effects (changes in body weights and extrapyramidal symptoms (EPS)) was measured at baseline and after 12 weeks of antipsychotic treatment. After 3 months of therapy, the weight increase was the greatest in the group treated with olanzapine and the least in the group treated with ziprasidone. None of the examined gene polymorphisms was associated with the body weight changes. Perazine treatment was associated with the significantly highest intensity of EPS. None of the examined polymorphisms was associated with the changes in extrapyramidal adverse events after antipsychotic treatment. The selected polymorphisms are not primarily involved in changes in body weights and EPS related to antipsychotic treatment in paranoid schizophrenia patients.
    Full-text · Article · Jun 2014
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