Olanzapine for schizophrenia

Abstract

Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. We updated the first search [Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000)] in October 2004 using the Cochrane Schizophrenia's Group's register of trials. We also searched references of all included studies for further trials, and contacted relevant pharmaceutical companies and authors. We included all randomised clinical trials comparing olanzapine with placebo or any antipsychotic treatment for people with schizophrenia or schizophreniform psychoses. We independently extracted data and, for homogeneous dichotomous data, calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences. Fifty five trials are included (total n>10000 people with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by six weeks, leaving interpretation of results problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27). Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight. When compared with typical antipsychotic drugs, data from several small trials are incomplete. With high attrition in both groups (14 RCTs, n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions included in all data are considerable. For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated olanzapine experienced fewer extrapyramidal adverse effects than those given typical antipsychotics. Weight change data for the short term are not statistically significant but results between three to 12 months suggest a clinically important average gain of four kilograms for people given olanzapine (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64). Twenty three percent of people in trials of olanzapine and other atypical drugs left by eight weeks; 48% by three to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose between the atypicals, although olanzapine may cause fewer extrapyramidal adverse effects than other drugs in this category. Olanzapine produces more weight gain than other atypicals with some differences reaching conventional levels of statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7). There are very few data for people with first episode illness (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457). The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data. Olanzapina para la esquizofrenia La olanzapina es un antipsicótico atípico que, según los informes, es efectiva y no produce los efectos adversos extrapiramidales invalidantes asociados a los fármacos antipsicóticos típicos anteriores. Determinar los efectos clínicos y la seguridad de la olanzapina comparada con placebo, fármacos antipsicóticos típicos y otros fármacos antipsicóticos atípicos para la esquizofrenia y las psicosis esquizofreniformes. La primera búsqueda (Biological Abstracts [1980 a 1999], La Cochrane Library [Número 2, 1999], EMBASE [1980 a 1999], MEDLINE [1966 a 1999], PsycLIT [1974 a 1999] y el Registro Especializdo de Ensayos del Grupo Cochrane de Esquizofrenia [octubre de 2000]) se actualizó en octubre de 2004 mediante el registro de ensayos del Grupo Cochrane de Esquizofrenia. También se realizaron búsquedas en las referencias de todos los estudios incluidos para obtener estudios adicionales, y se estableció contacto con las compañías farmacéuticas y los autores pertinentes. Se incluyeron todos los ensayos clínicos aleatorios que compararon la olanzapina con placebo o con cualquier tratamiento antipsicótico para personas con esquizofrenia o psicosis esquizofreniformes. Los datos se extrajeron de forma independiente y, para los datos dicotómicos homogéneos, se calculó el riesgo relativo de efectos aleatorios (RR), los intervalos de confianza (IC) del 95% y el número necesario a tratar (NNT), sobre la base de la intención de tratar (intention-to-treat). Para los datos continuos, se calcularon las diferencias de medias ponderadas (DMP). Se incluyeron 55 ensayos (n >10 000 personas con esquizofrenia). La deserción de los estudios de olanzapina versus placebo fue >50% a las 6 semanas, lo que dificultó la interpretación de los resultados. La olanzapina pareció ser superior al placebo a las 6 semanas para la medida de resultado "ausencia de respuesta clínica importante" (cualquier dosis; 2 ECA; n = 418; RR 0,88; IC: 0,8 a 0,1; NNT 8; IC: 5 a 27). Aunque en el grupo tratado...