Long-term antipsychotic treatment in schizophrenia: systematic review and network meta-analysis of randomised controlled trials

Abstract

BackgroundFor treatment of patients diagnosed with schizophrenia, comparative long-term effectiveness of antipsychotic drugs to reduce relapses when minimising adverse effects is of clinical interest, hence prompting this review.AimsTo evaluate the comparative long-term effectiveness of antipsychotic drugs.MethodWe systematically searched electronic databases for reports of randomised controlled trials (RCTs) of antipsychotic monotherapy aimed at reducing relapse risks in schizophrenia. We conducted network meta-analysis of 18 antipsychotics and placebo.ResultsStudies of 10 177 patients in 56 reports were included; treatment duration averaged 48 weeks (range 4–156). Olanzapine was significantly more effective than chlorpromazine (odds ratio (OR) 0.35, 95% CI 0.14–0.88) or haloperidol (OR=0.50, 95% CI 0.30–0.82); and fluphenazine decanoate was more effective than chlorpromazine (OR=0.31, 95% CI 0.11–0.88) in relapse reduction. Fluphenazine decanoate, haloperidol, haloperidol decanoate and trifluoperazine produced more extrapyramidal adverse effects than olanzapine or quetiapine; and olanzapine was associated with more weight gain than other agents.ConclusionsExcept for apparent superiority of olanzapine and fluphenazine decanoate over chlorpromazine, most agents showed intermediate efficacy for relapse prevention and differences among them were minor. Typical antipsychotics yielded adverse neurological effects, and olanzapine was associated with weight gain. The findings may contribute to evidence-based treatment selection for patients with chronic psychotic disorders.