Mega-review of meta-analyses investigating the short-term efficacy of pharmacologic augmentation strategies of antipsychotics in patients with schizophrenia

Abstract

Antipsychotics are the cornerstone of treatment for schizophrenia, but they have limited effectiveness, as most patients require subsequent strategies at some point of their treatment. Despite being widely used, the efficacy of pharmacologic augmentation of antipsychotics is controversial and no combination treatment has been approved for schizophrenia. We conducted a systematic review in PubMed and PsycInfo on June 1st 2015 and a random effects meta-analysis of meta-analyses of short-term, placebo-controlled studies of pharmacological augmentation strategies of antipsychotics in schizophrenia. Methodological quality of meta-analyses was measured using the AMSTAR, plus 6 additional items developed to rate the content quality of the meta-analyzed trials. Out of 3062 publications, we identified 36 eligible augmenting strategies. For total symptom reduction, 25 strategies augmenting antipsychotics and 5 strategies augmenting clozapine were eligible and examined. Eleven strategies were more efficacious than placebo, none of them augmenting clozapine. Significant effect sizes ranged between SMD −1.03 and −0.23. Efficacy was not correlated with the quality of the meta-analyses. Only the meta-analysis for NSAIDs augmentation had a score greater than half of the possible points for content quality. Only antipsychotics, azapirones, antidepressants and lithium were less discontinued than placebo. Serotonin-3-receptor antagonists, lamotrigine, mirtazapine/mianserine, minocycline and estrogens had large effect sizes augmenting antipsychotics. However the quality of the content of most meta-analyses was low. The NSAIDs augmentation meta-analysis had the best content quality, yet with a low effect size for efficacy. The evidence for short-term augmentation strategies of antipsychotics in schizophrenia is inconclusive, due to the limited quality of the available trials.Disclosure of interestThe authors have not supplied their declaration of competing interest.