Benzodiazepine augmentation of antipsychotic drugs in schizophrenia: a meta-analysis and Cochrane review of randomized controlled trials

Abstract

Applying various psychopharmacological combination and augmentation strategies in schizophrenia is common clinical practice. This meta-analysis evaluated the efficacy of benzodiazepines added to antipsychotics. The Cochrane Schizophrenia Group trial register (until February 2011) and PubMed/Medline (until July 2012) were searched for randomized controlled trials (RCTs) with a minimum duration of one week that compared benzodiazepine augmentation of antipsychotics with a control group receiving antipsychotic monotherapy in schizophrenia and schizophrenia-like psychoses. Study selection and data extraction were conducted independently by at least two authors. The primary outcome was response to treatment. Secondary outcomes were positive and negative schizophrenic symptoms, anxiety symptoms, and dropouts due to any reason, inefficacy of treatment, and adverse events. Pooled risk ratios (RRs) with the 95% confidence intervals (CIs) were calculated using a random-effects model, with number-needed-to-treat/harm (NNT/H) calculations where appropriate. Overall, 16 relevant RCTs with 1045 participants were identified. Benzodiazepine augmentation was not associated with statistically significantly more responders (N=6; n=511; RR 0.97, 95% CI 0.77-1.22). Adjunctive benzodiazepines were well accepted and tolerated according to dropout-rates and adverse effects apart from dizziness (N=3; n=190; RR 2.58, 95% CI 1.08-6.15) and somnolence (N=2; n=118; RR 3.30, 95% CI 1.04-10.40). There is no evidence for antipsychotic efficacy of additional benzodiazepine medication in schizophrenia. Therefore, benzodiazepines should be considered primarily for desired ultra short-term sedation of acutely agitated patients but not for augmentation of antipsychotics in the medium- and long-term pharmacotherapy of schizophrenia and related disorders.

Keywords: Antipsychotics; Augmentation treatment; Benzodiazepines; Meta-analysis; Schizophrenia.