Clozapine Monotherapy as a Treatment for Antipsychotic-Induced Tardive Dyskinesia: A Meta-Analysis

Objective: Tardive dyskinesia (TD) is an antipsychotic-induced movement disorder that typically occurs after long-term exposure to antipsychotic drugs. There is evidence that switching to clozapine reduces TD. This meta-analysis reviews the effect of switching to clozapine on the severity of TD.

Data Sources: The PubMed, PsycINFO, and Embase databases were searched for clozapine, tardive dyskinesia, and related keywords. The search was restricted to articles written in English and Dutch, and it was last updated on October 13, 2015.

Study Selection: Sixteen studies were included in the meta-analysis. Inclusion criteria were a diagnosis of schizophrenia or a related disorder, a switch to clozapine monotherapy, and reports of scores on a TD rating scale before and after the switch to clozapine.

Data Extraction: Two independent investigators extracted the data. Data were converted to standardized mean change scores and analyzed in a random-effects model.

Results: A random-effects model showed that the overall effect of switching to clozapine was a significant reduction in TD (npatients = 1,060, d = −0.40, P < .01), especially in the 4 studies that investigated the severity of TD as a primary outcome (npatients = 48, d = −2.56, P = .02).

Conclusions: The overall results show that clozapine treatment can yield a slight reduction in TD. The severity of TD was reduced greatly in patients with moderate to severe TD. In patients with minimal to mild TD, switching to clozapine seldom worsens TD and a trend toward reduction is seen. These results support that a switch to clozapine should be considered for patients with moderate to severe TD and/or patients who experience substantial discomfort due to TD.