Pimozide for schizophrenia or related psychoses

Abstract

Background: Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained deaths. Electrocardiogram monitoring is now required before and during use.

Objectives: To assess the clinical effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder.

Search strategy: We searched the Cochrane Schizophrenia Group's Register (July 2005).

Selection criteria: We sought all relevant randomised clinical trials comparing pimozide with other treatments.

Data collection and analysis: Working independently, we inspected citations, ordered papers, and then re-inspected and quality assessed the studies and extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), 95% confidence interval (CI), and, where appropriate, the number needed to treat (NNT) and the number needed to harm (NNH), on an intention-to-treat basis. We calculated weighted mean differences (WMD) for continuous data. We excluded data if loss to follow-up was greater than 50%.

Main results: We found 35 relevant studies (total n=1348), all including people with schizophrenia but none with delusional disorder. 123 people were randomised to pimozide versus placebo. Data suggest that pimozide prevents relapse (2 RCTs, n=66, RR 0.45 CI 0.2 to 0.9, NNT 4 CI 3 to 22). Compared with typical antipsychotic drugs, pimozide has similar efficacy for outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotic drugs. Pimozide was more likely than typical antipsychotic drugs to cause tremor in the short-term (6 RCTs, n=192, RR 1.6 CI 1.1 to 2.3, NNH 6 CI 3 to 44) and lead to need for antiparkinsonian medication (4 RCTs, n=124, RR 1.8 CI 1.2 to 2.6, NNH 3 CI 2 to 5) than other drugs. In the medium-term, however, pimozide was less likely to cause sedation (5 RCTs, n=231, RR 0.6 CI 0.5 to 0.9, NNH 6 CI 4 to 16).

Authors' conclusions: Although there are shortcomings in the data, there is enough overall consistency over different outcomes and time scales to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. There are no data to support or refute its use for those with delusional disorder.