Zotepine in the prevention of recurrence: a randomised, double-blind, placebo-controlled study for chronic schizophrenia.

RATIONALE: Zotepine is an antipsychotic drug with proven efficacy for treatment of acute episodes of schizophrenia. Antipsychotic drugs also require to be effective in prevention of recurrence.

OBJECTIVE

This trial was designed to compare the effects of zotepine and placebo in the prevention of recurrence of acute episodes in a population of patients with chronic schizophrenia.

METHODS

The study was a double-blind, parallel group, 26-week comparison of zotepine (300 mg daily, with fall back to 150 mg if necessary) versus placebo in 121 patients with chronic schizophrenia and a history of recurrence in the previous 18 months. The primary outcome measure was the time to recurrence. Other evaluations included the brief psychiatric rating scale (BPRS), the scale for the assessment of negative symptoms (SANS), the clinical global impression (CGI) severity and improvement scales, and the Simpson and Angus scale for extrapyramidal symptoms (EPS).

RESULTS

Fewer zotepine patients experienced recurrence over 26 weeks than placebo patients (4 versus 21, respectively). The estimated 26-week risk of recurrence was six times lower for zotepine than placebo (8.7% versus 52.8%; hazard ratio 0.16, 95% CI 0.053, 0.484; P<0.001). Scores on the BPRS and CGI supported the efficacy of zotepine. There was no difference between the treatments with respect to EPS.

CONCLUSIONS

Zotepine is effective in preventing recurrence in patients with chronic schizophrenia. The level of EPS was not different between zotepine and placebo.