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 treat ment of acute episodes of schizophrenia. Antipsychotic drugs also require t o be effective in prevention of recurrence. Objective: This trial was desig ned to compare the effects of zotepine and placebo in the prevention of rec urrence of acute episodes in a population of patients with chronic schizoph renia. Methods: The study was a double-blind, parallel group, 26-week compa rison of zotepine (300 mg daily, with fall back to 150 mg if necessary) ver sus placebo in 121 patients with chronic schizophrenia and a history of rec urrence in the previous 18 months. The primary outcome measure was the time to recurrence. Other evaluations included the brief psychiatric rating sca le (BPRS), the scale for the assessment of negative symptoms (SANS), the cl inical global impression (CGI) severity and improvement scales, and the Sim pson and Angus scale for extrapyramidal symptoms (EPS). Results: Fewer zote pine 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 0.1 6, 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 r espect 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.