Efficacy, safety and tolerability of quetiapine: short-term high doses with long-term follow-up.

Introduction Quetiapine is effective and well tolerated in the treatment of schizophrenia at doses up to 800 mg/day, but data on its use at doses above this level are limited. Methods In this open-label study, 35 hospitalised patients with schizophrenia, schizoaffective disorder, bipolar disorder or alcohol-induced psychosis, who received quetiapine at doses up to 1600 mg/day in a 4-week acute phase, were followed for up to 14 months as outpatients. The primary efficacy measure was the Clinical Global Impression of Improvement (CGI-I) scale. Results At the end of the 4-week hospitalisation period, overall 94.3% of patients had experienced improvements in symptoms, with 37.1% "very much improved", 37.1% "much improved", and 20% "minimally improved", according to the CGI-I scale. No patient experienced a worsening of symptoms during quetiapine treatment and there was no change in two (5.7%) patients. Among the 12 patients receiving >800 mg/day, 10 (83.3%) were "very much" or "much improved". Quetiapine was well tolerated: no increase in extrapyramidal symptoms or other adverse events was observed even at doses above 800 mg/day, with no changes in safety parameters. Conclusion Results indicate that short-term quetiapine therapy at doses up to 1600 mg/day, with maintenance doses up to 1000 mg/day, may be an effective and well-tolerated treatment for patients with psychoses who require high doses of antipsychotics for difficult-to-treat symptoms. However, large randomised, controlled trials are required to confirm these findings.