A multicentre, double-blind, randomized comparison of quetiapine (ICI 204,636, ‘Seroquel’) and haloperidol in schizophrenia

Background. Quetiapine (ICI 204,636, ‘Seroquel’) is a new atypical antipsychotic agent with a similar binding profile to the original atypical antipsychotic, clozapine. Its clinical efficacy has already been demonstrated at multiple fixed doses (150–750 mg/day) and has been suggested to be comparable with haloperidol (12 mg/day).Methods. This international, 6-week, multicentre, double-blind, randomized, parallel-group trial compared quetiapine with haloperidol (455 mg and 8 mg mean total daily doses, respectively) in 448 hospitalized patients with acute exacerbation of chronic or subchronic schizophrenia (DSM-III-R), in order to establish their equivalence in terms of efficacy, and the nature of their tolerability profiles, especially in terms of extrapyramidal symptoms (EPS) and serum prolactin levels.Results. Both quetiapine and haloperidol produced a clear reduction in the Positive and Negative Syndrome Scale (PANSS) scores and Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores. At day 42, the PANSS total score was reduced by −18·7±1·63 in the quetiapine group, and −22·1±1·63 in the haloperidol group (P = 0·13, between-treatment).Quetiapine was better tolerated than haloperidol in terms of EPS as demonstrated by the significant differences in the Simpson Scale and Abnormal Involuntary Movement Scale scores (P<0·05). Although patients in both groups had elevated serum prolactin concentrations at baseline, mean serum prolactin concentration decreased (by 16·5 μg/l) in quetiapine-treated patients, yet increased (by 5·9 μg/l) in patients treated with haloperidol.Conclusion. Quetiapine is an effective and well tolerated antipsychotic of comparable efficacy to haloperidol and lacks the latter compound's effect on prolactin and EPS.

Quetiapine: Results of four phase II and III clinical trials

SummaryThe data on efficacy and tolerance from four (phase II and III) trials of quetiapine (Seroquel® or ICI 204,636) in a total of 1,461 patients with acute exacerbations of chronic or sub-chronic schizophrenia are briefly reviewed. Together, the results of these trials have demonstrated antipsychotic efficacy in comparison with placebo and equivalent efficacy to haloperidol. In spite of its short plasma elimination half-life, quetiapine is equally effective when given in twice-daily and three-time daily doses. The optimum dose is between 300 mg and 400 mg per day, and the main and most consistent adverse effect is sedation. It has a low extrapyramidal side effect liability and does not produce sustained elevations in plasma prolactin levels.