Efficacy of quetiapine for the treatment of schizophrenia: a combined analysis of three placebo-controlled trials

SUMMARY

Objective: To determine the effectiveness of quetiapine (Seroquel*) against specific aspects of schizophrenic symptomatology.

Research design and methods: Combined data from three placebo-controlled, double-blind, randomised trials that had previously demonstrated quetiapine’s overall clinical effectiveness and tolerability were analysed. Efficacy assessments evaluated were the Clinical Global Impression (CGI) Severity of Illness score, Brief Psychiatric Rating Scale (BPRS) factors I–V, BPRS positive symptom cluster score and 18 individual BPRS items. The Simpson–Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), changes in weight and prolactin concentrations and the recording of adverse events comprised the main tolerability measures.

Results: Efficacy assessments were available for a total of 426 quetiapine patients (mean age 36.9 years) with a DSM-IIIR diagnosis of schizophrenia; 502 patients were included in the tolerability analyses. The mean quetiapine dose was 300.5 mg/day with a mean maximum dose of 686.0 mg/day. Quetiapine was efficacious across a broad range of symptoms, including depression, anxiety and hostility. Significant improvements compared with placebo were noted for CGI Severity of Illness ( p < 0.001) and in 14 of the 18 individual BPRS items ( p < 0.001). Positive symptoms also improved ( p < 0.01 at Week 2 and p < 0.001 from Week 3); greater improvements were observed in patients who received at least 400 mg/day quetiapine. Quetiapine was generally well tolerated: 4.0% of patients withdrew from treatment due to adverse events compared with 3.0% of placebo patients. Akathisia occurred in 2.0% and 2.5% of quetiapine and placebo patients, respectively. Similar decreases in prolactin levels for quetiapine (–10.0 µg/L) and placebo (–10.9 µg/L) were noted from baseline to end of treatment. Agitation and headache, the most common adverse events, were comparable in the quetiapine and placebo groups (agitation: 19.3% vs. 20.3%, respectively; headache: 19.1% vs. 17.3%, respectively).

Conclusions: The results of this combined analysis confirm the individual findings of the three pivotal studies to demonstrate that quetiapine is effective across several domains of schizophrenia, improving positive, negative and depressive symptoms and reducing agitation, aggression and hostility. Similarly, the analysis reiterated the good tolerability profile of quetiapine, particularly in terms of its placebo-like effects on prolactin levels and incidence of extrapyramidal symptoms (EPS).

Key words: :

• BPRS
• CGI
• Combined analysis
• Efficacy
• Quetiapine