Quetiapine and long-term weight change: a comprehensive data review of patients with schizophrenia.

BACKGROUND: To assess the magnitude and pattern of weight change during long-term treatment with the atypical antipsychotic quetiapine. METHOD: Data were collected from patients with a DSM-IV diagnosis of schizophrenia treated with quetiapine in the AstraZeneca clinical trials program from July 1993 to May 1999. Weight changes in patients treated for 12, 52, and 104 weeks were analyzed; the primary parameter was the change in weight at week 52. RESULTS: In total, 352 patients were treated with quetiapine for 52 weeks. The mean weight gain at this timepoint was 3.19 kg; median weight gain was 2.5 kg. Overall, 37% of patients gained >or= 7% of their baseline body weight; however, the degree of weight gain was inversely related to baseline body mass index in this cohort. In patients treated with < 200 mg/day of quetiapine, mean weight gain was 1.54 kg, compared with 4.08 kg for 200 to 399 mg/day, 1.89 kg for 400 to 599 mg/day, and 3.57 kg for >or= 600 mg/day; median weight gain was 0.95 kg, 3.40 kg, 2.00 kg, and 3.34 kg, respectively. Analysis of longitudinal weight changes indicated that most weight gain (> 60%) occurred within the first 12 weeks of quetiapine treatment, with modest changes after 6 months. CONCLUSIONS: Long-term treatment with quetiapine monotherapy is associated with moderate weight gain. Most weight gain occurs within the first 12 weeks of treatment and has no clear dose relationship.

Efficacy and tolerability of quetiapine in patients with schizophrenia who switched from haloperidol, olanzapine or risperidone.

A post hoc analysis of the SPECTRUM trial was carried out to evaluate whether the improvements in efficacy and tolerability gained on switching to quetiapine occurred consistently for patients previously treated with either: haloperidol (n = 43); olanzapine (n = 66); or risperidone (n = 55) monotherapy. Patients were initiated with quetiapine to 400 mg/day over 7 days, and then flexibly dosed (300-750 mg/day) for 11 weeks. The mean (SD) modal dose of quetiapine was 501 (138) mg/day in the haloperidol subgroup, 472 (147) mg/day in the olanzapine subgroup and 485 (141) mg/day in the risperidone subgroup at the study endpoint. Switching to quetiapine induced significant improvements from baseline in PANSS scores, with least square mean changes in total scores of -32.5, -15.4, and -18.5 for patients previously treated with haloperidol, olanzapine and risperidone, respectively, (all p < 0.001 vs baseline). Significant improvements were also noted in CDSS scores, particularly for patients clinically depressed at baseline (all p < 0.001 vs baseline). There were significant reductions in EPS on the SAS and BAS for all subgroups (all p < 0.001 vs baseline). Switching to quetiapine produced efficacy and tolerability benefits regardless of whether their previous antipsychotic was haloperidol, olanzapine or risperidone.

Differential effect of quetiapine on depressive symptoms in patients with partially responsive schizophrenia.

While atypical antipsychotics appear to be effective in reducing depressive symptoms in the acute phase of schizophrenia, little is known about their efficacy in patients with ongoing symptoms. The present study assessed whether quetiapine (Seroquel) is more effective than haloperidol in treating depressive symptoms in patients with persistent positive symptoms, and investigated whether this effect is independent, or secondary to, reductions in other symptoms such as positive, negative or extrapyramidal symptoms. Patients with schizophrenia and a history of partial refractoriness to conventional antipsychotics who had not responded to 4 weeks of fluphenazine treatment (20 mg/day) were randomized to receive either quetiapine (600 mg/day) or haloperidol (20 mg/day) for a further 8 weeks. Change in the Positive and Negative Syndrome Scale depression factor score from baseline to endpoint was calculated and path analyses were performed on data from 269 patients. Quetiapine produced a greater reduction in depressive scores than haloperidol (-1.60 versus -0.54; p = 0.006). The path analyses indicated that this was a direct effect on depressive symptoms. These findings extend the evidence for an antidepressant effect for the novel antipsychotics in schizophrenia, and suggest that this is not limited to acutely psychotic patients.