The profile and time-course of symptom response in acute schizophrenia is unclear. For the present study, we hypothesized that the time-course would be nonlinear. A meta-analysis was performed using randomized, controlled clinical trials of five atypical antipsychotics reported in nine electronic databases. Studies were of subjects experiencing an acute exacerbation of illness, with multiple BPRS or PANSS data-points as outcome measures. A mixed factorial repeated-measures ANOVA was used. Twenty-one published clinical trials were identified. Reduction in total symptoms from baseline to 4 wk was associated with a linear decline in symptomatology (F=23.4, d.f.=1, 7, p=0.002) without attenuation of effect. In contrast, from baseline to 6 wk the linear symptom reduction (F=76.5, d.f.=1, 12, p<0.001) eventually flattened at the end of the trial (F=87.2, d.f.=1, 12, p<0.001). Secondary analyses showed a similar pattern for typical antipsychotics, and the same profile for risperidone and olanzapine as for atypical agents as a whole. Inclusion of LOCF data altered the results at 4 wk, but not 6 wk; completion rates had no effect on results. In conclusion, this meta-analysis confirms our hypothesis for 6-wk data. The profile of symptom change is one of linear symptom reduction until 4 wk, with a flattening of treatment effects by 6 wk. A curvilinear profile of schizophrenia symptom reduction has possible implications with respect to trial design and clinical decision-making.
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