Early prediction of non-response – when should antipsychotic drugs be switched?

Background: Recent meta-analyses have shown that a substantial part of the antipsychotic drug effect in patients with schizophrenia is achieved in the first weeks of treatment. However, the crucial question for treatment is after how much time of ineffective treatment the antipsychotic should rather be switched. Method: We tried to predict non-response at 4 weeks and at 4–6 weeks from the percentage BPRS change at weeks 1 and 2 in two independent large samples of patients from double-blind trials using receiver operator curves and logistic regression analyses. The primary non-response criterion was a less than 25% BPRS reduction. Results: A zero percent BPRS reduction at 2 weeks predicted non-response at 4 weeks with a positive predictive value of approximately 80%. This result was obtained in the first sample and replicated later in an independent second study. When non-response was required to be present at weeks 4, 5 and 6, the findings were similar. Conclusion: Those patients who show no reduction of symptoms at week 2 are very likely not to show even minimal response at weeks 4 to 6 and may therefore benefit from a change of treatment.