How many patients with schizophrenia do not respond to antipsychotic drugs in the short term? An analysis based on individual patient data from randomized controlled trials

Objective: An important clinical question is how many patients with acute schizophrenia do not respond to antipsychotics despite being treated for adequate time and with an effective dose. However, up to date, the exact extent of the phenomenon remains unclear. Methods: We calculated the nonresponse and nonremission percentages using individual patient data from 16 randomized controlled trials (RCTs). Six thousand two hundred twenty-one patients were assigned to one antipsychotic (amisulpride, flupenthixol, haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone) at an adequate dose; the response was assessed at 4-6 weeks. As various definitions of nonresponse have been used in the literature, we applied 4 different cut-offs covering the whole range of percent Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) reduction (≤0%, <25%, <50%, <75%).For symptomatic remission, we used the definition proposed by Andreasen without employing the time criterion. Results: The overall nonresponse for the cut-off of ≤0% PANSS/BPRS reduction was 19.8% (18.8%-20.8%); for the cut-off of <25% reduction it was 43% (41.7%-44.3%); for the cut-off of <50% reduction it was 66.5% (65.3%-67.8%); and for the cut-off of <75% reduction it was 87% (86%-87.9%). The overall percentage of no symptomatic remission was 66.9% (65.7%-68.1%). Earlier onset of illness, lower baseline severity and the antipsychotic used were significantly associated with higher nonresponse percentages. Conclusions: Nonresponse and nonremission percentages were notably high. Nevertheless, the patients in our analysis could represent a negative selection since they came from short-term RCTs and could have been treated before study inclusion; thus, further response may not have been observed. Observational studies on this important question are needed.