Prediction of Response to Antipsychotic Drugs in Schizophrenia Patients within the Early Phase of Treatment

Abstract

Objective: Currently, schizophrenia guidelines recommend waiting for 3 to 6 weeks before considering a patient as non-responder. However, recent studies indicate that the response to antipsychotic medications starts within the first two weeks of treatment. The aim of this study is to determine the predictive value of early improvement at 2 or 4 weeks for non-response at 6 weeks. Methods: Twenty seven in- and out-patients with a diagnosis of schizophrenia according to DSM-IV, between the ages of 18 to 65 years, who were moderately-to-severely ill (baseline Positive and Negative Syndrome Scale (PANSS) total score ≥ 75, with at least “moderate” level of severity / score>4 on at least 2 of the 4 Brief Psychiatric Rating Scale (BPRS) psychotic cluster items) were included. Ten patients were receiving antipsychotic treatment for the first time, and 17 patients’ treatment was changed due to nonresponse to prior antipsychotic treatment. The patients were evaluated with the PANSS and the Clinical Global Impression-Severity (CGI-S) scale at 0, 2, 4 and 6 weeks of antipsychotic treatment. Non-response at endpoint was defined in 3 different ways to reflect the variations in the level of response to medication: “not minimally improved”, “not much improved” and “not remitted”. As previously described, “not minimally improved” and “not much improved” were defined as less than 28% and 53% improvement in the PANSS total scores, respectively. “Not remitted” was defined according to the criteria developed by “The Remission in Schizophrenia Working Group” without the time criterion. Signal detection methods using receiver operating characteristics (ROC) curves were implemented to detect the optimal threshold of early nonresponse at 2 and 4 weeks. Total accuracy, sensitivity, specificity and positive and negative predictive value of cut-off points were calculated for predicting “not minimally improved”, “not much improved” and “not remitted” at endpoint. Results: The early response threshold for predicting “not minimally improved’ was less than 15.3% reduction in PANSS total score at week 2, less than 15.5% reduction at week 4. The early response threshold for predicting “not much improved” was less than 22.1% reduction at week 2 and less than 44.3% reduction at week 4; for “not remitted” was less than 71.5% reduction at week 2 and less than 23.2% reduction at week 4. Specific thresholds of “much improvement” and “remission” were not identified at week 2, whereas thresholds calculated for week 4 had good discriminative power. Conclusion: The findings of this study did not support the findings of earlier studies indicating that nonresponse at 2 weeks accurately predicts subsequent lack of response in patients with schizophrenia. Instead, the findings revealed that non-response could best be predicted at 4 weeks as in some other previous studies. The question of which time point for early prediction of response could be best predicted in schizophrenia patients needs to be further addressed in subsequent studies with larger sample size.