Optimal thresholds of early response to atypical antipsychotics: Application of signal detection methods

ObjectiveIdentify the optimal magnitude of response to antipsychotic medication at various early time points that best predicts subsequent non-response at 8 weeks.MethodsData were pooled from 5 randomized, double-blind clinical trials of atypical antipsychotics in the treatment of schizophrenia and related disorders (n = 1137 moderately-to-severely ill; n = 300 less than moderately ill). Signal detection methods (receiver-operating characteristic curves) were used to identify the optimal response threshold based on percent change from baseline on the PANSS total score at different early time points (Weeks 1–4) to predict subsequent ‘non-response’ at 8 weeks (i.e., not ‘minimally improved’, ‘much improved’ or ‘remitted’) while holding the false positive rate to a level of 30% or less. Analyses were implemented separately for patients with schizophrenia who differed on baseline illness severity.ResultsUsing Area Under the Curve (AUC) ≥ 0.8 to define optimal discriminative ability at the earliest time point, the early response threshold in moderately-to-severely ill patients for predicting not ‘minimally improved’ was < 15% reduction in PANSS total at Week 2, not ‘much improved’ was < 23% at Week 2, and not ‘remitted’ was < 26% at Week 4. Similarly, in less than moderately ill patients, the optimal early response threshold for predicting not ‘minimally improved’ was < 12% reduction in PANSS total at Week 2, and not ‘much improved’ was < 14% at Week 1.ConclusionSpecific thresholds of response were identified at early time points for predicting subsequent non-response. Not attaining these early response thresholds may serve as important clinical markers of subsequent non-response to antipsychotic therapy.