Delayed- and early-onset hypotheses of antipsychotic drug action in the negative symptoms of schizophrenia.

The competing hypotheses that the action onset to antipsychotic medication assumes a course of early- or a delayed-response have been tested in positive and not negative symptoms in schizophrenia. The current study aims to test the early- and delayed-onset hypotheses with regard to negative symptoms. Data were re-analyzed from three clinical trials that compared placebo or amisulpride for up to 60 day. Participants had predominantly negative symptoms of schizophrenia (n=487). Response was examined with the incremental percentage Scale for the Assessment of Negative Symptoms (SANS) reduction over time. Response to the treatment, visit and treatment-visit interaction was assessed with mixed-modeling. Effect size differences on response between the amisulpride and placebo groups were reported at each visit. Across trials, mixed modeling showed that the incremental SANS reductions by the treatment-visit interaction that tests the action-onset hypothesis were not statistically significantly different across periods. The effect size differences of medication less placebo in the incremental percent SANS reduction showed non-significant differences based on overlapping confidence intervals with a moderate improvement at 8-14 day (ES=.33; 95% CI: -.07,.31), the least improvement at 28-30 day (ES=.12; 95% CI: -.07,.31), and a moderate improvement at 42-60 day to (ES=.39, 95%, CI: .19,.60). Generally, early- and delayed-response differences to antipsychotic were limited.