title: Delayed- and early-onset hypotheses of antipsychotic drug action in the negative symptoms of schizophrenia.
abstract: 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.
authors.affiliation: Department of Community Mental Health, University of Haifa, Haifa 31905, Israel. slevine@univ.haifa.ac.il
authors.forename: Stephen Z
authors.initials: SZ
authors.lastname: Levine
authors.forename: Stefan
authors.initials: S
authors.lastname: Leucht
mesh_terms: D000077582:Amisulpride; D059445:Anhedonia / Q000187:drug effects; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004351:Drug Resistance; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013469:Sulpiride / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride