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

Stephen Z. Levine, Stefan Leucht

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)812-817
Number of pages6
JournalEuropean Neuropsychopharmacology
Issue number11
StatePublished - Nov 2012


  • Delayed-response
  • Early-response
  • Negative symptoms
  • Scale for the Assessment of Negative Symptoms
  • Treatment

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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