title: Treatment response heterogeneity in the predominant negative symptoms of schizophrenia: analysis of amisulpride vs placebo in three clinical trials.
abstract: BACKGROUND
  The extent of heterogeneity in response to the psychopharmacological treatment of negative symptoms is unknown.
  
  
  OBJECTIVE
  To examine the extent of heterogeneity in response to the treatment of predominantly negative symptoms of schizophrenia.
  
  
  METHODS
  Data were analyzed from three clinical trials that compared placebo or amisulpride for up to 60days. Trial participants had predominantly negative symptoms of schizophrenia (n=485). Heterogeneity of percentage reduction on the Scale for the Assessment of Negative Symptoms (SANS) was examined with trajectory-group based modeling followed by descriptive statistics and the prediction of trajectory group membership with logistic regression modeling. Analyses were repeated separately for the placebo and amisulpride groups.
  
  
  RESULTS
  Trajectory group-based modeling identified groups of non- (n=297, 61.2%), gradual-moderate (n=135, 27.8%) and rapid- (n=53, 10.9%) responders. At baseline compared to non-responders, rapid-responders had consistently significantly (p<.05) higher SANS total and subscale scores. Percent SANS improvement at endpoint was greatest for the rapid-responders group, a finding that replicated stratifying by placebo and amisulpride treatment groups. Similarly, in the total sample and stratifying by placebo and amisulpride groups, dropout was not significantly associated with trajectory group membership.
  
  
  CONCLUSIONS
  Trajectories of treatment response to the psychopharmacological medication of the negative symptoms of schizophrenia demonstrate substantial heterogeneity. Approximately half of the patients included in our analysis showed little improvement, and the most severely ill at baseline responded the most.
authors.affiliation: Department of Community Mental Health, University of Haifa, Israel. Electronic address: slevine@univ.haifa.ac.il.
authors.forename: Stephen Z
authors.initials: SZ
authors.lastname: Levine
authors.affiliation: Klinik und Poliklinik für Psychiatrie und Psychotherapie, Klinikum rechts der Isar, Technische Universität München, München, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Leucht
mesh_terms: D000328:Adult; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy*; D013469:Sulpiride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride
keywords: Heterogeneity; Negative symptoms; Scale for the Assessment of Negative Symptoms; Symptom response; Trajectories; Treatment