Elaboration on the early-onset hypothesis of antipsychotic drug action: treatment response trajectories

Biol Psychiatry. 2010 Jul 1;68(1):86-92. doi: 10.1016/j.biopsych.2010.01.012. Epub 2010 Mar 15.


Background: To extend the early treatment response literature, this article aims to quantify the extent of heterogeneity and describe the characteristics of treatment response trajectories in schizophrenia.

Methods: Data were extracted from two double-blind, randomized clinical trials that compared amisulpride with risperidone in schizophrenia (n = 538). Available Brief Psychiatric Rating Scale (BPRS) administrations from baseline to Week 8 were used to assess treatment response. Trajectories were calculated with mixed-mode latent class regression modeling from which groups were derived. These groups were compared on clinical and background characteristics.

Results: At Week 8, five treatment response trajectories were identified, undifferentiated by medication received, and characterized by varied amelioration levels. Three trajectory groups (n = 414, 76.9%) showed a treatment response trend of amelioration. Of these, two trajectory groups had similar dropout rates (22%, 25%), and two did not significantly differ on BPRS % reduction (approximately 55%, approximately 58%). Trajectory Group 2 (n = 44, 8.2%) was characterized by being oldest, a 21.3 BPRS % reduction, the highest BPRS severity scores, the highest dropout rate (61.4%), and 11.8% meeting Andreasen's remission criterion. Among Trajectory Group 4 (n = 80, 14.9%) symptom reduction was considerable during the first 2 weeks and then gradual. This trajectory group was characterized by being youngest, male, suffering from paranoid schizophrenia, the lowest dropout rate (6.3%), average BPRS baseline scores, an 88.9% BPRS reduction, and 96% meeting Andreasen's remission criterion.

Conclusions: Generally, amelioration characterizes early treatment response, such that approximately 77% are moderate responders, approximately 15% are rapid treatment responders, and approximately 8% are poor responders.

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Brief Psychiatric Rating Scale
  • Chi-Square Distribution
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic
  • Schizophrenia / diagnosis*
  • Schizophrenia / drug therapy*
  • Time Factors


  • Antipsychotic Agents