Elaboration on the Early-Onset Hypothesis of Antipsychotic Drug Action: Treatment Response Trajectories

Stephen Z. Levine, Stefan Leucht

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalBiological Psychiatry
Issue number1
StatePublished - 1 Jul 2010
Externally publishedYes


  • Course
  • early treatment response
  • heterogeneity
  • rapid response
  • trajectories


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