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

Abstract

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. 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. 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. 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.