Time to Clinical Response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study

Abstract

Objectives: We investigated the time course of clinical response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study (TEOSS). Methods: TEOSS randomized 119 predominantly outpatient youth ages 8-19 years with schizophrenia or schizoaffective disorder to 8 weeks of treatment with molindone, risperidone, or olanzapine. We used proportional hazards regression to determine whether these three antipsychotics differed in the time until clinical response, defined as the time from treatment initiation to the point of achieving a Clinical Global Impressions-Improvement (CGI-I) scale score of 1 ("very much improved") or 2 ("much improved") that was maintained until week 8. Results: Of the 116 youth who initiated treatment, 56 (48%) achieved clinical response. Among clinical responders, the median (±interquartile range) time until clinical response was 4.0 (±4.0) weeks for olanzapine, 4.5 (±4.0) weeks for risperidone, and 6.0 (±4.0) weeks for molindone. There were no significant differences in time course for clinical response between medications (p = 0.84). Youth without symptom improvement (CGI-I ≥ 4) after 3 weeks were more likely to be clinical nonresponders at week 8 (relative risk ratio = 1.98, 95% confidence interval 1.29-3.05), compared with youth with at-least-minimal symptom improvement after 3 weeks when looking at all antipsychotics combined. Conclusion: To our knowledge, our study is the first to investigate medication differences in treatment response timing in early onset schizophrenia spectrum disorders. Clinical response times for molindone, risperidone, and olanzapine were not significantly different. Furthermore, while lack of early improvement predicted clinical nonresponse, whether or not to continue antipsychotic treatment after 3 or more weeks without symptom improvement should be based on clinical judgment after weighing potential risks, benefits, and alternatives. ClinicalTrials.gov Identifier: NCT00053703.

Keywords: antipsychotic; children and adolescents; early intervention; pediatric; psychosis; randomized controlled trial.

Conflict of interest statement

M.H.B. receives research support from Therapix Biosciences, Neurocrine Biosciences, Janssen Pharmacueticals, and Biohaven Pharmaceuticals, and he serves on the scientific advisory boards of Therapix Biosciences and Teva Pharmaceuticals, none of whom provided support for the current study. There are no conflicts of interest and no relevant disclosures for any other authors.

Figures

FIG. 1.

Distribution of clinical response times for those who responded to molindone, olanzapine, and risperidone.

FIG. 2.

Kaplan–Meier plot showing likelihood of achieving clinical response by week.