Antipsychotic switching versus augmentation among early non-responders to risperidone or olanzapine in acute-phase schizophrenia

Purpose: We examined whether augmentation with olanzapine would be superior to switching to olanzapine among early non-responders (ENRs) to risperidone, and whether augmentation with risperidone would be superior to switching to risperidone among ENRs to olanzapine. We performed a rater-blinded, randomized clinical trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. ENRs to the initial antipsychotic (Clinical Global Impressions-Improvement Scale: >= 4 at 2 weeks) were allocated to receive either augmentation with or switching to the other antipsychotic (RIS + OLZ vs. RIS-OLZ; OLZ + RIS vs. OLZ-RIS). Results: Sixty patients who completed 2 weeks of risperidone treatment were divided into 33 early responders (RIS-ER) and 27 ENRs (RIS + OLZ, n = 14; RIS-OLZ, n = 13). Although time to treatment discontinuation for any cause was significantly shorter in RIS + OLZ group (54.1 days [95% confidence interval, 41.3-67.0]) than in RIS-ER group (68.7 [61.2-76.2]; P = 0.050), it was not significantly shorter in RIS-OLZ group (58.5 [43.1-73.9]) than in RIS-ER group (P = 0.19). Sixty patients who completed 2 weeks of olanzapine treatment were divided into 36 early responders (OLZ-ER) and 24 ENRs (OLZ + RIS, n = 11; OLZ-RIS, n = 13). Although time to treatment discontinuation for any cause was significantly shorter in OLZ-RIS group (56.1 days [40.7-71.5]) than in OLZ-ER group (74.9 [68.5-81.3]; P = 0.008), it was not significantly shorter in OLZ + RIS group (64.6 [49.6-79.6]) than in OLZ-ER group (P= 0.20). Conclusion: Despite the lack of pharmacokinetic investigation of dose adequacy in this study, it is possible that switching to olanzapine among ENRs to risperidone might have a small advantage over augmentation with olanzapine, while augmentation with risperidone might have a small advantage over switching to risperidone among ENRs to olanzapine. Further research is required before itwould be appropriate tomodify routine practice in the direction of these findings. (C) 2014 The Authors. Published by Elsevier B. V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).