A comparison between augmentation with olanzapine and increased risperidone dose in acute schizophrenia patients showing early non-response to risperidone

We examined whether augmentation with olanzapine would be superior to increased risperidone dose among acute schizophrenia patients showing early non-response to risperidone. We performed a rater-blinded, randomized controlled trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as Clinical Global Impressions-Improvement Scale score ≤ 3 following 2 weeks of treatment. Early non-responders were allocated to receive either augmentation with olanzapine (RIS + OLZ group) or increased risperidone dose (RIS + RIS group). The 78 patients who completed 2 weeks of treatment were divided into 52 early responders to risperidone and 26 early non-responders to risperidone (RIS + OLZ group, n = 13; RIS + RIS group, n = 13). No difference in the achievement of ≥ 50% improvement in Positive and Negative Syndrome Scale total score was observed between RIS + OLZ and RIS + RIS groups. Although time to treatment discontinuation for any cause was significantly shorter in the RIS + RIS group (6.8 weeks [95% confidence interval, 5.2–8.4]) than in early responders to risperidone (8.6 weeks [7.9–9.3]; P = 0.018), there was no significant difference between the RIS + OLZ group (7.9 weeks [6.3–9.5]) and early responders to risperidone. Secondary outcomes justify the inclusion of augmentation arms in additional, larger studies comparing strategies for early non-responders.