Predictors of Early Worsening after Switch to Aripiprazole. A Randomized, Controlled, Open-Label Study

Background: Despite the increasing evidence relating to strategies for switching between different antipsychotics, little evidence is available about predictors of improvement or worsening while switching. In a previous study, we compared different options for switching to aripiprazole and found that patients with schizophrenia switched to aripiprazole with immediate discontinuation of the previous antipsychotic showed an increase in symptom severity after 1 week. Objective: To identify predictors of worsening in the first 4 weeks after the switch to aripiprazole in partial non-responders to previous treatments. Methods: This was a 12-week randomized, controlled, open-label study that was carried out in the Department of Psychiatry of the Catholic University of Korea, Seoul, Korea. The study included 77 patients with schizophrenia whose symptoms were not optimally controlled and/or who did not tolerate their current antipsychotic medications well. Patients were randomly assigned to one of three different strategies for switching to aripiprazole 10 mg, i.e.: (i) simultaneous discontinuation of the current antipsychotic; (ii) tapering off the current antipsychotic over 4 weeks with half the dose after the first 2 weeks; or (iii) tapering off the current antipsychotic over 4 weeks after maintenance of the current dose for 2 weeks. The main outcome measure was the difference in Brief Psychiatric Rating Scale (BPRS) scores from baseline to weeks 1, 2 and 4. Results: Baseline severity of disease, as measured by the Clinical Global Impression-Severity Scale, BPRS and Schedule for the Assessment of Negative Symptoms, significantly predicted worsening at weeks 1, 2 and 4. Specifically, lesser disease severity at baseline significantly predicted worsening after switching to aripiprazole. Conclusion: Patients with relatively mild illness severity might be more susceptible to early worsening of symptoms when switched to aripiprazole. However, the limitations of the present study, including a small sample size, absence of a control group designed to control for nonspecific factors such as regression to the mean, and implementation of a switching strategy that included only aripiprazole, mean the present findings should be considered with caution and further research is needed.