Comparison of somnolence associated with asenapine, olanzapine, risperidone, and haloperidol relative to placebo in patients with schizophrenia or bipolar disorder

Abstract

Keming Gao,1 Mary Mackle,2 Pilar Cazorla,2 Jun Zhao,2 Armin Szegedi2 1Department of Psychiatry, Mood and Anxiety Clinic in the Mood Disorders Program, Case Western Reserve University, School of Medicine, Cleveland, OH, USA; 2Merck, Rahway, NJ, USA Background: Patients with schizophrenia or bipolar disorder (BPD) may be differentially sensitive to antipsychotics. This study assessed the median time to onset, duration, and rate of somnolence associated with asenapine and other antipsychotics in both indications. Methods: Ten clinical trials (n = 4786) were analyzed as five cohorts pooled according to indication and study design. Results: In the short-term schizophrenia cohort, the incidence of somnolence was 13.1%, 19.1%, 8.5% 5.2%, and 6.9% with asenapine, olanzapine, risperidone, haloperidol, and placebo, respectively. Median time to onset of somnolence was 2 days for asenapine and olanzapine, and 6, 3, and 7 days for risperidone, haloperidol, and placebo, respectively. Median duration was 15 days for asenapine and olanzapine, and 3, 22.5, and 4.5 days for risperidone, haloperidol, and placebo, respectively. In the long-term schizophrenia cohort, the incidence, time to onset, and duration of somnolence with asenapine and olanzapine were 18.4% versus 19.6%, 9.0 days versus 12 days, and 22 days versus 21 days, respectively. In schizophrenia with persistent negative symptoms, the incidence, median time to onset, and duration of somnolence with asenapine and olanzapine were 18.5% versus 21.1%, 9.0 days versus 7.5 days, and 25.0 days versus 41.5 days, respectively. In the monotherapy for BPD cohort, the incidence of somnolence with asenapine, olanzapine, and placebo was 23.8%, 26.4%, and 6.4%, respectively. Median time to onset and duration of somnolence with asenapine, olanzapine, and placebo were 1, 2, and 2 days, respectively, and 7, 8.5, and 5 days. In the adjunctive therapy for BPD cohort, the incidence, median time to onset, and duration of somnolence with asenapine and placebo were 24.0% versus 10.2%, 1.5 days versus 2 days, and 12.5 days versus 7 days, respectively. Conclusion: In the short-term schizophrenia cohort, time to onset and duration of somnolence with asenapine was similar to that with olanzapine and haloperidol. Only asenapine and olanzapine had significantly higher rates of somnolence relative to placebo. The time to onset, duration, and incidence of somnolence with asenapine and olanzapine was similar in patients with long-term schizophrenia and those with BPD. Patients with BPD were more sensitive than those with schizophrenia to asenapine and olanzapine. Keywords: asenapine, somnolence, sedation, schizophrenia, bipolar disorder