Effects of adjunctive brexpiprazole in patients with major depressive disorder and sleep disturbance: a

Introduction: Sleep disturbances are common in major depressive disorder (MDD). This Methods: Data were pooled from three placebo-controlled trials of adjunctive brexpiprazole in patients with MDD and inadequate response to antidepressant treatments (ADTs) (ClinicalTrials.gov identifiers: NCT01360645, NCT01360632, NCT02196506). Using the Hamilton Depression Rating Scale Sleep Disturbance Factor (SDF) (sum of three insomnia items), patients were categorized by high (SDF ≥4) or low (SDF <4) baseline sleep disturbance. Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total, SDF, and other efficacy scores were evaluated for ADT + brexpiprazole 2 or 3 mg versus ADT + placebo. Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs). Results: At baseline, 689/1,160 (59.4%) patients had high sleep disturbance, and 471/1,160 (40.6%) had low sleep disturbance. At Week 6, ADT + brexpiprazole showed greater improvement in MADRS Total score versus ADT + placebo in both subgroups (high SDF: p<0.0001; low SDF: p=0.0058), and greater SDF score improvement in the high SDF subgroup (p=0.021). The incidence of TEAEs was higher with ADT + brexpiprazole than ADT + placebo in the high SDF subgroup (59.8%, 51.6%) and the low SDF subgroup (62.4%, 40.9%). Conclusion: Over 6 weeks, adjunctive brexpiprazole was associated with improved depression severity versus adjunctive placebo, regardless of baseline sleep disturbance. In patients with high baseline sleep disturbance, improvement in sleep disturbance was greater with adjunctive brexpiprazole versus adjunctive placebo, and was generally not accompanied by daytime sedation. No new safety signals were observed within each subgroup.