Adjunctive lumateperone improves symptoms in major depressive disorder

Lumateperone plus antidepressant therapy (ADT) demonstrates clinically meaningful improvements in depression symptoms and disease severity relative to placebo plus ADT, according to a study.

Adults who had DSM-5‒defined major depressive disorder (MDD) and inadequate response to one to two ADTs in the current depressive episode and a Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥24 were included in this randomized, double-blind, phase III trial.

The investigators randomized participants to 6 weeks of oral placebo plus ADT (n=238) or lumateperone 42 mg plus ADT (n=242) once daily in the evening. The ADT was the latest drug to which the participants had inadequate response (ie, <50-percent improvement).

The change from baseline to day 43 in MADRS total score and Clinical Global Impression Scale severity (CGI-S) score were the primary and secondary outcomes, respectively.

At day 43, lumateperone plus ADT significantly improved MADRS total score (least squares mean difference [LSMD] vs placebo, ‒4.5; effect size, ‒0.56) and CGI-S score (LSMD, ‒0.5; effect size, ‒0.51) compared with placebo plus ADT.

Likewise, patient-reported depression improved significantly in the lumateperone arm vs the placebo arm (16-item Quick Inventory of Depressive Symptomatology‒Self-Report, total score: LSMD, ‒2.2; effect size, ‒0.45).

Lumeteperone plus ADT was generally well tolerated. The most common treatment-emergent adverse events (TEAEs) were dizziness, somnolence, nausea, fatigue, diarrhoea, and dry mouth. The proportion of patients who discontinued treatment due to TEAEs were greater in the lumateperone plus ADT arm than the placebo plus ADT arm (12.4 percent vs 0.8 percent).

The risk of extrapyramidal symptoms was minimal. Cardiometabolic abnormalities and weight gain did not differ significantly between the two treatment groups. Furthermore, there was low emergence of suicidal ideation.