ADJUNCTIVE LUMATEPERONE 42 MG TREATMENT IN MAJOR DEPRESSIVE DISORDER: EFFICACY ACROSS PATIENT-REPORTED DEPRESSION SYMPTOMS

Background

Lumateperone is an atypical antipsychotic indicated for: treatment of schizophrenia in adults; treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate; and treatment of major depressive disorder (MDD) in adults as adjunct to antidepressant therapy (ADT). In the Phase 3, randomized, double-blind, placebocontrolled Study 501 trial (NCT04985942), adjunctive lumateperone 42mg met the primary endpoint, significantly improving Montgomery-Asberg Depression Rating Scale (MADRS) Total score vs adjunctive placebo and was generally well tolerated in patients with MDD with inadequate response to ADT. This analysis of Study 501 evaluated the efficacy of adjunctive lumateperone 42mg across patient-reported depression symptoms in patients with MDD, as measured by individual item scores of the Quick Inventory of Depressive SymptomatologySelf Report-16 item (QIDS-SR-16) collected at baseline and week 6/end of treatment (EOT).

Methods

Eligible adults (18-65 years) met DSM-5 criteria for MDD with inadequate response to 1-2 ADT courses and had MADRS Total score ≥24, Clinical Global ImpressionSeverity scale score ≥4, and QIDS-SR-16 item score ≥14. Patients were randomized 1:1 to 6week oral lumateperone 42mg or placebo adjunctive to ADT. Change from baseline in QIDSSR-16 Total score at EOT was measured using an analysis of covariance (ANCOVA) in the intent-to-treat (ITT) population. Post hoc analyses measured changes using an ANCOVA in the ITT population in the 9 symptom domains of the QIDS-SR-16 score: sleep disturbance (highest score of items 1-4), sad mood, appetite/weight (highest score of items 6-9), concentration, self-criticism, suicidal ideation, interest, energy/fatigue, and psychomotor (highest score of items 15-16).

Results

Of 484 patients in the ITT population (lumateperone+ADT, n=241; placebo+ADT, n=243), 93.4% (n=452) completed treatment. Lumateperone+ADT significantly improved QIDS-SR-16 Total score vs placebo+ADT from baseline to EOT (least squares mean difference [LSMD]=−2.4; effect size [ES]=−0.50; P < .0001). The QIDS-SR-16 symptom domains with highest baseline scores were sleep disturbance (mean: lumateperone+ADT, 2.7; placebo+ADT, 2.7) and feeling sad (lumateperone+ADT, 2.6; placebo+ADT, 2.6). From baseline to EOT, 8 of 9 QIDS-SR-16 symptom domains significantly improved with lumateperone+ADT vs placebo+ADT: sleep disturbance (LSMD, −0.5; ES, 0.55; P < .0001); sad mood (LSMD, −0.4; ES, 0.44; P < .0001); appetite/weight change (LSMD, −0.2; ES, 0.22; P < .05); concentration (LSMD, −0.2; ES, 0.28; P < .01); self-criticism (LSMD, −0.1; ES, 0.17; P=.065); suicidal ideation (LSMD, −0.1; ES, 0.19; P < .05); interest (LSMD, −0.3; ES, 0.29; P < .01); energy/fatigue (LSMD, −0.2; ES, 0.29; P < .01); and psychomotor agitation/retardation (LSMD, −0.2; ES, 0.30; P < .01).

Conclusion

In patients with MDD with inadequate ADT response, lumateperone 42mg adjunctive to ADT significantly improved a broad range of patient-reported depressive symptoms vs placebo, indicating lumateperone as a promising adjunctive therapy to ADT in this setting.