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, placebo-controlled Study 501 trial (NCT04985942), lumateperone 42 mg + ADT met the primary endpoint, significantly improving Montgomery-Asberg Depression Rating Scale (MADRS) Total score vs placebo + ADT 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 42 mg across patient-reported depression symptoms in patients with MDD, as measured by individual item scores of the Quick Inventory of Depressive Symptomatology-Self 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 Impression-Severity scale score ≥4, and QIDS-SR-16 item score ≥14. Patients were randomized 1:1 to 6-week oral lumateperone 42mg or placebo adjunctive to ADT. Change from baseline in QIDS-SR-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).

Conclusions

In patients with MDD with inadequate ADT response, lumateperone 42 mg 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.

References

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