Evaluation of Sexual Function With Adjunctive Lumateperone in Patients With Major Depressive Disorder.

Anita H Clayton; Willie R Earley; Susan G Kozauer; Yifan Mo; John B Edwards; Suresh Durgam

doi:10.4088/jcp.26m16387

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Evaluation of Sexual Function With Adjunctive Lumateperone in Patients With Major Depressive Disorder.

Anita H Clayton·Willie R Earley·Susan G Kozauer·Yifan Mo·John B Edwards·Suresh Durgam

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Abstract

Objective: Lumateperone is an atypical antipsychotic to treat schizophrenia, bipolar I or II depression, and major depressive disorder (MDD). Randomized phase 3 Study 502 (NCT05061706) investigated the impact of adjunctive lumateperone 42 mg/day on sexual functioning, per Changes in Sexual Functioning Questionnaire 14-item version (CSFQ-14). Methods: Adults meeting DSM-5 criteria for MDD with inadequate response to 1-2 antidepressant therapies (ADTs) in the current depressive episode, Montgomery-Åsberg Depression Rating Scale Total score ≥24, Clinical Global Impression Scale-Severity score ≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16-item score ≥14 were randomized to 6-week lumateperone 42 mg+ADT or placebo+ADT. Sexual function was assessed by CSFQ-14 Total and domain scores in the intent-to-treat (ITT) population and subgroups. Results: Of 480 patients in the ITT population, 82.5% had sexual dysfunction at baseline (women=284; men=112). Lumateperone+ADT significantly improved CSFQ-14 Total score at Day 43 vs placebo+ADT (least squares mean difference [LSMD]=2.7; effect size [ES]=0.38; P<.0001). Significantly greater improvements were observed in patients with baseline sexual dysfunction (LSMD=3.1; ES=0.42; P<.0001), with no change in those without. Improvements were observed in women (LSMD=3.5; ES=0.47; P<.0001) and in men (LSMD=1.9; ES=0.33; P=.08). Significant improvements in CSFQ-14 Total score at Day 43 were observed across age groups and CSFQ domain scores, with both sexes having significant improvements in pleasure and arousal/ excitement. Improvements in depressive symptoms may be linked to improvement in sexual functioning. Conclusions: Adjunctive lumateperone 42 mg did not worsen sexual functioning and was not associated with treatment-related sexual dysfunction in patients with MDD with inadequate response to ADT. Trial Registration: ClinicalTrials.gov identifier: NCT05061706.

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Humans Female Major Depressive Disorder Male Adult Middle Aged Drug Therapy, Combination Antipsychotic Agents Sexual Dysfunction, Physiological Double-Blind Method Antidepressive Agents Heterocyclic Compounds, 4 or More Rings Journal Article Randomized Controlled Trial Clinical Trial, Phase III Multicenter Study

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Anita H Clayton, Willie R Earley, Susan G Kozauer, Yifan Mo, John B Edwards, Suresh Durgam. 2026-09-02. Evaluation of Sexual Function With Adjunctive Lumateperone in Patients With Major Depressive Disorder.. https://doi.org/10.4088/jcp.26m16387

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Adult subject Antidepressive Agents subject Antipsychotic Agents subject Clinical Trial, Phase III subject Double-Blind Method subject Drug Therapy, Combination subject Female subject Humans subject Journal Article subject Major Depressive Disorder subject Male subject Middle Aged subject Multicenter Study subject Randomized controlled trials study

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