Clinical Summary
Clinical Summary: Evaluation of Sexual Function With Adjunctive Lumateperone in Patients With Major Depressive Disorder
Sexual dysfunction is common in major depressive disorder, often worsens with antidepressant therapy, and can drive nonadherence and discontinuation. For patients with inadequate antidepressant response, clinicians need adjunctive options that improve depressive symptoms without adding sexual adverse effects.
Design
This post hoc analysis of SD was based on data from Study 502, a phase 3, randomized, double-blind, placebo-controlled trial
N
All 480 randomized patients received adjunctive treatment and were included in the ITT population (lumateperone +ADT, n=242; placebo +ADT, n=238)
Population
Eligible male and female patients (aged 18–65 years) met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for MDD
Duration
the study consisted of a screening period (up to 2 weeks), a 6-week double-blind treatment period, and a 1-week safety follow-up period
Key Findings
- Adjunctive lumateperone 42 mg+ADT improved sexual functioning at Day 43 versus placebo +ADT in the ITT population, with LSMD, 2.7; ES, 0.38; P <.0001.
- Among patients with sexual dysfunction at baseline, more patients receiving lumateperone+ADT improved to normal sexual function than with placebo +ADT (26.3% vs 15.2%); among those with normal sexual functioning at baseline, retained normal function was 74.4% in both groups.
- Women showed significant benefit in CSFQ-14 Total score at Day 43 versus placebo +ADT overall (LSMD, 3.5; ES, 0.47; P <.0001) and in women with sexual dysfunction at baseline (LSMD, 3.8; ES, 0.50; P<.0001), while men showed numerical but nonsignificant improvement overall (LSMD, 1.9; ES, 0.33; P=.0791) and with baseline sexual dysfunction (LSMD, 2.2; ES, 0.36; P=.0975).
- Sexual-function benefit was seen across age groups, with significant improvement in CSFQ-14 Total score from baseline to Day 43 in both younger (<45 years; LSMD, 3.0; ES, 0.41; P<.05) and older (≥45 years; LSMD, 3.0; ES, 0.43; P<.001) patients.
- Lumateperone+ADT significantly improved all CSFQ-14 domains at Day 43 versus placebo+ADT: pleasure (LSMD, 0.3; ES, 0.39; P<.0001), desire/frequency (LSMD, 0.3; ES, 0.24; P<.05), desire/interest (LSMD, 0.7; ES, 0.39; P<.0001), arousal/excitement (LSMD, 0.6; ES, 0.28; P<.01), and orgasm/completion (LSMD, 0.7; ES, 0.33; P<.001).
Clinical Bottom Line
For patients with major depressive disorder and inadequate antidepressant therapy response, adjunctive lumateperone 42 mg improved depressive symptoms without worsening sexual function over 6 weeks and produced a clinically meaningful improvement in CSFQ-14 Total score. The clearest benefit was in patients with baseline sexual dysfunction and in women.
Practice Implications
- Assess sexual function routinely in patients with major depressive disorder who report inadequate antidepressant therapy response, as 82.5% of this study population met criteria for sexual dysfunction at baseline.
- When sexual adverse effects are limiting adherence or quality of life, adjunctive lumateperone 42 mg is a reasonable option to discuss because CSFQ-14 Total score improved by LSMD, 2.7 versus placebo +ADT and patients without baseline sexual dysfunction showed no evidence of worsening over 6 weeks.
- Set expectations that sexual-function improvement may track mood improvement: change in CSFQ-14 Total score correlated with MADRS change at Day 22 (r =−0.262) and Day 43 (r =−0.378), and approximately 66.2% of the treatment effect on CSFQ-14 Total score was mediated through changes in MADRS Total score.
- Interpret sex-specific results cautiously in men, because numerical improvements did not reach statistical significance and the male subgroup was relatively small (n=56 per group among those with sexual dysfunction at baseline).
