Add-on lumateperone improves mood and sexual function in depression

Clinical takeaway: For patients with depression who have an inadequate response to antidepressants and are concerned about sexual adverse effects, add-on lumateperone may improve depressive symptoms without worsening sexual function and may help restore sexual functioning in some patients.

Sexual dysfunction is common in patients with depression and is frequently worsened by antidepressant therapy, contributing to poor adherence and treatment discontinuation. As clinicians consider augmentation strategies for patients with persistent symptoms, preserving sexual function remains an important but often overlooked treatment goal.

A post hoc analysis of a phase 3 trial suggests add-on lumateperone may help address both challenges. Among 480 adults with major depressive disorder who had an inadequate response to one or two antidepressants, lumateperone 42 mg daily significantly improved sexual functioning compared with placebo over six weeks. More than 80% of participants had sexual dysfunction at baseline.

Patients receiving lumateperone experienced clinically meaningful improvements in overall sexual function, including desire, arousal, pleasure, and orgasm. Among those with sexual dysfunction at study entry, 26.3% achieved normal sexual functioning by the end of treatment, compared with 15.2% of patients receiving placebo. Importantly, patients who entered the study with normal sexual function generally maintained it, suggesting lumateperone was not associated with treatment-emergent sexual dysfunction.

Benefits were observed across age groups and were most pronounced in women, although improvements in pleasure and arousal were reported by both women and men. Patients treated with lumateperone also experienced greater improvement in depressive symptoms than those receiving placebo. Exploratory analyses suggested that much of the improvement in sexual functioning may have been driven by better control of depressive symptoms.

"Sexual dysfunction is one of the most important yet under-discussed barriers to depression treatment adherence. A therapy that improves depressive symptoms without adding to that burden may help clinicians better address both symptom control and quality of life for their patients," said lead investigator Anita H. Clayton, MD.

Source: Clayton AH, et al. (2026 Sep 2) J Clin Psychiatry. Evaluation of Sexual Function With Adjunctive Lumateperone in Patients With Major Depressive Disorder