Depression Drug Lumateperone May Improve Sexual Function, Study Finds

Patients with major depression who received the add-on drug lumateperone reported meaningful improvements in sexual function, according to a new study led by a researcher at the University of Virginia School of Medicine. The findings point to an option for people whose depression treatment has come at the cost of their sex lives.

The study followed 480 adults with major depressive disorder whose symptoms had not eased enough on standard antidepressants. In this case, "not enough" meant less than a 50 percent reduction in depressive symptoms. Half the participants received a daily 42 mg dose of lumateperone on top of their existing medication; the rest got a placebo. After 43 days, the lumateperone group reported better sexual function than the placebo group, measured by a standard questionnaire called the CSFQ-14.

The depression-sex problem the study tackles

About 68 percent of people with major depression experience sexual dysfunction, and the sexual side effects of antidepressant medication are a leading reason patients stop treatment, the researchers note. The most commonly prescribed antidepressants, selective serotonin reuptake inhibitors, contribute to sexual dysfunction in roughly 70 percent of patients, lead researcher Anita H. Clayton said. When an SSRI fails to lift depression and also suppresses libido, patients take a double hit: the illness remains and intimacy suffers.

Major depressive disorder affects about 21 million American adults, according to the Anxiety and Depression Association of America. Depression itself raises the risk of sexual problems, and the standard treatments for depression can cause them too. The research team wanted to know whether lumateperone could break that cycle.

What the 43-day trial found

Improvements showed up across the board: in patients who already had sexual dysfunction, in women and men, in younger and older adults, and across desire, arousal, orgasm and pleasure. At the start of the trial, 82.5 percent of participants had sexual dysfunction. By the end, more than a quarter reported regular sexual function. Participants also showed improved depression scores on the Montgomery-Asberg Depression Rating Scale.

The researchers also checked whether the sexual improvements were simply a side effect of feeling less depressed. Their analysis suggested the two moved together: as depressive symptoms eased, sexual function improved alongside, which points to the benefit being mediated through the improvement in depression itself rather than working as a standalone effect.

The trial measured outcomes with two standard clinical tools: the Changes in Sexual Functioning Questionnaire, a 14-item scale covering desire, arousal, orgasm and pleasure, and the Montgomery-Asberg Depression Rating Scale used to track depressive symptoms. Medscape reported that after six weeks of treatment, both men and women reported improvements in sexual functioning, pleasure and arousal, and that those improvements appeared to be mediated through the easing of depressive symptoms.

Women appeared to benefit more than men, though the researchers say that finding needs more study to verify. Both sexes reported gains in sexual pleasure and arousal. Participants who entered the trial with normal sexual function did not report any worsening while taking the drug.

Why the timing of approval matters

Lumateperone is an atypical antipsychotic already approved by the Food and Drug Administration to treat schizophrenia and bipolar depression. The agency recently cleared it as an add-on treatment for major depression when antidepressants alone have not done enough, which is exactly the use case the trial tested.

The study was funded by Intra-Cellular Therapies, the company behind the drug, and its findings were published in The Journal of Clinical Psychiatry in September 2026. An earlier report on the research noted the results were posted online on September 2.

Clayton positioned the drug as a potential option for people with an incomplete response to antidepressants who want to avoid sexual dysfunction as a side effect. If the findings hold up in longer studies, doctors would have a way to treat depression more aggressively without the tradeoff that drives so many patients to quit their medication. The full paper appears in The Journal of Clinical Psychiatry under DOI 10.4088/jcp.26m16387. Medical Xpress reported on the findings on September 15.