Podcast: Tips for Treating Sexual Dysfunction With Anita H. Clayton, MD

In this “Brain Trust Conversations in Clinical Psychopharmacology” episode, host Joseph F. Goldberg, MD, spoke with Anita Clayton, MD, who is the Wolford Spratlin professor and past chair of psychiatry and neurobehavioral sciences at the University of Virginia and current president of the American Society of Clinical Psychopharmacology (ASCP), about sexual dysfunction as an underrecognized but critical dimension of psychiatric care.

Clayton opened by noting that only about 1% of people identify as asexual, meaning sexual function matters to the vast majority of patients, yet stigma keeps roughly 75% of patients from raising the topic unprompted. She advised clinicians to normalize the conversation by folding sexual function into routine lifestyle questioning alongside diet and exercise, and to track changes over time, particularly in perimenopausal women, where genitourinary syndrome of menopause is driving a surge in interest in vaginal dryness, diminished desire, and orgasmic changes.

The discussion connected sexual dysfunction to core diagnostic work: anhedonia and loss of libido are hallmark depressive symptoms captured on the Hamilton Depression Rating Scale, and roughly 70% of patients with major depressive disorder episodes have baseline sexual dysfunction, which SSRIs often worsen further. Clayton described sexual complaints as a useful diagnostic assay that should prompt screening for depression, substance use, thyroid dysfunction, diabetes, and, in men over 45, declining testosterone. Impairments limited to arousal or orgasm rather than desire, she noted, point toward biological or medication-related causes; chronic opioid and NSAID use, antihypertensives, and hormonal contraceptives were flagged as underrecognized contributors. She also described how algorithm-driven pornography use can escalate and desensitize patients, straining relationships.

On hypoactive sexual desire disorder, Clayton traced its diagnostic history through DSM-5's merger with arousal disorder and the regulatory fight over flibanserin (Addyi), an FDA approval process she said reflected the agency's limited institutional understanding of sexual dysfunction. Flibanserin's approval was recently expanded to postmenopausal women, and Clayton also discussed bremelanotide (Vyleesi), an as-needed injectable alternative that acts on the melanocortin system.

On mechanisms, Clayton explained that serotonergic activity is broadly inhibitory to sexual function, while norepinephrine and dopamine are excitatory, and that elevated prolactin worsens dysfunction across the board. She reviewed relatively sexually sparing options, including bupropion, which can actively improve rather than merely spare function, plus mirtazapine, vortioxetine, vilazodone, and prolactin-sparing antipsychotics such as aripiprazole, brexpiprazole, and lumateperone. She also discussed antidote strategies, including bupropion at 300 mg/day, buspirone, sildenafil, and gepirone, noting that gepirone's QT concerns stem from its older immediate-release formulation rather than the newer product.

Clayton closed by urging clinicians to weigh 3 receptor-level factors—prolactin effects, 5-HT2A activity, and 5-HT1A activity—when selecting psychotropics. "Sex is important to almost everybody," she said, adding that clinicians should remember older adults remain sexually active and that both medications and illness can affect their function too.

Dr Goldberg is a clinical professor of psychiatry at The Icahn School of Medicine at Mount Sinai in New York, NY and the immediate-past president of the American Society of Clinical Psychopharmacology.

Dr Clayton is chair of psychiatry and neurobehavioral sciences and professor of clinical obstetrics and gynecology at the University of Virginia. She is also current president of the American Society for Clinical Psychopharmacology.