Antidepressant Sexual Dysfunction and Women's Health with Anita Clayton, MD

The short answer: After noticing fluoxetine's label listed it at under 2% while she saw roughly 20% in clinic, she built the Changes in Sexual Functioning Questionnaire (CSFQ), the validated scale now used in drug trials across many specialties. Dr. Anita Clayton, chair of psychiatry at UVA and a former Navy physician, is one of the people most responsible for medicine measuring antidepressant sexual dysfunction.

Takeaways:

• Why drug labels understate antidepressant sexual side effects, and why spontaneous-report data misses what a validated scale catches.
• The three kinds of sexual dysfunction clinicians should separate: disease-state, treatment-emergent, and relationship-based.
• Which antidepressants carry low sexual-side-effect risk, including bupropion and gepirone ER (Exxua), the 2023-approved drug with no sexual-dysfunction label warning.
• The FDA double standard Dr. Clayton fought during the flibanserin (Addyi) approval, where "successful sexual events" was the benchmark borrowed from Viagra trials.
• The faster-acting depression treatments she's studying now, including zuranolone and a single-dose psilocybin-analog injectable for postpartum depression.

The package insert for fluoxetine said 1.9% of patients experienced sexual dysfunction. Dr. Anita Clayton was a Navy psychiatrist in the early 1990s, putting most of her patients on the drug because it was safer in overdose than the tricyclics she'd watched kill people. Her patients, mostly Navy sailors and Marines, kept telling her the same thing: it was taking a lot longer to reach orgasm.

She checked the label. It said under 2%. What she was seeing in clinic was at least 20%. So she built the tool to prove it: the Changes in Sexual Functioning Questionnaire, the CSFQ, now used in drug trials across psychiatry, cardiology, and neurology.

On this episode of Psychiatry Tomorrow, Osmind Chief Medical Officer Dr. Will Sauvé and co-host Dr. Brittany Albright sit down with Dr. Clayton, chair of psychiatry at the University of Virginia, a former Navy physician, and a past president of the International Society for the Study of Women's Sexual Health. She's spent her career insisting women's sexual health was real, measurable, and treatable — a fight documented in the film The Pink Pill: Sex, Drugs and Who Has Control (2025) on Paramount+, in which she appears. This conversation traces how she got there, starting years before fluoxetine.

Treatment-emergent sexual dysfunction is sexual dysfunction caused by a medication rather than by the underlying illness. It can appear in a patient who had no sexual problems before starting the drug, which is why it has to be measured against a baseline rather than assumed from a patient's spontaneous report.

How did a nursing-home visit set Dr. Clayton on the path to medicine?

Clayton knew she wanted to be a doctor at five years old, after a childhood spent visiting a grandmother in a Mobile, Alabama nursing home. Her mother made the visits long on purpose, stopping to talk with every resident before they ever reached her grandmother's room. One day, young Anita asked who took care of all these people. Her mother said, the doctors. "Well, then I guess I wanna be one," she decided.

Surgery was her first rotation at UVA, where she excelled but knew she didn't want to be a surgeon. Pediatrics didn't fit either. She joked she wanted a Valium dispenser at the clinic door for the terrified parents. OB-GYN and psychiatry were the two that stuck, for the same reason: both let her into people's lives at the most intimate level.

OB-GYN is intimate the way psychiatry is intimate, Clayton says, only physically rather than emotionally. As Sauvé remembers it, a classmate put it even more bluntly back in medical school: he'd wanted to be a psychiatrist because, in his words, "it's the most invasive specialty there is."

What two years as the Navy “country doctor” taught her about treating the whole person

The Navy paid for Clayton's medical school, which meant two years owed as a general medical officer at Great Lakes Naval Hospital, the "country doctor" stretch military physicians do before specialty training. She pulled her one year of psychiatry training straight into primary care and started a women's group with a Navy psychologist: five minutes for physical complaints, then the real conversation about what was going on in their lives. It caught real diagnoses: a likely case of giardia, a patient whose seizures tracked to medication non-compliance after fights with her husband.

She kept finding things other providers missed, until radiology called to complain. "You send more people up here, and we find more things than everyone else in the hospital combined," they told her. Her answer: "Well, I'm examining them."

The group had an unplanned ending: one member ran hiring at a local Kmart and offered the others jobs. They took them, and started skipping sessions to go to work instead. Clayton never had to tell anyone they were done. As Sauvé put it, the best possible reason to skip the psychiatrist is that you're too busy living your life.

How common is sexual dysfunction with antidepressants, really?

"It's at least 20% from what I'm seeing," Clayton remembers thinking, after checking fluoxetine's label and finding 1.9%. Albright named the lesson directly: "We can't always trust the PI, the package insert, when it comes to sexual side effects."

The gap exists because label numbers come from spontaneous reports, patients volunteering information unprompted, which almost nobody does about sex. What you actually want is a scale that measures change from a baseline. There wasn't a good one, so Clayton built one after returning to UVA, using medical students as her general population sample. She set the CSFQ's cutoff scores where the confidence intervals didn't overlap. The scale has since been used well beyond psychiatry: cardiovascular disease, diabetes, and neurological disorders.

The three kinds of sexual dysfunction clinicians confuse

Depression itself causes sexual dysfunction, and treating it can help. But the treatment can also cause it: a patient with no sexual problems going in can develop them on the medication. A third source is the relationship itself, shaped by the social withdrawal that depression brings. Each of the three calls for a different response, which makes telling them apart the first clinical task.

Which antidepressants don't cause sexual dysfunction?

Clayton's studies showed bupropion, which came to market around the same time as fluoxetine, didn't cause sexual dysfunction, and that adding it can rescue sexual function lost to an SSRI. She took that finding to industry, and ran into a wall: companies were fixated on being a first-line treatment.

"What do you care if you're a first-line treatment or second-line treatment, or you're added in as a second drug?" she told them. "It's a prescription. Just count the prescriptions." Stop thinking of these as only antidepressants, she argued. They're potentially anti-sexual dysfunction drugs.

Why was flibanserin (Addyi), the drug at the center of The Pink Pill, approved only after a decade-long fight with the FDA?

The Pink Pill (2025), in which Clayton appears, flibanserin is the subject that eventually becomes approved as Addyi. Boehringer Ingelheim first tested it as an antidepressant, where it didn't separate from placebo. It turned out to affect the sexual dysfunction wrapped up in depression. Clayton was part of the research from the start.

The drug caused sedation, so dosing moved to nighttime, and regulators still worried about mothers falling asleep at the wheel the next morning. Clayton calls it "really prudish." The deeper absurdity was in how the FDA wanted desire measured: for men, with Viagra, the bar had been "successful sexual events," whether the penis was firm enough for penetration, nothing about orgasm or satisfaction.

"Have you ever talked to a woman and asked her if she's had a successful sexual event?" Clayton said. "Maybe satisfying, but successful? No." They eventually agreed to change the word to "satisfying," which she still found absurd. "Why don't you ask them about their desire? You think they forget?"

Boehringer Ingelheim eventually gave up on the drug. It was in-licensed by Cindy and Bob Whitehead's company Sprout, which ran the studies needed for approval. Women from those trials testified at FDA meetings about what the treatment had done for them. Addyi was approved in 2015.

Fast-acting mechanisms for postpartum depression, and a single-dose psilocybin analog

Clayton moved from reproductive psychiatry into PMDD and postpartum depression, chasing what she calls the newest possible mechanisms.

She ran trials on Zuranolone, an allopregnanolone analog that works fast at GABA receptors and uses a short dosing course instead of a daily pill.

She's now studying a psilocybin-analog injectable for postpartum depression, a shorter-acting metabolite needing far less monitoring than psilocybin, given as a single dose.

The FDA required an active very-low-dose comparator instead of placebo, to avoid unblinding patients. She describes the postpartum results as significantly positive, with the paper in progress, and the same compound is now being studied in adjustment disorder tied to serious illness: cancer, Parkinson's, MS, ALS, interstitial lung disease. Albright spoke about rapid acting treatments already in use for one such patient, treated for ALS with a full course of Spravato and TMS: "The month before he died, he told me he was happy, and he felt at peace, and that was the best gift."

And then there's a drug that closes the loop back to sexual dysfunction specifically: gepirone ER, sold as Exxua, the first oral selective 5-HT1A agonist for major depression, approved in 2023, with a label that carries no sexual-dysfunction warning because trials showed no difference from placebo on that measure. To prove it, the studies compared the drug head-to-head against an SSRI in people who didn't have depression, isolating the medication's effect on sexual function without depression itself muddying the results.

Mentorship, and staying curious

Clayton didn't have mentors for clinical research at UVA, so she found her own, reaching out to researchers whose papers she'd read and asking them to supervise her remotely. They were all men, and all said yes.

"They just said, 'Yes, you can do it. I'll help you,'" she said. Not, "'This is such a burden... this is gonna be so hard.' None of it."

Both she and Albright trace that support back further. Clayton's father, a Navy pilot, told his two daughters:

"You can do anything you want. And you should believe that."

Asked what she's proudest of, Clayton didn't name an accomplishment. She named a disposition. "I'm still excited," she said. "And I think I will be for a very long time."‍

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Clinical note: This article summarizes a clinical conversation for educational purposes and is not medical advice. Descriptions of investigational treatments and trials reflect Dr. Clayton's own account of work in progress; some results she references are not yet published and have not been independently verified here. FDA approval status, indications, and labeling for the medications named can change. Clinicians should base treatment decisions on current prescribing information, individual patient assessment, and applicable regulatory guidance.

Sources and notes

1. Clayton AH, McGarvey EL, Clavet GJ. The Changes in Sexual Functioning Questionnaire (CSFQ): development, reliability, and validity. Psychopharmacology Bulletin, 1997.
2. U.S. Food & Drug Administration. Approval of flibanserin (Addyi) for hypoactive sexual desire disorder in premenopausal women, 2015.
3. U.S. Food & Drug Administration. EXXUA (gepirone) extended-release tablets, prescribing information, 2023. accessdata.fda.gov

Timestamped show notes

Approximate.

• [00:00] Sauvé on finding psychiatry on an inpatient rotation at Walter Reed
• [02:30] Welcoming Dr. Anita Clayton and Dr. Brittany Albright
• [03:00] "Who takes care of all these people?" The nursing-home origin
• [04:30] One of few women in medical school; choosing OB-GYN and psychiatry
• [08:00] Wanting to know everyone's story: why psychiatry
• [12:00] The Navy, HPSP, and becoming a general medical officer at Great Lakes
• [13:30] Starting an all-women group; treating the whole person
• [16:30] "I'm examining them": finding what others missed
• [17:30] The Kmart story and choosing to live your life
• [18:30] The Pink Pill, and meeting Clayton in it
• [19:30] Fluoxetine, delayed orgasm, and a label that said 1.9%
• [21:00] Why you can't trust spontaneous-report side-effect data
• [21:30] Three kinds of sexual dysfunction: disease, treatment, relationship
• [24:30] Building the CSFQ scale
• [25:00] Bupropion, buspirone, and rescuing sexual function
• [27:00] "Just count the prescriptions": reframing antidepressants for industry
• [29:30] Should psychiatrists screen for primary sexual disorders?
• [30:30] Flibanserin, Boehringer Ingelheim, and training actors to model interviews
• [33:00] The FDA's sedation worries and the fight over approval
• [35:30] "Successful sexual events" vs. asking women about desire
• [37:00] Sprout, Cindy Eckert, and patients testifying at the FDA
• [38:00] Becoming a PI on industry trials since 1991
• [40:00] Career and family: a blended family and a summer in Provence
• [42:30] A father who said "you can do anything"
• [46:30] Reproductive psychiatry, the midlife clinic, PMDD, postpartum
• [47:30] Zuranolone and a GABA mechanism that changed the paradigm
• [48:30] A single-dose psilocybin-analog injectable for postpartum depression
• [50:30] Adjustment disorder in serious medical illness; an ALS patient at peace
• [51:30] Gepirone ER (Exxua) and a head-to-head sexual-function design
• [55:00] What she's proudest of: staying curious
• [56:30] Mentorship, women in the field, and "I'm still excited"