Publication Date: 07/13/2026

Duration: 17 minutes, 37 seconds

Transcript:

KELLIE NEWSOME: From gender-specific side effects to transgender psychopharmacology, we wrap it all up in this final episode of Psychopharmacology in Women.

CHRIS AIKEN: Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report.

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

CHRIS AIKEN: In this episode, you'll learn how side effects and drug metabolism differ by sex, how to select psychiatric medications to protect the bones and prevent urinary incontinence as women age, our top treatment for SSRI-induced sexual dysfunction, why recreational drugs are more dangerous for women, and how little we know about psychopharmacology in transgender patients. At the end, you'll learn about a new use for atomoxetine — as this preview of the CME quiz shows. Earn CME for each episode through the link in the show notes.

TRUE OR FALSE: In sleep apnea, atomoxetine improves the hypoxia index, but only in combination with a muscle relaxant.

KELLIE NEWSOME:

Pearl Number 9: Urinary Incontinence

CHRIS AIKEN: As people age, to paraphrase Yeats, the bladder does not hold. After age 60, about 40% of women and 20% of men have urinary incontinence. In women, the most common cause is a weakened pelvic floor — stress incontinence, where coughing, sneezing, or laughing triggers leakage. Childbirth, pregnancy, and menopause all contribute. In men, retention is the more common type, and it causes urge incontinence: a sudden, intense need to urinate followed by involuntary leakage, often tied to an enlarged prostate or to prior prostate surgery. Urinary retention is 13 times more common in men than women. These may not be psychiatric conditions, but they do affect psychiatric prescribing.

KELLIE NEWSOME: For women, the SNRI duloxetine may provide relief. By tightening the bladder sphincter, this noradrenergic reduces the risk of stress incontinence by 50%. In some countries, it's approved for this. That same mechanism, though, puts older men with enlarged prostates at risk for retention. So consider duloxetine in older women, but use it with caution in older men. Another one to watch for in older men with prostate problems is anticholinergics. These cause urinary retention, which leads to bladder infections and urge incontinence.

Number 10: Side Effects

Our job is assess risks and benefits with meds, and some risks are worse for women. Women are more prone to weight gain, hyperglycemia, and cardiac arrhythmias with psychiatric medications. Men face a higher risk of priapism with trazodone — a rare but serious adverse effect involving a painful, sustained erection — though the female equivalent can occur as well. There are rare reports of clitoral priapism on trazodone.

CHRIS AIKEN: Both sexes develop sexual side effects on SSRIs, and the best-studied remedy for men also works in women with SSRI-induced sexual dysfunction: phosphodiesterase-5 inhibitors. Most trials used sildenafil (Viagra), but I usually prescribe tadalafil (Cialis) for its longer half-life and 36-hour duration, which allows more spontaneity.

KELLIE NEWSOME: OK, not to kill the vibe, but there’s actually a lot of research on whether spontaneity is important for sexual health. In a sense, it is, but only because thinking makes it so. When researchers help parents of young children change their beliefs about planned sex, the dampening effect of scheduled fun disappears. They enjoy it more, have it more often, and develop stronger relationships. So let’s not reinforce rigid ideas about spontaneity, especially if we’re talking to working parents who need to schedule it in.

CHRIS AIKEN: OK, but I’m still going to prefer tadalafil because I don’t want patients to get anxious about having to have sex in a certain time frame.

KELLIE NEWSOME: Sure, but I have a hard time getting women to take those meds – I mean, I’ll tell them that they were developed for pulmonary hypertension, but they still wonder why they are taking a med for erectile dysfunction.

CHRIS AIKEN: The mechanism isn't purely vascular. The P5 inhibitors also enhance dopaminergic transmission in brain regions involved in arousal, so I’ll explain it that way to women and men.

KELLIE NEWSOME: In the first episode of this series, we warned about androgenizing hormones and polycystic ovarian disease with valproate. Another concern for women is prolactin-raising antipsychotics, and risperidone is the worst offender here. Elevated prolactin causes problems in both sexes: breast engorgement, lactation, bone thinning, and disrupted sex drive and reproductive function. In women, there's an additional risk. For women with a history of estrogen receptor-positive breast cancer, prolactin elevation can stimulate malignant growth, making these medications relatively contraindicated for them when prolactin goes up. Aripiprazole is prolactin-sparing and often the better choice in these situations.

CHRIS AIKEN: Bone mineral loss is also a problem with serotonergic antidepressants. The risk is similar in men and women, but women bear a greater impact and more fractures because they already have a greater risk of osteoporosis from menopause. Besides the SSRIs and SNRIs, worry about carbamazepine, which can weaken the bones by lowering vitamin D, so check vitamin D levels on this mood stabilizer. But there’s one medication that is more favorable for bone health: New studies suggest lithium protects against bone mineral loss. The takeaway: check prolactin on antipsychotics, and intervene promptly if it's elevated in women at risk for breast cancer. Avoid serotonergic antidepressants and prolactin-elevating medications in patients at high risk for osteoporosis. Use phosphodiesterase-5 inhibitors for sexual dysfunction on SSRIs in both sexes, and don’t get all rigid about being spontaneous.

Number 11: Drug Metabolism

Zolpidem is the only psychiatric medication with different dosing guidelines for women, but many other drugs are metabolized more slowly in women. Olanzapine clears about 30% more slowly. Compared to men, women have higher serum concentrations at the same doses of amitriptyline, nortriptyline, doxepin, citalopram, and mirtazapine. Watch for side effects like morning sedation on these.

Number 12: Drugs of Abuse Are More Dangerous in Women

The medical consequences of drug abuse are generally worse for women. Women clear alcohol more slowly, are less likely to benefit from any supposed health effects of low-dose drinking, and are more likely to develop alcohol-related medical problems, including cancer — especially breast cancer — as well as liver and heart disease. Women are 20 to 70% more likely to develop lung cancer from smoking than men, even when they smoke the same number of cigarettes.

KELLIE NEWSOME: And we have psychiatry to blame for this. In the 1920’s, Sigmund Freud’s nephew used his famous uncle’s ideas to lay the groundwork for modern advertising. His first conquest: Convincing women to smoke. We’ve come a long way, sort of. Smoking is on the decline, but alcohol use is on the rise in women. I don’t know who’s responsible for that, but the media seems to be normalizing it. One of my patients blames it two-buck chuck wines at Trader Joe’s.

Numbers 13 and 14: Transgender Patients and Psychotherapy

CHRIS AIKEN: OK, we’re down to the last straws, pearls 13 and 14. We’re going to break the mold here and stop talking about women and psychopharmacology. The next two tips concern Psychopharm in the transgender population and psychotherapy across the genders.

KELLIE NEWSOME: Transgender patients carry a higher burden of psychiatric problems — around 70% have a diagnosed mental illness. But there's no evidence they metabolize or respond to medications differently. If your transgender patient is taking estrogen and lamotrigine, you might expect lower lamotrigine levels. There’s no research on that specific scenario, but it would be worth checking a lamotrigine level.

CHRIS AIKEN: On the other side, if your patient is taking testosterone to transition to male, I guess it could lower zolpidem levels, so the transition to male may allow them to take the full 10 mg of zolpidem. Another theoretical possibility with female-to-male transition is that testosterone will increase serotonin transporter binding in limbic regions, but whether that changes antidepressant response in any clinically meaningful way is unknown. When patients transition to male, depression risk drops a little. When they transition to female, it rises a little. Why that is, we don't know. There’s just no research. The government hasn’t just cut funding for transgender research; they are also persecuting people for conducting that research, so we’re going to self-censure here and change the topic to psychotherapy.

KELLIE NEWSOME:

Pearl number 14: Psychotherapy.

Here’s where we get back to the narcissism of minor differences. Women and men have the same outcomes in psychotherapy, in large study after large study. Women and men have the same outcomes in psychotherapy across large study after large study. A possible exception is exposure-based therapy for PTSD and psychotherapy for borderline personality disorder, where women have somewhat better outcomes than men, but the difference is small. Still, there is a plausible mechanism behind it, at least for exposure therapy in PTSD:  Estradiol enhances fear extinction.

CHRIS AIKEN: If there's a meaningful difference between the sexes in psychotherapy, it's in engagement. Women are more likely to develop a strong therapeutic alliances, and men are more likely to drop out prematurely. And, I hate to say this as the differences are very minor, so men: but there’s some evidence that male patients don’t match as well with male therapists. Not a reason for men to throw in the proverbial towel, but something to watch for and maybe think about competitive transference reactions that get in the way of therapy. On the other hand, I once heard Marsha Linehan say at an APA conference that her research showed better outcomes when female borderline patients were matched with male therapists, but I don’t think she ever published that, so take it with a grain of salt, a minor difference.

KELLIE NEWSOME: This is an area where the law of averages doesn’t broadly apply, so if you’re thinking of changing your business plans based on this podcast, don’t. Seriously. In the US, female psychotherapists outnumber men by 3 to 1, and these male therapists are in high demand because plenty of people prefer a male therapist, and there aren’t enough to go around.

Research Update

Last week, we learned that sleep apnea is common in patients who present with ADHD, affecting 44% of children and 20 to 30% of adults, or up to 50% if we include all sleep-disordered breathing. Today's update tests an FDA-approved ADHD treatment, atomoxetine, in sleep apnea. It's a phase III randomized controlled trial by Patrick Strollo and colleagues from theAmerican Journal of Respiratory and Critical Care Medicine. The trial tested a combination pill — atomoxetine 75 mg plus the muscle relaxant oxybutynin 2.5 mg — in adults with obstructive sleep apnea who couldn't tolerate CPAP. The study was sponsored by the maker of this combination pill, which is seeking FDA approval.

CHRIS AIKEN: Here’s the rationale for the combination: atomoxetine is a norepinephrine reuptake inhibitor, and oxybutynin is an antimuscarinic. Together, they stimulate the hypoglossal motor nucleus, firming up the upper airway muscles so they don’t collapse during sleep.

KELLIE NEWSOME: The trial enrolled 646 adults across 69 sites in the US and Canada. At 26 weeks, the combination reduced the apnea-hypopnea index more than twice as much as placebo — 44% vs. 18% — shifting the sleep apnea severity from moderate to mild, and bringing 1 in 5 patients to full remission.

CHRIS AIKEN: The combination targets patients who can't tolerate CPAP, but it came with side effects of its own: dry mouth, insomnia, nausea, and urinary hesitation, causing 21% of patients to discontinue it. Most of us won't prescribe the muscle relaxant in this study, but what about using atomoxetine alone? Two earlier phase II trials tested that. They found that atomoxetine did reduce hypoxia as monotherapy at around 80 mg per day — the MARIPOSA and Schweiter trials. The combination worked better, but only by a small margin, suggesting atomoxetine accounts for around 80% of the improvement. We covered these earlier trials in the November 2025 issue of the Carlat Report, where David Liebers from NYU reviewed combination therapies in the pipeline — including another one to consider here: atomoxetine plus trazodone for sleep apnea. Trazodone raises the respiratory arousal threshold at 50 mg at bedtime, reducing nocturnal awakenings in obstructive sleep apnea.

KELLIE NEWSOME: The bottom line: screen for sleep apnea in every patient with ADHD. Use the STOP-BANG questionnaire for adults and the Pediatric Sleep Questionnaire SRBD subscale for children. If sleep apnea is likely, get a sleep study, and atomoxetine is a reasonable medication to start. A lot of today's material on personalizing medications came from our 2020 textbook Prescribing Psychotropics. Dr. Aiken wrote it to fill the gaps left by other psychopharmacology books — questions that come up every day, like whether branded Concerta is as effective as generic, whether you can use immediate-release clonidine and guanfacine for ADHD, and how much to raise an antipsychotic dose when carbamazepine drops its levels.