It’s long been known that antidepressants can cause sexual problems, with more than half of all people taking the drugs reporting various side effects including loss of libido, but now, a small but vocal group of patients is speaking out about severe sexual problems enduring even long after they stopped taking selective serotonin reuptake inhibitors (SSRIs), the most popular type of antidepressants.
The drugs’ effects have been devastating, they said, leaving them unable to enjoy sex or sustain romantic relationships.
The safety label on Prozac, one of the most widely prescribed SSRIs, warns that sexual problems may persist after the drug is discontinued.
And, reports The New York Times, health authorities in Europe and Canada recently acknowledged that the medications can lead to lasting sexual issues.
But researchers are only just beginning to quantify how many people have these long-term problems, known as post-SSRI sexual dysfunction. And the chronic condition remains contested among some psychiatrists, who point out that depression itself can curb sexual desire.
Clinical trials have not followed people after they stop the drugs to determine whether such sexual problems stem from the medications.
“I think it’s depression recurring. Until proven otherwise, that’s what it is,” said Dr Anita Clayton, chief of psychiatry at the University of Virginia School of Medicine and a leader of an expert group that will meet in Spain next year to formally define the condition.
Clayton published some of the earliest research showing that SSRIs come with widespread sexual side effects. She said patients with these problems should talk to their doctors about switching to a different antidepressant or a combination of drugs.
She worries that too much attention on seemingly rare cases of sexual dysfunction after SSRIs have been stopped could dissuade suicidal patients from trying the medications.
“I have a really big fear about this,” she said.
By the mid-2000s, the sexual effects of SSRIs were well recognised. In fact, the drugs so reliably dulled sexual responses that doctors began prescribing them for men with premature ejaculation.
But sexual symptoms that endure after stopping the drugs haven’t received much attention in the medical literature.
In 2006, a handful of cases of persistent genital numbness were reported in Canada and the United States. That same year, a newsletter for the American Psychological Association described emerging data on the lasting sexual effects of the drugs.
“I believe we have barely begun to appreciate the pervasiveness and complexity of the impact on sexuality of these medications,” Audrey Bahrick, then a psychologist at the University of Iowa, wrote in the article.
In an interview, Bahrick said she felt an ethical obligation to call attention to the condition because she had experienced it herself.
She started taking Prozac in 1993, when she was 37 and struggling with a difficult job in a new city. Within one day of taking the pill, her clitoris and vagina felt numb. “It was as if there were a glove over them – a very, very muffled sensation,” she recalled.
For a while, she said, the trade-off was worth it: the antidepressant made her feel energised and more resilient. But after two years, she stopped taking it for the sake of her relationship. The sexual symptoms persisted, however, and the relationship ended.
“It never occurred to me that this would be something that would in fact, in my life, never resolve,” said Bahrick, now 67.
In the decades since, the use of SSRIs has soared, especially among teenagers. They are prescribed not only for depression and anxiety, but for a range of other conditions, including irritable bowel syndrome, eating disorders and premenstrual symptoms.
Yet researchers are still struggling to understand how SSRIs work, and why the sexual problems are so pervasive.
The drugs target serotonin, an important chemical messenger in the brain as well as other parts of the body. The molecule is involved in blunting sexual responses, including the orgasm reflex that originates in the spinal cord. Serotonin also affects oestrogen levels, which in turn can affect arousal.
But depression, too, dulls the sex drive. Among unmedicated men with depression, 40% report a loss of sexual arousal and desire, and 20% struggle to reach orgasm. Common conditions like diabetes and cardiovascular disease can also cause sexual problems.
Drug trials rarely look at what happens when medications are stopped. And studying what happens after people get off SSRIs is particularly challenging because many people never stop taking them.
Given the lack of data, “persistent sexual dysfunction caused by SSRIs is a hypothesis, not a proven phenomena”, said Dr Robert Taylor Segraves, an emeritus professor of psychiatry at Case Western Reserve University School of Medicine who has studied the effects of antidepressants on sexuality.
Still, some researchers have found ways to estimate the prevalence of the condition. A recent study in Israel reported that about one in 216 men who discontinued SSRIs were subsequently prescribed medications for erectile dysfunction, a rate at least three times as high as that among the general population.
And when many patients report similar problems – like the distinctive symptom of genital numbness – the signal should not be dismissed, said Dr Jonathan Alpert, head of the American Psychiatric Association’s research council.
Some patients who have taken finasteride, which treats hair loss in men, or isotretinoin, an acne medication, have also reported genital numbness and other sexual problems after stopping the medications. That may point to a common biological mechanism, Alpert said.
“Everything begins with anecdotal reports, and science needs to follow,” he told The New York Times.
Other researchers are particularly worried about the growing number of young people who start the medications before their sexuality has fully developed.
“People put on these drugs at a young age may just never know who they might otherwise be if they hadn’t been on this drug,” said Yassie Pirani, a counsellor in Vancouver.
In a new survey of 6 000 LGBTQ young people that has not yet been peer-reviewed, Pirani and collaborators at Simon Fraser University in British Columbia found that people who had stopped antidepressants were 10 times more likely to report persistent genital numbness than those who had never taken the drugs.
Pirani described one of her patients, age 33, who had taken SSRIs from age 11 to her mid-20s. “Her whole sexual history, she could have sex, but she never really felt anything,” Pirani said.
Some of her patients, she added, wondered for years whether they were asexual before understanding that the medications may have played a role. When they turned to doctors for help, they were often dismissed.
In recent years, many patients have found support for their condition online. About 10 000 people are members of a Reddit group for those with post-SSRI sexual dysfunction, up from 750 members in 2020.
In 2018, dozens of patients and doctors petitioned regulators in Europe and the United States to add warnings about the risk of persistent sexual problems to drug labels, spurring the European Medicines Agency to do so the following year. (A spokeswoman for the US Food and Drug Administration said the agency was still reviewing the petition.)
For Bahrick, who has continued to publish research on the topic, the recent recognition of her condition is cold comfort, considering the unknown number of people who have lost a core experience of being human.
“It’s not just numb genitals,” Bahrick said. “It’s a reorientation to being in the world.”
Study details
Zuranolone for the Treatment of Adults With Major Depressive Disorder: A Randomised, Placebo-Controlled Phase 3 Trial
Anita Clayton, Robert Lasser, James Doherty, et al.
Published in PubMed on 1 September 2023
Abstract
Objective
This study assessed the efficacy and safety of a 14-day treatment course of once-daily zuranolone 50 mg, an investigational oral positive allosteric modulator of the γ-aminobutyric acid type A (GABAA) receptor, for the treatment of major depressive disorder.
Methods
Patients 18-64 years of age with severe major depressive disorder were enrolled in this randomised, double-blind, placebo-controlled trial. Patients self-administered zuranolone 50 mg or placebo once daily for 14 days. The primary endpoint was change from baseline in total score on the 17-item Hamilton Depression Rating Scale (HAM-D) at day 15. Safety and tolerability were assessed by incidence of adverse events.
Results
Of 543 randomised patients, 534 (266 in the zuranolone group, 268 in the placebo group) constituted the full analysis set. Compared with patients in the placebo group, patients in the zuranolone group demonstrated a statistically significant improvement in depressive symptoms at day 15 (least squares mean change from baseline HAM-D score, -14.1 vs. -12.3). Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, -9.8 vs. -6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study (through day 42, with the difference remaining nominally significant through day 12). Two patients in each group experienced a serious adverse event; nine patients in the zuranolone group and four in the placebo group discontinued treatment due to adverse events.
Conclusions
Zuranolone at 50 mg/day elicited a significantly greater improvement in depressive symptoms at day 15, with a rapid time to effect (day 3). Zuranolone was generally well tolerated, with no new safety findings compared with previously studied lower dosages. These findings support the potential of zuranolone in treating adults with major depressive disorder.
The New York Times article – After Antidepressants, a Loss of Sexuality (Restricted access)
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