Sexual dysfunction is a common side effect of antidepressants, affecting between 58% and 70% of patients treated with these medications.1 Sexual dysfunction has a significant impact on the patient’s quality of life, personal relationships, self-esteem, and recovery,1 and it is a common cause for nonadherence or discontinuation of treatment, creating the potential for relapse of symptoms.2 A 2003 survey found that approximately 41.7% of men and 15.4% of women discontinued psychiatric medications due to perceived sexual side effects.3
Sexual side effects of antidepressants affect both men and women, and can cause different types of dysfunction, including decreased libido, delayed orgasm, anorgasmia or no ejaculation, and erectile dysfunction (ED).4,5 Some patients taking antidepressants also report priapism, painful ejaculation, penile anesthesia, loss of sensation in the vagina and nipples, spontaneous ejaculation, persistent genital arousal, and non-puerperal lactation or galactorrhea in women.1,5
Despite the frequency of these side effects, practitioners tend to underemphasize them in their verbal interchanges with patients,4 and half of the subjects who experience sexual side effects may never or infrequently speak about sexual functioning with their primary mental health care providers. In a study, women with sexual side effects rarely discussed sex, and in fact, 80% of women with sexual side effects failed to discuss sexual dysfunction with their providers.3
“Many physicians and other prescribers are not comfortable talking about sexuality, and many patients are not comfortable initiating a discussion about sexuality, so the result is that the issues of potential sexual side effects of antidepressants tend not to be discussed,” as William D. Petok, PhD, Clinical Associate Professor of Obstetrics and Gynecology at Thomas Jefferson University/Sidney Kimmel Medical School, Philadelphia, Pennsylvania, stated in an interview.
“Patients want to talk about it, but they are waiting for the physician to initiate the conversation,” Dr Petok added.
Antidepressant-Induced Sexual Dysfunction: Mechanisms of Action
Sexuality is complex and involves a host of psychological and physiological processes. Neurotransmitters, including serotonin, norepinephrine, dopamine, acetylcholine, gamma-aminubutyric acid, nitric oxide, and oxytocin, all play a role in normal sexual function.5 In particular, sexual arousal and erections are associated with the parasympathetic nervous system, specifically acetylcholine, while the sympathetic nervous system—reliant on acetylcholine and norepinephrine—is more involved with orgasm and ejaculation.5
Selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) inhibit the parasympathetic as well as the sympathetic aspects of sexual function through their impact on alpha-1 adrenergic receptors. They may also inhibit dopamine.5 Some medications may inhibit nitrous oxide synthetase, resulting in a decrease in the availability of nitrous oxide, which plays an important role in the vascular erection.5 Although SSRIs and SNRIs are most frequently implicated in antidepressant-induced sexual dysfunction, other antidepressants may also produce this side effect.
Table 1: Antidepressant Subclasses and
Drug Class Drugs Mechanism of Action Sexual Dysfunction Tricyclic
Inhibits serotonin and norepinephrine uptake Decreased desire
Delayed or absent ejaculation/orgasm
Selective serotonin reuptake inhibitors Fluoxetine
Inhibits serotonin reuptake Decreased libido
Inability to orgasm
Selective norepinephrine reuptake inhibitors Venlafaxine
Inhibits serotonin and norepinephrine uptake Erectile dysfunction
Monoamine oxidase inhibitors Phenelzine Blocks monoamine oxidase, which normally inactivates the monoamines Decreased libido
Norepinephrine/dopamine reuptake inhibitors Bupropion Inhibits serotonin, norepinephrine, dopamine reuptake Increased desire
Altered sexual sensitivity (all less common)
Combined reuptake inhibitor and receptor blocker Trazodone Inhibits reuptake of serotonin Delayed orgasm
Erectile dysfunction (rare)
Combined reuptake inhibitor and receptor blocker Nefazodone Inhibits serotonin reuptake, blocks serotonin receptors Ejaculation dysfunction
Combined reuptake inhibitor and receptor blocker Mirtazapine Blocks presynaptic alpha-2 adrenergic receptors
Blocks postsynaptic serotonin 5HT2 and 5HT3, histaminergic H1 and alpha1 receptors
Combined reuptake inhibitor and receptor blocker Manserin Blocks presynaptic alpha-2 receptors
Blocks noradrenaline uptake
Combined reuptake inhibitor and receptor blocker Vortioxetine Blocks serotonin uptake
Directly modulates serotonin receptors
Occasional sexual side effects, more favorable profile Combined reuptake inhibitor and receptor blocker Vilazodone Serotonin partial agonist and reuptake inhibitor Occasional sexual side effects, more favorable profile
Take a Sexual History
Stephen B. Levine, MD, Clinical Professor of Psychiatry, Case Western Reserve University, Cleveland, stated in an interview that broaching sexual issues in patients to whom you are prescribing an antidepressant begins with taking a sexual history.
“Your patient may or may not have an active sexual life,” said Dr Levine, who is the author of the newly published book Psychotherapeutic Approaches to Sexual Problems (American Psychiatric Association Publishing, 2020). “And if we are prescribing a drug to people, who have no masturbatory or partner-related sexual behavior, there is little to worry about when it comes to sexual side effects. The concern rises in patients who are, or seek to be, sexually active, whatever the sexual orientation.”
To ascertain this information, clinicians should take a sexual history, he advised. Several scales are available for the purpose, including the Arizona Sexual
Experience Scale6 and the Sex Effects Scale.7 The sexual history will also help ascertain whether the sexual dysfunction is due to the antidepressant treatment or whether it existed prior to antidepressant use and is attributable to some other cause, Dr Levine said.
Rule Out Other Causes
Before assuming that antidepressants are the culprit in sexual dysfunction, it is important to rule out other potential causes, such as alcohol use, diabetes, atherosclerosis, cardiac disease, and central and peripheral nervous system conditions.5 Dr Petok noted that many medications other than antidepressants can be associated with sexual dysfunction. “These should be taken into account when inquiring into the patient’s sexual dysfunction, and medication interactions should also be considered,” he advised.
Depression and anxiety themselves, even in the absence of pharmacotherapy, are associated with sexual dysfunction. For example, diminished libido is one of the “hallmark symptoms” of major depression in both men and women and may be present in as many as 70% of patients with depression.8 Anxiety may also affect sexual function by contributing to lack of ability to achieve erections in men or inability to reach orgasm in men and women.8 Both Dr Petok and Dr Levine noted that age has an impact on sexual function and is part of the array of factors that should be taken into account when considering whether antidepressants are the culprit in sexual dysfunction.
Inform Patients of Potential Sexual Dysfunction
“Prior to prescribing an antidepressant, inform patients that it is possible, although not inevitable, that their sexual life will be affected,” Dr Levine advised.
Dr Petok recommended asking the patient to return for a follow-up visit after 4 to 6 weeks. “The patient then knows that we can assess how the medication is working and if there are unacceptable side effects—sexual or otherwise—they can be addressed.” Knowing what to expect and that solutions are available can enhance adherence and make it less likely that the patients will discontinue treatment on their own due to side effects.
There are several approaches to take if the patient is experiencing antidepressant-induced sexual dysfunction that is distressing, increasing anxiety or depression, or having a detrimental effect on their relationship. Physicians can consider switching to an antidepressant that does not have a high likelihood of sexual side effects. Dr Levine noted that 3 “well-known drugs” meet that criterion: bupropion,5 vortioxetine9 and vilazodone.10
Type-5 phosphodiesterase (PDE5) inhibitors are a first line therapy for ED, whether it results from a medication side effect or another cause.11 During sexual arousal, nitrous oxide, which is released from nerve terminals and endothelial cells in the corpus cavernosum, activate a cascade of events culminating in smooth-muscle relaxation in the corpus cavernosum and increased blood flow to the penis. PDE5 inhibitors block the activity of PDE5, which degrades some of the nucleotides in the cascade, thereby enhancing the effects of nitrous oxide and prolonging an erection.11
The 4 approved and available PDE5 inhibitors are sildenafil, tadalafil, vardenafil, and avanafil. “The advantage of these agents is that they do not have to be taken every day, but can be used only in anticipation of lovemaking,” Dr Levine noted.
Dr Levine noted that the most common sexual problem in people under age 60 years who are taking antidepressants is difficulty in achieving orgasm, or “not that they can never have an orgasm, but that the drug dampens the nervous system’s sexual response.” This issue can sometimes be addressed if the excitement is sufficient to override the dampening—for example, if there is a new partner. “But most of the people we see with depression and anxiety have a stable partner, so it is important that they are aware of the potential impact of the drug,” Dr Levine said. He recommended that the couple explore new and more exciting sexual activities.
Dr Petok added that it is important to “stack the deck in favor of having a good sexual experience” by taking more care to prepare conditions that are conducive to intimacy. “For some people, what tips them toward feeling sexual is different than for other people—for example, a sound, touch, word, or aroma. These can be used to create a more romantic and arousing atmosphere.”
Furthermore, in some patients, antidepressant-induced sexual dysfunction resolves over time, or at least becomes more tolerable.5 Patients can be encouraged to stay the course and see whether the side effects improve.
Patients and their providers may consider a drug holiday, during which the patient temporarily discontinues use of the medication. This tactic can be effective in antidepressant-induced sexual dysfunction, which typically remits when the drug is discontinued. A study found that discontinuing use of an SSRI on Friday and Saturday improved sexual function without causing worsening of depressive symptoms.12
“This approach may not be effective with some long-acting medications or medications with long half-lives, such as fluoxetine, so taking a weekend off will not help the problem if the intention is to engage in sexual relations during the weekend,” Dr Levine pointed out. It may be possible for the patient to skip a dose or discontinue for a couple of days before anticipated sexual relations, although “there is the problem of whether the antidepressant effect may be compromised,” he warned.
Some short-acting drugs (eg, paroxetine or venlafaxine) may cause withdrawal symptoms, which need to be taken into account. Another concern is that “some people may extend their ‘holiday’ and discontinue or reduce their medication, risking the return of their depressive symptoms,” Dr Levine advised.
Providers also need to set realistic expectations, as normal age-related physiologic changes can influence sexual response regardless of mental disorders or medications. Dr Petok noted that “expectations—often promulgated by the media or by manufacturers of PDE5 inhibitors in their advertising—suggest that sex will be fabulous. People have to understand that this is unrealistic, whether or not they are taking antidepressants.”
Dr Levine agreed, “Mental health professionals need to understand that the sexual effects of antidepressants will be greater in older than in younger people because younger people have stronger neuroendocrinological somatic capacities for sexual behavior.” However, younger people also need to have realistic expectations. “Hollywood conveys the message that sex will always be fabulous for both parties, but in real life, that takes place only a small percentage of the time and instead, sex is ‘good enough’ for one or other partner and people are satisfied with a ‘good enough’ sexual relationship most of the time,” Dr Petok stated.
Helping patients clarify their priorities is an important component of arriving at a strategy for handling antidepressant-induced sexual dysfunction. “Encourage patients to explore whether it is more important for them to feel good and happier or to have more frequent sex. Inquire whether the sex is satisfying,” Dr Petok advised.
For example, some people may have low libido and are less interested but once they get started with lovemaking, the desire increases and the activity becomes satisfying. Finding out each person’s individual needs and perspectives will help shape the most effective strategy, he said.
Planning sexual relations around certain times of the day that can be most conducive to intimacy may be a helpful tactic. For example, many men find that they have more desire in the morning upon awakening, which may be due to higher testosterone levels. “I have heard patients say that ‘planning’ isn’t sexy and that sex should be spontaneous, but I think spontaneity is overrated,” Dr Petok commented, “Being planful about your sexual relationship is important not only when you are taking medication but when you have other life commitments, such as young children or a work schedule.”
Cognitive behavioral therapy (CBT) may be incorporated into a biopsychosocial approach to sexual dysfunction, helping patients change how they think in order to increase positive coping.1 CBT is an established nonpharmacologic intervention for numerous psychiatric conditions, including depression and anxiety, and may be useful in “managing negative feelings that may have a hugely negative impact on the individual’s self-esteem and self-image.”1 Couples counseling can also be useful in helping the patient and his/her partner to address sexual side effects in the overall context of their relationship, Dr Petok added.
Other studies have suggested that ginkgo biloba may be helpful in treating antidepressant-induced sexual dysfunction.13 Ginseng, Maca, L-Arginine, yohimbine, dehydroepiandosterone, and some of the B vitamins are often contained in formulations seeking to boost male sexual function. A review article by Cui et al outlines the current evidence (or lack of evidence) behind these products.14
Several studies have suggested the effectiveness of physical exercise in improving sexual function.15,16,17 Beyond its potentially helpful sexual effects, it is generally an important component of a healthy lifestyle and should be encouraged regardless.
Pay Attention to Sexuality
It is important for clinicians to find out from patients what their own particular perspectives and needs are. What is “enough sex” to be satisfying? What kind of sex is satisfying? “There is no ‘gold standard’ or ‘correct amount,’ rather it is relationship-dependent,” Dr Petok said.
Dr Levine emphasized the importance of understanding sexuality and making it an important focus in the overall risk-benefit analysis of medication prescribing. “If we really want to help patients to experience remission from depression, we need to focus on sexual side effects and proactively discuss and address them,” he added.
As a common side effect of regularly prescribed psychiatric medications, sexual dysfunction is a significant consideration for providers and patients to discuss. Ignoring this serious side effect can only hinder patients’ recovery and contribute to a lack of connection in the doctor-patient relationship. By confronting patients’ concerns head on, providers can build more successful treatment strategies.
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