Antidepressant Sexual Side Effects

What sexual side effects can be caused by antidepressants?

Sexual side effects are most common with SSRIs and SNRIs.^1,3,5 Serotonergic medications may affect sexual function via an effect on the autonomic nervous system.⁵

Sexual side effects of SSRIs and SNRIs include problems with arousal (including erectile dysfunction), desire, and orgasm.^5,6

• Women are more likely to report problems with arousal.⁵
• Fluoxetine and fluvoxamine might have slightly less effect on arousal than other SSRIs.⁵

Tricyclic antidepressants (particularly amitriptyline, clomipramine, and imipramine), can cause problems with desire, female lubrication, and orgasm.¹⁰

Sexual side effects occur within the first three weeks of treatment, before a therapeutic effect is noticeable, placing patients at risk for nonadherence.⁵

Which antidepressants are least likely to cause sexual side effects?

Bupropion^1,5

• Does not affect serotonin.⁹

Mirtazapine^1,5

• 5-HT2 receptor antagonist⁹

Duloxetine may pose a lower risk of sexual side effects than SSRIs or venlafaxine.¹⁰

Vortioxetine³

• Is a partial agonist at the 5-HT1B receptor, an agonist at the 5-HT1A receptor, and an antagonist at the 5-HT3 and 5-HT7 receptors.³ These actions may mitigate its adverse effects on sexual function.³

Vilazodone⁵

• Is a partial agonist at the 5-HT1A receptor and has less serotonin reuptake inhibition vs SSRIs.²

What PRIMARY interventions can be recommended to address sexual side effects?

Consider:

• “Primary prevention;” in patients who are sexually active and will require long-term treatment with an antidepressant, choose among those least likely to cause sexual dysfunction (above).⁹
• Waiting to see if the problem improves or resolves as the treated condition improves.⁴
• Interestingly, the risk of sexual side effects appears to be independent of the condition being treated.⁵
• For 5% to 10% of patients, the problem resolves on its own after four to six months of continued antidepressant use.¹⁰ In the meantime, adherence may be an issue.¹⁰
• Advising exercise before sexual activity to increase sympathetic nervous system activity.⁴
• Advising the patient to adjust their medication schedule or plan sexual activity such that sexual activity occurs when antidepressant levels are at their lowest.⁴ This might not work with fluoxetine due to its long half-life.⁴
• Decreasing the dose while staying within the therapeutic dosing range. Risks include worsening control or a discontinuation syndome.⁴

What SECONDARY interventions can be recommended to address sexual side effects?

Consider:

• Switching antidepressants (a common strategy).^4,5,7
• Switching to bupropion has the most data and experience.⁹
• Keep in mind that mirtazapine may be difficult to tolerate due to sedative effects,⁴ and nausea and diarrhea are common with vortioxetine and vilazodone.⁹
• See our chart, Choosing and Switching Antidepressants, for cross-tapering help.
• Adding bupropion or mirtazapine.^4,6
• The addition of bupropion SR 150 mg twice daily can improve sexual dysfunction in women [Evidence level A-2]⁶ and desire in both men and women.^5,9
• Adding a phosphodiesterase inhibitor (tadalafil or sildenafil before sexual activity) to improve erectile dysfunction in men [Evidence level A-2],⁶ and orgasm dysfunction in men and perhaps women.^4,5,8
• Adding cyproheptadine (serotonin antagonist) 4 to 12 mg before sexual activity, based on case reports.⁴

What interventions are not helpful and should be AVOIDED in patients with antidepressant-associated sexual side effects?

AVOID:

• Buspirone, supplements (e.g., ginkgo, maca, yohimbe); any benefit likely a placebo effect.⁴
• Drug holidays (i.e., washout to allow for sexual activity, such as on the weekends) due to risk of worsening control or withdrawal symptoms.⁴ This approach would not work for fluoxetine, due to its long half-life.⁴
• Vyleesi (bremelanotide) or Addyi (flibanserin) due to lack of data.