Antidepressant Sexual Side Effects

Questions often arise in practice regarding antidepressant-associated sexual side effects. The chart below lists types of sexual side effects, antidepressants less likely to cause sexual side effects, and interventions to consider. Most interventions are not supported by high-level evidence, and a trial-and-error approach will be needed, keeping in mind the risks of the intervention vs risks of nonadherence due to intolerable sexual side effects.

Question

Answer/Pertinent Information

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?

Bupropion1,5

  • Does not affect serotonin.9

Mirtazapine1,5

  • 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.

 

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level

Definition

Study Quality

A

Good-quality patient-oriented evidence.*

  1. High-quality RCT
  2. SR/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study

C

Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. http://www.aafp.org/afp/2004/0201/p548.pdf.]

Prepared by the Editors of Therapeutic Research Center (370107).

References

  1. U.S. Department of Defense. Department of Veterans Affairs. VA/DoD clinical practice guideline or the management of major depressive disorder. April 2016. https://www.healthquality.va.gov/guidelines/MH/mdd/VADoDMDDCPGFINAL82916.pdf. (Accessed December 6, 2020).
  2. Hellerstein DJ, Flaxer J. Vilazodone for the treatment of major depressive disorder: an evidence-based review of its place in therapy. Core Evid 2015;10:49-62.
  3. Alvarez E, Perez V, Artigas F. Pharmacology and clinical potential of vortioxetine in the treatment of major depressive disorder. Neuropsychiatr Dis Treat 2014;10:1297-307.
  4. Francois D, Levin AM, Kutscher EJ, Asemota B. Antidepressant-induced sexual side effects: incidence, assessment, clinical implications, and management. Psychiatr Ann 2017;47:154-60.
  5. Lorenz T, Rullo J, Faubion S. Antidepressant-induced female sexual dysfunction. Mayo Clin Proc 2016;91:1280-6.
  6. Taylor MJ, Rudkin L, Bullemor-Day P, et al. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database Syst Rev 2013;(5):CD003382.
  7. Clinical Resource, Choosing and Switching Antidepressants. Pharmacist’s Letter/Prescriber’s Letter. July 2020.
  8. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2020. http://www.clinicalkey.com. (Accessed December 7, 2020).
  9. Montejo AL, Prieto N, de Alarcon R, et al. Management strategies for antidepressant-related sexual dysfunction: a clinical approach. J Clin Med 2019;8:1640.
  10. Clayton AH, Alkis AR, Parikh NB, Votta JG. Sexual dysfunction due to psychotropic medications. Psychiatr Clin North Am 2016;39:427-63.

Cite this document as follows: Clinical Resource, Antidepressant Sexual Side Effects. Pharmacist’s Letter/Prescriber’s Letter. January 2021.

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