What antidepressant has minimal risk of sexual dysfunction?

Antidepressant with Minimal Sexual Dysfunction

Bupropion is the antidepressant of choice when sexual dysfunction is a concern, as it has the lowest risk of sexual side effects among all antidepressants. 1

Primary Recommendation

• Bupropion should be considered as first-line therapy for patients who are sexually active or concerned about sexual side effects. 1
• The American College of Physicians supports selecting antidepressants based on adverse effect profiles and patient preferences, making bupropion an evidence-based choice for this population. 1

Evidence Supporting Bupropion

Comparative Sexual Dysfunction Rates

• In head-to-head trials, bupropion SR demonstrated dramatically lower rates of sexual dysfunction compared to SSRIs:
  • Men: 15% with bupropion vs 63% with sertraline 2
  • Women: 7% with bupropion vs 41% with sertraline 2
• Sexual dysfunction with sertraline appeared as early as day 7 at doses of 50 mg/day and persisted throughout 16 weeks of treatment. 2
• Orgasmic dysfunction specifically occurred significantly more with sertraline than bupropion or placebo throughout treatment studies. 3

Efficacy Equivalence

• Bupropion demonstrates equivalent antidepressant efficacy to SSRIs, so you are not sacrificing treatment effectiveness by choosing it for sexual side effect concerns. 1, 3
• Both bupropion SR and sertraline showed similar improvements on all depression rating scales and were superior to placebo. 3

Antidepressants to Avoid

• Paroxetine has the highest rates of sexual dysfunction among antidepressants and should be avoided when sexual function is a priority. 1
• Fluoxetine is associated with very high rates of sexual dysfunction (57.7% to 62.9%). 4
• SSRIs as a class cause sexual dysfunction in over 50% of patients, substantially higher than rates reported in package inserts. 5

Important Safety Consideration

• Bupropion carries a potential increased seizure risk, though the evidence is weak. 1
• Use caution and avoid bupropion in patients with seizure disorders, eating disorders, or abrupt discontinuation of alcohol/benzodiazepines. 6
• The seizure risk must be weighed against the substantial impact of sexual dysfunction on quality of life and medication adherence.

Clinical Pitfalls

• Sexual dysfunction from antidepressants is dramatically underreported in clinical trials and by patients. 1, 5
• Patients will not spontaneously report sexual problems and must be questioned directly about sexual function. 5
• Four patients discontinued sertraline specifically due to sexual dysfunction in comparative trials, highlighting the real-world impact on treatment adherence. 2

Alternative Management Strategies (If Bupropion Cannot Be Used)

For Men with Erectile Dysfunction on SSRIs

• Adding sildenafil or tadalafil is effective for antidepressant-induced erectile dysfunction. 7
• Sildenafil improved ability to achieve erections (MD 1.04) and maintain erections (MD 1.18) compared to placebo, representing improvement from "sometimes" to "most times." 7
• Tadalafil significantly improved erectile function (RR 11.50). 7

For Women on SSRIs

• Adding bupropion 150 mg twice daily (not once daily) to existing SSRI therapy shows benefit. 7
• Higher-dose bupropion augmentation (300 mg/day total) demonstrated significant improvement (SMD 1.60), while lower doses (150 mg/day) did not show statistically significant benefit. 7

Switching Strategies

• One trial showed switching from sertraline to nefazodone reduced sexual dysfunction (RR 0.34), but nefazodone is no longer clinically available. 7
• No randomized trials exist for switching to other currently-available antidepressants with lower sexual side effect profiles, representing a significant gap in the evidence. 7