Antidepressants with Fewer Libido Effects
Bupropion is the clear first-line choice when sexual side effects are a concern, with sexual dysfunction rates of only 8-10% compared to 70.7% with paroxetine and 57.7-62.9% with fluoxetine. 1
Primary Recommendation
Switch to or initiate bupropion (150-400 mg/day) as first-line therapy when depression requires treatment and sexual function is a priority. 2, 1 The American College of Physicians explicitly recommends bupropion due to its significantly lower sexual adverse event profile compared to all SSRIs. 1
Evidence-Based Ranking of Antidepressants by Sexual Dysfunction Risk
Lowest Risk (Preferred Options)
- Bupropion: 8-10% sexual dysfunction rate - significantly lower than any SSRI 1
- Mirtazapine: Lower rates than SSRIs - though causes sedation and weight gain 1
Intermediate Risk (If SSRIs Required)
- Escitalopram and fluvoxamine: Lowest rates among SSRIs (exact rates not specified) 1
- Sertraline: 14% in males, 6% in females 1
- Citalopram: Intermediate rates 1
- Fluoxetine: 57.7-62.9% sexual dysfunction 3
Highest Risk (Avoid When Sexual Function Matters)
- Paroxetine: 70.7% sexual dysfunction rate - consistently the worst offender among all SSRIs 1
- Venlafaxine/SNRIs: Impair sexual function and should be avoided when libido is a concern 2
Critical Safety Considerations for Bupropion
Bupropion carries increased seizure risk, particularly at doses above 300 mg/day. 2, 1 Contraindications include:
- Active seizure disorder 1
- Bulimia or anorexia nervosa 2
- Abrupt alcohol or benzodiazepine discontinuation 2
- Agitated patients 1
Clinical Decision Algorithm
If sexual function is a major concern: Start bupropion 150-400 mg/day as first-line 2, 1
If bupropion is contraindicated: Consider mirtazapine 15-30 mg/day (accept sedation/weight gain trade-off) 1
If SSRI must be used: Choose escitalopram, fluvoxamine, sertraline, or citalopram over paroxetine or fluoxetine 1
Avoid paroxetine entirely when sexual function matters - it has 7-fold higher dysfunction rates than bupropion 1
Important Clinical Caveats
Sexual dysfunction rates are vastly underreported in clinical trials - real-world incidence is substantially higher than published figures. 2, 1 Routine inquiry about sexual side effects is essential since patients often don't volunteer this information. 1
Most sexual adverse effects emerge within the first 1-2 weeks of treatment, so early monitoring is critical. 1 Begin assessment within 1-2 weeks of initiation and modify treatment if no adequate response within 6-8 weeks. 2, 1
For breast cancer patients on tamoxifen: Avoid paroxetine and fluoxetine due to CYP2D6 inhibition reducing tamoxifen efficacy; prefer venlafaxine or citalopram instead. 1 Bupropion has less pronounced but still present CYP2D6 inhibition. 1
Sexual dysfunction from SSRIs is dose-related - higher doses increase both antidepressant efficacy and sexual side effects. 1 However, simply reducing the dose may compromise depression control.
What Doesn't Work
Buspirone has no evidence supporting its use for SSRI-induced sexual dysfunction despite being mentioned in some guidelines. 2, 1 The American College of Physicians recommends against using it for this indication. 1
Bupropion 150 mg once daily is ineffective as an antidote for existing SSRI-induced sexual dysfunction. 2, 4 Higher doses (150 mg twice daily) show benefit when used as primary therapy, not as augmentation. 2