Antidepressant with Least Sexual Side Effects
Bupropion is the antidepressant with the lowest risk of sexual dysfunction and should be your first-line choice when sexual side effects are a concern. 1, 2
Primary Recommendation
- Bupropion causes significantly less sexual dysfunction than all SSRIs and SNRIs, with sexual dysfunction rates of only 15% in men and 7% in women, compared to 63% and 41% respectively with sertraline 3
- The American College of Physicians explicitly recommends selecting bupropion over fluoxetine and sertraline when sexual adverse events are a concern 1, 2
- Bupropion demonstrated superior sexual tolerability across all categories of sexual dysfunction (libido, arousal, orgasm) in both men and women 4, 5
Dosing Strategy for Bupropion
- Start with bupropion SR 150 mg daily, which can be titrated up to 300-400 mg/day as needed for antidepressant efficacy 2, 3
- Most improvement in sexual function occurs within the first 2 weeks at low doses (100-200 mg/day) 4
- The sustained-release formulation is preferred for better tolerability 6, 3
Critical Safety Consideration: Seizure Risk
- Bupropion carries an increased seizure risk, particularly at doses above 300 mg/day 1, 2
- Absolute contraindications include: seizure disorders, bulimia/anorexia nervosa, and abrupt discontinuation of alcohol or benzodiazepines 2
- Use caution in patients with predisposing factors for seizures 2
If You Must Use an SSRI
When bupropion is contraindicated or ineffective for depression (e.g., comorbid anxiety disorders where SSRIs are preferred), the hierarchy for lowest sexual dysfunction is:
- Escitalopram or fluvoxamine - lowest sexual dysfunction rates among SSRIs 7
- Sertraline or citalopram - intermediate rates (sertraline: 14% in males, 6% in females) 7
- Fluoxetine - moderate-high rates 7
- Paroxetine - highest rates at 70.7%, should be avoided entirely when sexual function matters 7
Avoid These Medications
- Paroxetine has the worst sexual dysfunction profile of all antidepressants and should never be used when sexual function is a concern 1, 7
- SNRIs (venlafaxine, duloxetine, desvenlafaxine) impair sexual function and should be avoided when libido is a priority 2, 7
Common Pitfalls
- Sexual dysfunction rates are substantially underreported in clinical trials, so real-world incidence is likely higher than published figures 2, 7
- Sexual dysfunction can emerge as early as day 7 of SSRI treatment at starting doses 3
- Don't combine bupropion with MAO inhibitors 6
- Monitor for therapeutic response within 1-2 weeks and adjust if no adequate response by 6-8 weeks 2, 7
Managing Existing SSRI-Induced Sexual Dysfunction
If a patient is already on an SSRI with sexual dysfunction:
- Switch to bupropion as the primary strategy 2
- Alternatively, add bupropion SR to the existing SSRI at escalating doses up to 300 mg daily, with most improvement occurring within 2 weeks 4
- For men with erectile dysfunction specifically, adding a PDE5 inhibitor (sildenafil or tadalafil) is robustly supported, but never use with nitrates 2