What medication therapy for anxiety and depression reduces episodes of erectile dysfunction?

Bupropion is the Antidepressant of Choice to Minimize Erectile Dysfunction

When treating anxiety and depression in men concerned about erectile dysfunction, bupropion should be the first-line antidepressant, as it has significantly lower rates of sexual dysfunction (8-10%) compared to all SSRIs. 1, 2

Evidence-Based Ranking of Sexual Dysfunction Risk

The hierarchy of antidepressants based on erectile dysfunction risk is clear:

• Paroxetine causes the highest rates of sexual dysfunction (70.7%) among all antidepressants and should be avoided entirely in men concerned about erectile function 1
• Sertraline causes significant erectile dysfunction, with 63% of men developing sexual dysfunction in head-to-head trials 3
• Bupropion causes the lowest rates of sexual dysfunction (8-10%), making it the preferred choice when sexual function is a priority 1, 2

Clinical Decision Algorithm

Step 1: Initial Antidepressant Selection

• Start with bupropion 150-400 mg/day as first-line therapy when depression or anxiety requires treatment and erectile function is a concern 1, 2
• Bupropion demonstrated superiority over placebo (SMD 1.60,95% CI 1.40 to 1.81) when dosed at 150 mg twice daily 4
• Note: Once-daily dosing of bupropion 150 mg did not show significant benefit, so use twice-daily dosing 4

Step 2: If Bupropion is Contraindicated

Bupropion should NOT be used in patients with: 2

• Seizure disorders (increased seizure risk, especially above 300 mg/day)
• Eating disorders (bulimia/anorexia nervosa)
• Abrupt alcohol or benzodiazepine discontinuation
• Significant agitation 1

Alternative options if bupropion is contraindicated:

• Mirtazapine 15-30 mg/day has lower sexual dysfunction rates than SSRIs, though it causes sedation and weight gain 1
• If an SSRI must be used, sertraline or citalopram are preferred over paroxetine or fluoxetine 1

Step 3: If Already on an SSRI with Erectile Dysfunction

Two evidence-based strategies exist:

Strategy A: Switch to Bupropion

• The American College of Physicians recommends switching to bupropion as first-line therapy when sexual dysfunction occurs with SSRIs 1
• Taper the SSRI gradually over 10-14 days to limit withdrawal symptoms, especially with fluoxetine 1
• Monitor for discontinuation symptoms and changes in depressive symptoms during the switch 2

Strategy B: Add a PDE5 Inhibitor

• For men with erectile dysfunction specifically, adding sildenafil or tadalafil represents a robustly supported augmentation strategy 2, 4
• Sildenafil improves ability to achieve erections (MD 1.04,95% CI 0.65 to 1.44) and maintain erections (MD 1.18,95% CI 0.78 to 1.59) 4
• A single point improvement on these ratings equals improvement in frequency from 'sometimes' to 'most times' 4
• Tadalafil significantly improves erectile function (RR 11.50,95% CI 3.03 to 43.67) 4
• PDE5 inhibitors are contraindicated in patients taking oral nitrates due to dangerous blood pressure decreases 5, 6

Important Clinical Caveats

Cardiovascular Risk Assessment

• All men with erectile dysfunction should have cardiovascular risk estimated, as ED and cardiovascular disease share risk factors and often coexist 5
• Men who cannot walk 1 mile in 20 minutes or climb 2 flights of stairs in 20 seconds without symptoms are high-risk and should be referred to cardiology before ED treatment 5

Monitoring Requirements

• Assess response and adverse effects within 1-2 weeks of initiating therapy 1, 2
• If inadequate response occurs within 6-8 weeks, modify treatment 1, 2
• Monitor for seizure risk factors when using bupropion, particularly at doses above 300 mg/day 2

Underreporting of Sexual Dysfunction

• Sexual dysfunction rates are vastly underreported in clinical trials, so real-world incidence is likely higher than published figures 1, 2
• Proactively ask about sexual function at regular intervals rather than waiting for patients to volunteer this information 5

Anxiety Disorder Considerations

• For patients with comorbid anxiety disorders, SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety 2
• In these cases, the PDE5 inhibitor augmentation strategy becomes more relevant 2, 4

Psychological Factors

• Depression and anxiety themselves contribute to erectile dysfunction 5
• Psychotherapy and psychosexual counseling should be offered as an alternative or adjunct to medical treatment, particularly for men with predominantly psychogenic ED 5