Can Wellbutrin XL (bupropion) be used to mitigate sexual side effects in patients taking Lexapro (escitalopram)?

Wellbutrin XL for SSRI-Induced Sexual Dysfunction

Adding bupropion (Wellbutrin XL) 150-300 mg daily is a reasonable strategy to mitigate sexual side effects from escitalopram (Lexapro), though the evidence is mixed and switching to bupropion monotherapy may be more effective than augmentation. 1, 2

Evidence for Bupropion as Treatment Strategy

Switching vs. Augmentation

The strongest approach is switching from escitalopram to bupropion monotherapy rather than adding it as augmentation. 1, 2

• Bupropion has significantly lower rates of sexual dysfunction (8-10%) compared to SSRIs like escitalopram 1, 2
• When used as monotherapy, bupropion demonstrates clear superiority over SSRIs for preserving sexual function 3
• In a head-to-head comparison, only 15% of men and 7% of women on bupropion SR developed sexual dysfunction versus 63% of men and 41% of women on sertraline 3

Augmentation Evidence (Mixed Results)

The evidence for adding bupropion to ongoing SSRI therapy is contradictory:

Negative evidence:

• A placebo-controlled trial found that bupropion SR 150 mg daily added to SSRIs showed no significant improvement in sexual function compared to placebo after 6 weeks 4
• This suggests that the fixed 150 mg dose may be insufficient when used as augmentation 4

Positive evidence:

• An open-label study showed 46% response rate in women and 75% in men when bupropion SR was escalated up to 300 mg daily 5
• Most improvement occurred within the first 2 weeks at doses of 100-200 mg/day 5
• The Cochrane review found bupropion 150 mg twice daily (300 mg total) showed benefit over placebo (SMD 1.60,95% CI 1.40 to 1.81), though once-daily dosing did not 1

Practical Dosing Algorithm

If augmentation is chosen:

• Start bupropion SR 150 mg daily in the morning 4
• If no improvement after 2 weeks, increase to 150 mg twice daily (300 mg total) 1, 5
• Assess response at 2 weeks and 6 weeks 5
• Maximum dose is 400 mg/day, but seizure risk increases above 300 mg/day 1

If switching is chosen:

• Taper escitalopram gradually over 1-2 weeks to minimize discontinuation symptoms 1
• Initiate bupropion SR 150 mg daily, then increase to 300 mg daily after one week 3

Critical Safety Considerations

Seizure risk is the most important caveat with bupropion:

• Risk increases at doses above 300 mg/day 1, 2
• Contraindicated in patients with seizure disorders, bulimia, or anorexia nervosa 2
• Use caution with abrupt alcohol or benzodiazepine discontinuation 2

Bupropion is not appropriate for:

• Patients with significant anxiety disorders (SSRIs have better established efficacy for anxiety) 1
• Agitated patients 2

Alternative Strategies if Bupropion Fails or Is Contraindicated

For erectile dysfunction specifically:

• Add a PDE5 inhibitor (sildenafil or tadalafil) to the existing SSRI 1
• Sildenafil improves ability to achieve and maintain erections (MD 1.04,95% CI 0.65 to 1.44) 1
• Tadalafil significantly improves erectile function (RR 11.50,95% CI 3.03 to 43.67) 1
• PDE5 inhibitors are contraindicated with nitrates 6

Other antidepressant alternatives:

• Mirtazapine has lower rates of sexual dysfunction than SSRIs, though it causes sedation and weight gain 2

Monitoring Requirements

• Assess sexual function improvement within 1-2 weeks of initiating bupropion 1, 5
• Monitor for seizure risk factors, particularly at higher doses 1, 2
• Evaluate antidepressant efficacy to ensure depression remains controlled during any medication changes 1
• If no adequate response within 6-8 weeks, consider alternative strategies 1

Important Clinical Reality

Sexual dysfunction from SSRIs is vastly underreported in clinical trials, so real-world incidence is likely much higher than published rates. 2 This means the problem is more common and more severe than the literature suggests, making proactive management essential for medication adherence and quality of life.