How to manage sexual dysfunction in patients taking Wellbutrin (bupropion) as an adjunct?

Managing Sexual Dysfunction in Patients Taking Wellbutrin (Bupropion)

Clarifying the Clinical Scenario

Wellbutrin (bupropion) is actually the solution, not the cause of sexual dysfunction. Bupropion has significantly lower rates of sexual adverse events compared to SSRIs and should be considered as a first-line antidepressant when sexual side effects are a concern 1.

However, if you are asking about using bupropion as an adjunct to treat sexual dysfunction caused by other antidepressants (particularly SSRIs), the evidence supports this strategy:

Bupropion as an Adjunct for SSRI-Induced Sexual Dysfunction

Primary Recommendation

Add bupropion 150 mg twice daily to the existing SSRI regimen to reverse sexual dysfunction, as this dosing demonstrates robust benefit over placebo. 2

Dosing Strategy

• Start with bupropion 75-150 mg taken 1-2 hours before sexual activity as a p.r.n. (as-needed) approach, which successfully improved sexual function in 38% of patients 3

• If p.r.n. dosing is insufficient, escalate to scheduled dosing:

  • Increase gradually to 75 mg three times daily and sustain for 2 weeks 3
  • If still inadequate, advance to 150 mg twice daily (total 300 mg/day), which shows the strongest evidence (SMD 1.60,95% CI 1.40 to 1.81) 2
  • Note: 150 mg once daily does NOT demonstrate significant benefit (RR 0.62,95% CI 0.09 to 4.41) 2

• Maximum dose: 400 mg/day 1

Expected Outcomes

• 66% of patients experience reversal of SSRI-induced sexual dysfunction with bupropion augmentation 3
• 69% of specific sexual complaints improve (including reduced desire, arousal difficulties, and orgasmic dysfunction) 3
• Improvement typically occurs within 2 weeks of scheduled dosing 3

Alternative Strategy: Switching Antidepressants

If augmentation fails or is not tolerated, switch from the offending SSRI to bupropion monotherapy rather than continuing the problematic medication 1.

• Bupropion is associated with significantly lower rates of sexual dysfunction than fluoxetine or sertraline 1
• Among SSRIs, paroxetine has the highest rates of sexual dysfunction and should be avoided when sexual side effects are problematic 1

Critical Safety Considerations

Seizure Risk with Bupropion

Bupropion increases seizure risk, particularly at doses above 300 mg/day or in patients with predisposing factors 1:

• Absolute contraindications: History of seizure disorder, bulimia, or anorexia nervosa 1
• High-risk situations: Abrupt alcohol or benzodiazepine discontinuation 1
• Use caution and consider lower doses in patients with these risk factors 1

Discontinuation Effects

• 15% of patients discontinue bupropion due to side effects, primarily anxiety and tremor 3
• Monitor for discontinuation symptoms when switching from SSRIs 1

Sex-Specific Considerations

For Men with Erectile Dysfunction

Add a phosphodiesterase-5 (PDE5) inhibitor (sildenafil or tadalafil) as the most robustly supported augmentation strategy for antidepressant-induced erectile dysfunction 2:

• 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) 2
• Tadalafil significantly improves erectile function (RR 11.50,95% CI 3.03 to 43.67) 2
• Critical contraindication: PDE5 inhibitors must NOT be used with nitrates due to serious cardiovascular interactions 4

For Women

Bupropion at higher doses (150 mg twice daily) appears to be the most promising approach for women with antidepressant-induced sexual dysfunction 2. Evidence for sildenafil in women remains uncertain 2.

Monitoring and Follow-Up

• Assess response within 1-2 weeks of initiating bupropion 1
• If inadequate response within 6-8 weeks, consider medication adjustment 1
• Screen for worsening depressive symptoms when making any medication changes 1
• Evaluate cardiovascular risk factors in all patients with sexual dysfunction, as erectile dysfunction shares common risk factors with cardiovascular disease 4

Important Clinical Caveats

• Sexual dysfunction rates are substantially underreported in clinical trials, so real-world incidence is likely higher than published rates 1
• Sexual counseling should involve the partner and address psychological factors, as almost all patients with organic causes are also affected psychologically 4
• For patients with comorbid anxiety disorders, SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety 1
• Lifestyle modifications (smoking cessation, weight loss, increased physical activity, reduced alcohol consumption) can improve sexual function and should be incorporated into treatment plans 1