Bupropion for SSRI-Induced Sexual Dysfunction
Direct Recommendation
Yes, bupropion is highly effective for treating SSRI-induced sexual dysfunction and should be your first-line intervention, either as an adjunctive agent or as a replacement antidepressant. 1, 2
Evidence-Based Treatment Algorithm
Step 1: Confirm SSRI-Induced Sexual Dysfunction
- Assess the specific type of dysfunction: decreased libido, erectile dysfunction, delayed/absent orgasm, or ejaculatory problems 1
- Recognize that sexual dysfunction rates are substantially underreported in clinical trials—actual incidence is likely higher than published figures 3, 2
Step 2: Choose Your Bupropion Strategy
Option A: Add Bupropion to Current SSRI (Augmentation)
- Start with 150 mg twice daily (300 mg/day total) of bupropion sustained-release 1
- This approach allows you to maintain antidepressant efficacy while addressing sexual side effects 4
- Open-label studies show 66% of patients experience improvement in sexual dysfunction with adjunctive bupropion 5
- Sexual function improves within 2 weeks of adding bupropion 6
- Critical caveat: One randomized controlled trial found that 150 mg once daily was NOT effective—you need the twice-daily dosing 7
Option B: Switch from SSRI to Bupropion Monotherapy
- Add bupropion SR 150 mg twice daily while continuing the SSRI for 2 weeks 6
- Then taper the SSRI over 2 weeks while maintaining bupropion 6
- Continue bupropion monotherapy at 150-400 mg/day 1
- This strategy showed 55% of patients successfully transitioned without depression recurrence, with progressive improvement in sexual function 6
Comparative Evidence: Why Bupropion Works
Sexual Dysfunction Rates by Antidepressant
- Bupropion: 8-10% incidence 3, 2
- Sertraline: 14% (males), 6% (females) 2
- Fluoxetine: 57.7-62.9% 8
- Paroxetine: 70.7% (highest of all antidepressants) 3, 2
Head-to-Head Trial Data
- In a 16-week double-blind trial comparing bupropion SR versus sertraline, 63% of men and 41% of women on sertraline developed sexual dysfunction, compared to only 15% of men and 7% of women on bupropion SR 9
- Sexual dysfunction appeared as early as day 7 on sertraline 50 mg/day and persisted throughout treatment 9
Critical Safety Warnings for Bupropion
Seizure Risk (Most Important Caveat)
- Bupropion increases seizure risk, particularly above 300 mg/day 1, 2
- Absolute contraindications: seizure disorders, bulimia, anorexia nervosa 2
- Relative contraindications: abrupt alcohol/benzodiazepine discontinuation, history of head trauma 2
- Keep doses ≤300 mg/day in most patients to minimize this risk 1
Other Considerations
- Do not use in agitated patients 2
- Less effective for comorbid anxiety disorders compared to SSRIs 1
- May reduce tamoxifen efficacy in breast cancer patients (though less than paroxetine/fluoxetine) 2
Monitoring and Follow-Up
- Assess sexual function improvement within 1-2 weeks of bupropion initiation 6
- Monitor for seizure risk factors throughout treatment 1
- If switching from SSRI to bupropion, watch for SSRI discontinuation symptoms during taper 1
- Evaluate depression symptoms at 6-8 weeks; if inadequate response, adjust treatment 1, 2
Alternative Strategies If Bupropion Fails or Is Contraindicated
For Men with Erectile Dysfunction
- Add a PDE5 inhibitor (sildenafil or tadalafil) to the existing SSRI 1
- Sildenafil improves ability to achieve erections (MD 1.04,95% CI 0.65-1.44) and maintain erections (MD 1.18,95% CI 0.78-1.59) 1
- Tadalafil significantly improves erectile function (RR 11.50,95% CI 3.03-43.67) 1
Switch to Mirtazapine
- Lower sexual dysfunction rates than SSRIs 2
- Trade-off: causes sedation and weight gain 2
- Dose: 15-30 mg/day 2