Adding Buspirone to Sertraline for Sexual Side Effects
The evidence does not support adding buspirone to sertraline for sexual side effects—instead, switch to bupropion SR 150-300 mg/day, which has proven efficacy with sexual dysfunction rates of only 8-15% compared to sertraline's 41-63%. 1, 2
Why Buspirone Is Not Recommended
The available evidence for buspirone as an augmentation strategy is extremely limited:
- A 2013 Cochrane systematic review found no randomized controlled trials supporting buspirone augmentation for SSRI-induced sexual dysfunction 3
- Only case reports and small uncontrolled studies exist for buspirone, which do not meet the threshold for evidence-based recommendations 4
- No guideline from the American College of Physicians, American Urological Association, or American Academy of Family Physicians recommends buspirone for this indication 1, 5, 6
The Evidence-Based Approach: Switch to Bupropion
The American College of Physicians recommends switching to bupropion as first-line therapy when sexual dysfunction occurs with sertraline 1:
- Bupropion SR causes sexual dysfunction in only 15% of men and 7% of women, compared to sertraline's 63% and 41% respectively 2
- In head-to-head trials, bupropion SR and sertraline have equivalent antidepressant efficacy, making the switch straightforward 2, 7
- Sexual dysfunction with sertraline appears as early as day 7 at doses of 50 mg/day and persists throughout treatment 2
Switching Protocol
- Taper sertraline gradually over 10-14 days to prevent withdrawal syndrome (dizziness, nausea, headache, flu-like symptoms) 1, 5
- Start bupropion SR at 150 mg/day, titrating to 300 mg/day as needed for depression control 8
- Monitor for therapeutic response within 1-2 weeks 1
Alternative Augmentation Strategy: Bupropion Addition
If switching is not feasible, adding bupropion SR to sertraline is supported by evidence 8, 3:
- In an open-label study, adding bupropion SR 100-300 mg/day to SSRIs resulted in 46% response rates in women and 75% in men 8
- Most improvement (>50%) occurred within the first 2 weeks at doses of 100-200 mg/day 8
- The Cochrane review found bupropion 150 mg twice daily showed significant benefit (SMD 1.60,95% CI 1.40 to 1.81), though once-daily dosing was less effective 3
Critical Safety Considerations
When adding any agent to sertraline:
- Monitor for serotonin syndrome (tremor, hyperreflexia, agitation, diaphoresis, fever, and in severe cases seizures and rhabdomyolysis) 5, 6
- Do not use bupropion in patients with seizure disorders or high agitation 1
- Monitor patients under age 24 for suicidal ideation when making medication changes 5
Other Options If Bupropion Is Contraindicated
Mirtazapine 15-30 mg at bedtime can be considered as an alternative, though it causes sedation and weight gain 1, 6:
- Mirtazapine has lower sexual dysfunction rates than SSRIs 1
- Initiate at 7.5-15 mg at bedtime and titrate to 30-45 mg daily as needed 6
For men with erectile dysfunction specifically, phosphodiesterase inhibitors are evidence-based:
- Sildenafil improves ability to achieve erections (MD 1.04) and maintain erections (MD 1.18) compared to placebo 3
- Tadalafil increases likelihood of improved erectile function (RR 11.50,95% CI 3.03 to 43.67) 3
Common Pitfall to Avoid
Do not continue sertraline with buspirone augmentation based on anecdotal evidence when switching to bupropion has robust randomized controlled trial data demonstrating both efficacy for depression and dramatically lower sexual dysfunction rates. 1, 2, 3