Antidepressant Selection to Minimize Sexual Side Effects
Bupropion is the antidepressant of choice when sexual side effects are a concern, as it has significantly lower rates of sexual dysfunction compared to SSRIs like fluoxetine and sertraline. 1, 2, 3
Primary Recommendation
Bupropion should be prescribed as first-line therapy for patients with depression who prioritize maintaining sexual function, with dosing at 150-400 mg/day (typically starting at 150 mg sustained-release formulation and titrating as needed). 2, 4
The American College of Physicians guideline explicitly states that bupropion is associated with lower rates of sexual adverse events than fluoxetine and sertraline, and physicians should discuss adverse event profiles before selecting medication. 1
Clinical trials demonstrate that 63% of men and 41% of women on sertraline develop sexual dysfunction, compared to only 15% of men and 7% of women on bupropion SR. 4
Comparative Sexual Dysfunction Rates Among Antidepressants
SSRIs to avoid if sexual function is a priority:
Paroxetine has the highest rates of sexual dysfunction among SSRIs—significantly worse than fluoxetine, fluvoxamine, nefazodone, or sertraline. 1, 2
Sertraline and fluoxetine cause sexual dysfunction in the majority of patients (41-63% depending on sex). 4
Sexual dysfunction with SSRIs can emerge as early as day 7 of treatment at doses as low as 50 mg/day and persists throughout treatment. 4
Alternative Newer Agent
Vortioxetine (Trintellix) demonstrates significantly less sexual dysfunction than escitalopram in head-to-head trials, with a 2.2-point superior improvement on validated sexual function scales when switching from other SSRIs. 5
Vortioxetine 10 mg (but not 20 mg) showed statistically significantly less sexual dysfunction than paroxetine 20 mg in healthy volunteers without depression. 5
Critical Safety Considerations for Bupropion
Seizure risk is increased with bupropion, particularly at doses above 300 mg/day or in patients with predisposing factors (history of seizures, eating disorders, abrupt alcohol/benzodiazepine discontinuation). 1, 2
Bupropion is contraindicated in patients with seizure disorders or bulimia/anorexia nervosa. 1
Bupropion has less established efficacy for comorbid anxiety disorders compared to SSRIs, so if significant anxiety is present, this must be weighed against sexual function concerns. 2
If Patient Must Remain on SSRI
Augmentation strategies when switching is not feasible:
Adding bupropion 150 mg twice daily to existing SSRI therapy improves sexual function (effect size 1.60,95% CI 1.40-1.81), though once-daily dosing is not effective. 2
For men with erectile dysfunction specifically, adding a PDE5 inhibitor (sildenafil or tadalafil) is robustly effective, with tadalafil showing particularly strong results (RR 11.50,95% CI 3.03-43.67). 2
Important Clinical Caveats
Sexual dysfunction rates are substantially underreported in clinical trials, so real-world incidence is likely higher than published rates. 1, 2, 3
When switching from an SSRI to bupropion, monitor for SSRI discontinuation syndrome and ensure depressive symptoms remain controlled during the transition. 2
Cognitive behavioral therapy should be considered as an alternative to pharmacotherapy entirely, as it has similar efficacy to antidepressants with no sexual side effects and lower relapse rates. 1
Nausea and vomiting are the most common reasons for discontinuation across all antidepressants, so patients should be counseled about this alongside sexual effects. 1