Best Antidepressant to Prevent 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
Primary Recommendation
- Start with bupropion 150-400 mg/day as first-line therapy when sexual function is a priority for the patient. 1
- The American College of Physicians explicitly recommends discussing adverse event profiles before selecting medication, noting bupropion's superior sexual side effect profile. 1
- Bupropion demonstrates significantly lower rates of sexual adverse events across multiple controlled trials, with only 7-15% of patients developing sexual dysfunction compared to 41-63% with sertraline. 3, 4
Comparative Sexual Dysfunction Rates
Among SSRIs, if bupropion is not suitable:
- Paroxetine has the highest rates of sexual dysfunction and should be avoided when sexual side effects are a concern. 1, 2
- Fluoxetine, fluvoxamine, and sertraline have lower rates than paroxetine but still substantially higher than bupropion. 1
- SNRIs (venlafaxine, desvenlafaxine, duloxetine) also impair sexual function and should be avoided when libido is a concern. 1
Critical Safety Considerations for Bupropion
Seizure risk is the primary concern with bupropion:
- Risk increases at doses above 300 mg/day or in patients with predisposing factors (history of seizures, eating disorders, abrupt alcohol/benzodiazepine discontinuation). 1
- Bupropion is absolutely contraindicated in patients with seizure disorders or bulimia/anorexia nervosa. 1
- Despite this risk, the evidence for increased seizures is considered weak. 2
Important Clinical Caveats
For patients with comorbid anxiety disorders:
- SSRIs may still be preferred despite sexual side effects, as bupropion has less established efficacy for anxiety. 1
- This represents a clinical trade-off where you must weigh sexual function against anxiety control.
Underreporting of sexual dysfunction:
- Sexual dysfunction rates are substantially underreported in clinical trials, so real-world incidence is likely higher than published rates for all antidepressants. 1, 2
- Proactively ask patients about sexual function at follow-up visits rather than waiting for them to report it.
Monitoring Timeline
- Assess patient response and adverse effects within 1-2 weeks of initiating bupropion therapy. 1
- If inadequate response to initial therapy occurs within 6-8 weeks, consider medication adjustment. 1
- Monitor for discontinuation symptoms if switching from an SSRI to bupropion. 1
Alternative Strategy: Cognitive Behavioral Therapy
- Consider cognitive behavioral therapy as an alternative to pharmacotherapy entirely, as it has similar efficacy to antidepressants with no sexual side effects and lower relapse rates. 1