Antidepressants and Sexual Function: Evidence-Based Guidance
Direct Answer
Most antidepressants, particularly SSRIs and SNRIs, significantly worsen sexual function rather than help it, with sexual dysfunction rates ranging from 58-73%, while bupropion is the notable exception that preserves sexual function comparable to placebo. 1, 2
Sexual Dysfunction Rates by Antidepressant Class
Highest Risk Antidepressants
- Paroxetine causes the most severe sexual dysfunction at 70.7%, significantly worse than all other SSRIs 1, 3, 4
- Citalopram causes sexual dysfunction in 72.7% of patients 4
- Venlafaxine (SNRI) causes sexual dysfunction in 67.3% of patients 4
- Sertraline causes sexual dysfunction in 62.9% of patients, with 14% experiencing ejaculatory failure 3, 4
- Fluoxetine causes sexual dysfunction in 57.7-62.9% of patients 5, 4
- Fluvoxamine causes sexual dysfunction in 62.3% of patients 4
Lower Risk Antidepressants
- Bupropion causes sexual dysfunction in only 8-10% of patients, comparable to placebo rates 2, 3, 6
- Mirtazapine causes sexual dysfunction in 24.4% of patients 4
- Nefazodone causes sexual dysfunction in only 8% of patients 4
- Moclobemide causes sexual dysfunction in 3.9% of patients 4
Clinical Decision Algorithm
Step 1: Initial Antidepressant Selection
When sexual function is a concern, start with bupropion 150-400 mg/day as first-line therapy rather than an SSRI 2, 3. Bupropion demonstrated equivalent antidepressant efficacy to SSRIs (62% vs 63% response rates, 47% vs 47% remission rates) but with significantly fewer sexual side effects 6.
Step 2: If Bupropion is Contraindicated
Avoid bupropion in patients with:
- Seizure disorders or history of seizures (increased seizure risk, particularly above 300 mg/day) 2, 3
- Eating disorders (bulimia/anorexia nervosa) 2
- Agitated patients 3
Alternative options in order of preference:
- Mirtazapine 15-30 mg/day (24.4% sexual dysfunction rate, but causes sedation and weight gain) 3, 4
- Nefazodone (8% sexual dysfunction rate) 4
Step 3: If SSRI Must Be Used
If an SSRI is clinically necessary, avoid paroxetine entirely due to its 70.7% sexual dysfunction rate 1, 3. Choose sertraline or citalopram over fluoxetine or paroxetine 3.
Step 4: Managing Existing SSRI-Induced Sexual Dysfunction
Switch to bupropion as the primary strategy when sexual dysfunction emerges on an SSRI 2, 3. For men with erectile dysfunction specifically, adding a PDE5 inhibitor (sildenafil or tadalafil) represents a robustly supported augmentation strategy 2.
Critical Clinical Caveats
Underreporting of Sexual Dysfunction
Sexual dysfunction rates are vastly underreported in clinical trials, with actual real-world incidence likely higher than published figures of 58-73% 1, 2, 3. This occurs because many studies do not use validated sexual function questionnaires and rely on spontaneous reporting 4.
Patient Tolerance and Adherence
Approximately 40% of patients show low tolerance of their sexual dysfunction, contributing to the 40% of patients who either refuse to begin or discontinue antidepressants within 12 months 3. This makes proactive assessment and management essential for treatment adherence 7.
Gender Differences
Men experience sexual dysfunction more frequently (62.4%) than women (56.9%) on SSRIs, though women report higher severity when dysfunction occurs 4.
Timing of Onset
Most sexual adverse effects emerge within the first few weeks of treatment 3, requiring assessment within 1-2 weeks of initiation 2.
Dose-Related Effects
Sexual side effects of SSRIs are strongly dose-related, with higher doses increasing both antidepressant efficacy and frequency of erectile dysfunction and decreased libido 3. Reducing to the minimum effective dose is a primary management strategy 3.
Post-SSRI Sexual Dysfunction
A rare but important adverse effect is persistent sexual dysfunction that continues after SSRI discontinuation and depression remission 7. Consider this possibility when sexual dysfunction was absent before starting antidepressants but persists after stopping them 7.