Antidepressant Selection to Minimize Libido Side Effects
Bupropion is the antidepressant of choice when low libido is a concern, with sexual dysfunction rates of only 8-15% compared to 58-73% with SSRIs. 1, 2, 3
Primary Recommendation
Start with bupropion sustained-release 150-400 mg/day as first-line therapy when sexual function, including libido, is a priority concern. 2, 3 This recommendation is based on multiple high-quality comparative studies and guideline consensus from the American College of Physicians showing bupropion has significantly lower rates of all sexual side effects—including decreased libido, orgasm dysfunction, and erectile problems—compared to all SSRIs. 1, 4, 5
Evidence Supporting Bupropion
Direct comparative trials demonstrate bupropion's superiority: In head-to-head studies, only 15% of men and 7% of women on bupropion SR developed sexual dysfunction versus 63% of men and 41% of women on sertraline. 4
Libido specifically is preserved with bupropion: Unlike SSRIs which reduce libido through serotonergic mechanisms, bupropion primarily increases dopamine and norepinephrine, which actually support sexual desire and function. 6, 7
The effect is consistent across studies: A prospective multicenter study of 1,022 patients found sexual dysfunction rates of 58-73% with SSRIs compared to essentially no sexual dysfunction with bupropion and similar non-serotonergic agents. 7
Critical Safety Consideration for Bupropion
Bupropion carries an increased seizure risk, particularly at doses above 300 mg/day or in patients with predisposing factors. 1, 2, 3 Absolute contraindications include:
- Current seizure disorder 2
- Bulimia or anorexia nervosa 2
- Abrupt discontinuation of alcohol or benzodiazepines 2
Do not use bupropion in agitated patients, as it can worsen agitation. 8
If SSRIs Must Be Used: Ranking by Sexual Dysfunction Risk
When bupropion is contraindicated or ineffective for depression, choose SSRIs based on this hierarchy:
Lowest sexual dysfunction among SSRIs:
- Escitalopram and fluvoxamine cause the lowest rates, though exact percentages are not well-defined 8
- Sertraline: 62.9% overall sexual dysfunction rate 7
Highest sexual dysfunction (AVOID if libido is a concern):
- Paroxetine has the worst sexual side effect profile at 70.7%, significantly higher than all other SSRIs 1, 2, 8, 7
- Citalopram: 72.7% 7
Alternative Non-SSRI Options
If bupropion fails or is contraindicated:
Mirtazapine 15-30 mg/day: Only 24.4% sexual dysfunction rate, but causes significant sedation and weight gain that may limit tolerability 8, 7
Nefazodone: Only 8% sexual dysfunction rate, but carries hepatotoxicity risk requiring monitoring 1, 7
Important Clinical Caveats
Sexual dysfunction is vastly underreported in clinical trials—real-world rates are likely higher than published figures, so proactive inquiry is essential. 1, 2, 8
Sexual side effects emerge early: Most sexual dysfunction appears within the first few weeks of SSRI treatment, not after months of use. 8
Timing of assessment matters: Begin monitoring for sexual side effects within 1-2 weeks of starting any antidepressant. 2, 8
About 40% of patients cannot tolerate their sexual dysfunction, leading to treatment discontinuation and potentially untreated depression. 8, 7
Special Population Considerations
In breast cancer patients on tamoxifen: Avoid paroxetine and fluoxetine due to CYP2D6 inhibition reducing tamoxifen efficacy; prefer bupropion, venlafaxine, or citalopram instead. 2, 8