Antidepressants with Lower Risk of Orgasm Problems
Bupropion is the first-line antidepressant choice when sexual dysfunction, including orgasm problems, is a concern, as it has significantly lower rates of sexual side effects compared to SSRIs. 1, 2
Primary Recommendation: Bupropion
- Bupropion should be considered as the initial antidepressant agent when sexual function is a priority, with sexual dysfunction rates of only 6-24% compared to 58-73% with SSRIs 1, 3
- Bupropion SR (sustained release) demonstrated significantly fewer sexual adverse events than fluoxetine or sertraline in direct comparison trials 1, 2
- In a pilot study of patients with orgasmic dysfunction, 70% of subjects reported improvement in libido, arousal, or orgasmic function during bupropion administration 4
- Bupropion can be initiated at 150 mg/day and titrated to 300-400 mg/day as needed 5, 2
Important Caveat for Bupropion
- Bupropion carries an increased seizure risk compared to SSRIs, particularly at higher doses or in patients with predisposing factors (eating disorders, seizure history, abrupt alcohol/benzodiazepine discontinuation) 1, 5
- Use extreme caution when combining with other medications that lower seizure threshold 5
Alternative Antidepressants with Lower Sexual Dysfunction Rates
If bupropion is contraindicated or ineffective, consider these alternatives in order of preference:
Mirtazapine
- Sexual dysfunction rate of approximately 24% compared to 58-73% with SSRIs 3
- Can be initiated at 7.5-15 mg at bedtime and titrated to 30-45 mg daily 6
- Primary drawbacks include sedation and weight gain, which may be undesirable for many patients 6
Nefazodone
- Sexual dysfunction rate of only 8% in prospective studies 3
- Significantly lower rates than SSRIs (paroxetine, fluoxetine, fluvoxamine, sertraline) 1
Moclobemide
- Sexual dysfunction rate of approximately 4% 3
- Not widely available in the United States
SSRIs to Avoid When Sexual Function is a Priority
If an SSRI must be used, avoid paroxetine, which has the highest rates of sexual dysfunction among SSRIs:
- Paroxetine: 70.7% sexual dysfunction rate 3
- Citalopram: 72.7% sexual dysfunction rate 3
- Venlafaxine (SNRI): 67.3% sexual dysfunction rate 3
- Sertraline: 62.9% sexual dysfunction rate 3
- Fluoxetine: 57.7% sexual dysfunction rate 3
Orgasm dysfunction specifically is more common with fluoxetine than bupropion or placebo, beginning at week 2 of treatment and persisting throughout therapy 2
Management Strategy if Already on an SSRI
If a patient is already taking an SSRI and experiencing orgasm problems:
Switching Strategy
- Switching from an SSRI to nefazodone significantly reduces sexual dysfunction (RR 0.34,95% CI 0.15-0.6) without worsening depression 7
Augmentation Strategies
- Adding bupropion to the existing SSRI improved sexual desire scores (WMD 0.88,95% CI 0.21-1.55) 7
- For men with erectile dysfunction specifically, adding sildenafil (a PDE5 inhibitor) significantly improves erectile function (WMD 19.36,95% CI 15.00-23.72) 7
- Buspirone can be considered as an off-label augmentation strategy, though evidence is limited 1
- Mirtazapine augmentation is another option, starting at 7.5-15 mg at bedtime 6
Clinical Pitfalls to Avoid
- Sexual dysfunction is significantly underreported in clinical practice—actively inquire about sexual side effects at follow-up visits rather than waiting for patients to volunteer this information 3, 8
- Do not assume that amenorrhea or lack of spontaneous sexual complaints means absence of sexual dysfunction 3
- When switching from an SSRI to bupropion, monitor for SSRI discontinuation symptoms 1
- For patients with comorbid anxiety disorders, bupropion may be less effective than SSRIs for anxiety symptoms, requiring careful risk-benefit assessment 1
- Assess response and adverse effects within 1-2 weeks of initiating therapy, with medication adjustment considered if inadequate response occurs within 6-8 weeks 1