SSRI with the Least Sexual Side Effects
Among SSRIs, escitalopram and fluvoxamine cause the lowest rates of sexual dysfunction, though bupropion (not an SSRI) has significantly lower sexual side effects than any SSRI and should be considered first-line when sexual function is a major concern. 1
Evidence-Based Ranking of SSRIs by Sexual Dysfunction Risk
Lowest Risk SSRIs
- Escitalopram and fluvoxamine demonstrate the lowest rates of sexual dysfunction among all SSRIs, though specific incidence rates are not well-quantified in guidelines 1
- Sertraline causes sexual dysfunction in approximately 14% of males (ejaculatory failure) and 6% decreased libido in combined male/female populations, placing it in the moderate range 1, 2
- Citalopram has intermediate rates of sexual dysfunction, though it is preferred over paroxetine or fluoxetine when an SSRI must be used 1
Highest Risk SSRIs
- Paroxetine has the highest rates of sexual dysfunction among all SSRIs at 70.7%, with significantly higher rates than fluoxetine, fluvoxamine, nefazodone, or sertraline 3, 1, 4
- Fluoxetine has intermediate to higher rates of sexual dysfunction compared to other SSRIs 1
Critical Clinical Considerations
Non-SSRI Alternative
- Bupropion has significantly lower sexual dysfunction rates (8-10%) compared to all SSRIs and should be considered first-line when sexual function is a major concern 3, 1
- Bupropion showed significantly lower rates of sexual adverse events than fluoxetine or sertraline in head-to-head comparisons 3
- Bupropion should not be used in agitated patients or those with seizure disorders due to increased seizure risk 3
Newer Antidepressants
- Vortioxetine shows low rates of sexual dysfunction and demonstrated significantly greater improvements in sexual function compared to escitalopram when switching from SSRIs causing sexual dysfunction 5, 6, 7
- Vortioxetine's multimodal mechanism (5-HT3, 5-HT7 antagonism plus SERT inhibition) may account for its lower sexual side effect profile 7
- Vilazodone (SSRI plus 5-HT1A partial agonist) has reduced sexual side effects compared to traditional SSRIs due to its dual mechanism 8
Important Caveats
Underreporting of Sexual Dysfunction
- Sexual dysfunction rates are vastly underreported in clinical trials, with actual rates likely higher than published figures 1
- Absolute rates of sexual dysfunction are probably underreported because patients and physicians may be reluctant to discuss them 2
- Physicians should routinely inquire about sexual function before and during SSRI treatment, as patients may not spontaneously report these symptoms 5, 2
Dose-Related Effects
- Sexual side effects of SSRIs are strongly dose-related, so reducing to the minimum effective dose may help 4
- Most sexual adverse effects emerge within the first few weeks of treatment 3
Management Strategy When Sexual Dysfunction Occurs
- Switching to bupropion is recommended as first-line therapy when sexual dysfunction occurs with an SSRI 1
- Bupropion-sustained release at doses of 100-200 mg/day showed improvement in SSRI-induced sexual side effects within the first 2 weeks, with global response rates of 75% in men and 46% in women 9
- Switching to vortioxetine may be beneficial for patients experiencing sexual dysfunction during SSRI therapy 6