SSRIs Increase Serotonin in the Genitals, But This Causes Sexual Dysfunction, Not Enhancement
SSRIs do increase serotonin levels in genital tissues, but this increased serotonin inhibits rather than enhances sexual function, causing widespread sexual dysfunction including decreased libido, delayed orgasm, and erectile problems. 1, 2
Mechanism of SSRI-Induced Sexual Dysfunction
The mechanism by which SSRIs affect genital function involves both central and peripheral serotonergic pathways:
Central serotonergic activity is increased throughout the brain and spinal cord, where serotonin exerts an inhibitory role on ejaculation and sexual response through 5-HT1A, 5-HT1B, and 5-HT2C receptors 2, 3
Peripheral effects occur in genital tissues where increased serotonin directly inhibits sexual arousal, orgasm, and ejaculation rather than enhancing these functions 1, 2
The effects are strongly dose-related, with higher SSRI doses increasing both the frequency and severity of sexual dysfunction 4
Clinical Impact: High Rates of Sexual Dysfunction
Paroxetine causes the highest rate of sexual dysfunction at 70.7%, significantly higher than other SSRIs 5:
- Sertraline causes sexual dysfunction in 14% of males and 6% of females 5
- Fluoxetine and citalopram have intermediate rates 5
- Sexual dysfunction includes delayed or absent orgasm, decreased libido, and erectile dysfunction 1
These published rates vastly underreport the true incidence, with actual rates likely much higher in clinical practice 5
The Paradox: Therapeutic Use in Premature Ejaculation
While SSRIs cause sexual dysfunction in most patients, this same mechanism is therapeutically exploited for premature ejaculation:
- Daily paroxetine increases ejaculatory latency time by 8.8-fold over baseline, the strongest effect among all SSRIs 4
- Daily sertraline (50-200 mg), fluoxetine (20-40 mg), and citalopram (20-40 mg) are also effective for delaying ejaculation 4
- This therapeutic effect occurs because increased serotonin in genital tissues and the central nervous system inhibits the ejaculatory reflex 2, 3
Important Clinical Caveat
About 40% of patients either refuse to begin or discontinue SSRIs within 12 months due to sexual side effects and concerns about taking antidepressants 4. This highlights that while increased genital serotonin can delay ejaculation therapeutically, it simultaneously causes distressing sexual dysfunction that significantly impacts quality of life and treatment adherence.
Differential Effects Based on SSRI Selectivity
Not all SSRIs affect genital function identically:
- Highly selective 5-HT1A SSRIs (paroxetine, sertraline) reduce norepinephrine efficiency more dramatically, causing more severe sexual dysfunction 6
- Less selective SSRIs (fluoxetine) have secondary norepinephrine binding that may partially counteract some sexual side effects 6
- Norepinephrine is the major neurotransmitter mediating genital arousal, particularly in women, so SSRIs that reduce norepinephrine activity cause more pronounced arousal difficulties 6