Pathophysiology
Clinical meaning
Sexual dysfunction is the most common reason for SSRI non-adherence and discontinuation, affecting 30-70% of patients (higher than reported in clinical trials due to underreporting). SSRIs cause sexual dysfunction through multiple serotonin-mediated mechanisms: (1) 5-HT2A receptor stimulation in the spinal cord inhibits the sexual arousal reflex arc, reducing genital sensation and arousal. (2) 5-HT2C receptor activation decreases dopamine and norepinephrine release in the mesolimbic reward pathway, reducing sexual desire and motivation. (3) Elevated serotonin stimulates 5-HT3 receptors in the spinal cord, inhibiting orgasmic reflexes โ this specifically causes delayed orgasm/anorgasmia. (4) Prolactin elevation from serotonin-mediated suppression of dopaminergic tone reduces libido. (5) Nitric oxide synthase inhibition may contribute to erectile dysfunction. The spectrum of SSRI-induced sexual dysfunction includes: decreased libido (most common and least likely to resolve spontaneously), delayed orgasm/anorgasmia, erectile dysfunction, and reduced genital sensitivity. Paroxetine has the HIGHEST rate of sexual dysfunction (strongest serotonin reuptake inhibition + anticholinergic effects); bupropion has the LOWEST rate (no serotonergic mechanism โ acts via dopamine and norepinephrine). Management strategies must be proactive โ providers should ASK about sexual function rather than waiting...