Detailed definition
Paroxetine, an SSRI, was the first non-hormonal medication FDA-approved for vasomotor symptoms (Brisdelle, 7.5 mg, approved 2013). Mechanism is thought to involve serotonergic modulation of hypothalamic thermoregulation. The 7.5-mg dose is lower than typical antidepressant doses (20–60 mg) and is generally well-tolerated, though common SSRI side effects (nausea, fatigue, sexual side effects, withdrawal symptoms on stopping) still apply. Paroxetine is a strong CYP2D6 inhibitor and should be avoided in women on tamoxifen, since CYP2D6 inhibition reduces conversion of tamoxifen to its active metabolite endoxifen. Other SSRIs/SNRIs used off-label for hot flashes include venlafaxine (effective at 75 mg/day; SKYLIGHT predecessor trials), escitalopram, citalopram, and desvenlafaxine — none FDA-approved for VMS, but supported by RCTs.
Why it matters in menopause
For women who cannot take estrogen and have either VMS or VMS-plus-mood symptoms, low-dose paroxetine or venlafaxine can be a reasonable choice. Fezolinetant has changed the calculus by offering a mechanism-targeted option, but cost and liver monitoring make older SSRIs/SNRIs still relevant.
Related terms
Sources
External references: Wikipedia.