Clinical comparison · Menopause & vasomotor symptoms · Updated 2026-07-02
Fezolinetant and low-dose paroxetine are the two non-hormonal medications FDA-approved for menopausal hot flashes. This table reproduces labeled and trial-reported facts verbatim, per cell. Their trials used different designs, so the efficacy figures are not a direct head-to-head. The page does not rank the two.
Every value below is reproduced verbatim from an FDA prescribing-information document or a published clinical trial, and each cell links to its source. This page does not rank the two options, does not declare one safer or more effective, and is not medical advice.
| Dimension | Fezolinetant | Low-dose paroxetine (Brisdelle) |
|---|---|---|
| Drug class | Neurokinin-3 (NK3) receptor antagonist[1] | Selective serotonin reuptake inhibitor (SSRI), 7.5 mg[2] |
| FDA-approved use | Moderate-to-severe vasomotor symptoms due to menopause[1] | Moderate-to-severe vasomotor symptoms of menopause[2] |
| Pivotal VMS efficacy | VMS frequency reduced ~6.3/day at week 12 vs ~3.7 placebo (45 mg, SKYLIGHT 1)[1] | VMS frequency reduced by a median 4.3/day at week 4 vs 3.1 placebo (Brisdelle Study 1)[2] |
| Boxed / class warning | Boxed warning (2024): rare serious liver injury; monitor LFTs[3] | SSRI class warning for suicidal thoughts in adults under 25[2] |
| Key interaction flag | Contraindicated with strong/moderate CYP1A2 inhibitors[1] | Inhibits CYP2D6 — may reduce tamoxifen activation[4] |
| Dosing | 45 mg once daily; no titration[1] | 7.5 mg once daily at bedtime; no titration[2] |
What the pivotal trials measured
SKYLIGHT 1 measured change in daily moderate-to-severe vasomotor frequency for fezolinetant (about a 6.3/day reduction at week 12 vs 3.7 with placebo; placebo-adjusted difference about 2.55/day). The pivotal Brisdelle trial (Study 1, published by Simon et al. 2013) measured the same endpoint for low-dose paroxetine (a median 4.3/day reduction at week 4 vs 3.1 with placebo; treatment difference 1.2/day), at a different timepoint. FDA Brisdelle PI
Why the tamoxifen flag matters
Low-dose paroxetine inhibits CYP2D6, which can reduce activation of tamoxifen; the BMJ 2010 analysis examined this interaction. Fezolinetant does not share this mechanism. Both facts are reproduced from their sources without recommendation. Kelly et al., BMJ 2010 (tamoxifen-paroxetine)
Two: fezolinetant (Veozah), an NK3-receptor antagonist, and low-dose paroxetine (Brisdelle), an SSRI dosed at 7.5 mg (FDA labels).
Low-dose paroxetine inhibits CYP2D6, which can reduce tamoxifen activation; the BMJ 2010 analysis examined this interaction. Discuss alternatives with your prescriber if you take tamoxifen.
Editorial reviews from ClearHormones of telehealth providers in this category. These are not treatment recommendations, and prescribing decisions rest with a licensed clinician.