Nonhormone pharmacologic agents currently available for management of vasomotor symptoms
| Class | Medication | Dosing for VMSa | Clinical pearls |
|---|---|---|---|
| SSRIs | Paroxetine salt10,11,23,24 Paroxetine10,11,23,24 Fluoxetine11,23,24,26 Sertraline11,23,24,27 Citalopram10,11,23,24 Escitalopram10,11,23–25 | 7.5 mg daily at bedtime 10–25 mg daily 10–30 mg daily 25–100 mg daily 10–20 mg daily 10–20 mg daily | Potent cytochrome P450 CYP2D6 enzyme inhibitors; do not use with tamoxifen as SSRIs reduce tamoxifen bioavailability and efficacy Paroxetine mesylate 7.5 mg was the first and only US Food and Drug Administration–approved nonhormone medication for moderate to severe menopausal VMS until the development of neurokinin-receptor antagonists Fluoxetine and sertraline are not recommended for VMS reduction owing to inconsistent data regarding efficacy in hot flash frequency and severity reduction Sertraline has a moderate effect on the CYP2D6 enzyme Citalopram and escitalopram may cause QT prolongation |
| SNRIs | Desvenlafaxine10,11,23,24 Venlafaxine10,11,23,24 Duloxetine11,23,25 | 100–150 mg daily 37.5–75 mg daily 30–60 mg daily | SNRIs may increase blood pressure, use with caution in patients with hypertension Venlafaxine is the most well studied SNRI in combination with tamoxifen Duloxetine has a moderate effect on the CYP2D6 enzyme |
| Gabapentinoid | Gabapentin10,11,28–31 | 300–2,400 mg daily (divided doses) | Consider for patients with a history of neuropathic pain or sleep concerns Consider nightly dosing (starting dose of 100–300 mg at bedtime) to minimize any adverse effects of daytime fatigue |
| Antimuscarinic | Oxybutynin11,24,31,32 | 2.5–5 mg twice a day (immediate release), up to 15 mg/day (extended release) | Consider for patients with concurrent overactive bladder or hyperhidrosis Use caution in older adults (≥ 65 years); avoid altogether in patients ≥ 65 years taking concomitant anticholinergic medications |
| Alpha-2 adrenergic agonist | Clonidine11,32,33 | 0.05–0.1 mg once or twice a day | Consider for patients with hypertension, especially if improved blood pressure control is desired Avoid in older adult patients (≥ 65 years) Less often used and no longer recommended by the Menopause Society owing to modest efficacy vs placebo and side-effect profile |
| Neurokinin-receptor antagonist | Fezolinetant11,34,35 | 45 mg daily | Exercise caution in patients taking concomitant CYP1A2 enzyme inhibitors, which increase potency of fezolinetant Check transaminase levels at baseline, 3 months, 6 months, and 9 months |
↵a Based on clinical efficacy demonstrated in randomized controlled trials and the Menopause Society recommendations.10,11
SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitors; VMS = vasomotor symptoms