What medications are used to treat hot flashes, particularly in menopause?

Medications for Hot Flashes in Menopause

For moderate to severe menopausal hot flashes, first-line pharmacological treatments include SSRIs/SNRIs (such as venlafaxine or paroxetine) or gabapentin, with gabapentin being the only non-hormonal treatment shown to have efficacy equivalent to estrogen. 1, 2

First-Line Non-Hormonal Pharmacological Options

SSRIs/SNRIs

• Venlafaxine (37.5 mg daily, increasing to 75 mg daily after 1 week if needed) reduces hot flash scores by 37-61% compared to 27% with placebo 1
• Paroxetine (10 mg daily, increasing to 20 mg daily after 1 week if symptoms persist) reduces hot flash composite scores by 62-65% 1
• Low-dose paroxetine 7.5mg daily effectively reduces frequency, severity, and nighttime awakenings 2
• These medications have a rapid onset of action (within 1 week) 1
• Side effects include headache, nausea, reduced appetite, dry mouth, anxiety/agitation, sleep disturbance, and sexual dysfunction 1
• Approximately 10-20% of patients discontinue treatment due to side effects 1

Gabapentin

• Recommended dose: 900 mg/day 1
• Reduces hot flashes by 51% compared to 26% with placebo 1
• Is the only non-hormonal treatment demonstrated to have efficacy equivalent to estrogen 1
• Has rapid onset of action (within 1 week) 1
• No known drug interactions and no absolute contraindications 1
• Does not cause sexual dysfunction 1
• Side effects include dizziness, unsteadiness, and drowsiness (affecting up to 20% of patients), but these typically improve after the first week and resolve by week 4 1
• Particularly useful when taken at bedtime for patients whose sleep is disturbed by hot flashes 2

Second-Line Options

Clonidine

• Centrally acting α-adrenergic agonist 1
• Provides mild to moderate efficacy, reducing hot flashes by up to 46% 1
• Available in oral and transdermal formulations 1
• May have a slower effect than venlafaxine but is often better tolerated 2
• Common side effects include dry mouth, insomnia or drowsiness 1
• Higher discontinuation rate (40%) compared to SSRIs/SNRIs (10-20%) or gabapentin (10%) 1

Vitamin E

• High-dose vitamin E (800 IU/day) shows limited efficacy for mild vasomotor symptoms 1
• May be appropriate for women with mild symptoms who prefer 'natural' treatments 1
• Caution: supplemental vitamin E >400 IU/day has been linked with increased all-cause mortality 1

Special Considerations

For Patients Taking Tamoxifen

• Avoid SSRIs that strongly inhibit CYP2D6 (paroxetine and fluoxetine) as they may interfere with tamoxifen metabolism 1
• Citalopram and venlafaxine have less impact on tamoxifen metabolism and are preferred options 1
• Gabapentin has no known drug interactions and is a good alternative 1

Treatment Algorithm

1. For severe hot flashes:

   • Start with either gabapentin 900 mg/day OR venlafaxine 37.5 mg/day (increasing to 75 mg/day after 1 week if needed) 1
   • Review for efficacy and side effects at 4-6 weeks for gabapentin or 2-4 weeks for SSRIs/SNRIs 1
   • If ineffective or intolerable, switch to the alternative first-line agent 1

2. For mild to moderate hot flashes:

   • Consider clonidine or vitamin E (800 IU/day) 1
   • If ineffective, escalate to first-line treatments 1

Important Clinical Pearls

• If no response is seen within 4 weeks, treatment is unlikely to be effective and an alternative should be considered 1
• There is no benefit to adding gabapentin to SSRI/SNRI therapy 1
• Consider gabapentin if sexual dysfunction is a concern before starting SSRIs/SNRIs or if it develops during therapy 1
• SSRIs/SNRIs should be tapered gradually when discontinuing to prevent withdrawal symptoms, particularly with short-acting agents like paroxetine and venlafaxine 1
• Hormone therapy (estrogen) remains the most effective treatment for hot flashes (reducing symptoms by 75-90%), but carries significant risks including increased breast cancer risk with combined estrogen/progestogen therapy used for more than 3-5 years 2, 3, 4