What selective serotonin reuptake inhibitor (SSRI) is effective for managing hot flashes?

SSRIs for Hot Flashes: Paroxetine and Venlafaxine Are Most Effective

Paroxetine and venlafaxine (an SNRI) are the most effective medications for managing hot flashes, with paroxetine reducing hot flash composite scores by 62-65% and venlafaxine reducing scores by 61% compared to 27% with placebo. 1

First-Line Options

Paroxetine

• Controlled-release paroxetine reduced hot flash composite score by 62% at 12.5 mg daily 1
• Most effective SSRI with fewest adverse effects 2
• Start with lowest available dose and titrate as needed
• Caution: Inhibits CYP2D6 and may interfere with tamoxifen metabolism - avoid in breast cancer patients on tamoxifen 1, 3

Venlafaxine (SNRI)

• Demonstrated 61% reduction in hot flash score at 75 mg/day (optimal dose) 1
• Rapid onset of efficacy within first week 2
• Particularly effective in breast cancer survivors 1
• Side effects (dose-related): dry mouth, decreased appetite, nausea, constipation 1
• Must be tapered gradually when discontinuing to prevent withdrawal symptoms 4

Second-Line Options

Citalopram

• May be effective in patients who don't respond to venlafaxine 1, 4
• Can further reduce hot flashes in those already taking hormone therapy 1
• Fewer adverse effects compared to other options 2

Desvenlafaxine (SNRI)

• Demonstrated 64% reduction in hot flashes at 12 weeks with 100 mg dose 1
• 50% of treated patients experienced 75% reduction in hot flashes 1
• Well-tolerated with rapid onset of efficacy 1

Less Effective Options

Fluoxetine

• Decreased hot flash composite score by 50% versus 36% for placebo 1
• Variable response: 42% improved by >50%, 30% improved by <50%, 27% worsened 1
• Not superior to placebo in long-term (9-month) studies 1
• Consider only if first and second-line options fail 5

Sertraline

• Mixed results for hot flash reduction 1, 6
• May benefit some women, but substantial variability in results 1
• Consider only if first and second-line options fail 5

Mirtazapine

• Preliminary studies show promise 1
• Limited by side effects: somnolence and weight gain 1
• Not recommended as first-line therapy 5

Treatment Considerations

1. Start with lowest effective dose and assess response after 4 weeks 4
2. Monitor for side effects, particularly in first week of treatment 4
   • Common side effects: nausea, constipation, dry mouth, decreased appetite
   • Most side effects resolve within first week of treatment 3
3. Special considerations for breast cancer patients:
   • Avoid paroxetine and fluoxetine if on tamoxifen due to CYP2D6 inhibition 1, 3
   • Venlafaxine is safer option for breast cancer patients on tamoxifen 3
4. Taper gradually when discontinuing, especially with short-acting agents like paroxetine and venlafaxine 1

Efficacy Expectations

• SSRIs/SNRIs can reduce hot flashes by approximately 65% 2
• Begin working within the first week of treatment 2
• Patient response is variable; if one medication doesn't work, another can be tried after 1-2 weeks 2
• Overall reduction is about one hot flash per day (25% reduction) 6

The evidence strongly supports paroxetine and venlafaxine as first-line non-hormonal options for managing hot flashes, with citalopram and desvenlafaxine as reasonable alternatives when first-line agents aren't tolerated or effective.