What are the treatment options for a patient with hot flashes who cannot take hormones?

Management of Hot Flashes in Patients Who Cannot Take Hormones

For patients with hot flashes who cannot take hormones, the first-line treatments are SSRIs/SNRIs (particularly venlafaxine or citalopram) or gabapentin, with the choice depending on patient-specific factors such as comorbidities and potential side effects. 1

First-Line Pharmacologic Options

SSRIs/SNRIs

• Venlafaxine (SNRI): Start at 37.5 mg daily, may increase to 75 mg daily after 1 week if symptoms persist

  • Rapid onset (within 1 week)
  • Reduces hot flash frequency and severity by 60-65%
  • Avoid in patients taking tamoxifen due to potential drug interactions
  • Side effects: nausea, reduced appetite, dry mouth, sleep disturbance
  • Must taper when discontinuing to prevent withdrawal symptoms 1

• Citalopram/Escitalopram (SSRI): 10-20 mg daily

  • Good option for tamoxifen users as it has minimal impact on tamoxifen metabolism
  • Side effects similar to other SSRIs but generally well-tolerated 1, 2

• Paroxetine: 7.5-10 mg daily (avoid in tamoxifen users)

  • Reduces hot flash frequency and severity by up to 65%
  • IMPORTANT: Avoid in women taking tamoxifen as it inhibits CYP2D6, potentially reducing tamoxifen efficacy 1

Gabapentin

• Start at 300 mg at bedtime, gradually increase to 900 mg/day (divided doses)
• Particularly useful for nighttime hot flashes due to sedating effect
• Reduces hot flashes by 45-50% (comparable to SSRIs/SNRIs)
• Side effects: dizziness, drowsiness, unsteadiness (typically improve after first week)
• No drug interactions with tamoxifen, making it an excellent choice for breast cancer patients 1

Second-Line Option

Clonidine

• 0.1 mg daily (oral or transdermal)
• Reduces hot flashes by up to 46%
• Side effects: dry mouth, insomnia or drowsiness
• Higher discontinuation rate (40%) compared to SSRIs/SNRIs (10-20%) or gabapentin (10%)
• Consider for patients with mild to moderate hot flashes who cannot tolerate first-line options 1

Decision Algorithm for Treatment Selection

1. If patient is on tamoxifen:

   • First choice: Venlafaxine or citalopram (avoid paroxetine and fluoxetine)
   • Alternative: Gabapentin (especially if sleep disturbance is prominent)

2. If patient has concurrent depression:

   • First choice: SSRI/SNRI (venlafaxine or citalopram/escitalopram)

3. If patient has sleep disturbance:

   • First choice: Gabapentin (take at bedtime)

4. If patient has neuropathic pain:

   • First choice: Gabapentin

5. If patient has hypertension:

   • Use caution with SNRIs (may increase blood pressure)
   • Consider gabapentin or clonidine (may help control blood pressure)

Monitoring and Follow-up

• Assess response after 4 weeks - if no improvement, treatment is unlikely to be effective
• If first agent is ineffective, try an alternative first-line agent
• Gradually taper SSRIs/SNRIs when discontinuing to prevent withdrawal symptoms
• Monitor for side effects, particularly in the first week of treatment

Important Considerations

• The placebo effect is substantial in hot flash treatment (up to 70% in some studies)
• Doses used for hot flashes are typically lower than those used for depression
• Side effects are often transient and dose-related
• No benefit to combining gabapentin with SSRI/SNRI 1
• The newest FDA-approved non-hormonal treatment is fezolinetant (neurokinin-3 receptor antagonist), which may approach the efficacy of hormone therapy with fewer side effects 3

Non-Pharmacologic Options

• Acupuncture: Some evidence of effectiveness, may be equivalent to venlafaxine 1
• Yoga: Mixed results but may improve quality of life 4
• Mindfulness-based stress reduction: Evidence of effectiveness for some patients 4

While hormone therapy remains the most effective treatment for hot flashes 5, these non-hormonal options provide significant relief for many patients who cannot or prefer not to use hormones.