What antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), can be used to manage hot flashes?

Antidepressants for Hot Flashes Management

Venlafaxine (37.5 mg daily increasing to 75 mg daily after 1 week) or paroxetine (10 mg daily increasing to 20 mg daily after 1 week if symptoms persist) are the first-line antidepressants for managing hot flashes, with gabapentin as an effective alternative. 1

First-Line Antidepressant Options

SSRIs and SNRIs

• Venlafaxine (SNRI)

  • Starting dose: 37.5 mg daily
  • Target dose: 75 mg daily (after 1 week)
  • Efficacy: 61% reduction in hot flash score at 75 mg dose 1
  • Onset: Rapid (less than 1 week)
  • Duration of action: Up to 6 weeks

• Paroxetine (SSRI)

  • Starting dose: 10 mg daily
  • Target dose: 20 mg daily (after 1 week if needed)
  • Efficacy: 40.6% reduction in hot flash frequency at 10 mg; 51.7% reduction at 20 mg 2
  • Lower discontinuation rate with 10 mg dose 2
  • Significantly improves sleep compared to placebo 2

Important Considerations for Selection

Tamoxifen Interactions

• Critical warning: Paroxetine and fluoxetine should be avoided in women taking tamoxifen due to inhibition of CYP2D6 enzyme, which converts tamoxifen to its active metabolite 1
• For tamoxifen users, prefer:
  • Venlafaxine
  • Desvenlafaxine
  • Citalopram
  • Gabapentin (no drug interactions with tamoxifen)

Side Effect Profiles

1. SSRI/SNRI side effects:

   • Dry mouth, blurred vision, sexual dysfunction
   • Headache, nausea, reduced appetite, gastrointestinal disturbance
   • Anxiety/agitation, sleep disturbance
   • 10-20% discontinuation rate in clinical trials 1

2. Special considerations:

   • Sexual dysfunction: Consider gabapentin if sexual dysfunction is a concern 1
   • Withdrawal symptoms: Taper gradually when discontinuing, especially with paroxetine and venlafaxine 1
   • Bipolar disorder: Use SSRIs/SNRIs cautiously or avoid in patients with bipolar disorder due to risk of inducing mania 1

Alternative Options

Gabapentin

• Dosing: Typically started at 300 mg and titrated up to 900 mg/day
• Efficacy: 46% reduction in hot flash severity score (comparable to SSRIs/SNRIs) 1
• Advantages:
  • No known drug interactions
  • No sexual dysfunction
  • No withdrawal syndrome
  • Effective for concurrent neuropathic pain
  • Equivalent efficacy to estrogen in one small study 1
• Side effects: Dizziness, unsteadiness, drowsiness (typically resolve by week 4) 1

Clonidine

• Dosing: 0.1 mg/day (oral or transdermal)
• Efficacy: Mild to moderate (up to 46% reduction in hot flashes) 1
• Consider for mild to moderate hot flashes when other agents are not suitable
• Side effects: Dry mouth, insomnia or drowsiness (40% discontinuation rate) 1

Treatment Algorithm

1. Assess severity of hot flashes:

   • For moderate to severe hot flashes: Start with SSRI/SNRI or gabapentin
   • For mild hot flashes: Consider clonidine or lifestyle modifications

2. Consider concurrent medications:

   • If on tamoxifen: Choose venlafaxine or gabapentin
   • If not on tamoxifen: Any SSRI/SNRI can be considered

3. Evaluate response after 4 weeks:

   • If no response: Treatment is unlikely to be effective; switch to alternative agent
   • If partial response: Consider dose adjustment

4. For sleep disturbance with hot flashes:

   • Consider augmentation with hypnotic agents (zolpidem has been shown to improve sleep and quality of life when added to SSRI/SNRI therapy) 3

Second-Line Options

If first-line agents fail:

• Try alternative SSRI/SNRI (if venlafaxine fails, try paroxetine and vice versa) 1
• Consider desvenlafaxine (100 mg): 64% reduction in hot flashes at 12 weeks 1
• Other options with less evidence: sertraline, fluoxetine, citalopram 4

Remember that antidepressants typically reduce hot flashes by approximately 25% (about one per day) compared to placebo 5, which is modest compared to estrogen therapy but significant for patients who cannot use hormonal treatments.