What is the best antidepressant, specifically a selective serotonin reuptake inhibitor (SSRI), for managing hot flashes?

Best Antidepressant for Hot Flashes

Paroxetine is the most effective SSRI for managing hot flashes, with controlled release (CR) formulations at 12.5mg daily reducing hot flash composite scores by 62.2% compared to placebo. 1

Evidence-Based Selection Algorithm

First-Line Options:

1. Paroxetine:

   • Dosing: Start with 10mg daily (or 12.5mg CR), may increase to 20mg daily after 1 week if symptoms persist
   • Efficacy: Reduces hot flash composite score by 62-65% 2, 1
   • Key benefit: Most extensively studied SSRI with consistent results

2. Venlafaxine (SNRI):

   • Dosing: Start with 37.5mg daily, increase to 75mg daily after 1 week
   • Efficacy: Reduces hot flash score by 61% at 75mg dose 2
   • Key benefit: Rapid onset of action (within 1 week)

Important Considerations

For Women Taking Tamoxifen:

• AVOID paroxetine and fluoxetine as they inhibit CYP2D6, potentially reducing tamoxifen's effectiveness 2
• For tamoxifen users, venlafaxine is preferred as it has minimal effect on tamoxifen metabolism 3

Efficacy Comparison:

• Paroxetine: 62-65% reduction in hot flashes 2, 1
• Venlafaxine: 61% reduction at 75mg dose 2
• Desvenlafaxine: 64% reduction at 100mg dose 2
• Fluoxetine: 50% reduction 2
• Citalopram: Variable results, less consistent than paroxetine 2, 4

Mechanism and Onset of Action

The mechanism by which these medications reduce hot flashes appears to be independent of their antidepressant effects, with benefits typically appearing more rapidly (within 1 week) than their antidepressant action 2. This makes them suitable even for patients without depression.

Side Effect Management

Common side effects include:

• Nausea, dry mouth, decreased appetite (10-20% of patients)
• Constipation
• Sleep disturbance
• Sexual dysfunction

Most side effects are:

• Dose-related (lower doses used for hot flashes have fewer side effects)
• Transient (typically resolving within the first week of treatment)
• Manageable with gradual dose titration

Important Clinical Pearls

• If no response is seen within 4 weeks, the treatment is unlikely to be effective 2
• Discontinuation should involve gradual tapering to prevent withdrawal symptoms, especially with paroxetine and venlafaxine 2
• There is marked variability in individual response, with some women experiencing worsening of symptoms (27% with fluoxetine) 2
• Consider switching medications if the first choice is ineffective - those who don't respond to venlafaxine may respond to citalopram 2

Alternative Options

If SSRIs/SNRIs are ineffective or contraindicated, consider:

• Gabapentin: 900mg/day (300mg three times daily)

  • Reduces hot flashes by 35-46% 2, 5
  • No drug interactions with tamoxifen
  • Main side effects: dizziness, drowsiness, unsteadiness (typically resolve after 4 weeks) 2

• Clonidine: 0.1mg/day (oral or transdermal)

  • Modest efficacy (reduces hot flashes by up to 46%) 2
  • Side effects: dry mouth, insomnia or drowsiness

By following this algorithm and selecting the appropriate medication based on patient characteristics and contraindications, hot flash symptoms can be effectively managed in most patients.