Is fluoxetine (selective serotonin reuptake inhibitor) effective for treating hot flashes?

Fluoxetine for Hot Flashes

Fluoxetine shows modest effectiveness for treating hot flashes, reducing hot flash frequency by approximately 50% compared to 36% with placebo, but is not recommended as a first-line option due to variable response and potential drug interactions with tamoxifen. 1

Effectiveness of Fluoxetine for Hot Flashes

Fluoxetine has been studied specifically for hot flash management with the following results:

• In breast cancer patients, fluoxetine decreased hot flash composite score (frequency × severity) by 50% versus 36% for placebo 1
• Response is highly variable:
  • 42% of patients improved by >50%
  • 30% improved by <50%
  • 27% experienced worsened hot flashes 1
• The clinical effect appears modest compared to estrogen therapy 1
• Fluoxetine works rapidly (within 1 week) for those who respond 1
• Long-term efficacy is questionable, with one study showing no superiority over placebo at 9 months 1

Important Considerations and Contraindications

Tamoxifen Interaction

• Fluoxetine is a potent inhibitor of CYP2D6 enzyme 1
• This can interfere with tamoxifen metabolism to its active form (endoxifen)
• Should be avoided in patients taking tamoxifen 1

Side Effects

• Common side effects include:
  • Headache
  • Nausea
  • Reduced appetite
  • Gastrointestinal disturbance
  • Dry mouth
  • Anxiety/agitation
  • Sleep disturbance
  • Sexual dysfunction 1
• Side effects are generally mild and short-lived
• Approximately 10-20% of individuals may withdraw from treatment due to adverse events 1

Treatment Algorithm for Hot Flashes

First-line options (preferred):

1. Venlafaxine (37.5 mg daily, increasing to 75 mg daily after 1 week if needed)

   • Reduces hot flash score by 61% at 75 mg dose 1
   • Minimal interaction with tamoxifen 1
   • Rapid onset of action (within 1 week) 1

2. Gabapentin (900 mg/day)

   • Reduces hot flashes by 51% vs 26% with placebo 1
   • No known drug interactions 1
   • No sexual dysfunction 1
   • Only non-hormonal treatment shown to have efficacy equivalent to estrogen 1
   • Side effects (dizziness, unsteadiness) typically improve after first week 1

Second-line options:

1. Paroxetine (10 mg daily, increasing to 20 mg if needed after 1 week)

   • Reduces hot flash score by 62% at 12.5 mg daily 1
   • Avoid in patients taking tamoxifen 1

2. Citalopram

   • May be effective in those who don't respond to venlafaxine 1
   • Minimal interaction with tamoxifen 1

3. Fluoxetine

   • Modest benefit (50% reduction vs 36% with placebo) 1, 2
   • Variable response 1
   • Avoid in patients taking tamoxifen 1

Third-line option:

1. Clonidine (0.1 mg/day oral or transdermal)
   • Mild to moderate efficacy (up to 46% reduction) 1
   • Higher discontinuation rate (40%) due to side effects 1

Monitoring and Duration

• Evaluate response after 4 weeks - if no improvement, treatment is unlikely to be effective 1
• Optimal duration of treatment is unknown 1
• SSRIs/SNRIs should be tapered gradually when discontinuing to prevent withdrawal symptoms, particularly with short-acting agents like paroxetine and venlafaxine 1

Summary

While fluoxetine can reduce hot flashes in some women, its variable response profile, potential interaction with tamoxifen, and modest efficacy make it a second or third-line option for hot flash management. Venlafaxine and gabapentin have more consistent evidence supporting their use as first-line non-hormonal treatments for hot flashes 1, 3.