Which is more effective for hot flashes in peri-menopausal or post-menopausal women, Paxil (paroxetine) or Effexor (venlafaxine)?

Venlafaxine (Effexor) is More Effective Than Paroxetine (Paxil) for Hot Flashes

Venlafaxine is the preferred first-line antidepressant for menopausal hot flashes, with superior efficacy (37-61% reduction in hot flash scores), faster onset of action (within 1 week), and better patient preference (68% vs 32%) compared to gabapentin, while paroxetine shows similar efficacy (62-65% reduction) but carries critical drug interaction concerns with tamoxifen. 1, 2

Direct Comparison and Efficacy

Both medications demonstrate comparable efficacy in reducing hot flashes, but venlafaxine has distinct advantages:

• Venlafaxine 37.5-75 mg daily reduces hot flash scores by 37-61% compared to 27% with placebo, with dose-dependent efficacy maximizing at 75-150 mg/day 1, 2, 3
• Paroxetine 7.5-12.5 mg daily reduces hot flash composite scores by 62-65% in controlled trials 1, 2, 4
• Venlafaxine has faster onset of action within 1 week, making it preferable when rapid symptom control is prioritized 2, 4
• Patients prefer venlafaxine over other nonhormonal options by a 68% vs 32% margin despite similar efficacy 1, 2

Critical Safety Considerations

The most important distinction is the dangerous drug interaction between paroxetine and tamoxifen:

• Paroxetine must be completely avoided in women taking tamoxifen due to potent CYP2D6 inhibition that blocks conversion of tamoxifen to active metabolites, potentially reducing anti-cancer efficacy 1, 2, 4
• The National Comprehensive Cancer Network explicitly recommends against coadministration of paroxetine (or fluoxetine) with tamoxifen 2
• Venlafaxine has minimal CYP2D6 interaction, making it the safe choice for tamoxifen users 2, 4
• This is particularly critical since 50-70% of women on tamoxifen experience hot flashes 1

Treatment Algorithm

Start with venlafaxine 37.5 mg daily, increasing to 75 mg after 1 week 1, 2, 4:

• Review efficacy at 2-4 weeks for SSRIs/SNRIs 1, 2
• Common side effects include dry mouth, nausea, constipation, headache, and sexual dysfunction, with 10-20% discontinuation rates 4, 5
• Always taper gradually when discontinuing to prevent withdrawal symptoms due to short half-life 2, 4

Consider paroxetine 7.5-12.5 mg CR daily only if:

• Patient is not taking tamoxifen (verify this explicitly) 1, 2, 4
• Venlafaxine is ineffective or not tolerated 1
• Patient has no history of breast cancer requiring tamoxifen 2, 4

Special Populations

For breast cancer survivors:

• Venlafaxine is the preferred SNRI, avoiding the paroxetine-tamoxifen interaction 4, 6
• Gabapentin 900 mg/day at bedtime is an excellent alternative with no drug interactions 1, 2

For women with both depression and hot flashes:

• Venlafaxine effectively treats both symptoms simultaneously, making it ideal for perimenopausal women with low mood 4

Common Pitfalls to Avoid

• Never prescribe paroxetine without explicitly verifying tamoxifen use - this is a dangerous oversight that could compromise cancer treatment 2, 4
• Do not abruptly discontinue either medication - both require gradual tapering to prevent withdrawal symptoms 2, 4
• Fluoxetine shows the weakest and most inconsistent efficacy (only 50% reduction vs 36% placebo), with no demonstrated long-term benefit at 9 months, making it a poor choice 2