SNRIs vs SSRIs for Hot Flashes
No, SNRIs do not cause fewer hot flashes than SSRIs—both classes are equally effective at reducing hot flash frequency and severity by approximately 25% to 65%, and neither causes hot flashes as a side effect. The question appears to conflate treatment efficacy with adverse effects; both drug classes are therapeutic options for hot flashes, not causes of them.
Comparative Efficacy
Both SSRIs and SNRIs reduce hot flashes with similar overall effectiveness, though specific agents within each class show variable results 1, 2, 3.
Venlafaxine (SNRI) at 75 mg shows superior efficacy with 61% reduction in hot flash severity compared to sertraline (SSRI) at 50 mg, making it a preferred alternative when fezolinetant is unavailable 4.
Among SSRIs, paroxetine, citalopram, and escitalopram demonstrate the most consistent efficacy, while sertraline and fluoxetine show more variable results and should be considered second-line options 5, 6.
Desvenlafaxine (SNRI) serves as an effective second-line option within the SNRI class 5, 6.
Clinical Selection Algorithm
For breast cancer patients on tamoxifen:
- SNRIs (venlafaxine, desvenlafaxine) are the safest choice because they lack significant CYP2D6 inhibition that could interfere with tamoxifen metabolism 1.
- Sertraline and citalopram are acceptable SSRI alternatives due to weak or absent CYP2D6 effects 4.
- Avoid paroxetine and fluoxetine entirely in this population due to strong CYP2D6 inhibition 4.
For women without tamoxifen concerns:
- Start with venlafaxine (SNRI) or paroxetine/citalopram (SSRIs) as first-line options based on tolerability profile and cost 5, 6.
- Paroxetine and citalopram offer the most cost-efficient SSRI options with fewer adverse effects 6.
Tolerability Considerations
Both classes share similar side effect profiles, with nausea and constipation being most common, typically resolving within the first week 1.
SNRIs carry a specific caution for blood pressure elevation and should be used carefully in hypertensive women 1.
SSRIs (particularly paroxetine, citalopram, escitalopram) may have slightly fewer adverse effects overall 6.
All agents require gradual tapering on discontinuation to prevent withdrawal symptoms 4.
Treatment Response Timeline
- Both SSRIs and SNRIs begin working within the first week of treatment 6.
- If one agent fails after a 1-2 week trial, switching to another within or between classes is reasonable given variable individual response 6.
- Significant improvements are typically seen by week 4 7.
Common Pitfall
The substantial placebo response (often matching medication efficacy) in hot flash trials means individual trial periods are essential to assess true therapeutic benefit 4, 2.