Does Zoloft Cause Hot Flashes?
No, Zoloft (sertraline) does not cause hot flashes—it is actually used to treat them, though with modest and highly variable effectiveness.
Sertraline as a Treatment for Hot Flashes
Sertraline is prescribed specifically to reduce hot flashes, not cause them. The evidence shows:
Sertraline 50 mg daily reduces hot flash frequency by approximately 5 fewer episodes per week compared to placebo, with statistically significant but clinically modest improvements in hot flash scores 1
In tamoxifen users, sertraline 50 mg was superior to placebo in reducing hot flashes, though it did not improve quality of life measures 2, 3
Individual response is highly variable: approximately 31% of women experience clinically significant reduction (≥30%), 32% have minimal or no response, and 37% actually worsen on sertraline 4
Comparative Effectiveness
Sertraline is among the less effective SSRIs for hot flash management:
Pooled analysis shows sertraline reduces hot flashes by only 3-18% compared to placebo, substantially less than paroxetine (41% reduction) or venlafaxine (33% reduction) 5
One large trial found sertraline 100 mg completely ineffective, with identical 38-39% reductions in both sertraline and placebo groups, while causing more gastrointestinal complaints, dry mouth, and dizziness 6
Clinical Advantages in Specific Populations
For breast cancer patients on tamoxifen, sertraline has a key advantage over other SSRIs:
Sertraline has weak or no effects on CYP2D6 enzyme, making it preferable to paroxetine or fluoxetine which strongly inhibit tamoxifen conversion to its active metabolite endoxifen 2, 3
Citalopram and venlafaxine also have minimal CYP2D6 effects and may be better therapeutic alternatives in tamoxifen users 2
Current Treatment Landscape
Newer options have largely superseded sertraline for hot flash management:
Fezolinetant is now recommended as first-line non-hormonal therapy, avoiding the 10-20% withdrawal rate from SSRIs/SNRIs and requiring no gradual discontinuation 7
If fezolinetant is unavailable, venlafaxine (75 mg) or gabapentin (900 mg) are more effective alternatives than sertraline, with venlafaxine showing 61% reduction and gabapentin showing 46% reduction in hot flash severity 2
Important Caveats
Sertraline must be tapered gradually on discontinuation to prevent withdrawal symptoms 2, 3
A trial period is warranted given substantial individual variability in response—some women respond vigorously while others worsen 3, 4
The optimal dose is 50 mg daily based on available evidence in tamoxifen users 2, 3