What is the recommended dosing of sertraline (selective serotonin reuptake inhibitor (SSRI)) for a peri- or postmenopausal woman experiencing hot flashes?

Sertraline Dosing for Menopausal Hot Flashes

Sertraline is not a preferred SSRI for menopausal hot flashes due to mixed efficacy data and substantial variability in response, with doses of 50-100 mg daily showing inconsistent results compared to other SSRIs like paroxetine or escitalopram. 1

Why Sertraline Is Not First-Line

The evidence base for sertraline specifically is weak compared to other options in this class:

• Sertraline shows mixed results with substantial variability in response when used at 50-100 mg daily for hot flashes 1
• While sertraline is superior to placebo in tamoxifen users, it did not improve quality of life measures, which is a critical outcome 1
• Among SSRIs tested for hot flashes, sertraline has the least consistent efficacy profile 1

Preferred SSRI/SNRI Alternatives

If you're considering an SSRI/SNRI approach, better-studied options include:

For Women NOT on Tamoxifen:

• Paroxetine 7.5 mg daily reduces hot flash frequency, severity, and nighttime awakenings by 62-65%, with the controlled-release formulation at 12.5 mg as an alternative 2, 1
• Escitalopram demonstrates superiority compared to other SSRIs in mixed treatment comparison analysis 3
• Citalopram reduces hot flash composite score by 50% versus 36% for placebo 1

For Women on Tamoxifen:

• Avoid paroxetine and fluoxetine entirely due to potent CYP2D6 inhibition that blocks tamoxifen conversion to active metabolites 2, 1
• Venlafaxine 37.5-75 mg daily is preferred, achieving 37-61% reduction in hot flash scores with minimal CYP2D6 interaction 2, 1
• Citalopram or sertraline may be considered due to weak CYP2D6 inhibition, though venlafaxine remains superior 1

First-Line Nonhormonal Recommendations

Rather than sertraline, current guidelines prioritize:

1. Gabapentin 900 mg/day at bedtime as first-line therapy, reducing hot flash severity by 46% versus 15% with placebo—equivalent efficacy to estrogen with no drug interactions 2

2. Venlafaxine 37.5 mg daily, increasing to 75 mg after 1 week if rapid onset is prioritized or gabapentin fails 2

3. Paroxetine 7.5 mg daily for women not on tamoxifen who prefer an SSRI 2

Treatment Algorithm

Start with gabapentin 900 mg at bedtime if:

• Concurrent sleep disturbance from hot flashes exists 2
• Patient is on multiple medications (no drug interactions) 2
• Patient is taking tamoxifen 2

Start with venlafaxine 37.5-75 mg daily if:

• Rapid onset is prioritized 2
• Gabapentin is ineffective or not tolerated 2

Consider paroxetine 7.5 mg daily only if:

• Patient is NOT on tamoxifen 2, 1
• Other options have failed or are not tolerated 1

Efficacy Review Timeline

• Review efficacy at 2-4 weeks for SSRIs/SNRIs (including sertraline if used) 2
• Review efficacy at 4-6 weeks for gabapentin 2
• Switch to another nonhormonal agent if intolerant or ineffective 2

Common Pitfalls

• Do not use sertraline as first-line when better-studied SSRIs with more consistent efficacy are available 1
• Recognize the robust placebo response (up to 70% in some studies) when evaluating any treatment efficacy 4
• Taper SSRIs/SNRIs gradually when discontinuing to minimize withdrawal symptoms, particularly with short-acting agents like paroxetine 4
• Common SSRI/SNRI side effects include nausea, headache, reduced appetite, dry mouth, and sexual dysfunction, which are typically mild and short-lived, with 10-20% withdrawal rates 4