Anxiolytics for Hot Flashes: Venlafaxine as First-Line Treatment
Venlafaxine (an SNRI antidepressant with anxiolytic properties) is the most effective anxiolytic for treating both anxiety and hot flashes, with a 61% reduction in hot flash scores compared to 27% with placebo. 1
First-Line Treatment: Venlafaxine
Venlafaxine has demonstrated superior efficacy in managing hot flashes while also providing anxiolytic effects:
- Dosing protocol: Start with 37.5 mg daily for 1 week, then increase to the optimal dose of 75 mg daily if tolerated 1
- Efficacy: Reduces hot flash frequency and severity scores by 61% (compared to 27% with placebo) 2, 1
- Side effects: Mouth dryness, reduced appetite, nausea, and constipation (dose-related) 2
- Special consideration: Has minimal effects on tamoxifen metabolism, making it safe for breast cancer patients on tamoxifen 2, 1
Second-Line Options
If venlafaxine is ineffective or poorly tolerated after 4 weeks, consider:
1. Citalopram (SSRI)
- Effective alternative for those who don't respond to venlafaxine 1
- Minimal effect on tamoxifen metabolism 2, 1
- May further reduce hot flashes in women already taking hormone therapy 2
2. Paroxetine (SSRI)
- Reduces hot flash composite score by 62% at 12.5 mg daily and 65% at 25 mg daily 2, 1
- Important caution: Avoid in women taking tamoxifen due to CYP2D6 inhibition 2, 1
- Side effects: nausea, dizziness, and insomnia 2
3. Gabapentin (Anticonvulsant with anxiolytic properties)
- Reduces hot flash severity by 46% at 8 weeks (vs 15% with placebo) at 900 mg/day 2, 1
- Particularly useful for nighttime hot flashes 1
- Side effects: somnolence and fatigue 2
Other Options with Variable Efficacy
1. Fluoxetine
- Decreases hot flash composite score by 50% versus 36% for placebo 2
- Highly variable response: 42% improve by >50%, 30% improve by <50%, and 27% experience worsening 2
- Caution: Interferes with tamoxifen metabolism 2, 1
2. Sertraline
- Mixed results in general population 2
- Superior to placebo in reducing hot flashes in tamoxifen users 2
- Substantial variability in individual response 3
3. Clonidine
- Reduces hot flashes in a dose-dependent manner 2
- Less well-tolerated than venlafaxine 1
- Side effects: dry mouth, constipation, drowsiness 2
Treatment Algorithm
- First-line: Venlafaxine 37.5 mg daily for 1 week, then increase to 75 mg daily
- If ineffective after 4 weeks or poorly tolerated:
- For women NOT on tamoxifen: Try paroxetine 12.5 mg daily
- For women on tamoxifen: Try citalopram
- For women with nighttime hot flashes: Consider gabapentin 900 mg daily
- If second-line treatment fails: Consider other options based on individual factors
Important Clinical Considerations
- Doses of antidepressants for hot flashes are typically lower than those needed for depression 1
- Response to treatment is faster than when treating depression 1
- Considerable placebo effect (25% or more) exists 1
- Avoid abrupt discontinuation of SNRIs/SSRIs; taper gradually to prevent withdrawal symptoms 1
- Women have markedly variable responses to treatment with antidepressants for hot flashes 3
- Women with higher education levels, those who are more active, and those who are postmenopausal (versus perimenopausal) may have better responses to SSRI treatment 3
Mechanism of Action
Hot flashes result from abnormal hypothalamic thermoregulatory control leading to vasodilatory responses 4. SNRIs and SSRIs help regulate neurotransmitters involved in thermoregulation, including serotonin and norepinephrine, which play important roles in the pathophysiology of hot flashes 4.