Pregabalin for Hot Flashes
Pregabalin is effective for treating hot flashes and can be used as a first-line nonhormonal option, with a target dose of 75 mg twice daily reducing hot flashes by approximately 65%. 1
Evidence for Efficacy
Pregabalin demonstrates significant efficacy in reducing hot flashes compared to placebo:
In a Phase III randomized controlled trial, pregabalin at 75 mg twice daily reduced hot flash scores by 65%, and 150 mg twice daily reduced them by 71%, compared to 50% reduction with placebo. 1
The 75 mg twice daily dose is the recommended target because it provides substantial benefit with better tolerability than the higher dose. 1
Pregabalin's efficacy is roughly comparable to gabapentin and newer antidepressants like venlafaxine. 1
Clinical Context and Positioning
While pregabalin is effective, it is important to understand where it fits among treatment options:
Current guidelines from the American Society of Clinical Oncology recommend SNRIs (venlafaxine 37.5-75 mg/day) or gabapentin (900 mg/day) as first-line nonhormonal treatments for moderate to severe hot flashes, reducing symptoms by 49-61%. 2
The Cancer and Leukemia Group B (CEPO) guidelines specifically recommend pregabalin as an effective option for breast cancer patients, both those on tamoxifen and those not on tamoxifen. 3
Pregabalin offers an advantage over SSRIs in patients taking tamoxifen, as it has no drug interactions with tamoxifen metabolism (unlike paroxetine and fluoxetine which inhibit CYP2D6). 4, 2
Practical Dosing and Tolerability
Start pregabalin at 75 mg twice daily as the target dose for optimal balance of efficacy and tolerability. 1
Common side effects include somnolence, dizziness, ataxia, fatigue, and peripheral edema, which are more pronounced at higher doses (150 mg twice daily). 5
Despite some toxicities being more common with pregabalin, it is generally well tolerated by most patients. 1
Assess treatment response after 4 weeks; if no response occurs by then, the treatment is unlikely to be effective. 4, 2
Comparative Considerations
Gabapentin (pregabalin's structural analog) has more extensive evidence in guidelines, showing 2.05 fewer hot flashes per day versus placebo, compared to 1.13 for SSRIs/SNRIs and 0.95 for clonidine. 2
Gabapentin at 900 mg/day reduces hot flashes by 49-51% and is the only nonhormonal treatment demonstrating equivalence to estrogen. 4, 2
Gabapentin has no known drug interactions, no absolute contraindications, does not cause sexual dysfunction, and lacks the withdrawal syndrome seen with some SSRIs/SNRIs. 4
However, pregabalin may offer dosing convenience with twice-daily administration compared to gabapentin's three-times-daily regimen. 1
Key Clinical Pitfalls to Avoid
Do not use paroxetine or fluoxetine in patients taking tamoxifen, as they potently inhibit CYP2D6 and reduce tamoxifen's conversion to active metabolites. 4, 2, 3
Avoid escalating to pregabalin 150 mg twice daily routinely, as the incremental benefit over 75 mg twice daily is modest (71% vs 65% reduction) while side effects increase significantly. 1
Do not combine pregabalin with gabapentin or add one to the other, as there is no demonstrated benefit of combining anticonvulsants for hot flashes. 4