Abstract
Background
Pharmacologic Treatments
The most well studied populations with cancer treatment related hot flashes are patients with breast and prostate cancer. Efficacy of pharmacologic treatments seems to be independent of whether the hot flashes are caused by treatment and independent of the patient's sex. The average improvement in hot flashes associated with placebo is around 25%, 1 so improvements associated with pharmacologic therapies are typically compared to placebo.
• Hormonal therapies: In general, hormonal therapies are more effective than nonhormonal therapies. Estrogen and progestins are effective in both men and women. Estrogen and progestins are contraindicated in women with a history of breast cancer, because of concern for increased risk of recurrence. In men, estrogen therapy is associated with breast tenderness and gynecomastia. Common side effects of progestins include weight gain, nausea, and edema. Both estrogen and progestins are associated with some risk of thromboembolic disease and cardiovascular disease. Cyproterone, an antiandrogen (not available in the United States), also works in men but may interfere with androgen deprivation therapy for prostate cancer.
• Antidepressants: The mechanism by which selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) reduce hot flashes is thought to be related to the role of serotonin and norepinephrine in thermoregulation. Randomized controlled trials have supported the efficacy of fluoxetine, paroxetine, sertraline, citalopram, escitalopram, venlafaxine, and desvenlafaxine. Pooled analysis of seven trials showed a positive effect greater than placebo as follows: paroxetine (10–25 mg) 41%, venlafaxine (75 mg) 33%, fluoxetine (20 mg) 13%, sertraline (50 mg) 3%–18%. 2 Citalopram (20 mg) works about as well as venlafaxine and paroxetine. 3
• Many SSRIs can interfere with the effectiveness of tamoxifen, as they inhibit cytochrome P450 enzyme CYP2D6, which is involved in tamoxifen metabolism. Paroxetine and fluoxetine are the strongest CYP2D6 inhibitors, followed, in order of decreasing potency of inhibition, by sertraline, citalopram, and venlafaxine. All SSRIs have similar side effect profiles, including sexual dysfunction, drowsiness, weight gain, insomnia, anxiety, dizziness, and headache.
• Gabapentin: A pooled analysis of three tria
• Clonidine: Appears to be marginally, but statistically significantly, better than placebo, with side effects including dry mouth, drowsiness, and constipation. 4
Procedural
Pilot data suggest that a stellate-ganglion block may be effective. A small study of 13 patients with a history of breast cancer treated with a stellate-ganglion block (once or twice) showed a reduction in hot flashes per week, as well as in very severe hot flashes per week over a three-month period. 5 Though standard procedural risks apply, there were no reported adverse effects from the block in this small series.
Summary
It is reasonable to use either gabapentin or an SSRI/SNRI as first-line treatment. Of the SSRI/SNRI group, venlafaxine and citalopram are among the most effective and have a low risk of interfering with tamoxifen. Paroxetine and fluoxetine should be avoided in patients on tamoxifen.