Other pharmacologic interventions
Numerous nonestrogenic, pharmacologic treatment interventions for hot flash management in women with a history of breast cancer and in some men who have undergone androgen deprivation therapy have been evaluated. Options with reported efficacy include androgens, progestational agents, gabapentin, SSRIs, selective serotonin norepinephrine inhibitors, alpha adrenergic agonists (e.g., methyldopa, clonidine), beta-blockers, and veralipride (an antidopaminergic agent). Inferior efficacy, lack of large definitive studies, and potential side effects limit the use of many of these agents.[20,21,22][Level of evidence: I]
Agents that have been found to be helpful in large, randomized, placebo-controlled clinical trials include venlafaxine, paroxetine, citalopram, fluoxetine, gabapentin, pregabalin, and clonidine.[20,21,22] These agents demonstrate a 40% to 60% reduction in hot flash frequency and score (a measure combining severity and frequency). Agents conferring a 55% to 60% reduction in hot flashes are venlafaxine extended release, 75 mg daily; paroxetine, 12.5 mg controlled release  or 10 mg daily; gabapentin, 300 mg tid;[27,28][Level of evidence: I][Level of evidence: II] and pregabalin, 75 mg bid.[Level of evidence: I] Other effective agents resulting in about a 50% reduction in hot flashes include citalopram, 10 to 20 mg per day, which was studied in clinical trial NCCTG-N05C9;[Level of evidence: I] and fluoxetine, 20 mg per day. Clonidine, 0.1 mg transdermal  or oral daily,[Level of evidence: I] can reduce hot flashes by about 40%.
One study compared the efficacy and patient preference of venlafaxine, 75 mg, once daily to gabapentin, 300 mg, 3 times per day for the reduction of hot flashes. Sixty-six women with histories of breast cancer were randomly assigned in an open-label fashion to receive venlafaxine or gabapentin for 4 weeks; after a 2-week washout period, they received the opposite treatment for an additional 4 weeks. Both treatments reduced hot flash scores (severity multiplied by frequency) by about 66%. However, significantly more women preferred venlafaxine over gabapentin (68% vs. 32%, respectively).
A study using citalopram to evaluate hot flashes examined how much of a reduction in hot flashes was needed to have a positive impact on activities of daily living and general health-related quality of life. The authors reported that hot flashes had to be reduced at least 46% for women to report significant improvements in the degree of bother they experienced in daily activities.
Agents that have been evaluated in phase II trials but have not shown efficacy include bupropion, aprepitant, and desipramine.[Level of evidence: II] Interestingly, these agents do not primarily modulate serotonin. In addition, randomized clinical trials with sertraline have not provided convincing evidence of its efficacy in hot flash management.[39,40,41][Level of evidence: I]