Which nonestrogenic drugs for hot flashes seem to work best?

Although no antidepressants quell menopausal hot flashes quite as well as estrogen (which reduces their frequency by about 80%), the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine and the selective serotonin reuptake inhibitor (SSRI) paroxetine have been studied the most in breast cancer survivors and shown to be quite effective for many women, a Mayo Clinic researcher told the audience at NAMS' 18^th Annual Meeting in Dallas, Tex. While focusing on an overview of his experience at the Mayo Clinic and citing his pilot study's 60% reduction in hot flash frequency with venlafaxine, Charles L. Loprinzi, MD, also cautioned that paroxetine should never be given to women taking tamoxifen because it interferes with the latter's metabolism to its active metabolite. In addition, he pointed out that "You must stop venlafaxine slowly. Venlafaxine (at low 75-mg/d doses, e.g.) is not working as an antidepressant because it affects hot flashes immediately-whereas depression improvement takes weeks. An antidepressant dose will be much higher."

Dr. Loprinzi also assessed the potential usefulness of progestational agents and gabapentin, noting in the first instance that impressive hot flash reductions of 80% and 85% have been shown for megestrol acetate and medroxyprogesterone acetate, respectively, not unlike estrogen. Even so, the hormonal nature of these progestational agents made clinicians reluctant to use them in breast cancer survivors.

The good news about the antiepileptic gabapentin was that in two large placebo-controlled, double-blinded clinical trials, 900 mg daily given to breast cancer survivors in three divided doses lowered hot flashes by 50%. And recently, Loprinzi added, even better results emerged from a small double-blinded, three-arm trial using higher doses of 2,400 mg daily, which seemed to reduce hot flashes nearly as much as standard conjugated estrogen.

Loprinzi CL, Levitt R, Barton D, et al. Phase III comparison of depomedroxyprogesterone acetate to venlafaxine for managing hot fashes: North Central Cancer Treatment Group Trial N99C7. J Clin Oncol. 2006;24:1409-1414.