Use of Antidepressants for Management of Hot Flashes

Dana G. Carroll, Pharm.D.; Kristi W. Kelley, Pharm.D.


Pharmacotherapy. 2009;29(11):1357-1374. 

In This Article

Pathophysiology of Hot Flashes

Although the exact mechanism of hot flashes is not completely understood, there is growing knowledge on the complexity of the neuroendocrine system's impact on the thermoregulatory nucleus in the hypothalamus. During menopause, women develop a downward shift and narrower trigger point in the thermoregulatory nucleus in the hypothalamus for heat loss; this results in small temperature changes (as little as 0.01°F) that trigger hot flashes.[4] When these changes in temperature occur, the body attempts to preserve heat loss and maintain the core body temperature through perspiration and vasodilation—the symptoms of hot flashes. Alterations in the neuroendocrine system that affect hot flashes begin with declines in estrogen and progesterone levels. This causes decreases in endorphins, which results in decreases of both norepinephrine and serotonin levels systemically. Even though systemic levels decline, norepinephrine and serotonin (specifically 5HT2A) receptors are upregulated in the hypothalamus. This upregulation lowers and narrows the trigger point for heat release.[4,5,6,7] Supplementation with estrogen with or without progesterone restores balance to the neuroendocrine system and readjusts the trigger point in the hypothalamus. Based on alterations in norepinephrine and serotonin receptors in the hypothalamus, antidepressants that work to inhibit either or both receptors should also help to restore balance, thus relieving hot flashes.


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