Trazodone is another possible agent to use for nighttime hot flashes, based on clinical experience. Trazodone, an atypical antidepressant that is often used as a sleeping aid, has anecdotally been shown to be particularly helpful in patients with nocturnal hot flashes. Doses range from 50 mg to 300 mg. Clinical experience suggests that trazodone can help patients fall asleep and can control hot flashes during the night, helping them to stay asleep. Trazodone is a tricyclic antidepressant and, as such, would not be expected to have a great impact on hot flashes: one open-label pilot trial conducted with a tricyclic antidepressant, desipramine, as a proof-of-principle study did not show a benefit. However, this study has not been replicated. The effect of trazodone on sleep may be so profound that hot flashes are not bothersome; this hypothesis needs further study.
Side effects for antidepressant agents in the doses used to treat hot flashes are minimal in the short term and primarily include nausea, sedation, dry mouth, and appetite suppression or stimulation. In the long term, the prevalence of decreases in sexual function with SSRIs at doses used to treat hot flashes is not known. The anticonvulsants gabapentin and pregabalin can cause sedation, dizziness, and difficulty concentrating, while clonidine can cause dry mouth, sedation, constipation, and insomnia.[27,28,30][Level of evidence: I] Patients respond as individuals to both the efficacy and the toxicity of various medications. Therefore, careful assessment and tailored treatment chosen collaboratively by provider and health care consumer are needed.
Data indicate that if one medication is not helpful for an individual, switching to another medication—whether a different antidepressant or gabapentin—may be worthwhile. In a randomized phase III trial (NCCTG-N03C5) of gabapentin alone versus gabapentin in conjunction with an antidepressant in women who had inadequate control of their hot flashes with an antidepressant alone,[Level of evidence: I] gabapentin use resulted in an approximately 50% median reduction in hot flash frequency and score, regardless of whether the antidepressant was continued. In other words, for women who were using antidepressants exclusively for the management of hot flashes that were inadequately controlled, initiation of gabapentin with discontinuation of the antidepressant produced results equal to those obtained with combined therapy, resulting in the need for fewer medications. Similarly, in a pilot study of women receiving inadequate benefit from venlafaxine for hot flash reduction, switching to open-label citalopram, 20 mg per day, resulted in a 50% reduction in hot flash frequency and score.