Augmentation of venlafaxine and selective serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer patients with hot flashes: a randomized, double-blind, placebo-controlled trial.

Hot flashes are a major quality-of-life issue for breast cancer survivors, interrupting sleep, reducing quality of life, and diminishing treatment adherence to adjuvant endocrine therapies. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are used widely but are only partially effective for hot flashes. Alternative strategies are needed. We hypothesized that augmentation of SSRI/SNRI therapy with hypnotic agents would optimize hot flash therapy by improving sleep and quality of life. Women with breast cancer or at high risk for developing the disease who had hot flashes in association with nocturnal awakenings were randomized to double-blinded treatment with zolpidem 10 mg or placebo for 5 weeks. SSRI/SNRI nonusers (81%) started venlafaxine XR 75 mg/day concurrently, whereas SSRI/SNRI users continued that therapy. We compared the proportion of responders, defined as study completers with improved subjective sleep quality (Pittsburgh Sleep Quality Index) and/or objectively assessed wake time after sleep onset on actigraphy, between groups. Of 53 women (aged 51 ± 8 y) randomized to zolpidem augmentation (n = 25) or placebo augmentation (n = 28), 38 completed the protocol (57% on placebo, 88% on zolpidem). More women augmented with zolpidem than placebo were responders on the sleep outcome (40% vs 14%; P = 0.035). Quality of life improved more with zolpidem than with placebo (P = 0.01). Treatment effects on hot flashes and mood did not differ between groups. Augmentation of SSRI/SNRI with zolpidem improves sleep and quality of life in breast cancer survivors with hot flashes and associated sleep disturbance. Adding a hypnotic agent to an SSRI/SNRI helps women to sleep through nighttime hot flashes. Treatments targeting sleep may be an important supplemental strategy to optimize well-being.