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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

Joffe, Hadine MD, MSc1; Partridge, Ann MD, MPH2; Giobbie-Hurder, Anita MS3; Li, Xiaochun PhD3; Habin, Karleen RN, MPH4; Goss, Paul MD, PhD4; Winer, Eric MD2; Garber, Judy MD, MPH2

doi: 10.1097/gme.0b013e3181dbee1b
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Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Augmentation of serotonin-norepinephrine reuptake inhibitors and selective-serotonin reuptake inhibitors with zolpidem improves sleep and quality of life in breast cancer survivors who have sleep disturbance associated with hot flashes. Adding a hypnotic agent to serotonin-norepinephrine reuptake inhibitors/selective-serotonin reuptake inhibitors optimizes hot flash therapy by helping women to sleep through nighttime hot flashes, suggesting that treatments targeting sleep may be an important supplemental strategy to optimize well-being.

From the 1Perinatal and Reproductive Psychiatry Program, Department of Psychiatry, Massachusetts General Hospital, Boston, MA; Departments of 2Medical Oncology and 3Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA; and 4Department of Medical Oncology, Massachusetts General Hospital, Boston, MA.

Received November 2, 2009; revised and accepted March 2, 2010.

Funding/support: This study was supported by the Susan G. Komen Breast Cancer Foundation. Study medication was provided by Wyeth-Ayerst Pharmaceuticals and Sanofi-Aventis.

Financial disclosure/conflicts of interest: Dr. Joffe-Research/product support for this protocol: Study medication provided by Wyeth-Ayerst Pharmaceuticals and Sanofi-Aventis. Research support/coinvestigator: Bayer HealthCare Pharmaceuticals, Forest Laboratories, Inc., GlaxoSmithKline, and Sepracor Inc. Advisory/Consulting: Sanofi-Aventis. Dr.Garber-Consultant for Generation Health. Coinvestigator on a trial sponsored by Astra Zeneca.

Address correspondence to: Hadine Joffe, MD, MSc, Massachusetts General Hospital, 185 Cambridge St, Suite 2286, Boston, MA 02114. E-mail: hjoffe@partners.org

©2010The North American Menopause Society