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Relapse of vasomotor symptoms after discontinuation of the selective serotonin reuptake inhibitor escitalopram: results from the Menopause Strategies Finding Lasting Answers for Symptoms and Health Research Network

Joffe, Hadine MD, MSc1; Guthrie, Katherine A. PhD2; Larson, Joseph MS2; Cohen, Lee S. MD1; Carpenter, Janet S. PhD, RN, FAAN3; LaCroix, Andrea Z. PhD2; Freeman, Ellen W. PhD4

Menopause: The Journal of The North American Menopause Society: March 2013 - Volume 20 - Issue 3 - p 261–268
doi: 10.1097/gme.0b013e31826d3108
Original Articles

Objective Vasomotor symptoms (VMS) recur after discontinuation of hormonal therapy. Selective serotonin reuptake inhibitors (SSRIs) are used increasingly to treat VMS, but whether VMS recur after cessation of SSRI is unknown. We hypothesized that relapse of VMS to baseline levels after SSRI cessation would be common and predicted by menopausal and psychological characteristics.

Methods Recurrence of VMS (frequency, severity, and bother) was measured with daily diaries for 3 weeks after cessation of escitalopram, which was administered to perimenopausal/postmenopausal women with hot flashes and night sweats in an 8-week randomized, placebo-controlled trial. Blinding of staff and participants was maintained throughout. Relapse was defined as mean daily VMS frequency, severity, or bother 20% or less lower than pretreatment levels.

Results Of 76, 57, and 51 women included in the analysis for VMS frequency, severity, and bother, 34.2%, 38.6%, and 37.3%, respectively, had relapse of VMS frequency, severity, and bother. In adjusted models, VMS frequency relapse was predicted by higher levels of pretreatment insomnia symptoms (P = 0.02) and a weaker response to escitalopram (P = 0.03).

Conclusions Among women whose VMS improved with escitalopram, approximately one third relapsed swiftly after discontinuation of the medication. Those with pretreatment insomnia and those with a weaker response to escitalopram may be at greatest risk for VMS relapse after treatment discontinuation. Women should be educated about the likelihood of VMS symptom relapse when they discontinue SSRIs after receiving benefits from short-term treatment.

From the 1Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA; 2Fred Hutchinson Cancer Research Center, Seattle, WA; 3School of Nursing, Indiana University, Indianapolis, IN; and 4Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA.

Received May 30, 2012; revised and accepted August 2, 2012.

Funding/support: This study was supported by a cooperative agreement issued by the National Institute on Aging, in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Center for Complementary and Alternative Medicine, and the Office of Research and Women’s Health, and by grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, and U01AG032700 from the National Institute on Aging. At the Indiana University site, the project was funded in part with support from the Indiana Clinical and Translational Sciences Institute, funded in part by grant UL1 RR025761 from the National Institutes of Health, National Center for Research Resources, Clinical and Translational Sciences Award. Escitalopram and matching placebo pills were provided by Forest Research Institute.

Financial disclosure/conflicts of interest: Dr. Joffe serves on the board of Noven Pharmaceuticals Inc., is an unpaid consultant to Sunovion Pharmaceuticals, and has received a research grant from Cephalon Inc. Dr. Cohen consults for Noven Pharmaceutical and PamLab LLC and has received grants from Forest Laboratories Inc., Ortho-McNeil Janssen, Pfizer Inc., Astra-Zeneca Pharmaceuticals, Bristol-Myers and Squib, Cephalon Inc., GlaxoSmithKline, and Sunovion Pharmaceuticals Inc. Dr. LaCroix is a board member of the Center for Outcomes Research at the University of Massachusetts and the Amgen Scientific Methodology Advisory Committee for Profile. She is also a consultant for the Pfizer Mammographic Breast Density Advisory Meeting. Dr. Freeman has received research grants from Forest Laboratories Inc. and Bionovo.

Address correspondence to: Hadine Joffe, MD, MSc, Center for Women’s Mental Health, Department of Psychiatry, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114. E-mail:

© 2013 by The North American Menopause Society.