> Table 61: Antidepressants and other non-hormone medications for menopausal symptoms
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Introduction: Although menopausal hormone therapy (postmenopausal hormone use) containing estrogen and progestin may ease menopausal symptoms, long-term use increases the risk of breast cancer (see Table 8) [1]. For this reason, many women seek other ways to reduce hot flashes and other symptoms
Antidepressants
Selective serotonin reuptake inhibitors (SSRIs) antidepressants and non-SSRI antidepressants have been shown to decrease the frequency and strength of hot flashes, with few side effects. SSRI antidepressants include citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil) and sertraline (Zoloft). Some SSRIs can interfere with tamoxifen [2-3]. If you are taking tamoxifen, talk to your health care provider before taking an SSRI.
Non-SSRI antidepressants include venlafaxine (Effexor) and desvenlafaxine (Pristiq).
Other non-hormone medications
Gabapentin (Neurontin), clonidine and megestrol acetate are under study for the relief of hot flashes.
Learn more about alternatives to menopausal hormone therapy for the relief of menopausal symptoms.
Learn about the strengths and weaknesses of different types of studies.
Study selection criteria: Randomized controlled trials that compared non-hormone medication use to placebo with at least 100 participants, pooled analyses and meta-analyses.
Table note: Relative risk above 1 indicates increased risk. Relative risk below 1 indicates decreased risk.
Study
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Study Population
(number of participants)
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Medication Studied
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Treatment Duration
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Medication Reduced Hot Flashes More Than Placebo?
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Randomized controlled trials
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SSRI antidepressants versus placebo
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Barton et al. [4]
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254
breast cancer survivors and cancer-free women
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Citalopram
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6 weeks
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Yes
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Stearns et al. [5]
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165
breast cancer survivors and cancer-free women
|
Paroxetine
|
6 weeks
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Yes
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Stearns et al. [6]
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151
breast cancer survivors and cancer-free women
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Paroxetine
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4 weeks
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Yes
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Suvanto-Luukkonen et al. [7]
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150
cancer-free women
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Fluoxetine
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9 months
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No
|
|
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Citalopram
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9 months
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No
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Non-SSRI antidepressants versus placebo
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Speroff et al. [8]
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620
cancer-free women
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Desvenlafaxine
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12 weeks
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Yes
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Archer et al. [9]
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567
cancer-free women
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Desvenlafaxine
|
12 weeks
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Yes
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Bouchard et al. [10]
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485
cancer-free women
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Desvenlafaxine
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12 weeks
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No
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Pinkerton et al. [11]
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365
cancer-free women
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Desvenlafaxine
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12 weeks
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Yes
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Loprinzi et al. [12]
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191
breast cancer survivors and cancer-free women
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Venlafaxine
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4 weeks
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Yes
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Gabapentin versus placebo
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Pandya et al. [13]
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420
cancer-free women
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Gabapentin
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8 weeks
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Yes
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Butt et al. [14]
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193
cancer-free women
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Gabapentin
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4 weeks
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Yes
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Loprinzi et al. [15]
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163
breast cancer survivors and cancer-free women
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Pregabalin
|
6 weeks
|
Yes
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Clonidine versus placebo
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Pandya et al. [16]
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149
breast cancer survivors
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Clonidine
|
8 weeks
|
Yes
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Megestrol acetate versus placebo
|
Goodwin et al. [17]
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286
breast cancer survivors
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Megestrol acetate
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3 months
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Yes
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Pooled and meta-analyses
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Loprinzi et al. [18]
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748
breast cancer survivors and cancer-free women
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SSRI and non-SSRI antidepressants*
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4 to 6 weeks
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Yes
|
|
550
breast cancer survivors and cancer-free women
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Gabapentin
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4 weeks
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Yes
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Nelson et al. [19]
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7 studies
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SSRI and non-SSRI antidepressants†
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4 weeks to 3 months
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Yes
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4 studies
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Clonidine
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4 to 8 weeks
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No
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Toulis et al. [20]
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4 studies
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Gabapentin
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4 to 12 weeks
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Yes
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* Pooled analysis included studies of fluoxetine, paroxetine, sertraline and venlafaxine.
† Meta-analysis included studies of citalopram, fluoxetine, paroxetine and venlafaxine.
References
- Rossouw JE, Anderson GL, Prentice RL, et al. for the Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 288(3):321-33, 2002.
- Goetz MP, Knox SK, Suman VJ, et al. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat. 101(1):113-21, 2007.
- Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 340:c693, 2010.
- Barton DL, LaVasseur BI, Sloan JA, et al. Phase III, placebo-controlled trial of three doses of citalopram for the treatment of hot flashes: NCCTG trial N05C9. J Clin Oncol. 28(20):3278-83, 2010.
- Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 289(21):2827-34, 2003.
- Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 23(28):6919-30, 2005.
- Suvanto-Luukkonen E, Koivunen R, Sundström H, et al. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopause. 12(1):18-26, 2005.
- Speroff L, Gass M, Constantine G, Olivier S for the Study 315 Investigators. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstet Gynecol. 111(1):77-87, 2008.
- Archer DF, Dupont CM, Constantine GD, Pickar JH, Olivier S for the Study 319 Investigators. Desvenlafaxine for the treatment of vasomotor symptoms associated with menopause: a double-blind, randomized, placebo-controlled trial of efficacy and safety. Am J Obstet Gynecol. 200(3):238.e1-238.e10, 2009.
- Bouchard P, Panay N, de Villiers TJ, et al. Randomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptoms. Climacteric. 15(1):12-20, 2012.
- Pinkerton JV, Constantine G, Hwang E, et al. for the Study 3353 Investigators. Desvenlafaxine compared with placebo for treatment of menopausal vasomotor symptoms: a 12-week, multicenter, parallel-group, randomized, double-blind, placebo-controlled efficacy trial. Menopause. 20(1):28-37, 2013.
- Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 356(9247):2059-63, 2000.
- Pandya KJ, Morrow GR, Roscoe JA, et al. Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet. 366(9488):818-24, 2005.
- Butt DA, Lock M, Lewis JE, Ross S, Moineddin R. Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial. Menopause. 15(2):310-8, 2008.
- Loprinzi CL, Qin R, Balcueva EP, et al. Phase III, randomized, double-blind, placebo-controlled evaluation of pregabalin for alleviating hot flashes, N07C1. J Clin Oncol. 28(4):641-7, 2010.
- Pandya KJ, Raubertas RF, Flynn PJ, et al. Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study. Ann Intern Med. 132(10):788-93, 2000.
- Goodwin JW, Green SJ, Moinpour CM, et al. Phase III randomized placebo-controlled trial of two doses of megestrol acetate as treatment for menopausal symptoms in women with breast cancer: Southwest Oncology Group Study 9626. J Clin Oncol. 26(10):1650-6, 2008.
- Loprinzi CL, Sloan J, Stearns V, et al. Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis. J Clin Oncol. 27(17):2831-7, 2009.
- Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 295(17):2057-71, 2006.
- Toulis KA, Tzellos T, Kouvelas D, Goulis DG. Gabapentin for the treatment of hot flashes in women with natural or tamoxifen-induced menopause: a systematic review and meta-analysis. Clin Ther. 31(2):221-35, 2009.
Updated 04/02/13
