Research table: Anti-depressants and other non-hormone medications for relief of menopausal symptoms

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s important to understand some key concepts. Learn how to read a research table.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) anti-depressants and non-SSRI anti-depressants have been shown to decrease the frequency and strength of hot flashes, with few side effects.

SSRI anti-depressants include:

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Sertraline (Zoloft)

Some SSRIs may interfere with tamoxifen though it’s not known if this impacts the effectiveness of tamoxifen in treating breast cancer [1]. If you are taking tamoxifen, talk with your health care provider before taking an SSRI.

Non-SSRI anti-depressants include:

• Venlafaxine (Effexor)
• 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	Study Population (number of participants)	Medication Studied	Treatment Duration	Medication Reduced Hot Flashes Better Than Placebo?
Randomized controlled trials
SSRI anti-depressants versus placebo
Barton et al. [2]	254 women who’ve had breast cancer and women never diagnosed with cancer	Citalopram	6 weeks	Yes
LaCroix et al. [3]	205 women never diagnosed with cancer	Escitalopram	8 weeks	Yes
Stearns et al. [4]	165 women who’ve had breast cancer and women never diagnosed with cancer	Paroxetine	6 weeks	Yes
Stearns et al. [5]	151 women who’ve had breast cancer and women never diagnosed with cancer	Paroxetine	4 weeks	Yes
Suvanto-Luukkonen et al. [6]	150 women never diagnosed with cancer	Fluoxetine	9 months	No
		Citalopram	9 months	No
Non-SSRI anti-depressants versus placebo
Speroff et al. [7]	620 women never diagnosed with cancer	Desvenlafaxine	12 weeks	Yes
Archer et al. [8]	567 women never diagnosed with cancer	Desvenlafaxine	12 weeks	Yes
Bouchard et al. [9]	485 women never diagnosed with cancer	Desvenlafaxine	12 weeks	No
Pinkerton et al. [10]	365 women never diagnosed with cancer	Desvenlafaxine	12 weeks	Yes
Joffe et al. [11]	242 women never diagnosed with cancer	Venlafaxine	8 weeks	Yes
Loprinzi et al. [12]	191 women who’ve had breast cancer and women never diagnosed with cancer	Venlafaxine	4 weeks	Yes
Gabapentin versus placebo
Pinkerton et al. [13]	600 women never diagnosed with cancer	Gabapentin	12 weeks	Yes
Pandya et al. [14]	420 women never diagnosed with cancer	Gabapentin	8 weeks	Yes
Butt et al. [15]	193 women never diagnosed with cancer	Gabapentin	4 weeks	Yes
Loprinzi et al. [16]	163 women who’ve had breast cancer and women never diagnosed with cancer	Pregabalin	6 weeks	Yes
Clonidine versus placebo
Pandya et al. [17]	149 women who’ve had breast cancer	Clonidine	8 weeks	Yes
Megestrol acetate versus placebo
Goodwin et al. [18]	286 women who’ve had breast cancer	Megestrol acetate	3 months	Yes
Pooled and meta-analyses
Loprinzi et al. [19]	748 women who’ve had breast cancer and women never diagnosed with cancer	SSRI and non-SSRI anti-depressants*	4-6 weeks	Yes
	550 women who’ve had breast cancer and women never diagnosed with cancer	Gabapentin	4 weeks	Yes
Shams et al. [20]	9 studies of women never diagnosed with cancer	SSRI anti-depressants	6-36 weeks	Yes
Nelson et al. [21]	7 studies	SSRI and non-SSRI anti-depressants†	4 weeks to 3 months	Yes
	4 studies	Clonidine	4-8 weeks	No
Yoon et al. [22]	7 studies	Gabapentin	1-6 months	Yes
Sun et al. [23]	6 studies	Desvenlafaxine	12 weeks	Yes
Toulis et al. [24]	4 studies	Gabapentin	4-12 weeks	Yes
Riemma et al. [25]	3 studies	Paroxetine	6-16 weeks	Yes

* Pooled analysis included studies of fluoxetine, paroxetine, sertraline and venlafaxine.

† Meta-analysis included studies of citalopram, fluoxetine, paroxetine and venlafaxine.

 

References  

1. 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.
2. 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.
3. LaCroix AZ1, Freeman EW, Larson J, et al. Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: a randomized controlled trial. Maturitas. 73(4):361-8, 2012.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Joffe H, Guthrie KA, LaCroix AZ, et al. Low-dose estradiol and the serotonin-norepinephrine reuptake inhibitor venlafaxine for vasomotor symptoms: a randomized clinical trial. JAMA Intern Med. 174(7):1058-66, 2014.
12. 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.
13. Pinkerton JV, Kagan R, Portman D, Sathyanarayana R, Sweeney M for the Breeze 3 Investigators. Phase 3 randomized controlled study of gastroretentive gabapentin for the treatment of moderate-to-severe hot flashes in menopause. Menopause. 21(6):567-73, 2014.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. Shams T, Firwana B, Habib F, et al. SSRIs for hot flashes: a systematic review and meta-analysis of randomized trials. J Gen Intern Med. 29(1):204-13, 2014.
21. 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.
22. Yoon SH, Lee JY, Lee C, Lee H, Kim SN. Gabapentin for the treatment of hot flushes in menopause: a meta-analysis. Menopause. 27(4):485-493, 2020.
23. Sun Z, Hao Y, Zhang M. Efficacy and safety of desvenlafaxine treatment for hot flashes associated with menopause: a meta-analysis of randomized controlled trials. Gynecol Obstet Invest. 75(4):255-62, 2013.
24. 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.
25. Riemma G, Schiattarella A, La Verde M, et al. Efficacy of low-dose paroxetine for the treatment of hot flushes in surgical and physiological postmenopausal women: systematic review and meta-analysis of randomized trials. Medicina (Kaunas). 55(9):554, 2019.

Updated 06/18/21