The Who, What, Where, When and Sometimes, Why.

Anti-depressants and other non-hormone medications for 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)
  • Fluvoxamine (Luvox)
  • 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 More Than Placebo?

Randomized controlled trials

SSRI anti-depressants versus placebo

Barton et al. [2]

254
breast cancer survivors 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
breast cancer survivors and women never diagnosed with cancer

Paroxetine

6 weeks

Yes

Stearns et al. [5]

151
breast cancer survivors 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
breast cancer survivors 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
breast cancer survivors and women never diagnosed with cancer

Pregabalin

6 weeks

Yes

Clonidine versus placebo

Pandya et al. [17]

149
breast cancer survivors

Clonidine

8 weeks

Yes

Megestrol acetate versus placebo

Goodwin et al. [18]

286
breast cancer survivors

Megestrol acetate

3 months

Yes

Pooled and meta-analyses

Loprinzi et al. [19]

748
breast cancer survivors and women never diagnosed with cancer

SSRI and non-SSRI antidepressants*

4-6 weeks

Yes

 

550
breast cancer survivors and women never diagnosed with cancer

Gabapentin

4 weeks

Yes

Shams et al. [20]

9 studies of women never diagnosed with cancer

SSRI antidepressants

6-36 weeks

Yes

Nelson et al. [21]

7 studies

SSRI and non-SSRI antidepressants†

4 weeks to 3 months

Yes

 

4 studies

Clonidine

4-8 weeks

No

Sun et al. [22]

6 studies

Desvenlafaxine

12 weeks

Yes

Toulis et al. [23]

4 studies

Gabapentin

4-12 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. 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.
  23. 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.

TOOLS & RESOURCES

Give for Metastatic Breast Cancer Research

Donate Now

Everything you do makes a difference

Discover the ways you can help Get Involved