Journal of General Internal Medicine

, Volume 29, Issue 1, pp 204–213 | Cite as

SSRIs for Hot Flashes: A Systematic Review and Meta-Analysis of Randomized Trials

  • Taghreed Shams
  • Belal Firwana
  • Farida Habib
  • Abeer Alshahrani
  • Badria AlNouh
  • Mohammad Hassan Murad
  • Mazen Ferwana
Review Aritcle

ABSTRACT

Background

Hot flashes are the most commonly reported vasomotor symptom during the peri- and early post-menopausal period.

Objectives

To systematically review, appraise and summarize the evidence of the impact of different SSRIs on peri-menopausal hot flashes in healthy women in randomized, controlled trials.

Methods

A comprehensive literature search was conducted of MEDLINE™, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus through March 2013. Two independent reviewers selected studies and extracted data. Random effects meta-analysis was used to pool outcomes across studies, and Bayesian mixed treatment methods were used to rank SSRIs in terms of effectiveness.

Results

We included a total of 11 randomized controlled trials with good methodological quality enrolling 2,069 menopausal and post-menopausal women (follow-up 1–9 months, mean age 36–76 years, mean time since menopause 2.3–6.6 years). Compared with placebo, SSRIs were associated with a statistically significant decrease in hot flash frequency (difference in means −0.93; 95 % CI −1.46 to −0.37; I2 = 21 %) and severity assessed by various scales (standardized difference in means −0.34; 95 % CI −0.59 to −0.10; I2 = 47 %). Adverse events did not differ from placebo. Mixed treatment comparison analysis demonstrated the superiority of escitalopram compared to other SSRIs in terms of efficacy.

Conclusion

SSRI use is associated with modest improvement in the severity and frequency of hot flashes but can also be associated with the typical profile of SSRI adverse effects.

KEY WORDS

SSRI hot flashes menopause 

Notes

Acknowledgement

Source of Funding

None

Disclosures

This study was made possible by support from the Center for the Science of Healthcare Delivery, Mayo Clinic, and CTSA grant UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Conflict of Interest

The authors declare that they do not have a conflict of interest.

REFERENCES

  1. 1.
    Freeman EW, Sherif K. Prevalence of hot flushes and night sweats around the world: a systematic review. Climacteric. 2007;10(3):197–214.PubMedCrossRefGoogle Scholar
  2. 2.
    National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med. 2005;142(12 Pt 1):1003–13.Google Scholar
  3. 3.
    Nelson HD, Vesco KK, Haney E, Fu R, Nedrow A, Miller J, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295(17):2057–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Shanafelt TD, Barton DL, Adjei AA, Loprinzi CL. Pathophysiology and treatment of hot flashes. Mayo Clin Proc. 2002;77(11):1207–18.PubMedCrossRefGoogle Scholar
  5. 5.
    Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004;291(13):1610–20.PubMedCrossRefGoogle Scholar
  6. 6.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321–33.PubMedCrossRefGoogle Scholar
  7. 7.
    Newton KM, Buist DS, Keenan NL, Anderson LA, LaCroix AZ. Use of alternative therapies for menopause symptoms: results of a population-based survey. Obstet Gynecol. 2002;100(1):18–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Hall E, Frey BN, Soares CN. Non-hormonal treatment strategies for vasomotor symptoms: a critical review. Drugs. 2011;71(3):287–304.PubMedCrossRefGoogle Scholar
  9. 9.
    Loprinzi CL, Sloan JA, Perez EA, Quella SK, Stella PJ, Mailliard JA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol. 2002;20(6):1578–83.PubMedCrossRefGoogle Scholar
  10. 10.
    Grady D, Cohen B, Tice J, Kristof M, Olyaie A, Sawaya GF. Ineffectiveness of sertraline for treatment of menopausal hot flushes: a randomized controlled trial. Obstet Gynecol. 2007;109(4):823–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Kalay AE, Demir B, Haberal A, Kalay M, Kandemir O. Efficacy of citalopram on climacteric symptoms. Menopause. 2007;14(2):223–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration; updated March 2011.Google Scholar
  13. 13.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34.PubMedCrossRefGoogle Scholar
  14. 14.
    Bonneterre J, Thurlimann B, Robertson JF, Krzakowski M, Mauriac L, Koralewski P, et al. Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study. J Clin Oncol. 2000;18(22):3748–57.PubMedGoogle Scholar
  15. 15.
    Hunter MS, Grunfeld EA, Mittal S, Sikka P, Ramirez AJ, Fentiman I, et al. Menopausal symptoms in women with breast cancer: prevalence and treatment preferences. Psychooncology. 2004;13(11):769–78.PubMedCrossRefGoogle Scholar
  16. 16.
    Gupta P, Sturdee DW, Palin SL, Majumder K, Fear R, Marshall T, et al. Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life. Climacteric. 2006;9(1):49–58.PubMedCrossRefGoogle Scholar
  17. 17.
    Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Brok J, Thorlund K, Gluud C, Wetterslev J. Trial sequential analysis reveals insufficient information size and potentially false positive results in many meta-analyses. J Clin Epidemiol. 2008;61(8):763–9.PubMedCrossRefGoogle Scholar
  19. 19.
    DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28(2):105–14.PubMedCrossRefGoogle Scholar
  20. 20.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.PubMedCrossRefGoogle Scholar
  21. 21.
    Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.PubMedCrossRefGoogle Scholar
  22. 22.
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.PubMedCrossRefGoogle Scholar
  23. 23.
    Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol. 2000;53(11):1119–29.PubMedCrossRefGoogle Scholar
  24. 24.
    Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med. 2004;23(20):3105–24.PubMedCrossRefGoogle Scholar
  25. 25.
    Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU Technical Support Document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials. 2012.Google Scholar
  26. 26.
    Suvanto-Luukkonen E, Koivunen R, Sundstrom H, Bloigu R, Karjalainen E, Haiva-Mallinen L, et al. Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study. Menopause. 2005;12(1):18–26.PubMedCrossRefGoogle Scholar
  27. 27.
    Gordon PR, Kerwin JP, Boesen KG, Senf J. Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population. Menopause. 2006;13(4):568–75.PubMedCrossRefGoogle Scholar
  28. 28.
    Aedo S, Cavada G, Campodonico I, Porcile A, Irribarra C. Sertraline improves the somatic and psychological symptoms of the climacteric syndrome. Climacteric. 2011;14(5):590–5.PubMedCrossRefGoogle Scholar
  29. 29.
    Freedman RR, Kruger ML, Tancer ME. Escitalopram treatment of menopausal hot flashes. Menopause. 2011;18(8):893–6.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Akhavan S, Zandvakili F, Arab M, Karimi H, Gharibi F. Comparison of the therapeutic effects of fluoxetine, citalopram, estrogen and progesterone and placebo in the treatment of hot flushes in perimenopausal women. Scientific Journal of Kurdistan University of Medical Sciences. 2011;16(3):31–8.Google Scholar
  31. 31.
    Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003;289(21):2827–34.PubMedCrossRefGoogle Scholar
  32. 32.
    Simon JA, Sanacora G, Bhaskar S, Lippman J. Safety and efficacy of low-dose mesylate salt of paroxetine (LDMP) for the treatment of vasomotor symptoms (VMS) associated with menopause: A 24-week, randomized, placebo-controlled phase 3 study. Menopause. 2012;19(12):1371.Google Scholar
  33. 33.
    Kaunitz A, Sanacora G, Bhaskar S, Lippman J. Safety and efficacy of low-dose mesylate salt of paroxetine (LDMP) for the treatment of vasomotor symptoms (VMS) associated with menopause: A 12-week, randomized, placebo-controlled phase 3 study. Menopause. 2012;19(12):1389.Google Scholar
  34. 34.
    Freeman EW, Guthrie KA, Caan B, Sternfeld B, Cohen LS, Joffe H, et al. Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial. JAMA. 2011;305(3):267–74.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Reed SD, Guthrie KA, Joffe H, Shifren JL, Seguin RA, Freeman EW. Sexual function in nondepressed women using escitalopram for vasomotor symptoms: A randomized controlled trial. Obstetrics and Gynecology. 2012;119(3):527–38.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Ensrud KE, Joffe H, Guthrie KA, Larson JC, Reed SD, Newton KM, et al. Effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes: a randomized controlled trial. Menopause. 2012;19(8):848–55.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Carpenter JS, Guthrie KA, Larson JC, Freeman EW, Joffe H, Reed SD, et al. Effect of escitalopram on hot flash interference: a randomized, controlled trial. Fertility and sterility. 2012;97(6):1399–404.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Kerwin JP, Gordon PR, Senf JH. The variable response of women with menopausal hot flashes when treated with sertraline. Menopause. 2007;14(5):841–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Desmarais JE, Looper KJ. Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. J Clin Psychiatry. 2009;70(12):1688–97.PubMedCrossRefGoogle Scholar
  40. 40.
    Reid R, Blake J, Abramson B, Khan A, Senikas V, Fortier M. Menopause and Osteoporosis Update 2009. SOGC Clinical Practice Guidelines. 2009;31(1):Supplement 1.Google Scholar
  41. 41.
    Rees MCP, Panay N. Alternatives to HRT for the Management of Symptoms of the Menopause (SAC Opinion Paper 6). 2010.Google Scholar
  42. 42.
    Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence–imprecision. J Clin Epidemiol. 2011;64(12):1283–93.PubMedCrossRefGoogle Scholar
  43. 43.
    Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence–indirectness. J Clin Epidemiol. 2011;64(12):1303–10.PubMedCrossRefGoogle Scholar

Copyright information

© Society of General Internal Medicine 2013

Authors and Affiliations

  • Taghreed Shams
    • 1
    • 2
  • Belal Firwana
    • 3
    • 4
  • Farida Habib
    • 1
    • 5
  • Abeer Alshahrani
    • 1
    • 6
  • Badria AlNouh
    • 1
    • 2
  • Mohammad Hassan Murad
    • 4
    • 7
  • Mazen Ferwana
    • 1
    • 6
  1. 1.National and Gulf Center for Evidence-Based Health PracticeKing Saud Bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia
  2. 2.Department of Obstetrics and GynecologyKing Saud Bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia
  3. 3.Department of Internal MedicineUniversity of MissouriColumbiaUSA
  4. 4.Knowledge and Evaluation Research Unit, Mayo ClinicRochesterUSA
  5. 5.Department of NursingKing Saud Bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia
  6. 6.Department of Family MedicineKing Saud Bin Abdulaziz University for Health SciencesRiyadhSaudi Arabia
  7. 7.Division of Preventive MedicineMayo ClinicRochesterUSA

Personalised recommendations