American Journal of Obstetrics & Gynecology
Volume 200, Issue 2 , Pages 172.e1-172.e10 , February 2009

A double-blind, randomly assigned, placebo-controlled study of desvenlafaxine efficacy and safety for the treatment of vasomotor symptoms associated with menopause

Presented at the 63rd Annual Meeting of the American Society for Reproductive Medicine, Washington, DC, Oct. 13-17, 2007, and the 2007 National Clinical Conference of the American College of Nurse Practitioners, San Antonio, TX, Oct. 24-28, 2007.

  • David F. Archer, MD

      Affiliations

    • Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA
    • Corresponding Author InformationReprints: David F. Archer, MD, The Jones Institute for Reproductive Medicine, 601 Colley Ave., Norfolk, VA 23507
  • ,
  • Larry Seidman, DO

      Affiliations

    • Philadelphia Clinical Research, Philadelphia, PA
  • ,
  • Ginger D. Constantine, MD

      Affiliations

    • Wyeth Research, Collegeville, PA
  • ,
  • James H. Pickar, MD

      Affiliations

    • Wyeth Research, Collegeville, PA
  • ,
  • Sophie Olivier, MD

      Affiliations

    • Wyeth Research, Collegeville, PA

Received 2 May 2008 ,Revised 8 August 2008 ,Accepted 30 September 2008.

References 

  1. Utian WH. Psychosocial and socioeconomic burden of vasomotor symptoms in menopause: a comprehensive review. Health Qual Life Outcomes. 2005;3:47–56
  2. Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition: the Harvard Study of Moods and Cycles. Arch Gen Psychiatry. 2006;63:385–390
  3. Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006;63:375–382
  4. Joffe H, Hall JE, Soares CN, et al. Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care. Menopause. 2002;9:392–398
  5. Kravitz HM, Ganz PA, Bromberger J, Powell LH, Sutton-Tyrrell K, Meyer PM. Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition. Menopause. 2003;10:19–28
  6. Woodward S, Freedman RR. The thermoregulatory effects of menopausal hot flashes on sleep. Sleep. 1994;17:497–501
  7. National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med. 2005;142:1003–1013
  8. Gundlah C, Pecins-Thompson M, Schutzer WE, Bethea CL. Ovarian steroid effects on serotonin 1A, 2A and 2C receptor mRNA in macaque hypothalamus. Brain Res Mol Brain Res. 1999;63:325–339
  9. Karkanias GB, Ansonoff MA, Etgen AM. Estradiol regulation of alpha 1b-adrenoceptor mRNA in female rat hypothalamus-preoptic area. J Neuroendocrinol. 1996;8:449–455
  10. McEwen B. Estrogen actions throughout the brain. Recent Prog Horm Res. 2002;57:357–384
  11. Bachmann GA. Menopausal vasomotor symptoms: a review of causes, effects and evidence-based treatment options. J Reprod Med. 2005;50:155–165
  12. Berendsen HHG. The role of serotonin in hot flushes. Maturitas. 2000;36:155–164
  13. Deecher DC. Physiology of thermoregulatory dysfunction and current approaches to the treatment of vasomotor symptoms. Expert Opin Investig Drugs. 2005;14:435–448
  14. Deecher DC, Alfinito PD, Leventhal L, et al. Alleviation of thermoregulatory dysfunction with the new serotonin and norepinephrine reuptake inhibitor desvenlafaxine succinate in ovariectomized rodent models. Endocrinology. 2007;148:1376–1383
  15. Freedman RR. Physiology of hot flashes. Am J Hum Biol. 2001;13:453–464
  16. Evans ML, Pritts E, Vittinghoff E, McClish K, Morgan KS, Jaffe RB. Management of postmenopausal hot flushes with venlafaxine hydrochloride: a randomized, controlled trial. Obstet Gynecol. 2005;105:161–166
  17. Kimmick GG, Lovato J, McQuellon R, Robinson E, Muss HB. Randomized, double-blind, placebo-controlled, crossover study of sertraline (Zoloft) for the treatment of hot flashes in women with early stage breast cancer taking tamoxifen. Breast J. 2006;12:114–122
  18. Loprinzi CL, Kugler JW, Sloan JA, et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000;356:2059–2063
  19. Loprinzi CL, Sloan JA, Perez EA, et al. Phase III evaluation of fluoxetine for treatment of hot flashes. J Clin Oncol. 2002;20:1578–1583
  20. Stearns V, Beebe KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003;289:2827–2834
  21. 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. 2005;23:6919–6930
  22. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA. 2006;295:2057–2071
  23. DeMartinis NA, Yeung PP, Entsuah R, Manley AL. A double-blind, placebo-controlled study of the efficacy and safety of desvenlafaxine succinate in the treatment of major depressive disorder. J Clin Psychiatry. 2007;68:677–688
  24. Septien-Velez L, Pitrosky B, Padmanabhan SK, Germain J-M, Tourian KA. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder. Int Clin Psychopharmacol. 2007;22:338–347
  25. Liebowitz M, Manley AL, Padmanabhan SK, Ganguly R, Tummala R, Tourian KA. Efficacy, safety, and tolerability of desvenlafaxine 50 mg/d and 100 mg/d in outpatients with major depressive disorder. Curr Med Res Opin. 2008;24:1877–1890
  26. Speroff L, Gass M, Constantine G, Olivier S Study 315 Investigators. Efficacy and tolerability of desvenlafaxine succinate treatment for menopausal vasomotor symptoms: a randomized controlled trial. Obstet Gynecol. 2008;111:77–87
  27. Goldstein BJ, Goodnick PJ. Selective serotonin reuptake inhibitors in the treatment of affective disorders—III (Tolerability, safety and pharmacoeconomics). J Psychopharmacol. 1998;12:S55–S87
  28. Masand PS, Gupta S. Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry. 1999;7:69–84
  29. Schatzberg AF, Haddad P, Kaplan EM, et al. Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition (Discontinuation Consensus Panel). J Clin Psychiatry. 1997;58(Suppl 7):5–10
  30. European Medicines Agency Committee for Medical Products for Human Use. Guideline on clinical investigation of medicinal products for hormone replacement therapy of oestrogen deficiency symptoms in postmenopausal women. London, UK: European Medicines Agency; 2005;
  31. US Food and Drug Administration. Guidance for Industry (Estrogen and estrogen/progestin drug products to treat vasomotor symptoms and vulvar and vaginal atrophy symptoms—recommendations for clinical evaluation). Rockville, MD: US Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER); 2003;
  32. McNair DM, Lorr L, Droppleman LF. EDITS manual for the profile of mood states. San Diego: Educational and Industrial Testing Service; 1992;
  33. DeLoach LJ, Higgins MS, Caplan AB, Stiff JL. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg. 1998;86:102–106
  34. Greene JG. Constructing a standard climacteric scale. Maturitas. 1998;29:25–31
  35. Hill CD, Fehnel SE, Bobula JD, Yu H, McLeod LD. Development and preliminary validation of the Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ). Menopause. 2007;14:1047–1055
  36. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika. 1988;75:800–809
  37. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004;CD002978.
  38. Cassano P, Fava M. Tolerability issues during long-term treatment with antidepressants. Ann Clin Psychiatry. 2004;16:15–25
  39. Clayton AH, Pradko JF, Croft HA, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002;63:357–366
  40. Fava M, Amsterdam JD, Deltito JA, Salzman C, Schwaller M, Dunner DL. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry. 1998;10:145–150
  41. Fava M. Weight gain and antidepressants. J Clin Psychiatry. 2000;61(Suppl 11):37–41
  42. Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM. Antidepressant-induced sexual dysfunction. Ann Pharmacother. 2002;36:1577–1589
  43. Harrison CL, Ferrier N, Young AH. Tolerability of high-dose venlafaxine in depressed patients. J Psychopharmacol. 2004;18:200–204
  44. Montejo-Gonzalez AL, Llorca G, Izquierdo JA, et al. SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients. J Sex Marital Ther. 1997;23:176–194
  45. Cymbalta. [package insert] Indianapolis, IN: Eli Lilly and Co; 2005;
  46. Effexor XR. [package insert] Collegeville, PA: Wyeth Pharmaceuticals Inc; 2006;
  47. Haddad PM. Antidepressant discontinuation syndromes: clinical relevance, prevention and management. Drug Saf. 2001;24:183–197
  48. Gutierrez MA, Stimmel GL, Aiso JY. Venlafaxine: a 2003 update. Clin Ther. 2003;25:2138–2154

 Cite this article as: Archer DF, Seidman L, Constantine GD, et al. A double-blind, randomly assigned, placebo-controlled study of desvenlafaxine efficacy and safety for the treatment of vasomotor symptoms associated with menopause. Am J Obstet Gynecol 2009;200:172.e1-172.e10.

 This study was supported in part by Wyeth Research. Dr Archer is a consultant for Wyeth Research and has received grants and honoraria from the Wyeth Speakers Bureau. Dr Seidman is a consultant for Wyeth Research, Duramed Pharmaceuticals, Inc, and Bayer Pharmaceuticals Corp. Drs Constantine, Pickar, and Olivier are employees of Wyeth Research.

PII: S0002-9378(08)02001-2

doi: 10.1016/j.ajog.2008.09.877

American Journal of Obstetrics & Gynecology
Volume 200, Issue 2 , Pages 172.e1-172.e10 , February 2009