CNS Drugs

, Volume 25, Issue 3, pp 227–238

Open-Label Treatment with Desvenlafaxine in Postmenopausal Women with Major Depressive Disorder Not Responding to Acute Treatment with Desvenlafaxine or Escitalopram

  • Claudio N. Soares
  • Michael E. Thase
  • Anita Clayton
  • Christine J. Guico-Pabia
  • Kristen Focht
  • Qin Jiang
  • Susan G. Kornstein
  • Phillip T. Ninan
  • Cecelia P. Kane
Original Research Article

Abstract

Background: Preliminary clinical evidence indicates that menopausal status might impact on the efficacy of certain classes of antidepressants.

Objective: The aim of this study was to evaluate open-label desvenlafaxine treatment (administered as desvenlafaxine succinate) in postmenopausal women who did not achieve clinical response to acute, double-blind treatment with desvenlafaxine or escitalopram.

Study Design: This phase IIIb, multicentre study included a 6-month open-label extension phase of patients who did not respond in the initial 8-week, randomized, double-blind acute phase.

Patients: Postmenopausal women aged 40–70 years with a primary diagnosis of major depressive disorder were recruited.

Primary Intervention: Non-responders to acute treatment with double-blind desvenlafaxine or escitalopram received flexible-dose, open-label desvenlafaxine 100–200 mg/day for the 6-month extension phase.

Main Outcome Measure: The primary efficacy assessment was the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score. Secondary efficacy outcome measures were the Clinical Global Impressions-Improvement (CGI-I) and -Severity scales, Hamilton Rating Scale for Anxiety, Quick Inventory of Depressive Symptomatology-Self-Report, Visual Analogue Scale-Pain Intensity and the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary health assessments were the Changes in Sexual Functioning Questionnaire, 5-Dimension EuroQoL Index, Health State Today, Menopause Rating Scale, Sheehan Disability Scale, treatment response (≥50% decrease in total HAM-D17 and MADRS score from acute-phase baseline and CGI-I total score ≤2), HAM-D17 remission (total score ≤7) and safety. Descriptive statistics were used to summarize outcomes.

Results: The efficacy analysis included 123 patients (desvenlafaxine/ desvenlafaxine = 64; escitalopram/desvenlafaxine = 59). At final evaluation of the open-label extension phase, mean reductions from acute-phase baseline in HAM-D17 total scores were −11.33 for the desvenlafaxine/desvenlafaxine group and −11.41 for the escitalopram/desvenlafaxine group. HAM-D17 response or remission after 6 months of open-label extension phase desvenlafaxine treatment were achieved in 56–58% and 41–48% of patients, respectively. The results of the other secondary efficacy outcome measures and other definitions of treatment response were generally consistent with the primary analyses. The observed adverse events were similar to those reported during previous desvenlafaxine clinical trials.

Conclusions: Postmenopausal women with major depressive disorder who did not respond to acute, double-blind treatment with escitalopram or desvenlafaxine achieved modest, continued improvement with long-term, open-label desvenlafaxine therapy. Further interpretation of these findings is limited by aspects of the study design (i.e. open-label, non-placebo-controlled) and the lack of randomized comparison groups in the extension phase, which prevents statistical assessment of the efficacy of longer term treatment with desvenlafaxine.

Clinicaltrials.gov identifier: NCT00406640.

References

  1. 1.
    Pinto-Meza A, Usall J, Serrano-Blanco A, et al. Gender differences in response to antidepressant treatment prescribed in primary care: does menopause make a difference? J Affect Disord 2006 Mar; 93(1–3): 53–60PubMedCrossRefGoogle Scholar
  2. 2.
    Thase ME, Entsuah R, Cantillon M, et al. Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health 2005 Sep; 14(7): 609–16CrossRefGoogle Scholar
  3. 3.
    Grigoriadis S, Kennedy SH, Bagby RM. A comparison of antidepressant response in younger and older women. J Clin Psychopharmacol 2003; 23(4): 405–7PubMedCrossRefGoogle Scholar
  4. 4.
    Deecher DC, Beyer CE, Johnston G, et al. Desvenlafaxine succinate: a new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther 2006; 318(2): 657–65PubMedCrossRefGoogle Scholar
  5. 5.
    Pristiq® (desvenlafaxine) [package insert]. Philadelphia (PA): Wyeth Pharmaceuticals Inc., 2008Google Scholar
  6. 6.
    Riederer P, Brucke T, Buhmann C, et al. Workshop II: “neuroprotection”. The Lugano consensus. J Neurol 2000; 247 Suppl. 4: IV/36–7Google Scholar
  7. 7.
    Kornstein SG, Young EA, Harvey AT, et al. The influence of menopause status and postmenopausal use of hormone therapy on presentation of major depression in women. Menopause 2010; 17(4): 828–39PubMedCrossRefGoogle Scholar
  8. 8.
    Soares CN, Thase ME, Clayton A, et al. Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder. Menopause 2010; 17(4): 700–11PubMedGoogle Scholar
  9. 9.
    Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960 Feb; 23: 56–62PubMedCrossRefGoogle Scholar
  10. 10.
    Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59 Suppl. 20: 22–33Google Scholar
  11. 11.
    Benagiano G, Primiero FM. Seventy-five microgram desogestrel minipill, a new perspective in estrogen-free contraception. Ann N Y Acad Sci 2003; 997: 163–73PubMedCrossRefGoogle Scholar
  12. 12.
    Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134: 382–9PubMedCrossRefGoogle Scholar
  13. 13.
    Guy W. Clinical global impressions. In: Rush Jr JA, Pincus HA, First MB, et al., editors. ECDEU assessment manual for psychopharmacology. Rockville (MD): US Department of Health, Education, and Welfare, 1976: 217–22Google Scholar
  14. 14.
    Katon W, Von KM, Lin E, et al. Population-based care of depression: effective disease management strategies to decrease prevalence. Gen Hosp Psychiatry 1997; 19(3): 169–78PubMedCrossRefGoogle Scholar
  15. 15.
    Hamilton MM. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32(1): 50–5PubMedCrossRefGoogle Scholar
  16. 16.
    Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), Clinician rating (QIDS-C), and Self-Report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003; 54(5): 573–83PubMedCrossRefGoogle Scholar
  17. 17.
    DeLoach LJ, Higgins MS, Caplan AB, et al. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg 1998; 86(1): 102–6PubMedGoogle Scholar
  18. 18.
    Clayton AH, McGarvey EL, Clavet GJ. The Changes in Sexual Functioning Questionnaire (CSFQ): development, reliability, and validity. Psychopharmacol Bull 1997; 33(4): 731–45PubMedGoogle Scholar
  19. 19.
    EuroQol: a new facility for the measurement of health-related quality of life. The EuroQol Group. Health Policy 1990; 16(3): 199–208CrossRefGoogle Scholar
  20. 20.
    Heinemann K, Ruebig A, Potthoff P, et al. The Menopause Rating Scale (MRS) scale: a methodological review [abstract]. Health Qual Life Outcomes 2004; 2: 45PubMedCrossRefGoogle Scholar
  21. 21.
    Sheehan DV. Sheehan disability scale. In: Rush AJ, Pincus HA, First MB, editors. Handbook of psychiatric measures. 1st ed. Washington, DC: American Psychiatric Association, 2000: 113–5Google Scholar
  22. 22.
    Romera I, Montejo AL, Delgado-Cohen H, et al. Switching to duloxetine from selective serotonin reuptake inhibitors in non-or partial responders: results from a Spanish sample. Int J Psychiatry Clin Pract 2009; 13(2): 100–8CrossRefGoogle Scholar
  23. 23.
    de Montigny C, Silverstone PH, Debonnel G, et al. Venlafaxine in treatment-resistant major depression: a Canadian multicenter, open-label trial. J Clin Psychopharmacol 1999; 19(5): 401–6PubMedCrossRefGoogle Scholar
  24. 24.
    Mitchell PB, Schweitzer I, Burrows G, et al. Efficacy of venlafaxine and predictors of response in a prospective open-label study of patients with treatment-resistant major depression. J Clin Psychopharmacol 2000; 20(4): 483–7PubMedCrossRefGoogle Scholar
  25. 25.
    Thase ME, Shelton RC, Khan A. Treatment with venlafaxine extended release after SSRI nonresponse or intolerance: a randomized comparison of standard-and higher-dosing strategies. J Clin Psychopharmacol 2006; 26(3): 250–8PubMedCrossRefGoogle Scholar
  26. 26.
    Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 2006; 354(12): 1231–42PubMedCrossRefGoogle Scholar
  27. 27.
    Wohlreich MM, Martinez JM, Mallinckrodt CH, et al. An open-label study of duloxetine for the treatment of major depressive disorder: comparison of switching versus initiating treatment approaches. J Clin Psychopharmacol 2005; 25(6): 552–60PubMedCrossRefGoogle Scholar
  28. 28.
    Perahia DG, Quail D, Desaiah D, et al. Switching to duloxetine from selective serotonin reuptake inhibitor antidepressants: a multicenter trial comparing 2 switching techniques. J Clin Psychiatry 2008; 69(1): 95–105PubMedCrossRefGoogle Scholar
  29. 29.
    Guo SS, Zeller C, Chumlea WC, et al. Aging, body composition, and lifestyle: the Fels longitudinal study. Am J Clin Nutr 1999; 70(3): 405–11PubMedGoogle Scholar
  30. 30.
    Hayes RD, Dennerstein L, Bennett CM, et al. Risk factors for female sexual dysfunction in the general population: exploring factors associated with low sexual function and sexual distress. J Sex Med 2008; 5(7): 1681–93PubMedCrossRefGoogle Scholar
  31. 31.
    Posternak MA, Solomon DA, Leon AC, et al. The naturalistic course of unipolar major depression in the absence of somatic therapy. J Nerv Ment Dis 2006; 194(5): 324–9PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Claudio N. Soares
    • 1
  • Michael E. Thase
    • 2
  • Anita Clayton
    • 3
  • Christine J. Guico-Pabia
    • 4
  • Kristen Focht
    • 4
  • Qin Jiang
    • 4
  • Susan G. Kornstein
    • 5
  • Phillip T. Ninan
    • 4
  • Cecelia P. Kane
    • 4
  1. 1.Mood Disorders Division, Department of Psychiatry and Behavioural NeurosciencesMcMaster UniversityHamiltonCanada
  2. 2.Department of PsychiatryUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of Psychiatry and Neurobehavioral SciencesUniversity of VirginiaCharlottesvilleUSA
  4. 4.Pfizer Inc., formerly Wyeth ResearchCollegevilleUSA
  5. 5.Department of Psychiatry and Institute for Women’s HealthVirginia Commonwealth UniversityRichmondUSA

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