Open-Label Treatment with Desvenlafaxine in Postmenopausal Women with Major Depressive Disorder Not Responding to Acute Treatment with Desvenlafaxine or Escitalopram
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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.
- Pinto-Meza, A, Usall, J, Serrano-Blanco, A (2006) Gender differences in response to antidepressant treatment prescribed in primary care: does menopause make a difference. J Affect Disord 93: pp. 53-60 CrossRef
- Thase, ME, Entsuah, R, Cantillon, M (2005) Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health 14: pp. 609-16 CrossRef
- Grigoriadis, S, Kennedy, SH, Bagby, RM (2003) A comparison of antidepressant response in younger and older women. J Clin Psychopharmacol 23: pp. 405-7 CrossRef
- Deecher, DC, Beyer, CE, Johnston, G (2006) Desvenlafaxine succinate: a new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther 318: pp. 657-65 CrossRef
- Pristiq® (desvenlafaxine) [package insert]. Philadelphia (PA): Wyeth Pharmaceuticals Inc., 2008
- Riederer, P, Brucke, T, Buhmann, C (2000) Workshop II: “neuroprotection”. The Lugano consensus. J Neurol 247: pp. IV/36-7
- Kornstein, SG, Young, EA, Harvey, AT (2010) The influence of menopause status and postmenopausal use of hormone therapy on presentation of major depression in women. Menopause 17: pp. 828-39 CrossRef
- Soares, CN, Thase, ME, Clayton, A (2010) Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder. Menopause 17: pp. 700-11
- Hamilton, M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23: pp. 56-62 CrossRef
- Sheehan, DV, Lecrubier, Y, Sheehan, KH (1998) 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 20: pp. 22-33
- Benagiano, G, Primiero, FM (2003) Seventy-five microgram desogestrel minipill, a new perspective in estrogen-free contraception. Ann N Y Acad Sci 997: pp. 163-73 CrossRef
- Montgomery, SA, Asberg, M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134: pp. 382-9 CrossRef
- Guy, W Clinical global impressions. In: Rush, JA, Pincus, HA, First, MB eds. (1976) ECDEU assessment manual for psychopharmacology. US Department of Health, Education, and Welfare, Rockville (MD), pp. 217-22
- Katon, W, Von, KM, Lin, E (1997) Population-based care of depression: effective disease management strategies to decrease prevalence. Gen Hosp Psychiatry 19: pp. 169-78 CrossRef
- Hamilton, MM (1959) The assessment of anxiety states by rating. Br J Med Psychol 32: pp. 50-5 CrossRef
- Rush, AJ, Trivedi, MH, Ibrahim, HM (2003) 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 54: pp. 573-83 CrossRef
- DeLoach, LJ, Higgins, MS, Caplan, AB (1998) The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg 86: pp. 102-6
- Clayton, AH, McGarvey, EL, Clavet, GJ (1997) The Changes in Sexual Functioning Questionnaire (CSFQ): development, reliability, and validity. Psychopharmacol Bull 33: pp. 731-45
- The EuroQol Group. Health Policy 16: pp. 199-208 CrossRef
- Heinemann, K, Ruebig, A, Potthoff, P (2004) The Menopause Rating Scale (MRS) scale: a methodological review [abstract]. Health Qual Life Outcomes 2: pp. 45 CrossRef
- Sheehan, DV Sheehan disability scale. In: Rush, AJ, Pincus, HA, First, MB eds. (2000) Handbook of psychiatric measures. American Psychiatric Association, Washington, DC, pp. 113-5
- Romera, I, Montejo, AL, Delgado-Cohen, H (2009) Switching to duloxetine from selective serotonin reuptake inhibitors in non-or partial responders: results from a Spanish sample. Int J Psychiatry Clin Pract 13: pp. 100-8 CrossRef
- Montigny, C, Silverstone, PH, Debonnel, G (1999) Venlafaxine in treatment-resistant major depression: a Canadian multicenter, open-label trial. J Clin Psychopharmacol 19: pp. 401-6 CrossRef
- Mitchell, PB, Schweitzer, I, Burrows, G (2000) Efficacy of venlafaxine and predictors of response in a prospective open-label study of patients with treatment-resistant major depression. J Clin Psychopharmacol 20: pp. 483-7 CrossRef
- Thase, ME, Shelton, RC, Khan, A (2006) Treatment with venlafaxine extended release after SSRI nonresponse or intolerance: a randomized comparison of standard-and higher-dosing strategies. J Clin Psychopharmacol 26: pp. 250-8 CrossRef
- Rush, AJ, Trivedi, MH, Wisniewski, SR (2006) Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 354: pp. 1231-42 CrossRef
- Wohlreich, MM, Martinez, JM, Mallinckrodt, CH (2005) An open-label study of duloxetine for the treatment of major depressive disorder: comparison of switching versus initiating treatment approaches. J Clin Psychopharmacol 25: pp. 552-60 CrossRef
- Perahia, DG, Quail, D, Desaiah, D (2008) Switching to duloxetine from selective serotonin reuptake inhibitor antidepressants: a multicenter trial comparing 2 switching techniques. J Clin Psychiatry 69: pp. 95-105 CrossRef
- Guo, SS, Zeller, C, Chumlea, WC (1999) Aging, body composition, and lifestyle: the Fels longitudinal study. Am J Clin Nutr 70: pp. 405-11
- Hayes, RD, Dennerstein, L, Bennett, CM (2008) Risk factors for female sexual dysfunction in the general population: exploring factors associated with low sexual function and sexual distress. J Sex Med 5: pp. 1681-93 CrossRef
- Posternak, MA, Solomon, DA, Leon, AC (2006) The naturalistic course of unipolar major depression in the absence of somatic therapy. J Nerv Ment Dis 194: pp. 324-9 CrossRef
- Open-Label Treatment with Desvenlafaxine in Postmenopausal Women with Major Depressive Disorder Not Responding to Acute Treatment with Desvenlafaxine or Escitalopram
Volume 25, Issue 3 , pp 227-238
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- 1. Mood Disorders Division, Department of Psychiatry and Behavioural Neurosciences, McMaster University, 301 James St. South, FB 638, Hamilton, Ontario, L8P 3B6, Canada
- 2. Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
- 3. Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia, USA
- 4. Pfizer Inc., formerly Wyeth Research, Collegeville, Pennsylvania, USA
- 5. Department of Psychiatry and Institute for Women’s Health, Virginia Commonwealth University, Richmond, Virginia, USA