Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-22T13:20:28.908Z Has data issue: false hasContentIssue false
  • English
  • Français

An Integrated Analysis of the Efficacy of Desvenlafaxine Compared with Placebo in Patients with Major Depressive Disorder

Published online by Cambridge University Press:  07 November 2014

Michael E. Thase ,
Susan G. Kornstein ,
Jean-Michel Germain ,
Qin Jiang ,
Christine Guico-Pabia  and
Philip T. Ninan
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction: To assess the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) in outpatients with major depressive disorder.

Methods: A meta-analysis of individual patient data was performed on the complete set of registration trials (nine randomized, double-blind, placebo-controlled 8-week studies) of desvenlafaxine. Patients received fixed (50, 100, 200, or 400 mg/day; n = 1,342) or flexible doses (100–400 mg/day; n = 463) of desvenlafaxine or placebo (n = 1,108). The primary efficacy variable was the 17-item Hamilton Rating Scale for Depression (HAM-D17); the primary intent to treat analyses used the last-observation-carried-forward method.

Results: Significantly greater improvement with desvenlafaxine versus placebo on the HAM-D17 total score was observed for the full data set (difference in adjusted means: −1.9; P<.001), each fixed-dose group (all P<.001), and the flexible-dose group (P=.024). Overall rates of HAM-D17 response (≥50% decrease from baseline score: 53% vs 41%) and remission (HAM-D17 ≤7: 32% vs 23%) were significantly greater for desvenlafaxine versus placebo (all P<.001). Discontinuation rates due to adverse events increased with dose (4% to 18%; placebo: 3%).

Conclusion: Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed.

Type
Original Research
Information
CNS Spectrums , Volume 14 , Issue 3 , March 2009 , pp. 144 - 154
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Pristiq [package insert]. Philadelphia, Penn: Wyeth Pharmaceuticals; 2008.Google Scholar
2.Deecher, DC, Beyer, CE, Johnston, G, et al.Desvenlafaxine succinate: a new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther. 2006;318:657–665.Google Scholar
3.Bymaster, FP, Dreshfield-Ahmad, LJ, Threlkeld, PG, et al.Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001;25:871–880.CrossRefGoogle ScholarPubMed
4. Effexor XR [package insert]. Philadelphia, Penn: Wyeth Pharmaceuticals Inc.; 2008.Google Scholar
5.Liebowitz, M, Yeung, PP, Entsuah, R. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder. J Clin Psychiatry. 2007;68:1663–1672.Google Scholar
6.Lieberman, DZ, Montgomery, SA, Tourian, KA, et al.A pooled analysis of two placebo-controlled trials of desvenlafaxine in major depressive disorder. Int Clin Psychopharmacol. 2008;23:188–197.Google Scholar
7.Feiger, AD, Tourian, KA, Rosas, GR, Padmanabhan, SK. A placebo-controlled study evaluating the efficacy and safety of flexible-dose desvenlafaxine treatment in outpatients with major depressive disorder. CNS Spectr. 2009;14:41–50.Google Scholar
8.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.Google Scholar
9.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.Google Scholar
10.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.Google Scholar
11.Boyer, P, Montgomery, S, Lepola, U, et al.Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo-controlled trial. Int Clin Psychopharmacol. 2008;23:243–253.Google Scholar
12.Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.CrossRefGoogle ScholarPubMed
13.Montgomery, SA, Åsberg, M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–389.CrossRefGoogle ScholarPubMed
14.Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
15.Guy, W. Clinical Global Impressions. ECDEU Assessment Manual for Psychopharmacology. Rockville, Md: US Department of Health, Education, and Welfare; 1976:217–22. Publication ADM 76-338.Google Scholar
16.Lipman, RS. Differentiating anxiety and depression in anxiety disorders: use of rating scales. Psychopharmacol Bull. 1982;18:69–77.Google Scholar
17.Raskin, A, Schulterbrandt, J, Reatig, N, McKeon, JJ. Replication of factors of psychopathology in interview, ward behavior and self-report ratings of hospitalized depressives. J Nerv Ment Dis. 1969;148:87–98.Google Scholar
18.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):22–33.Google Scholar
19.Bech, P, Gram, LF, Dein, E, Jacobsen, O, Vitger, J, Bolwig, TG. Quantitative rating of depressive states. Acta Psychiatr Scand. 1975;51:161–170.Google Scholar
20.Lane, P, Handling drop-out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches. Pharm Stat. 2008;7:93–106.CrossRefGoogle ScholarPubMed
21.Mallinckrodt, CH, Clark, WS, David, SR. Accounting for dropout bias using mixed-effects models. J Biopharm Stat. 2001;11:9–21.Google Scholar
22.Cohen, J. A power primer. Psychol Bull. 1992;112:155–159.CrossRefGoogle ScholarPubMed
23.Turner, EH, Matthews, AM, Linardatos, E, Tell, RA, Rosenthal, R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358:252–260.Google Scholar
24.Rudolph, RL, Fabre, LF, Feighner, JP, Rickels, K, Entsuah, R, Derivan, AT. A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry. 1998;59:116–122.Google Scholar
25.Khan, A, Upton, GV, Rudolph, RL, Entsuah, R, Leventer, SM. The use of venlafaxine in the treatment of major depression and major depression associated with anxiety: a dose-response study. Venlafaxine Investigator Study Group. J Clin Psychopharmacol. 1998;18:19–25.CrossRefGoogle ScholarPubMed
26.Preskorn, SH. Flat dose-response curves for efficacy: what do they mean to the clinician? J Psychiatr Pract. 2008;14:232–236.Google Scholar
27.Khan, A, Khan, SR, Walens, G, Kolts, R, Giller, EL. Frequency of positive studies among fixed and flexible dose antidepressant clinical trials: an analysis of the food and drug administration summary basis of approval reports. Neuropsychopharmacology. 2003;28:552–557.Google Scholar
28.Kelsey, JE. Dose-response relationship with venlafaxine. J Clin Psychopharmacol. 1996;16(3 suppl 2):21S–26S.CrossRefGoogle ScholarPubMed
29.Bech, P, Kajdasz, DK, Porsdal, V. Dose-response relationship of duloxetine in placebo-controlled clinical trials in patients with major depressive disorder. Psychopharmacology (Berl). 2006;188:273–280.CrossRefGoogle ScholarPubMed
30.Pritchett, YL, Marciniak, MD, Corey-Lisle, PK, Berzon, RA, Desaiah, D, Detke, MJ. Use of effect size to determine optimal dose of duloxetine in major depressive disorder. J Psychiatr Res. 2007;41:311–318.Google Scholar
31.Kornstein, S. Maintenance therapy to prevent recurrence of depression: summary and implications of the PREVENT study. Expert Rev Neurother. 2008;8:737–742.Google Scholar
32.Wernicke, JF, Gahimer, J, Yalcin, I, Wulster-Radcliffe, M, Viktrup, L. Safety and adverse event profile of duloxetine. Expert Opin Drug Saf. 2005;4:987–993.CrossRefGoogle ScholarPubMed
33.Mucci, M. Reboxetine: a review of antidepressant tolerability. J Psychopharmacol. 1997;11(4 suppl):33–37.Google Scholar
34.Tanum, L. Reboxetine tolerability and safety profile in patients with major depression. Acta Psychiatr Scand. 2000;101(suppl 402):37–40.CrossRefGoogle Scholar