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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
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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

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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