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An indirect comparison of the efficacy and safety of desvenlafaxine and venlafaxine using placebo as the common comparator

Published online by Cambridge University Press:  13 August 2012

Kristina A. Coleman ,
Vanessa Y. Xavier ,
Trish L. Palmer ,
James V. Meaney ,
Libby M. Radalj  and
Louise M. Canny
Kristina A. Coleman
Affiliation:
Health Technology Analysts, Sydney, NSW, Australia
Vanessa Y. Xavier
Affiliation:
Wyeth Australia, Sydney, NSW, Australia
Trish L. Palmer
Affiliation:
Wyeth Australia, Sydney, NSW, Australia
James V. Meaney*
Affiliation:
Wyeth Australia, Sydney, NSW, Australia
Libby M. Radalj
Affiliation:
Health Technology Analysts, Sydney, NSW, Australia
Louise M. Canny
Affiliation:
Pfizer Australia and New Zealand, Sydney, NSW, Australia
*
*Address for correspondence: James Meaney, Scientific & Regulatory Affairs Director, Pfizer Australia, 17–19 Solent Circuit, Baulkham Hills NSW 2153, Australia. Telephone: 61 2 9850 8408; Fascimile: 61 2 9023 0033.(Email Jim.Meaney@pfizer.com)
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Abstract

Background

This meta-analysis compared the efficacy and safety of desvenlafaxine and venlafaxine at the Australian approved doses.

Methods

A systematic literature search was conducted to identify all placebo-controlled studies of desvenlafaxine and venlafaxine in the treatment of major depression. The pivotal outcome measure used to assess comparative efficacy was the mean change in Hamilton Rating Scale for Depression-17 score from baseline. Tolerability and safety were compared by an evaluation of reported adverse events. Standard and Bayesian methods were used to conduct the indirect comparisons.

Findings

Using a mixed model repeated measures analysis, the pooled weighted mean difference for the mean change in Hamilton Rating Scale for Depression-17 score from baseline was −2.81 (−3.72, −1.91; p < 0.001) for desvenlafaxine and −2.61 (−3.17, −2.05; p < 0.001) for venlafaxine. An indirect Bayesian analysis adjusted for baseline Hamilton Rating Scale for Depression-17 score showed no significant difference between the two treatments (weighted mean difference −0.27; −1.17, 0.65). A standard indirect comparison of any adverse events showed no significant difference between desvenlafaxine and venlafaxine (relative risk 1.01; 0.96, 1.06; p = 0.70 and risk difference −0.01; −0.05, 0.03; p = 0.59). Standard indirect comparisons of both nausea and drop-outs identified potential differences between treatments, with the risk difference analyses suggesting a trend in favor of desvenlafaxine (nausea: relative risk 0.97; 0.77, 1.22; p = 0.80/RD −0.07; −0.12, −0.01; p = 0.02; and drop-outs due to adverse events: RR 0.86; 0.58, 1.29; p = 0.48/RD −0.04; −0.08, 0.00; p = 0.06).

Conclusions

Based on the results of this meta-analysis, desvenlafaxine was shown to be non-inferior to venlafaxine in terms of efficacy, and has an advantage in terms of less nausea.

Keywords

Cyclohexanolsdepressive disorderO-desmethylvenlafaxinemajormeta-analysisvenlafaxine
Type
Original Research
Information
CNS Spectrums , Volume 17 , Issue 3 , September 2012 , pp. 131 - 141
Copyright
Copyright © Cambridge University Press 2012

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References

1.Australian Bureau of Statistics. National Survey of Mental Health and Wellbeing: Summary of Results, 2007. ABS Cat No. 4326.0. Canberra: ABS.Google Scholar
2.Mant, A, Rendle, VA, Hall, WD, et al. . Making new choices about antidepressants in Australia: the long view 1975–2002. Med J Aust. 2004; 181(7 suppl.): S21–S24.CrossRefGoogle Scholar
3.Hickie, IB, Davenport, TA, Scott, EM, et al. . Unmet need for recognition of common mental disorders in Australian general practice. Med J Aust. 2001; 175(suppl.): S18–S24.Google ScholarPubMed
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): 657–665.CrossRefGoogle ScholarPubMed
5.Preskorn, S, Patroneva, A, Silman, H, et al. . Comparison of the pharmacokinetics of venlafaxine extended release and desvenlafaxine in extensive and poor cytochrome P450 2D6 metabolizers. J Clin Psychopharmacol. 2009; 29(1): 39–43.CrossRefGoogle ScholarPubMed
6.Shams, MEE, Arneth, B, Hiemke, C, et al. . CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther. 2006; 31(5): 493–502.CrossRefGoogle ScholarPubMed
7.Hermann, M, Hendset, M, Fosaas, K, Hjerpset, M, Refsum, H. Serum concentrations of venlafaxine and its metabolites O-desmethylvenlafaxine and N-desmethylvenlafaxine in heterozygous carriers of the CYP2D6*3,*4 or*5 allele. Eur J Clin Pharmcol. 2008; 64(5): 483–487.CrossRefGoogle ScholarPubMed
8.McAlpine, DE, O'Kane, DJ, Black, JL, Mrazek, DA. Cytochrome P450 2D6 genotype variation and venlafaxine dosage. Mayo Clin Proc. 2007; 82(9): 1065–1068.CrossRefGoogle ScholarPubMed
9.Septien-Velez, L, Pitrosky, B, Padmanabhan, SK, Germain, JM, Tourian, KA. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder. Int Clin Psychopharmacol. 2007; 22(6): 338–347.CrossRefGoogle ScholarPubMed
10.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(5): 677–688.CrossRefGoogle ScholarPubMed
11.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(4): 188–197.CrossRefGoogle ScholarPubMed
12.Liebowitz, M, Manley, A, Padmanabhan, S, et al. . Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder. Curr Med Res Opin. 2008; 24(7): 1877–1890.CrossRefGoogle ScholarPubMed
13.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(5): 243–253.CrossRefGoogle Scholar
14. Pristiq® (desvenlafaxine succinate) Product Information, Wyeth Australia.Google Scholar
15.Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
16.Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. Washington, DC: American Psychiatric Association; 1987.Google Scholar
17.Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23(1): 56–62.CrossRefGoogle ScholarPubMed
18.Bucher, HC, Guyatt, GH, Griffith, LE, Walter, SD. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol. 1997; 50(6): 683–691.CrossRefGoogle ScholarPubMed
19. Spiegelhalter D, Thomas A, Best N, Lunn D. WinBUGS: User Manual, Version 2.10. Medical Research Council Biostatistics Unit, Cambridge, UK, 2005.Google Scholar
20. Data on file, Wyeth Australia. A multicentre, randomized, double-blind, placebo-controlled study of 2 fixed doses of DVS-233 SR in adult outpatients with major depressive disorder. CSR 49148, 2004.Google Scholar
21.Liebowitz, MR, 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(11): 1663–1672.CrossRefGoogle ScholarPubMed
22. Data on file, Wyeth Australia. A multicentre, randomized, double-blind, placebo-controlled, duloxetine-referenced, parallel-group study to evaluate the efficacy and safety of 2 fixed doses (50 mg, 100 mg) of desvenlafaxine sustained-release tablets in adult outpatients with major depressive disorder. Protocol 3151A1-335. CSR 70296, 2008.Google Scholar
23.Khan, A, Fabre, LF, Rudolph, R. Venlafaxine in depressed outpatients. Psychopharmacol Bull. 1991; 27(2): 141–144.Google ScholarPubMed
24.Nemeroff, CB, Thase, ME. A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed putpatients. J Psychiatr Res. 2007; 41(3–4): 351–359.CrossRefGoogle Scholar
25.Schatzberg, A, Roose, S. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Am J Geriatr Psychiatry. 2006; 14(4): 361–370.CrossRefGoogle ScholarPubMed
26.Rudolph, RL, Fabre, LF, Feighner, JP, et al. . A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry. 1998; 59(3): 116–122.CrossRefGoogle ScholarPubMed
27.Cunningham, LA. Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Ann Clin Psychiatry. 1997; 9(3): 157–164.CrossRefGoogle ScholarPubMed
28.Thase, ME. Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. J Clin Psychiatry. 1997; 58(9): 393–398.CrossRefGoogle ScholarPubMed
29.Rudolph, RL, Feiger, AD. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord. 1999; 56(2–3): 171–181.CrossRefGoogle ScholarPubMed
30. Data on file, Wyeth Australia. Double-blind, placebo-controlled study of venlafaxine-ER and venlafaxine-OROS in outpatients with major depression. Protocol 0600C-217-US. CSR 45150, 2002.Google Scholar
31.Schweizer, E, Feighner, J, Mandos, LA, Rickels, K. Comparison of venlafaxine and imipramine in the acute treatment of major depression in outpatients. J Clin Psychiatry. 1994; 55(3): 104–108.Google ScholarPubMed
32.Cunningham, LA, Borison, RL, Carman, JS, et al. . A comparison of venlafaxine, trazodone, and placebo in major depression. J Clin Psychopharmacol. 1994; 14(2): 99–106.CrossRefGoogle ScholarPubMed
33. Data on file, Wyeth Australia. Randomized, double-blind comparison of venlafaxine (WY 45030), imipramine and placebo capsules in outpatients with major depression. Protocol 0600A-303-US. GMR 20448, 1991.Google Scholar
34. Data on file, Wyeth Australia. A multicentre, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of DVS-233 SR and venlafaxine ER in adult outpatients with major depressive disorder. Protocol 3151A1-309, 2007.Google Scholar
35.Mendels, J, Johnston, R, Mattes, J, Riesenberg, R. Efficacy and safety of b.i.d. doses of venlafaxine in a dose-response study. Psychopharmacol Bull. 1993; 29(2): 169–174.Google Scholar
36. Data on file, Wyeth Australia. A multicentre, randomized, double-blind, placebo-controlled, parallel-group, flexible-dose study of DVS-233 SR and venlafaxine ER in adult outpatients with major depressive disorder. Protocol 3151A1-317, 2007.Google Scholar
37. Data on file, Wyeth Australia. A double-blind, placebo-controlled, parallel-group dosage comparison study of BID and TID dosing of venlafaxine in outpatients with major depression. Protocol 0600A1-341-US. CSR 42676, 2001.Google Scholar
38.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. J Clin Psychopharmacol. 1998; 18(1): 19–25.CrossRefGoogle ScholarPubMed
39.Lecrubier, Y, Bourin, M, Moon, CAL, et al. . Efficacy of venlafaxine in depressive illness in general practice. Acta Psychiatr Scand. 1997; 95(6): 485–493.CrossRefGoogle ScholarPubMed
40.Silverstone, PH, Ravindran, A. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. J Clin Psychiatry. 1999; 60(1): 22–28.CrossRefGoogle ScholarPubMed
41. Salinas E. Once-daily venlafaxine XR vs. paroxetine in outpatients with major depression. Presented at the 11th European College of Neuropsychopharmacology Congress Paris, France, October 31–November 4, 1998.CrossRefGoogle Scholar
42. Data on file, Wyeth Australia. A double-blind, placebo-controlled comparative efficacy study of venlafaxine ER and sertraline in producing remission in outpatients with major depressive disorder. Protocol 0600B1-402-US. CSR 48579, 1999.Google Scholar
43.Troy, SM, Dilea, C, Martin, PT, et al. . Pharmacokinetics of once-daily venlafaxine extended release in healthy volunteers. Current Therapeutic Research. 1997; 58(8): 504–514.CrossRefGoogle Scholar
44.Deecher, DC, Beyer, CE, Johnston, G, et al. . Desvenlafaxine succinate: a new serotonin and norepinephrine reuptake inhibitor. J Pharmacol Exp Ther. 2006; 318(2): 657–665.CrossRefGoogle ScholarPubMed
45.Caraco, Y. Genes and the response to drugs. N Engl J Med. 2004; 351(27): 2867–2869.CrossRefGoogle ScholarPubMed
46.Siddiqui, O, Hung, HM, O'Neill, R. MMRM vs LOCF: a comprehensive comparison based on simulation study and 25 NDA datasets. J Biopharm Stat. 2009; 19(2): 227–246.CrossRefGoogle ScholarPubMed
47.Song, F, Altman, DG, Glenny, A-M, Deeks, JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ. 2003; 326(7387): 472.CrossRefGoogle ScholarPubMed
48.Perahia, DG, Pritchett, YL, Kajdasz, DK, et al. . A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. J Psychiatr Res. 2008; 42(1): 22–34.CrossRefGoogle ScholarPubMed
49.Lee, P, Shu, L, Xu, X, et al. . Once-daily duloxetine 60 mg in the treatment of major depressive disorder: multicenter, double-blind, randomized, paroxetine-controlled, non-inferiority trial in China, Korea, Taiwan and Brazil. Psychiatry and Clinical Neurosciences. 2007; 61(3): 295–307.CrossRefGoogle Scholar
50.Szegedi, A, Kohnen, R, Dienel, A, Kieser, M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ. 2005; 330(7490): 503–507.CrossRefGoogle ScholarPubMed
51.Kirsch, I, Deacon, BJ, Huedo-Medina, TB, et al. . Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med. 2008; 5(2): e45.CrossRefGoogle ScholarPubMed