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Abstract

Spanish

French

Objective:

To evaluate the clinical literature on and potential clinical role of vilazodone for the treatment of major depressive disorder.

Data Sources:

Searches were conducted on MEDLINE (1948-February 2011), Iowa Drug Information Service (1988-February 2011), EBSCO Academic Search Premier (1975-February 2011), Google Scholar (1992-February 2011), PsycINFO (1980-February 2011), and PsycARTICLES (1985-February 2011), and on general Internet search engines including Google and Bing (no lower limit-February 2011). Search terms were vilazodone, EMD 68843, depression, and major depressive disorder. Potential prior marketers of vilazodone, including Merck KGaA in Germany and Genaissance Pharmaceuticals, were contacted for any available unpublished Phase 1, Phase 2, Phase 3 studies, or preclinical information.

Study Selection and Data Extraction:

All applicable full-text English-language articles, abstracts, and professional poster presentations found were evaluated and included in the review, as well as marketing and Securities and Exchange Commission filings available from the patent holders.

Data Synthesis:

Vilazodone is an antidepressant recently approved by the Food and Drug Administration (FDA) that is first in a new class regarding mechanism of action. It has demonstrated efficacy in the primary outcome of the Montgomery-Asberg Depression Rating Scale (MADRS) response in an 8-week pivotal Phase 3 trial. Phase 2 trials did not demonstrate efficacy for primary outcomes of the 17-item Hamilton Rating Scale for Depression but showed statistically significant improvements in select secondary outcomes such as Clinical Global Impressions severity and MADRS. Long-term efficacy data are still forthcoming. An emerging aspect to vilazodone's development has been the identification and assessment of potential genetic biomarkers associated with both therapeutic response and more serious adverse effects. Initial studies into biomarkers have been inconclusive.

Conclusions:

Vilazodone is a new agent recently approved by the FDA for treating major depressive disorder. Response rates seen with vilazodone are similar to those of currently available antidepressants.

Keywords

depression EMD 68843 major depressive disorder vilazodone

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References

Strine

, Mokdad

, Balluz

. Depression and anxiety in the United States: findings from the 2006 behavioral risk factor surveillance system. Psychiatr Serv 2008; 59:1383–90.

Kessler

, Berglund

, Demler

, Jin

, Kortez

, Merikkangas

. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication. JAMA 2003; 289:3095–105.

Perovic

, Jovanovic

, Miljkovic

, Vezmar

. Getting the balance right: established and emerging therapies for major depressive disorders. Neuropsychiatr Dis Treat 2010; 6:343–64.

Israel

. Remission in depression: definition and initial treatment approaches. J Psychopharmacol 2006; 20:5–10.

Zimmerman

, Chelminski

, Posternak

. A review of studies of the Montgomery-Asberg Depression Rating Scale in controls: implications for the definition of remission in treatment studies of depression. Int Clin Psychopharmacol 2004; 19:1–7.

Nierenberg

, Wright

. Evolution of remission as the new standard in the treatment of depression. J Clin Psychiatry 1999; 60(S22):7–11.

Prien

, Carpenter

, Kupfer

. The definition and operational criteria for treatment outcome of major depressive disorder: a review of the current research literature. Arch Gen Psychiatry 1991; 48:796–800.

Hawley

, Gale

, Sivakumaran

. Defining remission by cut off score on the MADRS: selecting the optimal value. J Affect Disord 2002; 72:177–84.

Zimmerman

, McGlinchey

, Michael

, Freidman

, Attiullah

. How should remission from depression be defined? The depressed patient's perspective. Am J Psychiatry 2006; 163:148–50.

10.

Thase

, Entsuah

, Rudolph

. Remission rates during treatment with venlafaxine or selective serotonin reuptake inhibitors. Br J Psychiatry 2001; 178:234–41.

11.

Keller

, McCollough

, Klein

. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000; 342:1462–70.

12.

Rush

, Trivedi

, Wisniewski

. Buproprion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med 2006; 354:1231–42.

13.

Mallinckrodt

, Goldstein

, Detke

, Lu

, Watkin

, Tran

. Duloxetine: a new treatment for the emotional and physical symptoms of depression. J Clin Psychiatry 2003; 5:19–28.

14.

Gelenberg

, Freeman

, Markowitz

. Practice guideline for the treatment of patients with major depressive disorder. November 2010. www.psychiatryonline.com/pracGuide/pracGuideChapToc_7.aspx (accessed 2011 Jan 8).

15.

Form 8-K: Clinical Data, Inc., report no. 000-12716. Washington, DC: Securities and Exchange Commission, 2011.

16.

Khan

. Vilazodone, a novel duel-acting serotonergic antidepressant for managing major depression. Exp Opin Investig Drugs 2009; 18:1753–64.

17.

Rickels

, Athanasiou

, Reed

. Vilazodone, a novel, duel-acting antidepressant: current status, future promise and potential for individualized treatment of depression. Per Med 2009; 6:217–24.

18.

Roberts

, Hagan

, Bartoszyk

, Kew

. Effect of vilazodone on 5-HT efflux and re-uptake in the guinea-pig dorsal raphe nucleus. Eur J Pharmacol 2005; 517:59–63.

19.

Hughes

, Starr

, Langmead

. Neurochemical evaluation of the novel 5-HT_1A receptor partial agonist/serotonin reuptake inhibitor, vilazodone. Eur J Pharmacol 2005; 510:49–57.

20.

Bartoszyk

, Hegenbart

, Ziegler

. EMD 68843. a serotonin reuptake inhibitor with selective presynaptic 5-HT_1A receptor agonistic properties. Eur J Pharmacol 1997; 322:147–53.

21.

Page

, Cryan

, Sullivan

. Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther 2002; 302:1220–7.

22.

Celada

, Puig

, Amargos-Bosch

, Adell

, Artigas

. The therapeutic role of 5-HT_1A and 5-HT_2A receptors in depression. J Psychiatry Neurosci 2004; 29:252–65.

23.

Dawson

, Watson

. Vilazodone: a 5-HT_1A receptor agonist/serotonin transporter inhibitor for the treatment of affective disorders. CNS Neurosci Ther 2009; 15:107–17.

24.

Product information. Viibryd (vilazodone). New Haven, CT: Trovis Pharmaceuticals, LLC, January 2011.

25.

Rickels

, Athanasiou

, Robinson

, Gibertini

, Whalen

, Reed

. Evidence for efficacy and tolerability of vilazadone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2009; 70:326–33.

26.

Khan

, Khan

, Walens

. 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. Neuropsychopharmacol 2003; 28:552–7.

27.

Storosum

, Elferink

, van Zwieten

. Natural course and placebo response in short-term, placebo-controlled studies in major depression: a meta-analysis of published and non-published studies. Pharmacopsychiatry 2004; 37:32–6.

28.

Kennedy

, Anderson

, Lam

. Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis. J Psychiatry Neurosci 2006; 31:122–31.

29.

National Institutes of Health. A one year open label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. www.clinicaltrials.gov/ct2/show/NCT00644358?term=vilazodone&rank=1 (accessed 2010 Nov 22).

30.

Robinson

, Kajdasz

, Gallipoli

, Whalen

, Wamil

. A 1-year open label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. Presented at: 163rd Annual Meeting of the American Psychiatric Association, New Orleans, LA, May 22-26, 2010.

31.

National Institutes of Health. Effectiveness study of vilazodone to treat depression and to discover genetic markers associated with response. http://www.clinicaltrials.gov/ct2/show/NCT00644358?term=vilazodone&rank=3 (accessed 2010 Nov 22).

32.

National Institutes of Health. Safety and efficacy study of vilazodone and discovering genetic markers associated with response in patients with major depressive disorder. www.clinicaltrials.gov/ct2/show/NCT00644358?term=vilazodone&rank=2 (accessed 2010 Nov 22).

33.

Ray

. Clinical data to submit vilazodone NDA without PGx marker; reports 11 percent revenue growth in q3. Pharmacogenomics reporter. www.genomeweb.com/dxpgx/clinical-data-submit-vilazodone-nda-with-out-pgx-marker-reports-11-percent-revenu (accessed 2011 Feb 6).

34.

Clayton

, Montejo

. Major depressive disorder, antidepressants, and sexual dysfunction. J Clin Psychiatry 2006; 67(S6):33–7.

35.

Clayton

, Pradko

, Croft

. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002; 63:357–66.

36.

Murck

, Frieboes

, Antonijevic

, Steiger

. Distinct temporal pattern of the effects of the combined serotonin-reuptake inhibitor and 5-HT_1A agonist EMD 68843 on the sleep EEG in healthy men. Psychopharmacol 2001; 155:187–92.

37.

Morganroth

, Thorn

, Gallipoli

, Sperry

. An evaluation of the effect of vilazodone on cardiac safety. Presented at: American Society of Health-System Pharmacy Midyear Clinical Meeting and Exhibition, Anaheim, CA, Dec 5-9, 2010.

38.

Nassar

, Hollenberg

, Scatina

, eds. Drug metabolism handbook: concepts and applications. Hoboken, NJ: John Wiley and Sons, 2009.

Vilazodone for the Treatment of Depression