The efficacy profile of vilazodone, a novel antidepressant for the treatment of major depressive disorder

Abstract

Objective:

Vilazodone is a novel serotonin reuptake inhibitor and serotonin 1A receptor partial agonist approved for the treatment of major depressive disorder (MDD). This evaluation presents side-by-side efficacy data from two randomized, double-blind, placebo-controlled, short-term 8-week trials (referred to as randomized controlled trial [RCT]-1 [N = 410] and RCT-2 [N = 481]); efficacy data for demographic and clinical subgroups (derived from pooled RCT data); and effectiveness data from a 52-week, open-label, long-term study (N = 616). The objective is to summarize the efficacy profile of vilazodone at its approved dose of 40 mg/day.

Methods:

The main assessment in individual pivotal trials and pooled subgroup analyses was the change from baseline to end of treatment (EOT, 8 weeks) in the Montgomery–Åsberg Depression Rating Scale (MADRS) total score. Mixed-effects repeated-measures analyses were conducted in the placebo-controlled trials. Effectiveness analyses in the long-term study included mean MADRS score change over time.

Results:

Vilazodone-treated patients in both short-term studies showed greater improvement from baseline to EOT in mean MADRS scores than placebo-treated patients (least-squares mean [LSM] treatment difference: −3.2 [p = 0.001], RCT-1; −2.5 [p = 0.009], RCT-2). Clinical Global Impressions–Improvement mean scores at EOT reflected greater improvement with vilazodone compared with placebo in both studies (LSM treatment difference: −0.4 [p = 0.001], RCT-1; −0.3 [p = 0.004], RCT-2). MADRS response rates were significantly greater among patients receiving vilazodone versus those receiving placebo (RCT-1: 40.4% versus 28.1%, respectively [p = 0.007]; RCT-2: 43.7% versus 30.3%, respectively [p = 0.002]). The greater efficacy of vilazodone versus placebo was consistent for the majority of demographic and MDD characteristic subgroups. In the long-term study, the mean MADRS score improved from 29.9 (baseline) to 11.4 (week 8), 8.2 (week 24), and 7.1 (week 52).

Conclusion:

Vilazodone 40 mg/day resulted in clinically meaningful, statistically significant improvement in MDD symptoms in two placebo-controlled, 8-week studies. Findings are supported by subgroup analysis and open-label, long-term effectiveness data.

Trial registration:

Trial registration: ClinicalTrials.gov identifier: NCT00285376.

Trial registration: ClinicalTrials.gov identifier: NCT00683592.

Trial registration: ClinicalTrials.gov identifier: NCT00644358.

Key words::

• Antidepressant
• Depression
• Efficacy
• Major depressive disorder
• Vilazodone

Transparency

Declaration of funding

The development of this paper was supported by funding from Forest Laboratories, Inc. Study investigators received a patient grant from PGxHealth, LLC, for the studies reported in this paper.

Declaration of financial/other relationships

D.K.K. and H.W. have disclosed that they are full-time employees of Forest Laboratories, Inc. C.R.R. and S.G. are former employees of Forest Laboratories, Inc. M.E.T. is a consultant to Forest Laboratories, Inc. He also reports the following other relationships: advisor/consultant for Aldolor, Alkermes, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Dey Pharma, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Inc., Merck and Co., Inc., Neuronetics, Inc., Novartis, Otsuka, Ortho-McNeil Pharmaceuticals, Pamlab, LLC, Pfizer (formerly Wyeth Ayerst Pharmaceuticals), Pharmaneuroboost, Rexahn, Schering-Plough, Shire US Inc., Supernus Pharmaceuticals, Takeda, and Transcept Pharmaceuticals; grant support from Agency for Healthcare Research and Quality, Eli Lilly, Forest, GlaxoSmithKline, National Institute of Mental Health, Otsuka, PamLab, Rexahn; honoraria for talks from AstraZeneca, Bristol-Myers Squibb, Dey, Eli Lilly, Merck and Co., Inc., Pfizer (formerly Wyeth Ayerst Pharmaceuticals); equity holdings of MedAvante, Inc.; royalties received from American Psychiatric Publishing, Guilford Publications, Herald House, and W.W. Norton & Company, Inc. At the time the studies were conducted, M.C.A. was an employee of Dogwood Pharmaceuticals.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank the following investigators for study NCT00285376 (RCT-1): Robert Bielski, MD (Summit Research Network, Farmington Hills, MI, USA), Arif Khan, MD (Northwest Clinical Research Center, Bellevue, WA, USA), R. Bruce Lydiard, MD (Ralph H. Johnson VA Medical Center, Charleston, SC, USA), Nader Oskooilar, MD (Pharmacology Research Institute, Newport Beach, CA, USA), Frederick Reimherr, MD (University of Utah Health Sciences Center, Salt Lake City, UT, USA), Karl Rickels, MD (University of Pennsylvania Department of Psychiatry, Philadelphia, PA, USA), Angelo Sambunaris, MD (Atlanta Institute of Medicine & Research, Atlanta, GA, USA), Ward T. Smith, MD (Summit Research Network, Portland, OR, USA), Jerry C. Steiert, MD (Summit Research Network, Seattle, WA, USA), Nick Vatakis, MD (Social Psychiatry Research Institute, Brooklyn, NY, USA).

The authors thank the following investigators for study NCT00683592 (RCT-2): Andrew Cutler, MD (Florida Clinical Research Center, Bradenton, FL, USA), Arif Khan, MD (Northwest Clinical Research Center, Bellevue, WA, USA), Nader Oskooilar, MD (Pharmacology Research Institute, Newport Beach, CA, USA), Fred Reimherr, MD (University of Utah Health Sciences Center, Salt Lake City, UT, USA), Karl Rickels, MD (University of Pennsylvania, Philadelphia, PA, USA), Angelo Sambunaris, MD (Atlanta Institute of Medicine & Research, Atlanta, GA, USA), Ward Smith, MD (Summit Research Network, Portland, OR, USA), Jerry Steiert, MD (Summit Research Network, Seattle, WA, USA), Madhukar Trivedi, MD (Mood Disorders Research Program and Clinic Exchange Park, Dallas, TX, USA).

The authors also thank the investigators for study NCT00644358 (long-term safety study): Ai-Li Arias, MD (Upland, CA, USA), Bijan Bastani, MD (Beachwood, OH, USA), Thomas Bonacorsi, MD (Pittsburgh, PA, USA), John Carman, MD (Smyrna, GA, USA), Harry Croft, MD (San Antonio, TX, USA), Patricia Daly, MD (Woodstock, VT, USA), Michael DePriest, MD (Las Vegas, NV, USA), Dolores DiGaetano, MD (Memphis, TN, USA), Michael Downing, MD (Dallas, TX, USA), Neil Dubin, MD (Cincinnati, OH, USA), Anne Fedyszen, MD (Midlothian, VA, USA), Donald Garcia, DO (Austin, TX, USA), Armen Goenjian, MD (Torrance, CA, USA), Michael Greenbaum, MD (Libertyville, IL, USA), Linda Harper, MD (Orlando, FL, USA), Shivkumar Hatti, MD (Media, PA, USA), John Mark Joyce, MD (Jacksonville, FL, USA), Ethan Kass, DO (Coral Springs, FL, USA), Debra Kelsh, MD (Overland Park, KS, USA), Richard Knapp, DO (Lady Lake, FL, USA), David Krakow, MD (Mt. Kisco, NY, USA), Michael Liebowitz, MD (New York, NY, USA), Charles Merideth, MD (San Diego, CA, USA), Kevin Miller, MD (St. Louis, MO, USA), P. Ryan Moe, MD (Indianapolis, IN, USA), Leslie Moldauer, MD (Denver, CO, USA), Rajendra Nigam, MD (Bridgeville, PA, USA), Angela Pinheiro, MD (Okemos, MI, USA), Brett Plyler, MD (Chicago, IL, USA), John Prater, DO (Fort Myers, FL, USA), Norman Rosenthal, MD (Rockville, MD, USA), Elias Sarkis, MD (Gainesville, FL, USA), Keith Saylor, PhD (Herndon, VA, USA), Williard Shanken, MD (Colmar, PA, USA), Ram Shrivastava, MD (New York, NY, USA), Mary Stedman, MD (Tampa, FL, USA), Louise Thurman, MD (Oklahoma City, OK, USA), David Walling, PhD (Garden Grove, CA, USA), Marc Mark Woyshville, MD (Middleburg Heights, OH, USA).

The authors acknowledge the writing and editorial assistance provided by Nicholas C. Stilwell, PhD, a former employee of ApotheCom (supported by funding from Dogwood Pharmaceuticals, a subsidiary of Forest Laboratories, Inc.), in the development and submission of this manuscript.

Previous presentation: the data in this paper were presented at the 23rd Annual US Psychiatric and Mental Health Congress, November 18–21, 2010, Orlando, FL. Portions of this paper were also presented in the following publications: Rickels K, Athanasiou M, Robinson DS, et al. Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2009;70:326-33; Khan A, Cutler AJ, Kajdasz DK, et al. Efficacy and tolerability of vilazodone, a dual-acting serotonergic antidepressant, in the treatment of patients with major depressive disorder (MDD). J Clin Psychiatry 2011; 31(5):643-646. Robinson DS, Kajdasz DK, Gallipoli S, et al. A 1-year open-label study assessing the safety and tolerability of vilazodone in patients with major depressive disorder. J Clin Psychopharmacol 2011 Aug 24 [Epub ahead of print].