Safety and Efficacy of Vilazodone in Major Depressive Disorder (VLZ-MD-01)

A Double-blind, Placebo- and Active-controlled, Fixed-dose Study of Vilazodone in Patients With Major Depressive Disorder

The purpose of this study was to evaluate the efficacy, safety, and tolerability of 2 fixed dose levels of vilazodone compared to placebo in patients with major depressive disorder.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo to citalopram; Drug: Placebo to vilazodone; Drug: Vilazodone; Drug: Citalopram

• Study Type: Interventional
• Enrollment (Actual): 1162
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Forest Investigative Site 036
    • Dothan, Alabama, United States, 36303
      • Forest Investigative Site 016
  • Arizona
    • Scottsdale, Arizona, United States, 85254
      • Forest Investigative Site 033
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Forest Investigative Site 027
  • California
    • Cerritos, California, United States, 90703
      • Forest Investigative Site 029
    • Costa Mesa, California, United States, 92626
      • Forest Investigative Site 002
    • Murrieta, California, United States, 92562
      • Forest Investigative Site 019
    • Oceanside, California, United States, 90703
      • Forest Investigative Site 025
    • Orange, California, United States, 92868
      • Forest Investigative Site 043
    • Redlands, California, United States, 92374
      • Forest Investigative Site 003
    • Sherman Oaks, California, United States, 33026
      • Forest Investigative Site 046
    • Upland, California, United States, 91786
      • Forest Investigative Site 057
  • Connecticut
    • Cromwell, Connecticut, United States, 06416
      • Forest Investigative Site 034
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Forest Investigative Site 038
    • Gainsville, Florida, United States, 32607
      • Forest Investigative Site 018
    • Hallandale Beach, Florida, United States, 33003
      • Forest Investigative Site 055
    • Jacksonville, Florida, United States, 32256
      • Forest Investigative Site 063
    • Miami, Florida, United States, 33134
      • Forest Investigative Site 035
    • Orlando, Florida, United States, 32806
      • Forest Investigative Site 030
    • Orlando, Florida, United States, 32806
      • Forest Investigative Site 062
    • Pembroke Pines, Florida, United States, 33026
      • Forest Investigative Site 045
    • Tampa, Florida, United States, 33613
      • Forest Investigative Site 051
    • West Palm Beach, Florida, United States, 33407
      • Forest Investigative Site 032
    • Winter Park, Florida, United States, 32789
      • Forest Investigative Site 022
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Forest Investigative Site 060
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Forest Investigative Site 037
    • Chicago, Illinois, United States, 60640
      • Forest Investigative Site 050
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Forest Investigative Site 040
    • Lafayette, Indiana, United States, 47905
      • Forest Investigative Site 012
  • Kansas
    • Prairie Village, Kansas, United States, 66206
      • Forest Investigative Site 053
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • Forest Investigative Site 020
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Forest Investigative Site 031
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • Forest Investigative Site 061
  • New Jersey
    • Willingboro, New Jersey, United States, 08046
      • Forest Investigative Site 024
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Forest Investigative Site 010
    • Albuquerque, New Mexico, United States, 87109
      • Forest Investigative Site 011
  • New York
    • Brooklyn, New York, United States, 11214
      • Forest Investigative Site 004
    • Cedarhurst, New York, United States, 11516
      • Forest Investigative Site 007
    • New York, New York, United States, 10021
      • Forest Investigative Site 047
    • New York City, New York, United States, 10003
      • Forest Investigative Site 058
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Forest Investigative Site 039
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Forest Investigative Site 048
    • Oklahoma City, Oklahoma, United States, 73112
      • Forest Investigative Site 042
  • Oregon
    • Portland, Oregon, United States, 97210
      • Forest Investigative Site 066
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Forest Investigative Site 014
    • Bridgeville, Pennsylvania, United States, 15017
      • Forest Investigative Site 049
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Forest Investigative Site 064
  • Texas
    • Austin, Texas, United States, 78731
      • Forest Investigative Site 013
    • Dallas, Texas, United States, 75230
      • Forest Investigative Site 021
  • Washington
    • Bellevue, Washington, United States, 98007
      • Forest Investigative Site 059
    • Seattle, Washington, United States, 98104
      • Forest Investigative Site 065
    • Spokane, Washington, United States, 99204
      • Forest Investigative Site 054
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Forest Investigative Site 052
    • Milwaukee, Wisconsin, United States, 53223
      • Forest Investigative Site 056

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women, 18-70 years of age.
• Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder.
• The patient's current major depressive episode must be at least 8 weeks and no longer than 12 months in duration.

Exclusion Criteria:

• Women who are pregnant, women who will be breastfeeding during the study, and women of childbearing potential who are not practicing a reliable method of birth control.

• Patients with a history of meeting DSM-IV-TR criteria for:

  • Any manic, hypomanic or mixed episode, including bipolar disorder and substance-induced manic, hypomanic, or mixed episode
  • Any depressive episode with psychotic or catatonic features
  • Panic disorder with or without agoraphobia
  • Obsessive-compulsive disorder
  • Schizophrenia, schizoaffective, or other psychotic disorder
  • Bulimia or anorexia nervosa
  • Presence of borderline personality disorder or antisocial personality disorder
  • Mental retardation, dementia, amnesia, or other cognitive disorders.
• Patients who are considered a suicide risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants received 2 placebo to vilazodone tablets, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study.	Drug: Placebo to citalopram; Placebo to citalopram was supplied as a capsule.; Other Names: Celexa; Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.
EXPERIMENTAL: Vilazodone 20 mg/day; Participants received 1 vilazodone tablet, 1 placebo to vilazodone tablet, and 1 placebo to citalopram capsule orally once daily for the 11 weeks of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20 mg/day during Weeks 2 to 10, and vilazodone 10 mg/day during Week 11.	Drug: Placebo to citalopram; Placebo to citalopram was supplied as a capsule.; Other Names: Celexa; Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.; Drug: Vilazodone; Vilazodone was supplied as film-coated tablets.; Other Names: Viibryd
EXPERIMENTAL: Vilazodone 40 mg/day; Participants received 1 placebo to vilazodone tablet, 1 vilazodone tablet, and 1 placebo to citalopram capsule orally once daily during Weeks 1 and 2 of the study. Participants received 2 vilazodone tablets and 1 placebo to citalopram capsule orally once daily during Weeks 3 -10 of the study. Participants received vilazodone 10 mg/day during Week 1, vilazodone 20/day mg during Week 2, and vilazodone 40 mg/day during Weeks 3 to 10. During Week 11, participants received vilazodone 20 mg/day for 4 days and 10 mg/day for 3 days.	Drug: Placebo to citalopram; Placebo to citalopram was supplied as a capsule.; Other Names: Celexa; Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.; Drug: Vilazodone; Vilazodone was supplied as film-coated tablets.; Other Names: Viibryd
ACTIVE_COMPARATOR: Citalopram 40 mg/day; Participants received 2 placebo vilazodone tablets, and 1 citalopram capsule once daily for the 11 weeks of the study. Participants received citalopram 20 mg/day during Weeks 1 and 2, citalopram 40 mg/day during Weeks 3 to 10, and citalopram 20 mg/day during Week 11.	Drug: Placebo to vilazodone; Placebo to vilazodone was supplied as film-coated tablets.; Drug: Citalopram; Citalopram was supplied as encapsulated tablets.; Other Names: Celexa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score at Week 10	The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A negative change score indicates improvement.	Baseline to Week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 10 in the Clinical Global Impressions-Severity (CGI-S) Scale Score	The Clinical Global Impressions-Severity scale is a clinician-rated scale used to rate the severity of the participant's current state of mental illness compared with a patient population with major depressive disorder. In particular, the clinician is asked to respond to the following question: "Considering your total clinical experience with this population, how mentally ill is the patient at this time?" The patient is rated on the following 7-point scale: 1-normal, not at all ill, 2-borderline ill, 3-mildly ill, 4-moderately ill, 5-markedly ill, 6-severely ill, 7-among the most extremely ill patients. A higher score indicates more mental illness. A negative change score indicates improvement.	Baseline to Week 10
Percentage of Participants With a Montgomery-Åsberg Depression Rating Scale (MADRS) Sustained Response	The MADRS is a clinician-rated scale based on participant interviews. The scale assesses depressive symptomatology that occurred in participants during the week preceding each interview. Participants were rated on 10 items: Apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item was scored on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score was the sum of the scores of the 10 items and ranged from 0 to 60. A higher score indicates more depressive symptomatology. A MADRS sustained response was defined as a MADRS total score ≤ 12 for at least the last 2 visits during the double-blind treatment period (Weeks 1-10). A total MADRS score ≤ 12 corresponds to an average score of 1 per item and is indicative of very low level of depressive symptoms.	Baseline to Week 10

Collaborators and Investigators

• Sponsor: Forest Laboratories

Publications and helpful links

General Publications

• Kornstein S, Chang CT, Gommoll CP, Edwards J. Vilazodone efficacy in subgroups of patients with major depressive disorder: a post-hoc analysis of four randomized, double-blind, placebo-controlled trials. Int Clin Psychopharmacol. 2018 Jul;33(4):217-223. doi: 10.1097/YIC.0000000000000217.
• Rele S, Millet R, Kim S, Paik JW, Kim S, Masand PS, Patkar AA. An 8-Week Randomized, Double-Blind Trial Comparing Efficacy, Safety, and Tolerability of 3 Vilazodone Dose-Initiation Strategies Following Switch From SSRIs and SNRIs in Major Depressive Disorder. Prim Care Companion CNS Disord. 2015 Aug 6;17(4):10.4088/PCC.14m01734. doi: 10.4088/PCC.14m01734. eCollection 2015.
• Clayton AH, Gommoll C, Chen D, Nunez R, Mathews M. Sexual dysfunction during treatment of major depressive disorder with vilazodone, citalopram, or placebo: results from a phase IV clinical trial. Int Clin Psychopharmacol. 2015 Jul;30(4):216-23. doi: 10.1097/YIC.0000000000000075.
• Mathews M, Gommoll C, Chen D, Nunez R, Khan A. Efficacy and safety of vilazodone 20 and 40 mg in major depressive disorder: a randomized, double-blind, placebo-controlled trial. Int Clin Psychopharmacol. 2015 Mar;30(2):67-74. doi: 10.1097/YIC.0000000000000057.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (ACTUAL): June 1, 2013
• Study Completion (ACTUAL): June 1, 2013

Study Registration Dates

• First Submitted: November 14, 2011
• First Submitted That Met QC Criteria: November 16, 2011
• First Posted (ESTIMATE): November 17, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 8, 2014
• Last Update Submitted That Met QC Criteria: August 6, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Depression; Major Depressive Disorder
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Antidepressive Agents, Second-Generation; Antiparkinson Agents; Anti-Dyskinesia Agents; Citalopram; Dexetimide; Vilazodone Hydrochloride
• Other Study ID Numbers: VLZ-MD-01