Study Comparing Discontinuation Symptoms Of DVS SR In Subjects With Major Depressive Disorder (MDD)

A Randomized, Double-Blind, Parallel Group Study To Compare Discontinuation Symptoms In Abrupt Discontinuation Versus A 1-Week Tapering Regimen In Subjects With MDD Treated For 24 Weeks With Open-Label 50 mg DVS SR Formulation

Study Comparing Discontinuation Symptoms in subjects with Major Depressive Disorder treated for 24 Weeks with Open-label 50 mg Desvenlafaxine Succinate Sustained-Release Formulation (DVS SR)

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Desvenlafaxine Succinate Sustained-Release Formulation 50 mg; Drug: Desvenlafaxine Succinate Sustained-Release Formulation 25 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary Diagnosis of Major Depressive Disorder
• Hamilton Psychiatric Rating Scale for Depression-17-Item score of greater than or equal to 14 at baseline

Exclusion Criteria:

• Current psychoactive substance abuse or dependence, manic episode, or a lifetime diagnosis of bipolar or psychotic disorder
• Potentially violent to others or is at significant risk for suicide
• History or current evidence of gastrointestinal disease or history of surgery known to interfere with absorption or excretion
• Known presence of raised intraocular pressure or history of narrow angle glaucoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; DVS SR Placebo Abrupt Discontinuation Group/Arm, oral tablet, 2 tablets/day during the first week and 1 tablet/day during weeks 2 through 4 of the double-blind treatment phase.
Active Comparator: Desvenlafaxine Succinate Sustained-Release Formulation 50 mg	Drug: Desvenlafaxine Succinate Sustained-Release Formulation 50 mg; DVS SR 50 mg Reference Group/Arm, oral tablet, 2 tablets/day during the first week and 1 tablet/day during weeks 2 through 4 of the double-blind treatment phase.
Active Comparator: Desvenlafaxine Succinate Sustained-Release Formulation 25 mg	Drug: Desvenlafaxine Succinate Sustained-Release Formulation 25 mg; DVS SR 25 mg Taper Group/Arm, oral tablet, 2 tablets/day during the first week and 1 tablet/day during weeks 2 through 4 of the double-blind treatment phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Discontinuation - Emergent Signs and Symptoms (DESS) Score Over the First 2 Weeks of the Double-blind Phase	Clinician-administered 43-item assessment to evaluate discontinuation-emergent symptoms resulting from withdrawal from study treatment. Total score=sum of number of new symptoms and old (but worse) symptoms (score=1) and old and unchanged symptom, absent, or old symptom but improved (score=0); total possible range 0 to 43. Higher score=more symptoms. New symptom=any symptom that appeared within 7 days before DESS administration; old symptom=any symptom that appeared 7 days before DESS administration and continued into 7-day period. DESS calculated as 2*mean(of DESSDB Week 1, DESSDB Week 2).	Double-blind phase: Week 1 (Study Day 175), Week 2 (Study Day 182)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Taper Adverse Events (AEs) in the Double-blind Phase	Any untoward medical occurrence in a patient who received study drug was considered an AE without regard to possibility of causal relationship. Taper-emergent AEs (TPAEs) are those events which occurred during the double-blind period but did not occur during the last 7 days of the on-therapy period or existed during the last 7 days and worsened in the double-blind period.	Double-blind phase: Baseline (Study Day 168) up to Week 4 (Study Day 196)
Percentage of Participants Who Were Unable to Successfully Complete Tapering of the Study Drug Because of the Number and/or Severity of Their Discontinuation Symptoms	Discontinuation symptoms may occur following abrupt cessation of serotonergic antidepressants in a minority of participants following short-term treatment of an episode of Major Depressive Disorder (MDD). The symptoms include emotional and somatic symptoms such as dizziness, nausea, and paresthesia and typically appear within 2 to 3 days of reducing the dose or stopping the antidepressant medication. Discontinuation symptoms are usually mild and resolve spontaneously within a week in the majority of patients, though a minority can have intense and prolonged symptoms.	Double-blind phase: Baseline (Study Day 168) up to Week 4 (Study Day 196)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Ninan PT, Musgnung J, Messig M, Buckley G, Guico-Pabia CJ, Ramey TS. Incidence and Timing of Taper/Posttherapy-Emergent Adverse Events Following Discontinuation of Desvenlafaxine 50 mg/d in Patients With Major Depressive Disorder. Prim Care Companion CNS Disord. 2015 Feb 5;17(1):10.4088/PCC.14m01715. doi: 10.4088/PCC.14m01715. eCollection 2015.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: January 22, 2010
• First Submitted That Met QC Criteria: January 22, 2010
• First Posted (Estimate): January 26, 2010

Study Record Updates

• Last Update Posted (Estimate): February 28, 2012
• Last Update Submitted That Met QC Criteria: February 25, 2012
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Desvenlafaxine Succinate
• Other Study ID Numbers: 3151A1-4437; B2061010