Efficacy of Vortioxetine on Cognitive Dysfunction in Patients With Partial or Full Remission of Major Depressive Disorder

An Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled Study on the Efficacy of Vortioxetine on Cognitive Dysfunction in Patients With Partial or Full Remission of Major Depressive Disorder

To assess the efficacy of vortioxetine (10 to 20 mg/day) as adjunctive treatment to stable selective serotonin reuptake inhibitor (SSRI) dose versus stable SSRI monotherapy on cognitive performance (focusing on the aspect concerning speed of processing, executive functioning and attention) in patients who are in partial or full remission from their Major Depressive Episode (MDE).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Vortioxetine 10-20 mg; Drug: SSRI

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia
    • EE001
  • Tallinn, Estonia
    • EE002
• Finland
  • Helsinki, Finland
    • FI005
  • Helsinki, Finland
    • FI002
  • Helsinki, Finland
    • FI003
  • Kuopio, Finland
    • FI001
  • Kupio, Finland
    • FI006
  • Turku, Finland
    • FI004
• Germany
  • Berlin, Germany
    • DE002
  • Bielefeld, Germany
    • DE001
  • Bochum, Germany
    • DE005
  • Frankfurt, Germany
    • DE003
  • Mittweida, Germany
    • DE004
• Serbia
  • Belgrade, Serbia
    • RS002
  • Kragujevac, Serbia
    • RS001
• Slovakia
  • Levice, Slovakia
    • SK003
  • Rimavska Sobota, Slovakia
    • SK002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has achieved either partial (some symptoms of a MDE are present but full criteria are not met) or full remission of major depressive disorder (MDD), diagnosed according to DSM-IV-TR™.
• The patient has HAMD-17 total score ≤10.
• The patient has received SSRI monotherapy for the MDE from which the patient is currently in full or partial remission for ≥12 weeks at licensed doses and been on stable dose ≥8 weeks prior to Screening Visit.
• The patient has ≥50% response to current SSRI treatment (Antidepressant Treatment Response Questionnaire [ATRQ]).
• The patient has a PDQ-D total score >25.
• The patient is a man or woman, aged ≥18 and ≤65 years.

Exclusion Criteria:

• The patient has a score ≥70 on the DSST (numbers of correct symbols) at the Baseline Visit.
• The patient is, in the opinion of the investigator, not able to complete the neuropsychological tests validly at the Baseline Visit.
• The patient has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
• The patient is diagnosed with reading disability (dyslexia).
• The patient has a history of lack of response to previous adequate treatment with vortioxetine.
• The patient has any current psychiatric disorder or Axis I disorder (according to DSM-IV-TR™ criteria) other than MDD, as assessed using Mini International Neuropsychiatric Interview (MINI).
• The patient has a current or has had a diagnosis of dysthymic disorder within 3 months preceding the onset of the depressive episode from which the patient is currently in full or partial remission (DSM-IV-TR™ criteria).
• The patient has borderline, schizotypal, schizoid, paranoid, histrionic, antisocial personality disorders (axis II) as comorbid or primary diagnosis (DSM-IV-TR™ criteria).
• The patient suffers from personality disorders, mental retardation, pervasive development disorder, attention-deficit/hyperactivity disorder, organic mental disorders, or mental disorders due to a general medical condition (DSM-IV-TR™ criteria).
• The patient has a current diagnosis or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including major depression with psychotic features (DSM-IV-TR™ criteria).

Other protocol-defined inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vortioxetine 10-20 mg; daily, encapsulated, orally	Drug: Placebo; Drug: Vortioxetine 10-20 mg; Other Names: Lu AA21004; Brintellix®
Experimental: Vortioxetine 10-20 mg + SSRI; daily, encapsulated, orally	Drug: Vortioxetine 10-20 mg; Other Names: Lu AA21004; Brintellix®; Drug: SSRI; escitalopram, citalopram or sertraline
Experimental: SSRI; licensed doses, encapsulated, orally	Drug: Placebo; Drug: SSRI; escitalopram, citalopram or sertraline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Digit Symbol Substitution Test (DSST): number of correct symbols	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in University of San Diego Performance-based Skills Assessment - Brief (UPSA-B) total score	Baseline to Week 8
Change in Trail Making Test (TMT) score: TMT-A; speed of processing	Baseline to Week 8
Change in reaction time score: Choice Reaction Time (CRT); attention	Baseline to Week 8
Change in Stroop Colour Naming Test (STROOP): incongruent score; executive functioning	Baseline to Week 8
Change in STROOP: congruent score; speed of processing	Baseline to Week 8
Change in Perceived Deficits Questionnaire - Depression (PDQ-D) total score	Baseline to Week 8
Change in Clinical Global Impression - Severity of Illness (CGI-S)	Baseline to Week 8
Clinical Global Impression - Global Improvement (CGI-I) score	Week 8
Change in Rey Auditory Verbal Learning Test (RAVLT) score: memory (delayed recall) and learning [acquisition])	Baseline to Week 8
Change in TMT score: TMT-B; executive functioning	Baseline to Week 8
Change in reaction time score: Simple Reaction Time (SRT); psychomotor speed	Baseline to Week 8
Change in Hamilton Depression Rating Scale-17 (HAMD-17) total score	Baseline to Week 8
Number of adverse events	Baseline to Week 12
Columbia Suicide Severity Rating Scale (C-SSRS) categorisation based on Columbia Classification Algorithm of Suicide Assessment (C-CASA) definitions (1, 2, 3, 4 and 7)	Baseline to Week 8

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Publications and helpful links

Helpful Links

• Results EudraCT 2014-000229-19

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: October 21, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): May 24, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Neurocognitive Disorders; Cognition Disorders; Depression; Depressive Disorder; Cognitive Dysfunction; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Vortioxetine
• Other Study ID Numbers: 15905A; 2014-000229-19 (EudraCT Number)