Efficacy of Vortioxetine on Cognitive Dysfunction in Working Patients With Major Depressive Disorder

An Interventional, Randomised, Double-blind, Parallel-group, Placebo-controlled, Active-referenced (Paroxetine), Fixed-dose Study on the Efficacy of Vortioxetine on Cognitive Dysfunction in Working Patients With Major Depressive Disorder

To assess the efficacy of acute treatment with 10 mg/day vortioxetine versus placebo on cognitive performance (focusing on the aspect concerning speed of processing, executive functioning, attention) in working patients with major depressive disorder (MDD).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 3

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia
    • EE001
  • Tallinn, Estonia
    • EE002
  • Voru, Estonia
    • EE004
• Finland
  • Helsinki, Finland
    • FI002
  • Helsinki, Finland
    • FI003
  • Kuopio, Finland
    • FI001
  • Oulu, Finland
    • FI008
  • Tampere, Finland
    • FI007
• Germany
  • Berlin, Germany
    • DE002
  • Bielefeld, Germany
    • DE001
  • Frankfurt, Germany
    • DE003
  • Frankfurt, Germany
    • DE007
  • Schwerin, Germany
    • DE008
• Lithuania
  • Kaunas, Lithuania
    • LT002
  • Palanga, Lithuania
    • LT006
  • Silute, Lithuania
    • LT003
  • Vilnius, Lithuania
    • LT001
  • Vilnius, Lithuania
    • LT005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has MDD, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR™) recurrent major depressive disorder (MDD) (classification 296.3x).
• The patient has a MADRS total score ≥26.
• The patient has had the current major depressive episode (MDE) for ≥3 months.
• The patient is aged ≥18 and ≤65 years.
• The patient is employed full or part-time (defined as minimum 50% full time working hours per week). Part time work should not be due to a medical or mental illness other than MDD.
• The patient has been in the current job/position for at least 3 months.
• The patient has no plans to change jobs or retire within treatment period.
• The patient is not on a sick leave, and at the Screening and Randomisation Visits, there are no plans to send the patient on a sick leave.
• The patient is not receiving disability benefits.

Exclusion criteria:

• The patient has a score ≥70 on the DSST (number 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 or paroxetine.
• The patient has any current psychiatric disorder or Axis I disorder (according to DSM-IV-TR™ criteria) other than MDD, as assessed using MINI.
• The patient has a current or has had a diagnosis of dysthymic disorder within 3 months preceding the onset of current episode (DSM-IV-TR™ criteria).
• The patient has borderline, schizotypal, schizoid, paranoid, or 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 mg; daily, encapsulated, orally	Drug: Vortioxetine 10 mg; Other Names: Lu AA21004; Brintellix®
Other: Paroxetine 20 mg (active reference); daily, encapsulated, orally	Drug: Paroxetine 20 mg
Placebo Comparator: Placebo; capsules, orally	Drug: Placebo

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 TMT-B; executive functioning	Baseline to Week 8
Change in reaction time score: Choice Reaction Time (CRT); attention	Baseline to Week 8
Change in reaction time score: Simple Reaction Time (SRT); psychomotor speed)	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 Montgomery and Asberg Depression Rating Scale (MADRS) 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 the Functioning Assessment Short Test (FAST) total score	Baseline to Week 8

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Publications and helpful links

General Publications

• Christensen MC, Sluth LB, McIntyre RS. Validation of the University of California San Diego Performance-based Skills Assessment (UPSA) in major depressive disorder: Replication and extension of initial findings. J Affect Disord. 2019 Feb 15;245:508-516. doi: 10.1016/j.jad.2018.11.034. Epub 2018 Nov 5.

Helpful Links

• EMA EudraCT Results: 2014-000230-34

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 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): February 28, 2017
• Last Update Submitted That Met QC Criteria: February 27, 2017
• Last Verified: February 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; Enzyme Inhibitors; 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; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Paroxetine; Vortioxetine
• Other Study ID Numbers: 15906A; 2014-000230-34 (EudraCT Number)