Efficacy of Vortioxetine Versus Escitalopram on Cognitive Function in Patients With Inadequate Response to Current Antidepressant Treatment of Major Depressive Disorder

An Interventional, Randomised, Double-blind, Parallel-group, Active-comparator, Flexible-dose Study on the Efficacy of Vortioxetine Versus Escitalopram on Cognitive Dysfunction in Patients With Inadequate Response to Current Antidepressant Treatment of Major Depressive Disorder

This study aims at evaluating the effect of vortioxetine on cognitive dysfunction in major depressive disorder (MDD) patients with inadequate response to current antidepressant treatment.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • FI005
  • Kuopio, Finland
    • FI001
  • Kupio, Finland
    • FI006
  • Tampere, Finland
    • FI007
  • Turku, Finland
    • FI004
• Germany
  • Bochum, Germany
    • DE005
  • Mittweida, Germany
    • DE004
• Serbia
  • Belgrade, Serbia
    • RS002
  • Belgrade, Serbia
    • RS003
  • Belgrade, Serbia
    • RS004
  • Belgrade, Serbia
    • RS005
  • Kragujevac, Serbia
    • RS001
• Slovakia
  • Bratislava, Slovakia
    • SK004
  • Hronovce, Slovakia
    • SK001
  • 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 MDD, diagnosed according to DSM-IV-TR™ recurrent MDE (classification 296.3x) as confirmed using the Mini International Neuropsychiatric Interview (MINI).
• The patient has depressive symptoms currently considered as non- or only partially responsive (inadequate response), to one adequate course of SSRI/SNRI antidepressant monotherapy and is candidate for a switch in the investigator's opinion.
• The patient wants to stop taking his/her current SSRI/SNRI treatment due to inadequate response confirmed by the Antidepressant Treatment Response Questionnaire (ATRQ), <50% response to current treatment).
• The patient must have been treated by SSRI/SNRI monotherapy (citalopram, paroxetine, sertraline, duloxetine, or venlafaxine) for at least 6 weeks at licensed doses prior to the Screening Visit.
• The patient has a PHQ-9 total score ≥14.
• The patient has a MADRS total score ≥ 22.
• The patient has had the current MDE for ≤1 year.
• The patient has a Perceived Deficits Questionnaire - Depression (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 (Number of Correct Symbols) 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 has any current psychiatric disorder or Axis I disorder (according to DSMIV-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, histrionic, antisocial personality disorders (axis II) as comorbid or primary diagnosis (DSM-IV-TR™ criteria).
• The patient has history of previous MDEs considered as treatment resistant defined as inadequate response (incomplete or no therapeutic response) to two prior courses of at least 6 weeks of conventional antidepressant drugs in adequate dosages or, the patient has treatment-resistant depression in the investigator's judgement.
• 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 diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) (DSM-IV-TR™ criteria) that has not been in sustained full remission at least 2 years prior to the Screening Visit.
• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Escitalopram 10-20 mg; Encapsulated tablets once daily for 8 weeks	Drug: Escitalopram 10-20 mg
Experimental: Vortioxetine 10-20 mg; Encapsulated tablets once daily for 8 weeks	Drug: Vortioxetine 10-20 mg; Other Names: Lu AA21004; Brintellix®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Digit Symbol Substitution Test (DSST)	The DSST is recognised as covering all of the cognitive performance aspects: speed of processing, executive functioning, and attention	Baseline to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Rey Auditory Verbal Learning Test (RAVLT)	Learning [acquisition] and memory [delayed recall])	Baseline to Week 8
Change in Trail Making Test A (TMT-A)	Speed of processing	Baseline to Week 8
Change in Trail Making Test B (TMT-B)	Executive functioning	Baseline to Week 8
Change in Reaction time score; CRT attention		Baseline to Week 8
Change in reaction time score SRT - simple reaction time		Baseline to week 8
Change in 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	Patient-reported cognitive function outcome including attention concentration, retrospective memory, prospective memory, and, planning organization	Baseline to Week 8
Change in Patient Health Questionnaire-9 (depressive symptoms) (PHQ-9) total score	Patient-reported outcome	Baseline to Week 8
Change in Clinical Global Improvement - Severity (CGI-S)		Baseline to Week 8
Clinical Global Improvement (CGI-I)		Week 8
Change in Functioning Assessment Short Test (FAST)		Baseline to Week 8
Change in University of San Diego Performance-based Skills Assessment - Brief (UPSA-B) 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): December 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: October 21, 2014
• First Submitted That Met QC Criteria: October 21, 2014
• First Posted (Estimate): October 23, 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

• Keywords: Cognition; Vortioxetine
• 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; 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; Antidepressive Agents, Second-Generation; Serotonin 5-HT3 Receptor Antagonists; Citalopram; Vortioxetine
• Other Study ID Numbers: 15907A; 2014-000231-16 (EudraCT Number)