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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Vortioxetine 10-20 mg
* Drug: Escitalopram 10-20 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Escitalopram 10-20 mg<br>Encapsulated tablets once daily for 8 weeks | Drug: Escitalopram 10-20 mg<br> <br> |
| Experimental: Vortioxetine 10-20 mg<br>Encapsulated tablets once daily for 8 weeks | Drug: Vortioxetine 10-20 mg<br> <br> * Other names: Lu AA21004;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vortioxetine, Cognition