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Center for Global Research Data

Cognitive predictors of antidepressant treatment outcome in patients with major depressive disorder

Lead Investigator: Amit Etkin, Alto Neuroscience, Inc.
Title of Proposal Research: Cognitive predictors of antidepressant treatment outcome in patients with major depressive disorder
Vivli Data Request: 7663, 7385
Funding Source: Employee salaries at Alto Neuroscience, Inc. are supported by internal Alto funds
Potential Conflicts of Interest: -Full-time employees of Alto Neuroscience-work being proposed is part of the job responsibilities for Alto. Alto is supporting this project.
-Dr. Etkin has equity in Mindstrong Health and Akili Interactive for unrelated work.
-Dr. Savitz owns stock in Johnson&Johnson and was a full time employee of J&J (Janssen Research & Development) until July 2021. No conflict with this project. J&J has no involvement in the project

Summary of the Proposed Research:
Cognitive difficulties, such as problems with attention, concentration, decision-making and memory, are a core component of major depression. While symptom questionnaires can assess subjective experience of cognitive difficulties, objective task-based measures are required for more directly assessing cognition. Using such task-based measures, prior studies have in general found that patients with a more profound impairment in cognition have a worse response to treatment with antidepressants. However, these studies have primarily not been gold-standard studies where the patient does not know if they are taking a drug or a placebo. There is, as a consequence, very little information about what either predicts antidepressant response differently from placebo, or predicts placebo response differently from antidepressants. As such, understanding the relationship between pretreatment cognition and placebo response is of paramount importance as doing so may elucidate what sort of cognitive profile is associated with a larger (or smaller) net benefit of antidepressants over placebo, as well as whether the ability of pre-treatment cognition to predict improvement in depression symptoms is something that is equally relevant to placebo as active antidepressants. The consequence of such analyses may allow identification of subgroups of depressed patients that may be particularly sensitive to antidepressants relative to placebo, and others which derive little or no benefit from antidepressants over placebo and thus particularly in need for new types of interventions being developed across the field. We will address these questions using a variety of statistical analyses of cognitive and clinical data from several studies of vortioxetine in patients with depression, which included a placebo arm and in some cases also a different antidepressant. These datasets were chosen for their size relative to previously published individual lab datasets, as well as the ability to replicate findings across studies. Our statistical methods will be ones common to clinical trial research, as well as those more closely related to simple forms of machine learning. Given the broad relevance of the proposed analyses, meaningful impact is expected for the general population of depressed patients (22M in the US alone), as well as patients with anxiety or trauma-related disorders in which antidepressant treatment is also a mainstay (10M’s in the US). Indeed, at present it is estimated that one in eight in the US is on an antidepressant at any given time, thus illustrating both the breadth and need for a precision approach such as that described herein.

Requested Studies:
Randomised, Double-blind, Parallel-group, Placebo-controlled, Duloxetine-referenced, Fixed Dose Study Comparing the Efficacy and Safety of [Vortioxetine] Lu AA21004 in Acute Treatment of Major Depressive Disorder in Elderly Patients
Data Contributor: Lundbeck
Study ID: NCT00811252
Sponsor ID: 12541A

Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed Dose Study on the Efficacy of [Vortioxetine] Lu AA21004 on Cognitive Dysfunction in Adult Patients With Major Depressive Disorder (MDD)
Data Contributor: Lundbeck
Study ID: NCT01422213
Sponsor ID: 14122A

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Active-Referenced, Flexible Dose Study on the Efficacy of Lu AA21004 on Cognitive Dysfunction in Adult Subjects With Major Depressive Disorder (MDD)
Data Contributor: Takeda
Study ID: NCT01564862
Sponsor ID: LuAA21004_202

(Note: additional studies added as part of data request 7663)

Duloxetine Versus Placebo in the Long-Term Treatment of Patients With Late-Life Major Depression
Data Contributor: Lilly
Study ID: NCT00406848
Sponsor ID: 10815

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase III Study to Evaluate the Efficacy and Safety of Once Daily Oral Lu AA21004 in Patients With Major Depressive Disorder
Data Contributor: Takeda
Study ID: NCT02389816
Sponsor ID: LuAA21004/CCT-004

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
Data Contributor: Lundbeck
Study ID: NCT02279966
Sponsor ID: 15906A

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
Data Contributor: Lundbeck
Study ID: NCT02279953
Sponsor ID: 15905A

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
Data Contributor: Lundbeck
Study ID: NCT02272517
Sponsor ID: 15907A

Duloxetine Versus Placebo in the Treatment of Elderly Patients With Major Depressive Disorder
Data Contributor: Lilly
Study ID: NCT00062673
Sponsor ID: 6091