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Trials
Published in: Trials 1/2022

Open Access 01-12-2022 | Antidepressant Drugs | Study protocol

The Appalachia Mind Health Initiative (AMHI): a pragmatic randomized clinical trial of adjunctive internet-based cognitive behavior therapy for treating major depressive disorder among primary care patients

Authors: Robert M. Bossarte, Ronald C. Kessler, Andrew A. Nierenberg, Ambarish Chattopadhyay, Pim Cuijpers, Angel Enrique, Phyllis M. Foxworth, Sarah M. Gildea, Bea Herbeck Belnap, Marc W. Haut, Kari B. Law, William D. Lewis, Howard Liu, Alexander R. Luedtke, Wilfred R. Pigeon, Larry A. Rhodes, Derek Richards, Bruce L. Rollman, Nancy A. Sampson, Cara M. Stokes, John Torous, Tyler D. Webb, Jose R. Zubizarreta

Published in: Trials | Issue 1/2022

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Abstract

Background

Major depressive disorder (MDD) is a leading cause of disease morbidity. Combined treatment with antidepressant medication (ADM) plus psychotherapy yields a much higher MDD remission rate than ADM only. But 77% of US MDD patients are nonetheless treated with ADM only despite strong patient preferences for psychotherapy. This mismatch is due at least in part to a combination of cost considerations and limited availability of psychotherapists, although stigma and reluctance of PCPs to refer patients for psychotherapy are also involved. Internet-based cognitive behaviorial therapy (i-CBT) addresses all of these problems.

Methods

Enrolled patients (n = 3360) will be those who are beginning ADM-only treatment of MDD in primary care facilities throughout West Virginia, one of the poorest and most rural states in the country. Participating treatment providers and study staff at West Virginia University School of Medicine (WVU) will recruit patients and, after obtaining informed consent, administer a baseline self-report questionnaire (SRQ) and then randomize patients to 1 of 3 treatment arms with equal allocation: ADM only, ADM + self-guided i-CBT, and ADM + guided i-CBT. Follow-up SRQs will be administered 2, 4, 8, 13, 16, 26, 39, and 52 weeks after randomization. The trial has two primary objectives: to evaluate aggregate comparative treatment effects across the 3 arms and to estimate heterogeneity of treatment effects (HTE). The primary outcome will be episode remission based on a modified version of the patient-centered Remission from Depression Questionnaire (RDQ). The sample was powered to detect predictors of HTE that would increase the proportional remission rate by 20% by optimally assigning individuals as opposed to randomly assigning them into three treatment groups of equal size.
Aggregate comparative treatment effects will be estimated using intent-to-treat analysis methods. Cumulative inverse probability weights will be used to deal with loss to follow-up. A wide range of self-report predictors of MDD heterogeneity of treatment effects based on previous studies will be included in the baseline SRQ. A state-of-the-art ensemble machine learning method will be used to estimate HTE.

Discussion

The study is innovative in using a rich baseline assessment and in having a sample large enough to carry out a well-powered analysis of heterogeneity of treatment effects. We anticipate finding that self-guided and guided i-CBT will both improve outcomes compared to ADM only. We also anticipate finding that the comparative advantages of adding i-CBT to ADM will vary significantly across patients. We hope to develop a stable individualized treatment rule that will allow patients and treatment providers to improve aggregate treatment outcomes by deciding collaboratively when ADM treatment should be augmented with i-CBT.

Trial registration

ClinicalTrials.gov NCT04120285. Registered on October 19, 2019.
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Metadata
Title
The Appalachia Mind Health Initiative (AMHI): a pragmatic randomized clinical trial of adjunctive internet-based cognitive behavior therapy for treating major depressive disorder among primary care patients
Authors
Robert M. Bossarte
Ronald C. Kessler
Andrew A. Nierenberg
Ambarish Chattopadhyay
Pim Cuijpers
Angel Enrique
Phyllis M. Foxworth
Sarah M. Gildea
Bea Herbeck Belnap
Marc W. Haut
Kari B. Law
William D. Lewis
Howard Liu
Alexander R. Luedtke
Wilfred R. Pigeon
Larry A. Rhodes
Derek Richards
Bruce L. Rollman
Nancy A. Sampson
Cara M. Stokes
John Torous
Tyler D. Webb
Jose R. Zubizarreta
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-022-06438-y

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