Protocol No: ECCT/20/01/01 Date of Protocol: 08-08-2019

Study Title:
Study Objectives:

Aim 1: Determine the effectiveness of non-specialist-delivered Interpersonal Psychotherapy(IPT), fluoxetine, or combination for MDD and PTSD. 

Aim 2: Investigate key presumed mediators of the relationship between treatment and remission  

Aim 3: Identify demographic and clinical moderators of the relationship between treatment and remission.  

 Aim 4. Estimate the costs and cost-benefit ratios for fluoxetine and IPT treatment of depression and PTSD.

Laymans Summary:

Mental disorders are a leading cause of disability. Commonest of these disorders are depression and anxiety. Most of this disease burden is in Low and Middle Income Countries (LMICs), where 75% of adults with mental disorders have no service access. Despite nearly 15 years of efficacy research showing that local non-specialists can provide evidence-based care for depression and anxiety in LMICs, few studies have advanced to the critical next step: identifying strategies for sustainable “real world” non-specialist treatment including integration with existing healthcare platforms and response to common clinical dilemmas, such as what treatment to start with and how to modify it.

There is a need to personalize mental health treatment. Due to the few number of mental health specialists in LMIC, treatment for depression and anxiety will benefit from research findings that demonstrate first line and second line treatment as delivered by non-specialist. In this study we will test the effectiveness of non-specialist delivery of psychotherapy and antidepressant for treatment of depression and trauma disorder in a government facility (Kisumu County Hospital). We will further test how best to implement these two arms of treatment in the facility. Lastly we will examine how the two arms of treatment compare in terms of cost of care. In the first part of the study participants in the study will either by given talk therapy treatment (IPT) or antidepressant medication as treatment. The ones who do not recover will be switched treatments or will receive both treatments. We plan to recruit a total of 2710 participants. Our study will compare short and long outcomes for the talk therapy versus the antidepressant treatment. The results will provide a strategy of treatment that can be adapted to work in larger settings of this region.

Abstract of Study:
Dominated by depression, mental disorders are a leading cause of global disability. Most of the disease burden is in Low and Middle Income Countries (LMICs), where 75% of adults with mental disorders have no service access. Despite nearly 15 years of efficacy studies showing that local non-specialists can provide evidence-based care for depression in LMICs, few studies have advanced to implementation research. As emphasized by a recent World Health Organization (WHO) initiative, integration of depression treatment into existing systems of care is critical to achieving public health impact. Kenyan leaders recently launched an initiative to scale-up treatment for mental disorders in primary healthcare, prioritizing depression. Yet, they lack an evidence base for the two essential treatments – psychotherapy and second-generation antidepressants - without which the scale-up will fall short of its potential. The proposed research responds to this need and builds on our current work in Kisumu, showing that Interpersonal Psychotherapy (IPT) can be delivered by trained non-specialists with high efficacy for the treatment of depression and/or PTSD using fluoxetine or Interpersonal therapy. Additionally, the study applies a SMART design to manage non-responsiveness to the given treatment by switching or combination.
Objectives: We propose to partner with local and national mental health stakeholders in Kenya to evaluate: (1) non-specialist delivery of evidence-based depression and/or PTSD treatment integrated within existing healthcare centers in regard to clinical effectiveness and implementation parameters; including (2) costs and cost-benefit ratios for depression and/or PTSD care. Given that evidence-based psychotherapy and second-generation antidepressants are the two leading first-line treatments for depression and/or PTSD and are feasible to deliver in Kenya, our goal is to test an implementation strategy for improving equitable access to these treatments by integrating them with primary care.
Given the novelty of non-specialist depression care and primary care integration for Kenya, we will use an effectiveness-implementation hybrid design type I, which emphasizes effectiveness outcomes for the new setting and study population, while also gathering implementation data for future scale up. In collaboration with the 80-member FACES team currently providing integrated HIV care to Kisumu County Hospital (KCH) primary care outpatient clinics (~10,000 patients/month), we will randomize 2000 adult KCH primary care patients with Major Depressive Disorder (MDD) to receive IPT delivered by non-specialists trained in the study or fluoxetine delivered by fluoxetine trained providers in the study and follow them for 30 months. We will use the Exploration, Preparation, Implementation and Sustainment (EPIS) framework to inform the research and incorporate positive findings into practice. Given the high prevalence of MDD-PTSD co- morbidity, we will leverage the U01 to support a Sequential, Multiple Assignment Randomized Trial (SMART) by recruiting an additional 710 participants with MDD and/or PTSD (irrespective of HIV status) for a total of 2710 participants. Local non-specialists will be trained in mental health care for the SMART and hired
August 22, 2019 iv Version 1.9
through the Kenyan Ministry of Health to work at KCH. After the study, Kisumu County will continue their payroll and the fluoxetine supply.
Data analysis: the study will compare short and long term (relapse) outcomes for IPT versus fluoxetine treatment (Aim 1), and calculate costs and cost-benefit ratios for each treatment arm (Aim 2).
The results of the proposed research will (1) produce a scalable strategy for delivering depression treatments in sub-Saharan Africa using non-specialists integrated within existing primary care structures and (2) offer policy makers short and long-term cost-benefit options for integrated depression care with corresponding effectiveness and implementation values.