Introduction:

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.

Methodology:

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

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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).

Results:

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.