Project Abstract 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. Our research team has worked in western Kenya for 5 years with a UCSF-Kenya collaboration that supports integrated HIV services at over 70 primary healthcare facilities in Kisumu County (Family AIDS Care and Education Services [FACES]). With high prevalence of Major Depressive Disorder (MDD) in Kenyan primary care populations (26.3%, 3-5 times higher than in the U.S.), treatment for depression is a top concern for Kenyan mental health leaders. Kenyan leaders recently launched a government-funded 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 Kenyan care scale-up will fall short of its potential. The proposed research responds to this need. We propose to partner with local and national mental health stakeholders in Kenya to evaluate: (1) non- specialist delivery of evidence-based depression treatment integrated within existing healthcare centers in regards to clinical effectiveness and implementation parameters; including (2) costs and cost-benefit ratios for depression care. Given that evidence-based psychotherapy and second-generation antidepressants are the two leading first-line treatments for depression 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. Our proposed study uses an effectiveness-implementation hybrid design type I to assess outcomes of non-specialist delivered Interpersonal Psychotherapy (IPT) compared to fluoxetine, including assessment of the service delivery mechanism. Our approach differs from most prior work in our field because it uses an effectiveness-implementation design, compares outcomes for IPT versus second generation antidepressant, integrates depression treatment into primary care, and analyses depression care costs and cost-benefit ratios for each treatment arm. The results of the proposed research will be significant in two ways: (1) they will produce a scalable strategy for delivering depression treatments in sub-Saharan Africa using non-specialists integrated within existing primary care structures and (2) they will produce a policy maker ?menu? of short and long-term cost-benefit options for integrated depression care with corresponding effectiveness and implementation values.