SMART-DAPPER: Leveraging the Depression And Primary-care Partnership for Effectiveness-implementation Research Project (SMART-DAPPER)

A Sequential, Multiple Assignment Randomized Trial (SMART) for Non-specialist Treatment of Common Mental Disorders in Kenya: Leveraging the Depression And Primary-care Partnership for Effectiveness-implementation Research (DAPPER) Project

Despite carrying the vast majority of the global mental disorder burden, 75% of adults with mental disorders in Low and Middle Income Countries have no access to services. This study will test strategies for integrating first and second line evidence-based depression and trauma-related disorder treatments with primary care services at a large public sector hospital and conduct robust cost and cost-benefit analyses of each treatment to produce a "menu" of cost-benefit options for personalized, integrated mental health care with corresponding effectiveness and implementation values.

Study Overview

• Status: Completed
• Conditions: Trauma; Posttraumatic Stress Disorder; Depression, Unipolar
• Intervention / Treatment: Drug: Fluoxetine; Behavioral: Interpersonal Psychotherapy

Detailed Description

Mental disorders are a leading cause of global disability, driven by depression and anxiety. 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 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.

Given the need to personalize treatment to achieve remission (absence of disease) and the scarcity of mental health specialists in LMICs, successful reduction of population-level disability caused by depression and anxiety requires (1) evidence-based strategies for first-line and second-line (non-remitter) treatment delivered by non-specialists, with (2) confirmation of presumed mechanism of action and (3) patient-level moderators of treatment outcome to inform personalized, non-specialist treatment algorithms.

The research team has worked in western Kenya for 6 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]). Primary care populations in Kenya have high prevalence of Major Depressive Disorder (MDD) (26%) and Posttraumatic Stress Disorder (PTSD) (35%). Kenyan leaders lack an evidence base for two essential treatments - psychotherapy and second generation antidepressants- without which scale-up will fall short of its potential. We conducted a randomized, controlled trial in Kisumu County of Interpersonal Psychotherapy (IPT) delivered by non-specialists for HIV-positive patients with MDD and PTSD. In our study, IPT achieved full remission of MDD and PTSD in the majority of participants.

Given the high prevalence of MDD-PTSD co-morbidity, we will collaborate with the FACES team providing services to Kisumu County Hospital (KCH) primary care outpatient clinic (~10,000 patients/month) to conduct a randomized trial of IPT versus fluoxetine for MDD and/or PTSD. Local non-specialists will be trained in mental health care for the SMART and hired through the Kenyan Ministry of Health to work at KCH. SMART participants will be randomized to: (1) first line treatment with IPT or fluoxetine; (2) second line treatment for non-remitters- treatment "switch" (e.g., IPT to fluoxetine) or treatment "combination" (e.g., addition of IPT to fluoxetine). Research with mental health specialists in high income countries suggests that antidepressants and psychotherapy have equivalent short-term efficacy and that psychotherapy yields superior long-term relapse prevention. We will test the role of previously identified mechanisms in mediating remission and key moderators of treatment effect. Results of moderator and Q learning analyses will produce first and second-line non-specialist treatment algorithms.

• Study Type: Interventional
• Enrollment (Actual): 2162
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Kenya
  • Kisumu, Kenya
    • Kisumu County Hospital
  • Kisumu, Kenya
    • Lumumba Health Center
  • Kisumu, Kenya
    • Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Kisumu County Hospital (KCH) adult primary care outpatient clinic attendees who screen positive for depression and/or PTSD
2. Ability to attend weekly IPT sessions/fluoxetine monitoring; (3) 18 years or older

Exclusion Criteria:

1. Cognitive dysfunction compromising ability to participate in IPT or accurately take fluoxetine (lack of orientation to person, place, time and situation)
2. acute suicidality requiring higher level of care
3. drug/alcohol use disorders requiring substance use treatment (AUDIT score of 8 or higher, DAST score of 3 or higher)
4. history of mania or requiring treatment for hypomania
5. Outside mental health treatment during the study treatment phases (any mental health treatment is allowed during follow-up phases and is recorded by study team).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interpersonal psychotherapy; IPT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.	Behavioral: Interpersonal Psychotherapy; IPT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.; Other Names: IPT
Active Comparator: fluoxetine; Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.	Drug: Fluoxetine; Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.
Active Comparator: Fluoxetine after IPT; participants who do not remit from MDD and PTSD after treatment with IPT may be randomized to fluoxetine.	Drug: Fluoxetine; Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.
Active Comparator: IPT after fluoxetine; participants who do not remit from MDD and PTSD after treatment with fluoxetine may be randomized to IPT.	Behavioral: Interpersonal Psychotherapy; IPT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.; Other Names: IPT
Active Comparator: IPT + fluoxetine; participants who do not remit from MDD and PTSD after treatment with fluoxetine may be randomized to IPT + fluoxetine.	Drug: Fluoxetine; Fluoxetine is a selective serotonin reuptake inhibitor that is FDA approved for the treatment of depression. Compared to placebo, fluoxetine is more likely to produce symptom response for MDD. Despite the interim development of many other antidepressants since the development of fluoxetine, it remains a first line treatment for depression.; Behavioral: Interpersonal Psychotherapy; IPT was developed in the 1980s by Gerald Klerman and Myrna Weissman to address interpersonal issues in depression. IPT is now considered evidence-based, first-line treatment for depression. IPT improves symptoms by addressing problems in social relationships. IPT is traditionally delivered as weekly one-hour sessions over 12 weeks, focused on one interpersonal problem area.; Other Names: IPT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Major Depression at End of Treatment	Number of Participants with Major Depression. The Beck Depression Inventory-Second Edition (BDI-II) was used and a score of 19 or greater was defined as positive for major depression. BDI-II score below 19 is defined as negative for major depression. Scores range from 0 to 63 with higher total scores indicating more severe depressive symptoms.	End of 1st line Treatment (up to month 6) and end of 2nd line Treatment (up to month 12)
Number of Participants With PTSD	Number of Participants with PTSD. The PTSD Checklist for DSM-5 (PCL-5) was used and score of 23 or greater is defined as positive for PTSD. PCL-5 score below 23 is defined as negative for PTSD. Score range from 0 to 80 with higher total scores indicating more severe PTSD symptoms.	End of 1st line Treatment (up to month 6) and end of 2nd line Treatment (up to month 12)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Mental Health (NIMH); University of California, San Diego; University of Nairobi; Makerere University; Kenya Medical Research Institute
• Investigators: Principal Investigator: Muthoni J Mathai, MDChB, MMed, University of Nairobi; Principal Investigator: Susan M Meffert, MD, MPH, University of California, San Francisco

Publications and helpful links

General Publications

• Levy R, Mathai M, Chatterjee P, Ongeri L, Njuguna S, Onyango D, Akena D, Rota G, Otieno A, Neylan TC, Lukwata H, Kahn JG, Cohen CR, Bukusi D, Aarons GA, Burger R, Blum K, Nahum-Shani I, McCulloch CE, Meffert SM. Implementation research for public sector mental health care scale-up (SMART-DAPPER): a sequential multiple, assignment randomized trial (SMART) of non-specialist-delivered psychotherapy and/or medication for major depressive disorder and posttraumatic stress disorder (DAPPER) integrated with outpatient care clinics at a county hospital in Kenya. BMC Psychiatry. 2019 Dec 28;19(1):424. doi: 10.1186/s12888-019-2395-x.
• Mwai D, Meffert SM, Olwanda EE, Mathai MA, Ongeri L, Burger RL, Mbwayo A, Rota G, Otieno A, Cohen CR, Bukusi D, Aarons GA, Neylan TC, McCulloch CE, Jin C, Akena D, Kahonge S, Kahn JG. Productivity benefits of treatment of depression and post-traumatic stress disorder in Kenya. BMJ Glob Health. 2025 Nov 3;10(11):e018204. doi: 10.1136/bmjgh-2024-018204.
• Burger RL, Meffert SM meffert, Ongeri L, Wangia J, Wambura R, Ajore P, Rota G, Otieno A, Obura RR, Muchembre P, Bukusi D, Mbwayo A, Neylan TC, Akena D, Jin C, McCulloch C, Mathai MA. Factors associated with fluoxetine adherence among outpatients with common mental disorders in Western Kenya. BMJ Glob Health. 2025 Aug 25;10(8):e017929. doi: 10.1136/bmjgh-2024-017929.
• Olwanda E, Mwai D, Mathai M, Burger R, Ongeri L, Bukusi D, Mbwayo A, Rota G, Otieno A, Rota R, Meffert S, Kahn JG. Cost-Benefit Analysis of Interpersonal Therapy and Fluoxetine for Treating Depression and PTSD in Primary Care Settings in Kenya. Res Sq [Preprint]. 2025 Jul 28:rs.3.rs-6977800. doi: 10.21203/rs.3.rs-6977800/v1.
• Meffert S, Mathai M, Neylan T, Mwai D, Onyango DO, Rota G, Otieno A, Obura RR, Wangia J, Opiyo E, Muchembre P, Oluoch D, Wambura R, Mbwayo A, Kahn JG, Cohen CR, Bukusi D, Aarons GA, Burger RL, Jin C, McCulloch C, Kahonge S, Ongeri L. Preference of mHealth versus in-person treatment for depression and post-traumatic stress disorder in Kenya: demographic and clinical characteristics. BMJ Open. 2024 Nov 18;14(11):e083094. doi: 10.1136/bmjopen-2023-083094.
• Getahun M, Mathai MA, Rota G, Allen A, Burger RL, Opiyo E, Oluoch D, Wangia J, Wambura R, Mbwayo A, Muchembre P, Obura RR, Neylan TC, Aarons GA, Ongeri L, Meffert SM. "The peace that I wanted, I got": Qualitative insights from patient experiences of SMART DAPPER interventions for major depression and traumatic stress disorders in Kenya. PLOS Glob Public Health. 2024 Sep 5;4(9):e0002685. doi: 10.1371/journal.pgph.0002685. eCollection 2024.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Actual): May 6, 2024
• Study Completion (Actual): May 6, 2024

Study Registration Dates

• First Submitted: March 2, 2018
• First Submitted That Met QC Criteria: March 8, 2018
• First Posted (Actual): March 15, 2018

Study Record Updates

• Last Update Posted (Estimated): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Trauma and Stressor Related Disorders; Mental Disorders; Mood Disorders; Stress Disorders, Traumatic; Depressive Disorder; Wounds and Injuries; Stress Disorders, Post-Traumatic; Organic Chemicals; Amines; Psychotherapy; Behavioral Disciplines and Activities; Propylamines; Fluoxetine; Interpersonal Psychotherapy
• Other Study ID Numbers: 1R01MH115512 1R01MH113722-01A1; 1R01MH115512 (U.S. NIH Grant/Contract); 1R01MH113722-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NIMH Data Archive The National Institutes of Health (NIH) and NIMH have developed a federation of data repositories called the NIMH Data Archive (NDA) to store the collection of data from participants in research studies related to mental health, regardless of the source of funding. The extensive information collected by these studies, and subsequently stored in the National Database for Autism Research (NDAR), the NIH Pediatric MRI Repository (PedsMRI), the National Database for Clinical Trials Related to Mental Illness (NDCT), and the Research Domain Criteria Database (RDoCdb) provides a rare and valuable scientific resource. The NIH and the NIMH seek to encourage the use of these resources to achieve rapid scientific progress. In order to take full advantage of such resources and maximize their research value, it is important that data be made available, on appropriate terms and conditions, to the largest possible number of qualified investigators in a timely manner.
• IPD Sharing Time Frame: Data will be made available to the NIMH data archive as soon as it is verified as clean and complete, with at least annual updates throughout the duration of the study. Data will be be available indefinitely or for as long as the NIMH repositories supports the electronic data storage.
• IPD Sharing Access Criteria: The investigative team and our NIMH and GACD partners will review requests for data. Evaluation will include scientific merit of the proposal, overlap versus building upon the study goals.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No