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

NCT ID: NCT03466346

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2162 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-31
• Study Completion Date: 2024-05-06

Brief Summary

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.

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.

Conditions

Depression, Unipolar; Posttraumatic Stress Disorder; Trauma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Interpersonal Psychotherapy

Intervention Type: BEHAVIORAL

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.

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.

Group Type: ACTIVE_COMPARATOR

Fluoxetine

Intervention Type: DRUG

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.

Fluoxetine after IPT

participants who do not remit from MDD and PTSD after treatment with IPT may be randomized to fluoxetine.

Group Type: ACTIVE_COMPARATOR

Fluoxetine

Intervention Type: DRUG

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.

IPT after fluoxetine

participants who do not remit from MDD and PTSD after treatment with fluoxetine may be randomized to IPT.

Group Type: ACTIVE_COMPARATOR

Interpersonal Psychotherapy

Intervention Type: BEHAVIORAL

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.

IPT + fluoxetine

participants who do not remit from MDD and PTSD after treatment with fluoxetine may be randomized to IPT + fluoxetine.

Group Type: ACTIVE_COMPARATOR

Fluoxetine

Intervention Type: DRUG

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.

Interpersonal Psychotherapy

Intervention Type: BEHAVIORAL

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

IPT

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nairobi

OTHER

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Kenya Medical Research Institute

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: collaborator

Makerere University

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Muthoni J Mathai, MDChB, MMed

Role: PRINCIPAL_INVESTIGATOR

University of Nairobi

Susan M Meffert, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH)

Kisumu, , Kenya

Kisumu County Hospital

Kisumu, , Kenya

Lumumba Health Center

Kisumu, , Kenya

Countries

Kenya

References

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.

Reference Type: DERIVED

PMID: 41184028 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40854809 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40766223 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39557549 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39236052 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31883526 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

1R01MH115512

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01MH113722-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1R01MH115512 1R01MH113722-01A1

Identifier Type: -

Identifier Source: org_study_id