Clinical trial NCT03466346: SMART-DAPPER: Leveraging the Depression And Primary-care Partnership for Effectiveness-implementation Research Project
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression, Unipolar
Posttraumatic Stress Disorder
Trauma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of Nairobi
name: National Institute of Mental Health (NIMH)
name: Kenya Medical Research Institute
name: University of California, San Diego
name: Makerere University
First posted: 2018-03-15
Enrollment: 2162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: fluoxetine versus interpersonal psychotherapy (IPT) for treatment of Major Depressive Disorder (MDD) and/or Posttraumatic Stress Disorder (PTSD)
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

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).

Primary outcomes:
measure: Depression
timeFrame: Baseline, End of study (an average of 30 months)
measure: PTSD
timeFrame: Baseline, End of study (an average of 30 months)
Secondary outcomes:
Other outcomes:
Locations:
city: Kisumu
country: Kenya
facility: Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH)
city: Kisumu
country: Kenya
facility: Kisumu County Hospital
city: Kisumu
country: Kenya
facility: Lumumba Health Center
Study officials:
affiliation: University of Nairobi
name: Muthoni J Mathai, MDChB, MMed
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Susan M Meffert, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.