Integrating a Stepped Care Model of Screening and Treatment for Depression Into Malawi's National HIV Care Delivery Platform

NCT04777006 | Completed Phase 4 Results DMC

• 1 other identifier: R01MH117760
• Study Type: interventional
• Target: 487
• Locations: 1 country
• Sites: 1

Brief Summary

Malawi is a low-income country in sub-Saharan Africa that has limited resources to address a significant burden of disease-including HIV/AIDS. Additionally, depression is a leading cause of disability in the country but largely remains undiagnosed and untreated. Lack of cost-effective, scalable solutions is a fundamental barrier to expanding depression treatment. Against this backdrop, one major success has been the scale-up of a network of more than 700 HIV clinics, with over half a million patients enrolled in ART. As a chronic care system with dedicated human resources and infrastructure, this presents a strategic platform for integrating depression care, and responds to a robust evidence base outlining the bi-directionality of depression and HIV outcomes. The investigators will evaluate a stepped model of depression care that combines group-based Problem Management Plus (group PM+) with antidepressant therapy (ADT) for 420 adults with moderate/severe depression in Neno District, Malawi, as measured by the Patient Health Questionnaire-9 (PHQ-9). Rollout will follow a stepped-wedge cluster randomized design in which 14 health facilities are randomized to implement the model in five steps over a 15-month period. Primary outcomes (depression symptoms, functional impairment, and overall health) and secondary outcomes (e.g. HIV: viral load, ART adherence; diabetes: A1C levels, treatment adherence; hypertension: systolic blood pressure, treatment adherence) will be measured every three months through 12-month follow-up. The investigators will also evaluate the model's cost-effectiveness, quantified as an incremental cost-effectiveness ratio (ICER) compared to baseline chronic care services in the absence of the intervention model. This study will conduct a stepped-wedge cluster randomized trial to compare the effects of an evidence-based depression care model versus usual care on depression symptom remediation as well as physical health outcomes for chronic care conditions. The investigators will also look at the indirect effects of the intervention at the household level. The investigators' hypothesis is that the intervention will be effective at reducing depression symptoms, improving physical health, and improving household members' wellbeing, compare to treatment as usual. The investigators also hypothesize that the intervention will be highly cost-effective, meaning that the cost per QALY gained will be less than Malawi's median GDP per capita. If determined to be effective and cost-effective, this study will provide a model for integrating depression care into HIV clinics in additional districts of Malawi and other low-resource settings with high HIV prevalence.

Conditions

Depressive Disorder

Keywords

depression; stepped care; behavioral therapy; Problem Management Plus; antidepressant therapy

Outcome Measures

Primary Outcomes (16)

• Depression Symptoms (PHQ-9), 3 Months Post-intervention for All Participants (i.e., for Each Arm)

  Depression symptoms will be measured with the Patient Health Questionnaire 9 (PHQ-9). This will be quantified as PHQ-9 score at 3-months (post-intervention). It is not a change score. Scale Name: Patient Health Questionnaire - 9 Scale Range (Min-Max): 0-27 Scale Notes: Higher value is considered more severe depression symptoms. There are no combined subscales.

  3 months post-intervention for all participants (i.e., for each arm)

• Depression Symptoms (PHQ-9), 6 Months Post-intervention for All Participants (i.e., for Each Arm)

  Depression symptoms will be measured with the Patient Health Questionnaire 9 (PHQ-9). This will be quantified as PHQ-9 score at 6-months (post-intervention). It is not a change score. Scale Name: Patient Health Questionnaire - 9 Scale Range (Min-Max): 0-27 Scale Notes: Higher value is considered more severe depression symptoms. There are no combined subscales.

  6 months post-intervention for all participants (i.e., for each arm)

• Depression Symptoms (PHQ-9), 9 Months Post-intervention for All Participants (i.e., for Each Arm)

  Depression symptoms will be measured with the Patient Health Questionnaire 9 (PHQ-9). This will be quantified as PHQ-9 score at 9-months (post-intervention). It is not a change score. Scale Name: Patient Health Questionnaire - 9 Scale Range (Min-Max): 0-27 Scale Notes: Higher value is considered more severe depression symptoms. There are no combined subscales.

  9 months post-intervention for all participants (i.e., for each arm)

• Depression Symptoms (PHQ-9), 12 Months Post-intervention for All Participants (i.e., for Each Arm).

  Depression symptoms will be measured with the Patient Health Questionnaire 9 (PHQ-9). This will be quantified as PHQ-9 score at 12-months (post-intervention). It is not a change score. Scale Name: Patient Health Questionnaire - 9 Scale Range (Min-Max): 0-27 Scale Notes: Higher value is considered more severe depression symptoms. There are no combined subscales.

  12 months post-intervention for all participants (i.e., for each arm).

• Functional Impairment (WHO Disability Assessment Schedule), 3 Months Post-intervention for All Participants (i.e., for Each Arm).

  Functional impairment will be measured with the World Health Organization (WHO) Disability Assessment Schedule (WHODAS). This will be quantified as WHODAS score at 3-months (post-intervention). It is not a change score. Scale Name: WHO Disability Assessment Schedule Scale Range (Min-Max): 12-60 Scale Notes: Higher value is considered more severe functional impairment. There are no combined subscales.

  3 months post-intervention for all participants (i.e., for each arm).

• Functional Impairment (WHO Disability Assessment Schedule), 6 Months Post-intervention for All Participants (i.e., for Each Arm).

  Functional impairment will be measured with the World Health Organization (WHO) Disability Assessment Schedule (WHODAS). This will be quantified as WHODAS score at 6-months (post-intervention). It is not a change score. Scale Range (Min-Max): 12-60 Scale Notes: Higher value is considered more severe functional impairment. There are no combined subscales.

  6 months post-intervention for all participants (i.e., for each arm).

• Functional Impairment (WHO Disability Assessment Schedule), 9 Months Post-intervention for All Participants (i.e., for Each Arm).

  Functional impairment will be measured with the World Health Organization (WHO) Disability Assessment Schedule (WHODAS). This will be quantified as WHODAS score at 9-months (post-intervention). It is not a change score. Scale Name: WHO Disability Assessment Schedule Scale Range (Min-Max): 12-60 Scale Notes: Higher value is considered more severe functional impairment. There are no combined subscales.

  9 months post-intervention for all participants (i.e., for each arm).

• Functional Impairment (WHO Disability Assessment Schedule), 12 Months Post-intervention for All Participants (i.e., for Each Arm).

  Functional impairment will be measured with the World Health Organization (WHO) Disability Assessment Schedule (WHODAS). This will be quantified as WHODAS score at 12-months (post-intervention). It is not a change score. Scale Name: WHO Disability Assessment Schedule Scale Range (Min-Max): 12-60 Scale Notes: Higher value is considered more severe functional impairment. There are no combined subscales.

  12 months post-intervention for all participants (i.e., for each arm).

• Overall Health Profile (EQ-5D-5L), 3 Months Post-intervention for All Participants (i.e., for Each Arm).

  A health profile will be generated for each individual using the EuroQol (EQ-5D-5L). This will be quantified as EQ-5D-5L score at 3-months (post-intervention). It is not a change score. Scale Name: EuroQol, EQ-5D-5L Scale Range (Min-Max): 5-25 Scale Notes: Higher value is considered worse overall health. There are no combined subscales.

  3 months post-intervention for all participants (i.e., for each arm).

• Overall Health Profile (EQ-5D-5L), 6 Months Post-intervention for All Participants (i.e., for Each Arm).

  A health profile will be generated for each individual using the EuroQol (EQ-5D-5L). This will be quantified as EQ-5D-5L score at 6-months (post-intervention). It is not a change score. Scale Name: EuroQol, EQ-5D-5L Scale Range (Min-Max): 5-25 Scale Notes: Higher value is considered worse overall health. There are no combined subscales.

  6 months post-intervention for all participants (i.e., for each arm).

• Overall Health Profile, 9 Months Post-intervention for All Participants (i.e., for Each Arm).

  A health profile will be generated for each individual using the EuroQol (EQ-5D-5L). This will be quantified as EQ-5D-5L score at 9-months (post-intervention). It is not a change score. Scale Name: EuroQol, EQ-5D-5L Scale Range (Min-Max): 5-25 Scale Notes: Higher value is considered worse overall health. There are no combined subscales.

  9 months post-intervention for all participants (i.e., for each arm).

• Overall Health Profile, 12 Months Post-intervention for All Participants (i.e., for Each Arm).

  A health profile will be generated for each individual using the EuroQol (EQ-5D-5L). This will be quantified as EQ-5D-5L score at 12-months (post-intervention). It is not a change score. Scale Name: EuroQol, EQ-5D-5L Scale Range (Min-Max): 5-25 Scale Notes: Higher value is considered worse overall health. There are no combined subscales.

  12 months post-intervention for all participants (i.e., for each arm).

• Prevalence of Depression (PHQ-9 Score > 9), 3-months Post-intervention for All Participants (for Each Arm).

  Prevalence of depression is calculated as the number of participants with a PHQ-9 score of 9 or greater at the time of measurement.

  3 months post-intervention for all participants (for each arm).

• Prevalence of Depression (PHQ-9 Score > 9), 6-months Post-intervention for All Participants (for Each Arm).

  Prevalence of depression is calculated as the number of participants with a PHQ-9 score of 9 or greater at the time of measurement.

  6 months post-intervention for all participants (for each arm).

• Prevalence of Depression (PHQ-9 Score > 9), 9-months Post-intervention for All Participants (for Each Arm).

  Prevalence of depression is calculated as the number of participants with a PHQ-9 score of 9 or greater at the time of measurement.

  9 months post-intervention for all participants (for each arm).

• Prevalence of Depression (PHQ-9 Score > 9), 12-months Post-intervention for All Participants (for Each Arm).

  Prevalence of depression is calculated as the number of participants with a PHQ-9 score of 9 or greater at the time of measurement.

  12 months post-intervention for all participants (for each arm).

Secondary Outcomes (24)

• ART Adherence (Medication Pick-Up Every 3 Months), 3-Months Post-Intervention for Participants With HIV (for Each Arm)

  3 months post-intervention for participants with HIV (i.e., for each arm).

• ART Adherence (Medication Pick-Up Every 3 Months), 6-Months Post-Intervention for Participants With HIV (for Each Arm)

  6 months post-intervention for participants with HIV (i.e., for each arm).

• ART Adherence (Medication Pick-Up Every 3 Months), 9-Months Post-Intervention for Participants With HIV (for Each Arm)

  9 months post-intervention for participants with HIV (i.e., for each arm).

• ART Adherence (Medication Pick-Up Every 3 Months), 12-Months Post-Intervention for Participants With HIV (for Each Arm)

  12 months post-intervention for participants with HIV (i.e., for each arm)

• Viral Suppression (<500 Copies of the Virus Per mL of Blood), 3-Months Post-Intervention for Participants With HIV (for Each Arm)

  3-months post-intervention for participants with HIV (i.e., for each arm).

Other Outcomes (16)

• Perceived Burden of Care (BAS) Among Household Member, 6 Months After the Start of Study Participant Treatment Eligibility

  6-months after initiation of treatment eligibility for the study trial participant (for each arm).

• Prevalence of Depression (PHQ-9 Score > 9) Among Household Members, 6 Months After the Start of Study Participant Treatment Eligibility

  6-months after initiation of treatment eligibility for the study trial participant (for each arm).

• Functional Impairment (WHO Disability Assessment Schedule) Among Household Members, 6 Months After the Start of Study Participant Treatment Eligibility

  6-months after initiation of treatment eligibility for the study trial participant (for each arm).

Study Arms (5)

Cluster 1 (First Cluster of Clinics Randomized to Receive Care)

EXPERIMENTAL

Arm 1 represents a cluster of 2-3 clinics randomized to begin delivering the intervention at month 3 of the trial

Behavioral: Problem Management Plus; Drug: Antidepressant Therapy

Cluster 2 (Second Cluster of Clinics Randomized to Receive Care)

EXPERIMENTAL

Arm 2 represents a cluster of 2-3 clinics randomized to begin delivering the intervention at month 6 of the trial

Behavioral: Problem Management Plus; Drug: Antidepressant Therapy

Cluster 3 (Third Cluster of Clinics Randomized to Receive Care)

EXPERIMENTAL

Arm 3 represents a cluster of 2-3 clinics randomized to begin delivering the intervention at month 9 of the trial

Behavioral: Problem Management Plus; Drug: Antidepressant Therapy

Cluster 4 (Fourth Cluster of Clinics Randomized to Receive Care)

EXPERIMENTAL

Arm 4 represents a cluster of 2-3 clinics randomized to begin delivering the intervention at month 12 of the trial

Behavioral: Problem Management Plus; Drug: Antidepressant Therapy

Cluster 5 (Fifth Cluster of Clinics Randomized to Receive Care)

EXPERIMENTAL

Arm 5 represents a cluster of 2-3 clinics randomized to begin delivering the intervention at month 15 of the trial

Behavioral: Problem Management Plus; Drug: Antidepressant Therapy

Interventions

Problem Management Plus BEHAVIORAL

PM+ is a cognitive-behavioral intervention that trains recipients to improve their management of practical problems, and uses the term "problem management" rather than "problem solving" to emphasize that many problems encountered by individuals living in adverse circumstances may not be "solvable". The "plus" in PM+ underscores additional evidence-based behavioral strategies incorporated into the model, including: stress management strategies, behavioral activation, and social support strengthening. In total, PM+ comprises five sessions held once per week for 1.5. to 2.5 hours per session. The model has shown success in reducing depression symptoms in low-resource settings such as Nepal and Pakistan.4

Also known as: PM+

Cluster 1 (First Cluster of Clinics Randomized to Receive Care); Cluster 2 (Second Cluster of Clinics Randomized to Receive Care); Cluster 3 (Third Cluster of Clinics Randomized to Receive Care); Cluster 4 (Fourth Cluster of Clinics Randomized to Receive Care); Cluster 5 (Fifth Cluster of Clinics Randomized to Receive Care)

Antidepressant Therapy DRUG

Fluoxetine, a serotonin selective reuptake inhibitor (SSRI), and amitriptyline, a tricyclic antidepressant (TCA), are part of Malawi's national formulary. Neno District supply chain is supported by PIH, which reduces stock-outs relative to those observed in other Malawian settings. Fluoxetine is typically the first drug of choice because it is safer and better tolerated. Daily dose will commence at 20 mg of fluoxetine, or 25 mg of amitriptyline. At monthly follow-up visits, a dose increment or medication change may be considered based on measures of treatment response and side effects, using an Antidepressant Side Effect Checklist. This algorithm-based process will be repeated every other week until the patient is fully responding to treatment (PHQ-9 \< 5) for a period of three months. Dose escalations of more than one increment and medication changes will be reviewed with the doctor-in-charge. If on ADT at end of study, it will be sustained as part of usual care.

Also known as: Fluoxetine, Amitriptyline

Cluster 1 (First Cluster of Clinics Randomized to Receive Care); Cluster 2 (Second Cluster of Clinics Randomized to Receive Care); Cluster 3 (Third Cluster of Clinics Randomized to Receive Care); Cluster 4 (Fourth Cluster of Clinics Randomized to Receive Care); Cluster 5 (Fifth Cluster of Clinics Randomized to Receive Care)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Attendance at integrated chronic care centers (IC3) in Neno District, Malawi
• Adult, age 18 or older

You may not qualify if:

• Psychosis, or indication of other Axis I psychiatric illness

Sponsors & Collaborators

• RAND: lead
• National Institute of Mental Health (NIMH): collaborator
• Ministry of Health, Malawi: collaborator
• Partners in Health: collaborator
• Brigham and Women's Hospital: collaborator
• Blantyre College of Medicine: collaborator
• University of Birmingham: collaborator

Study Sites (1)

Partners In Health

Neno, Neno District, Malawi

Location

Related Publications (12)

• Udedi M. The prevalence of depression among patients and its detection by primary health care workers at Matawale Health Centre (Zomba). Malawi Med J. 2014 Jun;26(2):34-7.

  PMID: 25157314 BACKGROUND

• World Economic Forum. The Global Economic Burden of Non-Communicable Diseases. World Economic Forum; Harvard School of Public Health; 2011.

  BACKGROUND

• Passchier RV, Abas MA, Ebuenyi ID, Pariante CM. Effectiveness of depression interventions for people living with HIV in Sub-Saharan Africa: A systematic review & meta-analysis of psychological & immunological outcomes. Brain Behav Immun. 2018 Oct;73:261-273. doi: 10.1016/j.bbi.2018.05.010. Epub 2018 May 13.

  PMID: 29768184 BACKGROUND

• McBain RK, Salhi C, Hann K, Kellie J, Kamara A, Salomon JA, Kim JJ, Betancourt TS. Improving outcomes for caregivers through treatment of young people affected by war: a randomized controlled trial in Sierra Leone. Bull World Health Organ. 2015 Dec 1;93(12):834-41. doi: 10.2471/BLT.14.139105. Epub 2015 Oct 16.

  PMID: 26668435 BACKGROUND

• Dawson KS, Bryant RA, Harper M, Kuowei Tay A, Rahman A, Schafer A, van Ommeren M. Problem Management Plus (PM+): a WHO transdiagnostic psychological intervention for common mental health problems. World Psychiatry. 2015 Oct;14(3):354-7. doi: 10.1002/wps.20255. No abstract available.

  PMID: 26407793 BACKGROUND

• Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13. doi: 10.1046/j.1525-1497.2001.016009606.x.

  PMID: 11556941 BACKGROUND

• Mwale O, Mpinga K, Rukundo T, Kamwiyo M, Kayira W, Matanje B, Munyaneza F, Ruderman T, Raviola G, Smith S, Okunogbe A, Kachimanga C, McBain RK. Cost analysis of integrating depression treatment into chronic care in Malawi: evidence from a cluster randomised controlled trial. BMJ Open. 2025 Oct 7;15(10):e095494. doi: 10.1136/bmjopen-2024-095494.

  PMID: 41062145 DERIVED

• Mwale O, Kasambala C, Houde A, Mpinga K, Kayira W, Harawa M, Kamwiyo M, Isaacs R, Nhlema B, Ruderman T, Liwimbi O, Udedi M, Kelly K, McBain RK. Patient perspectives on group problem management plus for adults with major depressive disorder in rural Malawi. Glob Health Action. 2025 Dec;18(1):2500785. doi: 10.1080/16549716.2025.2500785. Epub 2025 May 9.

  PMID: 40340587 DERIVED

• McBain RK, Mwale O, Mpinga K, Kamwiyo M, Kayira W, Ruderman T, Connolly E, Watson SI, Wroe EB, Munyaneza F, Dullie L, Raviola G, Smith SL, Kulisewa K, Udedi M, Patel V, Wagner GJ. Effectiveness, cost-effectiveness, and positive externalities of integrated chronic care for adults with major depressive disorder in Malawi (IC3D): a stepped-wedge, cluster-randomised, controlled trial. Lancet. 2024 Nov 9;404(10465):1823-1834. doi: 10.1016/S0140-6736(24)01809-9. Epub 2024 Oct 30.

  PMID: 39488229 DERIVED

• Mpinga K, Rukundo T, Mwale O, Kamwiyo M, Thengo L, Ruderman T, Matanje B, Munyaneza F, Connolly E, Kulisewa K, Udedi M, Kachimanga C, Dullie L, McBain R. Depressive disorder at the household level: prevalence and correlates of depressive symptoms among household members. Glob Health Action. 2023 Dec 31;16(1):2241808. doi: 10.1080/16549716.2023.2241808.

  PMID: 37554074 DERIVED

• Mpinga K, Lee SD, Mwale O, Kamwiyo M, Nyirongo R, Ruderman T, Connolly E, Kayira W, Munyaneza F, Matanje B, Kachimanga C, Zaniku HR, Kulisewa K, Udedi M, Wagner G, McBain R. Prevalence and correlates of internalized stigma among adults with HIV and major depressive disorder in rural Malawi. AIDS Care. 2023 Nov;35(11):1775-1785. doi: 10.1080/09540121.2023.2195609. Epub 2023 Mar 31.

  PMID: 37001058 DERIVED

• McBain RK, Mwale O, Ruderman T, Kayira W, Connolly E, Chalamanda M, Kachimanga C, Khongo BD, Wilson J, Wroe E, Raviola G, Smith S, Coleman S, Kelly K, Houde A, Tebeka MG, Watson S, Kulisewa K, Udedi M, Wagner G. Stepped care for depression at integrated chronic care centers (IC3) in Malawi: study protocol for a stepped-wedge cluster randomized controlled trial. Trials. 2021 Sep 16;22(1):630. doi: 10.1186/s13063-021-05601-1.

  PMID: 34530894 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Depression

Interventions

Fluoxetine; Amitriptyline

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

PIH was unable to collect data for two outcomes, leading to 0 participants analyzed: (1) WHO Staging, because National Guidelines were revised to focus on viral load; and (2) HbA1C, because supply chains were unable to store samples for transport. Earlier communication should have clarified that blood glucose (a proxy) was collected in some instances--but never HbA1c, the pre-specified outcome measure (this was only recently clarified by the field team). We thus don't have analyzable data.

Results Point of Contact

• Title: Ryan McBain
• Organization: RAND

rmcbain@rand.org

(703) 413-1100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Those who are screening and diagnosing depression will not be made aware of the randomization sequence. Likewise, those assessing outcomes will not be made aware of the randomization sequence.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Stepped wedge cluster randomized trial

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: March 2, 2021
• Study Start: September 1, 2021
• Primary Completion: April 30, 2023
• Study Completion: June 30, 2025
• Last Updated: June 9, 2026
• Results First Posted: June 9, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: Data will become available in July 2025 and remain available at Harvard's DataVerse indefinitely.
• Access Criteria: Access to data files on Harvard's DataVerse requires that researchers complete compliance and authorization forms.

Locations

MA (1)