Improving Outcomes in Depression in Primary Care in a Low Resource Setting

NCT ID: NCT05944926

Last Updated: 2025-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1500 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-18
• Study Completion Date: 2027-03-31

Brief Summary

The OptimizeD study aims to improve outcomes in depression in primary care in India. This study will randomize 1500 patients with moderate to severe depression to either psychotherapy based on behavioral activation called the Healthy Activity Program (HAP) or antidepressant medication (fluoxetine).

The study has two primary objectives:

1. Use patient characteristics to generate a precision treatment rule based on baseline information for predicting in advance what works best for whom (and which patients are unlikely to respond to either treatment and should be referred to specialist care).

2. Conduct a cost-effectiveness analysis by comparing relative costs and effectiveness between those who were randomly allocated to their optimal treatment with those who were randomly allocated to a non-optimal treatment based on the precision treatment rule.

Detailed Description

Depression is the leading mental health contributor to the Global Burden of Disease. The World Health Organization's mhGAP initiative advocates the use of brief psychological therapies such as behavioral activation or antidepressant medications as first-line options for the treatment of moderate to severe depression in primary care settings, but not all patients will fully remit on either treatment. It is likely that different patients will respond to different treatments, but the optimal treatment for each individual remains unknown (and which patients are unlikely to respond to either treatment and should be referred to specialist care). Enhancing our ability to determine the optimal intervention for a particular patient has the potential to enhance the overall effectiveness of mental health care delivery in a more cost-efficient manner. This is a critical gap in knowledge in the treatment of depression across clinical settings globally.

The main objective of the OptimizeD study is to determine whether different patients respond differentially to brief psychological treatment or a widely used generic SSRI and, if so, whether one can optimize outcomes in a cost-effective fashion for primary care patients with moderate to severe depression.

The study has two specific aims and two exploratory aims:

• Specific Aim 1 (Clinical and Functional Outcomes): To evaluate the effectiveness of optimization via generating a precision treatment rule (PTR) on patients with moderate to severe depression randomized to either psychotherapy based on behavioral activation called the Healthy Activity Program (HAP) or antidepressant medication (fluoxetine). The study will use machine learning to develop the PTR, using a wide range of clinical, socio-economic, and neuro-cognitive characteristics measured at baseline as predictors. The investigators hypothesize that patients randomized by chance to their optimal intervention will be more likely to remit and recover than patients who are not.
• Specific Aim 2 (Cost-effectiveness Outcomes): To assess the costs of optimal vs. non-optimal treatments and to conduct a cost-effectiveness analysis by comparing relative costs and effectiveness between those who were randomly allocated to their optimal treatment with those who were randomly allocated to a non-optimal treatment, based on the PTR developed in Aim 1. The investigators hypothesize that optimizing will be more cost-effective than not.
• Exploratory Aim 1 (Mediators): To explore whether one can use the PTR to make our tests of mediation more precise. Patients who respond differentially to different treatments adhere to different causal mechanisms, and inclusion of the PTR in interaction terms with the purported mediators should facilitate the detection of moderated mediation among patients who show specificity of response. The investigators will also consider whether treatment-related factors (e.g., adherence, quality) act as mediators of the effects of each treatment on remission and recovery. This exploratory aim will offer insights into mechanisms of action for each treatment.
• Exploratory Aim 2 (Genetic Predictors): To explore whether polygenic risk scores and other biomarkers can enhance the prediction of both general and differential response to either treatment.

As a secondary objective, the study will evaluate the effectiveness of optimization in the long-term. The investigators hypothesize that patients allocated to their optimized treatment will be more likely to recover than patients who are allocated to their non-optimal treatment.

All trial procedures used in the main trial were first evaluated in a pilot study (NCT06153004), which employed the same design and methods to assess feasibility across recruitment, randomization, retention, treatment adherence and fidelity, and data quality assurance.

Conditions

Depression; Depressive Disorder

Study Design

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

Study Groups

Antidepressant medication (fluoxetine)

Fluoxetine is a selective serotonin reuptake inhibitors (SSRIs) and one of the safest medications used to treat depression. It is a routinely used medication and part of the Essential Drug List (EDL) in India.

Group Type: EXPERIMENTAL

Antidepressant medication (fluoxetine)

Intervention Type: DRUG

Patients assigned to antidepressant medication will start on fluoxetine 20 mg/day and can be raised to 40 mg/day (the maximum mandated by treatment guidelines for primary care in India) at week 3 or 6 for patients who have yet to remit. Participants who do not tolerate fluoxetine can be switched to escitalopram at week 6 (10mg which can be titrated up to 20 mg).

Healthy Activity Program (HAP)

HAP is a brief psychological treatment adapted from behavioral activation therapy, an empirically supported psychological treatment recommended by WHO.

Group Type: EXPERIMENTAL

Healthy Activity Program (HAP)

Intervention Type: BEHAVIORAL

HAP, delivered over 6-8 sessions by non-specialist healthcare workers, has behavioural activation as the core psychological strategy along with other strategies such as problem-solving and activation of social networks.

Interventions

Healthy Activity Program (HAP)

HAP, delivered over 6-8 sessions by non-specialist healthcare workers, has behavioural activation as the core psychological strategy along with other strategies such as problem-solving and activation of social networks.

Intervention Type: BEHAVIORAL

Antidepressant medication (fluoxetine)

Patients assigned to antidepressant medication will start on fluoxetine 20 mg/day and can be raised to 40 mg/day (the maximum mandated by treatment guidelines for primary care in India) at week 3 or 6 for patients who have yet to remit. Participants who do not tolerate fluoxetine can be switched to escitalopram at week 6 (10mg which can be titrated up to 20 mg).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants will be adults aged 18 or over of any gender attending one of the selected Primary Health Care Centers with a "diagnosis" of moderate to severe depression based on scores of 10 or above on the Patient Health Questionnaire-9 (PHQ-9).

Exclusion Criteria

1. Women who are pregnant or are breastfeeding or lactating

2. Patients with a history of psychosis, including schizophrenia spectrum disorders or bipolar disorder.

3. Participants planning to permanently move out of the study area during the follow-up period.

4. Patients with evidence of cognitive impairment.

5. Patients who do not speak either English or Hindi.

6. Patients who are undergoing treatment for depression at the time of recruitment or who completed treatment within one month prior to recruitment

7. Patients at imminent risk for suicide

8. Patients from households in which another member has been recruited into the study

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

Sponsors

Sangath

OTHER

Sponsor Role: collaborator

All India Institute of Medical Sciences, Bhopal

OTHER

Sponsor Role: collaborator

Vanderbilt University

OTHER

Sponsor Role: collaborator

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role: collaborator

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role: lead

Responsible Party

Vikram Patel

Co-Principal Investigator; The Pershing Square Professor of Global Health at Harvard Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Vikram Patel, MD

Role: PRINCIPAL_INVESTIGATOR

Vikram_Patel@hms.harvard.edu

Locations

Sangath

Bhopal, Madhya Pradesh, India

Site Status: RECRUITING

Countries

India

Central Contacts

Julia R Pozuelo, PhD

Role: CONTACT

julia_ruizpozuelo@hms.harvard.edu

617-432-1707

Facility Contacts

Deepak Tugnawat, MSW

Role: primary

deepak.tugnawat@sangath.in

91-8523843957

References

Pozuelo JR, Lahiri A, Singh RSP, Kushwah A, Khanduri M, Shukla A, Khan A, G S, Shende V, Parashar Y, Mehra YK, Bhan A, Kessler RC, Singla DR, Naslund JA, Choi KW, Cuijpers P, DeRubeis R, Herzallah MM, Lu C, Smoller JW, VanderWeele TJ, Rozatkar AR, Modak T, Joel MM, Biswas D, Atal S, Kulsum U, Hollon SD, Patel V. Optimizing treatment for depression in primary care using psychotherapy versus antidepressant medication in a low-resource setting: protocol for the OptimizeD randomized controlled trial. BMC Psychiatry. 2025 Jul 30;25(1):744. doi: 10.1186/s12888-025-07030-9.

Reference Type: DERIVED

PMID: 40739549 (View on PubMed)

Weobong B, Weiss HA, McDaid D, Singla DR, Hollon SD, Nadkarni A, Park AL, Bhat B, Katti B, Anand A, Dimidjian S, Araya R, King M, Vijayakumar L, Wilson GT, Velleman R, Kirkwood BR, Fairburn CG, Patel V. Sustained effectiveness and cost-effectiveness of the Healthy Activity Programme, a brief psychological treatment for depression delivered by lay counsellors in primary care: 12-month follow-up of a randomised controlled trial. PLoS Med. 2017 Sep 12;14(9):e1002385. doi: 10.1371/journal.pmed.1002385. eCollection 2017 Sep.

Reference Type: BACKGROUND

PMID: 28898283 (View on PubMed)

Pozuelo JR, Lahiri A, Singh RSP, Kushwah A, Khanduri M, Shukla A, Khan A, G S, Shende V, Parashar Y, Mehra YK, Bhan A, Kessler RC, Singla DR, Naslund JA, Choi K, Cuijpers P, DeRubeis R, Herzallah M, Lu C, Smoller JW, VanderWeele TJ, Rozatkar A, Joel MM, Biswas D, Atal S, Kulsum U, Hollon SD, Patel V. Optimizing Treatment for Depression in Primary Care Using Psychotherapy Versus Antidepressant Medication in a Low-Resource Setting: Protocol for the OptimizeD Randomized Controlled Trial. Res Sq [Preprint]. 2025 May 23:rs.3.rs-6716211. doi: 10.21203/rs.3.rs-6716211/v1.

Reference Type: DERIVED

PMID: 40470239 (View on PubMed)

Related Links

https://mentalhealthforalllab.hms.harvard.edu/optimized

Study overview

Other Identifiers

CTRI/2024/01/061932

Identifier Type: OTHER

Identifier Source: secondary_id

1R01MH121632-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB20-2144

Identifier Type: -

Identifier Source: org_study_id