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

NCT05944926 | Active Not Recruiting Phase 3 DMC

• 3 other identifiers: IRB20-2144CTRI/2024/01/0619321R01MH121632-01A1
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 1

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. 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. 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.

Conditions

Depression; Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Depression remission

  Remission is defined as PHQ-9 total score \< 5. The PHQ-9 is a self-report measure of depressive symptoms in the prior 2 weeks. Items are rated on a 4-point Likert scale from 0 (not at all) to 3 (nearly every day), with total scores ranging from 0 to 27, where higher scores indicate more severe depressive symptoms. We will dichotomised the total score using the cut-off score of 5.

  3 months post recruitment

Secondary Outcomes (6)

• Cost-effectiveness of optimization

  3-, 6-, 9-, 12-months post recruitment

• Depression severity, as measured by the Patient Health Questionnaire-9 (PHQ-9)

  3-, 6-, 9-, 12-months post recruitment

• Generalized Anxiety Disorder Assessment (GAD-7)

  3-, 6-, 9-, 12-months post recruitment

• WHO Disability Assessment Schedule II (WHODAS-II)

  3-, 6-, 9-, 12-months post recruitment

• Minimal Clinically Important Difference (MCID)

  3-, 6-, 9-, 12-months post recruitment

Other Outcomes (3)

• Recovery from depression as measured by the PHQ-9

  12-month post recruitment

• Client Service Receipt Inventory (CSRI)

  3-, 6-, 9-, 12-months post recruitment

• Quality Adjusted Life Years (QALYs) as measured by WHODAS II

  3-, 6-, 9-, 12-months post recruitment

Study Arms (2)

Healthy Activity Program (HAP)

EXPERIMENTAL

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

Behavioral: Healthy Activity Program (HAP)

Antidepressant medication (fluoxetine)

EXPERIMENTAL

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.

Drug: Antidepressant medication (fluoxetine)

Interventions

Healthy Activity Program (HAP) 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.

Healthy Activity Program (HAP)

Antidepressant medication (fluoxetine) 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).

Antidepressant medication (fluoxetine)

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• Women who are pregnant or are breastfeeding or lactating
• Patients with a history of psychosis, including schizophrenia spectrum disorders or bipolar disorder.
• Participants planning to permanently move out of the study area during the follow-up period.
• Patients with evidence of cognitive impairment.
• Patients who do not speak either English or Hindi.
• Patients who are undergoing treatment for depression at the time of recruitment or who completed treatment within one month prior to recruitment
• Patients at imminent risk for suicide
• Patients from households in which another member has been recruited into the study

Sponsors & Collaborators

• Harvard Medical School (HMS and HSDM): lead
• Sangath: collaborator
• All India Institute of Medical Sciences, Bhopal: collaborator
• Vanderbilt University: collaborator
• Brigham and Women's Hospital: collaborator
• Centre for Addiction and Mental Health: collaborator
• Massachusetts General Hospital: collaborator
• Harvard School of Public Health (HSPH): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Sangath

Bhopal, Madhya Pradesh, 462016, India

Location

Related Publications (3)

• 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.

  PMID: 28898283 BACKGROUND

• 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.

  PMID: 40739549 DERIVED

• 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.

  PMID: 40470239 DERIVED

Related Links

• Study overview

MeSH Terms

Conditions

Depression; Depressive Disorder

Interventions

Antidepressive Agents; Fluoxetine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Psychotropic Drugs; Central Nervous System Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Propylamines; Amines; Organic Chemicals

Study Officials

• Vikram Patel, MD

  Vikram_Patel@hms.harvard.edu

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Masked (blinded) field-based assessors will conduct all outcome assessments
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator; The Pershing Square Professor of Global Health at Harvard Medical School

Model Details: Fluoxetine versus a contextually adapted version of behavioral activation called the Healthy Activity Program (HAP) delivered by non-specialists for treatment of depression

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: July 13, 2023
• Study Start: March 18, 2024
• Primary Completion: April 10, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available indefinitely or for as long as the NIMH repositories support it.
• Access Criteria: Researchers and interested parties who wish to access the data can submit a formal data access request to the NIMH Data Archive. Researchers who gain access to the data will be required to comply with the data usage policies and guidelines set forth by the NIMH Data Archive.

Locations

IN (1)