Clinical trial NCT05944926: Improving Outcomes in Depression in Primary Care in a Low Resource Setting
Official title: Improving Outcomes in Depression in Primary Care in a Low Resource Setting
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Depression
Depressive Disorder
Lead sponsor: Harvard Medical School (HMS and HSDM)
Sponsor class: OTHER
Collaborators: name: Sangath
name: All India Institute of Medical Sciences, Bhopal
name: Vanderbilt University
name: Brigham and Women's Hospital
name: Centre for Addiction and Mental Health
name: Massachusetts General Hospital
name: Harvard School of Public Health (HSPH)
name: National Institute of Mental Health (NIMH)
First posted: 2023-07-13
Enrollment: 1500
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 a contextually adapted version of behavioral activation called the Healthy Activity Program (HAP) delivered by non-specialists for treatment of depression
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

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

Primary outcomes:
measure: Depression remission
timeFrame: 3 months post recruitment
Secondary outcomes:
measure: Cost-effectiveness of optimization
timeFrame: 3-, 6-, 9-, 12-months post recruitment
measure: Depression severity, as measured by the Patient Health Questionnaire-9 (PHQ-9)
timeFrame: 3-, 6-, 9-, 12-months post recruitment
measure: Generalized Anxiety Disorder Assessment (GAD-7)
timeFrame: 3-, 6-, 9-, 12-months post recruitment
measure: WHO Disability Assessment Schedule II (WHODAS-II)
timeFrame: 3-, 6-, 9-, 12-months post recruitment
measure: Minimal Clinically Important Difference (MCID)
timeFrame: 3-, 6-, 9-, 12-months post recruitment
measure: World Health Organization Well-Being Index (WHO-5)
timeFrame: 3-, 6-, 9-, 12-months post recruitment
Other outcomes:
measure: Recovery from depression as measured by the PHQ-9
timeFrame: 12-month post recruitment
measure: Client Service Receipt Inventory (CSRI)
timeFrame: 3-, 6-, 9-, 12-months post recruitment
measure: Quality Adjusted Life Years (QALYs) as measured by WHODAS II
timeFrame: 3-, 6-, 9-, 12-months post recruitment
Locations:
city: Bhopal
country: India
facility: Sangath
state: Madhya Pradesh
Study officials:
affiliation: Vikram_Patel@hms.harvard.edu
name: Vikram Patel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.