OptimizeD Pilot Study

Study Overview
=================
Brief Summary
-----------------
This pilot study aims to explore and refine the trial procedures that will be implemented in a larger-scale clinical trial scheduled to commence in March 2024 (NCT05944926). As part of this study, 60 patients with moderate to severe depression will be randomized to either psychotherapy based on behavioral activation called the Healthy Activity Program (HAP) or antidepressant medication. The pilot study has two primary objectives: Evaluate the feasibility and acceptability of the study Collect essential outcome data in preparation for the larger trial

Detailed Description
-----------------
This pilot study will play a pivotal role in preparation for the forthcoming larger clinical trial, named the OptimizeD study, scheduled for launch in March 2024 (NCT05944926). The primary objective of the OptimizeD study is to explore whether different patients respond differentially to a brief psychological treatment, known as the Healthy Activity Program, or a widely used generic Selective Serotonin Reuptake Inhibitor (fluoxetine). If such differences exist, this study aims to explore whether one can develop a machine learning-generated precision treatment rule to predict the most effective treatment based on individual baseline characteristics. The pilot study has two primary objectives: Evaluate the feasibility and acceptability of the study: This pilot study will focus on assessing the feasibility and acceptability of the research protocol, including recruitment strategies, data collection methods, interventions, and risk management procedures. This evaluation will help refine and tailor the study procedures and play a critical role in setting the stage for the subsequent OptimizeD study. Collect essential outcome data in preparation for the larger trial: This study will test and refine the data instruments, gather initial data on efficacy, and refine the baseline assessment (which will serve as the cornerstone for the development of the precision treatment rule).

Official Title
-----------------
Improving Outcomes in Depression in Primary Care in a Low Resource Setting: Evidence From a Pilot Study

Conditions
-----------------
Depression, Depressive Disorder

Intervention / Treatment
-----------------
* Behavioral: Healthy Activity Program (HAP)
* Drug: Antidepressant medication (ADM)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants will be adults aged 18 or over of any gender attending one of eight 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: 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 move out of the study area during the follow-up period. Patients over 65 years of age with evidence of cognitive impairment - Patients who do not speak the study or local language (English or Hindi) Patients who are undergoing treatment for depression at the time of recruitment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Fluoxetine versus a contextually adapted version of behavioral activation called the Healthy Activity Program (HAP) delivered by non-specialists for the treatment of depression
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Activity Program (HAP)<br>HAP is a brief psychological treatment adapted from behavioral activation therapy, an empirically supported psychological treatment recommended by the World Health Organization. | Behavioral: Healthy Activity Program (HAP)<br>* 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.<br>|
| Experimental: Antidepressant medication (ADM)<br>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 (ADM)<br>* Patients assigned to antidepressant medication will start on fluoxetine 20 mg/day which 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. Patients who cannot tolerate fluoxetine will be switched to escitalopram.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility as measured by recruitment rate | The investigators will assess enrolment rate for eligible participants | 3-months | 
| Feasibility as measured by retention rate | The investigators will evaluate retention rates, which are calculated as the ratio of patients who complete the study to the total number of patients enrolled | 3-months | 
| Feasibility of study assessments | The investigators will examine adherence rates to study procedures and the barriers to study participation reported by participants over the course of the study. | 3-months | 
| Acceptability of interventions by participants | The investigators will assess treatment compliance. For the HAP arm, this will be defined as having completed at least six sessions. For the ADM arm, this will be defined as having completed more than 80% of the recommended 12-week course of antidepressant medication. | 3-months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Depressive Symptoms | The investigators will measure depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 is a 9-item self-report scale to screen for symptoms of depression. 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. | 3-months |