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:

1. Evaluate the feasibility and acceptability of the study
2. Collect essential outcome data in preparation for the larger trial

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:

1. 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.

2. 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).

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

Individual participant data will be shared through the National Institute of Mental Health (NIMH) Data Archive. To ensure participant privacy and data security, all shared data will be de-identified according to established protocols and guidelines. The data sharing plan will be periodically reviewed and updated, as necessary, to align with evolving best practices, policies, and guidelines for data sharing.

Data will be available indefinitely or for as long as the NIMH repositories support it.

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.

Masked (blinded) field-based assessors will conduct all outcome assessments