The CONTROL (COgNitive Therapy for depRessiOn in tubercuLosis treatment) programme of research to improve outcomes for depression and TB in Pakistan and Afghanistan.

Introduction: Tuberculosis (TB) is the 10th leading cause of death globally. Common mental disorders, such as depression, are significant multimorbidities with TB in most Low and Middle Income Countries (LMIC). Pakistan is ranked fifth among TB high-burden countries. Afghanistan has an even worse TB situation due to ongoing conflict. About half of people with TB also have comorbid depression. TB and depression is a typical multimorbidity in which each disease increases the risk of poorer outcomes for the other. Importantly, depression in TB increases risk of poor treatment adherence with anti TB treatment (ATT) that can lead to Multidrug resistant TB (MDRTB) which is considered as health security risk. No effective interventions are available to treat depression in people with TB. We aim to develop and test a psychosocial intervention for treating depression in TB and improving adherence with antidepressants treatment (ATT). Research Plan: We will develop CONTROL (COgNitive Therapy for depRessiOn in tubercuLosis treatment), a complex intervention consisting of 4 key elements (i) screening for depression in TB patients using the Patient Health Questionnaire–2 (ii) a brief psychological intervention based on cognitive therapy principles consisting of six sessions (iii) intervention delivery using a cascade model of training to train TB health workers to provide therapy (iv) Integration of mental health outcomes in TB control programme. The research programme will be based in Pakistan and Afghanistan to develop and evaluate the CONTROL intervention and identify early implementation outcomes. The research programme will consist of four WPs:- Developing intervention using evidence synthesis, ethnographic and qualitative methods incorporating patients perspective Inbuilt pilot RCT to test and refine intervention with a clear progression criterion to the definitive trial. The definitive trial will test CONTROL versus Enhanced Treatment as Usual. The evaluation of intervention will consist of a combination of quantitative and qualitative methods, including a pragmatic RCT following a hybrid type-1 implementation approach. The primary effectiveness outcomes will include depressive symptoms and adherence with ATT. Implementation outcomes include cost and cost-effectiveness, adoption, feasibility and acceptability of the CONTROL to all stakeholders, intervention fidelity and barriers and facilitators of implementation assessed through process evaluation. A sample size of 560 (280 each arm) will have adequate power to test two primary outcomes (a) improvement in depression (b) adherence to ATT. Developing a strategy and plan for the scale up using theory of behaviour change approach. Capacity building, involving stakeholders, patients and public are integrated in all WPs. The research programme is geared towards implementation and scale up of the intervention in routine TB care which will help to overcome the stigma associated with TB and depression. Expected outcomes: A successful CONTROL programme will uniquely address two major problems in TB control worldwide; depression and poor treatment adherence with ATT. This will potentially have enormous public health impact by reducing TB deaths, reducing infection spread and decreasing the risk of MDRTB. With its implementation approach the programme will also enhance capacity for implementation research in LMIC.