Clinical and economic burden of treatment-resistant depression : current and future perspectives

Abstract

Depression presents significant global disease burden. Despite the advancement in therapeutic development, a significant proportion of patients still fail to respond to antidepressants and suffer from treatment-resistant depression (TRD). To inform evidence-based policy practice, a timely and comprehensive evaluation about the disease burden of depression with a focus on TRD is a key step to facilitate long-term mental health policy planning. In contrast to the chronic and recurrent nature of depression, many studies that assessed the burden of TRD had short follow-ups and horizon. Evidence regarding the interrelationships between mental health and physical health was limited, which resulted in many decision models overlooking the potential intensifying effect of comorbidities on the burden of depression.

To address these literature gaps and improve policy planning, this thesis aimed to identify the unmet care needs and gaps in service provision of depression care, and facilitate early resource planning for the future burden. These were achieved by the objectives: 1) to evaluate the clinical and economic burden of depression and TRD from the current and future perspectives, and 2) to explore the interplay between depression and physical health. Territory-wide electronic medical record database was utilized to design three epidemiological studies to evaluate depression burden from the current perspective. The established relationships and estimates from the studies then offered important model elements and parameters to design a health economic study using Markov modelling to project the future 10-year depression burden. The main findings of the studies were: 1) 18% of depression patients could develop TRD with a higher risk of all-cause mortality that was partially mediated by subsequent psychiatric conditions, and a higher cost of healthcare service use, than patients without TRD; 2) TRD appeared to be associated with an increased risk of autoimmune diseases compared with depression patients without TRD; 3) the COVID-19 pandemic was associated with an immediate increase in incidence of depression with a sustained effect that lasted near the end of the pandemic, but also associated with a decline of overall healthcare resources among both the newly diagnosed and pre-existing depression patients accompanied by a gradual rebound; and, 4) the costs of care and mortality burden of depression is likely to persist in the coming decade with the majority of costs contributed by TRD and comorbidities, despite a relatively limited proportion of patients living with the two statuses. Key cost drivers were related to early disease stages particularly before the development of TRD and/or comorbidities.

This thesis comprehensively presents the long-term burden of depression with both the current and future perspectives, and both the clinical and economic aspects. The research undertaken highlights that the clinical and economic burden of depression is further escalated under the presence of TRD with a strong contributing role of comorbidities. The findings provide reference estimates for budget planning early and offer insights into the directions of future intervention programmes that target TRD. Future efforts could evaluate the cost-effectiveness of the suggested strategies, which alleviate depression burden and maximize societal benefits via appropriate resource allocation.