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Researchers from the Department of Pharmacology and Pharmacy, Department of Medicine, Department of Pediatrics and Adolescent Medicine of the LKS Faculty of Medicine, The University of Hong Kong (HKUMed) and Department of Social Work and Social Administration at The University of Hong Kong (HKU), in collaboration with The Chinese University of Hong Kong, London School of Economics and Political Science and University College London, identified that 18% of patients with newly diagnosed depression would develop treatment resistance, with increased risk of mortality partially mediated by post-treatment psychiatric conditions, such as self-harm behaviours, psychosis and schizophrenia, compared with treatment-responsive patients. Patients with treatment-resistant depression (TRD) also consumed greater healthcare resources in both psychiatric and non-psychiatric services. The findings have been published in The Lancet Regional Health Western Pacific [link to the publication].

Background
In Hong Kong, there has been a rising burden of mental health problems in recent years. Members of the public have been enduring negative emotions vis-à-vis socio-economic changes from the social unrest¹ through the COVID-19 outbreak², which also increases awareness of mental health. Despite the growing global consumption of psychotropic medicines over the last decade, a discovery by the research team’s previous work published in The Lancet Psychiatry [link to the publication] shows that depression remains an unresolved public health issue worldwide. With available antidepressants, a significant portion of patients still fail to reach remission. These patients are defined to have TRD following treatment failure of at least two trials of antidepressants at adequate doses, duration, and adherence. In this connection, the research team examined the mortality-causing mechanism and the long-term healthcare utilisation pattern of TRD, as compared with patients without TRD.

Research methods and findings
Using the territory-wide longitudinal electronic medical records in Hong Kong, this study identified patients with incident depression diagnosed in 2014 and followed them up to six years. The TRD group (n=1,479) was matched to the treatment-responsive group (n=5,856) by age, gender, and medical history for comparison in risk of death and healthcare resource utilisation pattern. The research team found that 18% of the incident patients had developed TRD within six years of follow-up. Compared with treatment-responsive patients, treatment-resistant patients had 52% greater risk of all-cause mortality, and the relationship was significantly mediated by post-TRD psychiatric conditions, including self-harm behaviours, psychosis and schizophrenia. In the economic aspect, patients with TRD had 1.8-fold higher healthcare costs compared to treatment-responsive patients. The healthcare cost burdened all service settings of outpatient, inpatient and emergency used for both psychiatric and non-psychiatric care.

Research significance
This study highlights the difficult-to-treat nature of TRD and its subsequent burden to the health system, both clinically and economically. The findings suggest that identifying treatment resistance early and subsequent clinical monitoring for post-TRD psychiatric conditions could be important to prevent premature mortality.

‘Healthcare providers and policy makers should expect that increased service demand arisen from TRD would manifest in both psychiatric and general medical services. A multi-disciplinary management plan, which involves crosstalk between psychiatric and non-psychiatric specialties, could be oriented to prevent disease progression; this would be beneficial to improve the multifaceted patient outcomes and save medical costs in a wide range of healthcare resources,’ said Dr Shirley Li, Assistant Professor, Department of Medicine of the School of Clinical Medicine and the Department of Pharmacology and Pharmacy, HKUMed.

About the research team
The research was co-led by Dr Shirley Li, Assistant Professor, Department of Medicine of the School of Clinical Medicine, Department of Pharmacology and Pharmacy; and Professor Ian Wong Chi-kei, Lo Shiu Kwan Kan Po Ling Professor in Pharmacy and Head of Department of Pharmacology and Pharmacy, HKUMed. Other members of the research team include Ms Vivien Chan, Mr Edmund Cheung and Mr Fan Min, PhD students; Dr Francisco Lai, Dr Rosa Wong, Research Assistant Professor; Dr Esther Chan, Associate Professor; and Ms Lauren Lau, Research Assistant, from the Department of Pharmacology and Pharmacy, HKUMed; Dr Luo Hao, Assistant Professor; Dr Gloria Wong, Associate Professor; Professor Terry Lum, Henry G Leong Professor in Social Work and Social Administration, from the Department of Social Work and Social Administration, Faculty of Social Science, HKU; Dr Eric Wan, Assistant Professor from the Department of Family Medicine and Primary Care, HKUMed; Dr Patrick Ip, Clinical Associate Professor from the Department of Pediatrics and Adolescent Medicine, HKUMed; Dr Sandra Chan, Associate Professor, from the Department of Psychiatry, The Chinese University of Hong Kong; Professor Martin Knapp from the Department of Health Policy, London School of Economics and Political Science; and Dr Joseph Hayes from the Faculty of Brain Sciences, University College London.

Acknowledgements
This study was supported by an unconditional educational grant from Janssen, a division of Johnson & Johnson (Hong Kong) Limited.

Media enquiries
Please contact LKS Faculty of Medicine of The University of Hong Kong by email (medmedia@hku.hk).

¹ Ni MY, Yao XI, Leung KSM, et al. Depression and post-traumatic stress during major social unrest in Hong Kong: a 10-year prospective cohort study. Lancet. 2020;395(10220):273-284.

² Choi EPH, Hui BPH, Wan EYF. Depression and Anxiety in Hong Kong during COVID-19. Int J Environ Res Public Health. 2020;17(10):3740.