Antidepressant use and risk of self-harm among people aged 40 years or older: A population-based cohort and self-controlled case series study

Yi Chai; Hao Luo; Kenneth K C Man; Wallis C Y Lau; Sherry K W Chan; Paul S F Yip; Ian C K Wong

doi:10.1016/j.lanwpc.2022.100557

Antidepressant use and risk of self-harm among people aged 40 years or older: A population-based cohort and self-controlled case series study

Lancet Reg Health West Pac. 2022 Aug 10:27:100557. doi: 10.1016/j.lanwpc.2022.100557. eCollection 2022 Oct.

Authors

Yi Chai^{1

2}, Hao Luo^{1

3

4}, Kenneth K C Man^{5

2

6}, Wallis C Y Lau^{5

2

6}, Sherry K W Chan^{7

8}, Paul S F Yip^{1

4}, Ian C K Wong^{5

2

6}

Affiliations

¹ Department of Social Work and Social Administration, Faculty of Social Sciences, The University of Hong Kong, Hong Kong Special Administration Region, China.
² Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administration Region, China.
³ Sau Po Centre on Aging, The University of Hong Kong, Hong Kong Special Administration Region, China.
⁴ The Hong Kong Jockey Club Centre for Suicide Research and Prevention, Department of Social Work and Social Administration, Faculty of Social Sciences, The University of Hong Kong, Hong Kong Special Administration Region, China.
⁵ Research Department of Practice and Policy, School of Pharmacy, University College London, London, England.
⁶ Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong Special Administrative Region, China.
⁷ Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administration Region, China.
⁸ State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong Special Administration Region, China.

Abstract

Background: Studies on the association between antidepressants and self-harm in adults were mostly conducted over a decade ago and have inconsistent findings. We aimed to compare self-harm risks by antidepressant classes among people aged 40 years or older with depression.

Methods: Individuals aged ≥40 years with depression who initiated antidepressant treatment between 2001 and 2015 were retrieved from the Hong Kong Clinical Data Analysis & Reporting system, and were followed up until December 31, 2016. We conducted self-controlled case series (SCCS) analyses to estimate the incidence rate ratio (IRR) of self-harm comparing the pre-exposure (90 days before the first antidepressant use), index exposure (the first antidepressant use), and subsequent exposure (subsequent antidepressant use) periods to nonexposed periods. We applied Cox proportional hazard regressions to estimate the hazard ratio (HR) of self-harm comparing five antidepressant classes (tricyclic and related antidepressant drugs [TCAs], selective serotonin reuptake inhibitors [SSRIs], noradrenergic and specific serotonergic antidepressants [NaSSAs], serotonin-norepinephrine reuptake inhibitors [SNRIs], and others).

Findings: A total of 48,724 individuals were identified. SCCS analyses (N = 3,846) found that the increased self-harm risk occurred during the pre-exposure (IRR: 22.24; 95% CI, 20.25-24.42), index exposure (7.03; 6.34-7.80), and subsequent exposure periods (2.47; 2.18-2.79) compared to the unexposed period. Cohort analyses (N = 48,724) found an association of higher self-harm risks in short-term (one year) for NaSSAs vs. TCAs (HR, 2.13; 95% CI, 1.53-2.96), SNRIs vs. TCAs (1.64; 1.01-2.68), and NaSSAs vs. SSRIs (1.75; 1.29-2.36) in the 40-64 years group. The higher risk remained significant in long-term (> one year) for NaSSAs vs. TCAs (1.55; 1.26-1.91) and NaSSAs vs. SSRIs (1.53; 1.26-1.87). In the 65+ group, only short-term differences were observed (SSRIs vs. TCAs [1.31; 1.03-1.66], SNRIs vs. SSRIs [0.44; 0.22-0.87], and SNRIs vs. NaSSAs [0.43; 0.21-0.87]).

Interpretation: Within-person comparisons did not suggest that antidepressant exposure is causally associated with an increased risk of self-harm in people with depression. Between-person comparisons revealed differences in self-harm risks between certain pairs of antidepressant classes. These findings may inform clinicians' benefit-risk assessments when prescribing antidepressants.

Funding: Nil.

Keywords: Antidepressants; CDARS; Depression; Hong Kong; Older adults; Self-harm; Suicide.