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Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records

Joseph, Rebecca M.; Jack, Ruth H.; Morriss, Richard; Knaggs, Roger David; Butler, Debbie; Hollis, Chris; Hippisley-Cox, Julia; Coupland, Carol

Association between mirtazapine use and serious self-harm in people with depression: an active comparator cohort study using UK electronic health records Thumbnail


Rebecca M. Joseph

Senior Research Fellow

Professor of Psychiatry and Community Mental Health

Debbie Butler

Professor of Child and Adolescent Psychiatry and Digital Mental Health

Julia Hippisley-Cox

Professor of Medical Statistics


BACKGROUND: Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants. OBJECTIVES: To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments. DESIGN AND SETTING: Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018. PARTICIPANTS: 24 516 people diagnosed with depression, aged 18-99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine. MAIN OUTCOME MEASURES: Hospitalisation or death due to deliberate self-harm. Age-sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates. RESULTS: Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose. CONCLUSIONS: There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm. CLINICAL IMPLICATIONS: Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.

Journal Article Type Article
Acceptance Date Jan 10, 2022
Online Publication Date Mar 4, 2022
Publication Date 2022-11
Deposit Date Jan 20, 2022
Publicly Available Date Mar 4, 2022
Journal Evidence-based mental health
Electronic ISSN 1468-960X
Publisher BMJ
Peer Reviewed Peer Reviewed
Volume 25
Issue 4
Pages 169-176
Keywords Psychiatry and Mental health
Public URL
Publisher URL


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