www.thelancet.com/psychiatry Published online XXXX, 2021 https://doi.org/10.1016/S2215-0366(21)00392-8 1 Articles Self-harm and suicide during and after opioid agonist treatment among primary care patients in England: a cohort study Prianka Padmanathan, Harriet Forbes, Maria Theresa Redaniel, David Gunnell, Dan Lewer, Paul Moran, Ben Watson, Louisa Degenhardt, Matthew Hickman Summary Background The frst 4 weeks after initiation and cessation of opioid agonist treatment for opioid dependence are associated with an increased risk of all-cause mortality and overdose. We aimed to investigate whether the rate of self- harm and suicide among people who were prescribed opioid agonist treatment difers during initiation, cessation, and the remainder of time on and of treatment. Methods We did a retrospective cohort study and used health-care records from UK Clinical Practice Research Datalink, linked to mortality and hospital admission data, for adults (age 18–75 years at cohort entry) who were prescribed opioid agonist treatment at least once in primary care in England between Jan 2, 1998, and Nov 30, 2018. We estimated rates and adjusted risk ratios (aRRs) of hospital admissions for self-harm and death by suicide, comparing time during and after treatment, as well as comparing stable periods of time on treatment with treatment initiation, cessation, and the remaining time of treatment. Findings Between Jan 2, 1998, and Nov 30, 2018, 8070 patients (5594 [69·3%] men and 2476 [30·7%] women) received 17 004 episodes of opioid agonist treatment over 40 599 person-years. Patients were mostly of White ethnicity (7006 [86·8%] patients). 807 episodes of self-harm (1·99 per 100 person-years) and 46 suicides (0·11 per 100 person- years) occurred during the study period. The overall age-standardised and sex-standardised mortality ratio for suicide was 7·5 times (95% CI 5·5–10·0) higher in the study cohort than in the general population. Opioid agonist treatment was associated with a reduced risk of self-harm (aRR in periods of treatment 1·50 [95% CI 1·21–1·88]), but was not signifcantly associated with suicide risk (aRR in periods of treatment 1·21 [0·64–2·28]). Risk of self-harm (aRR 2·60 [95% CI 1·83–3·70]) and suicide (4·68 [1·63–13·42]) were both elevated in the frst 4 weeks after stopping opioid agonist treatment compared with stable periods on treatment. Interpretation Stable periods of opioid agonist treatment are associated with reduced risk of self-harm, emphasising the importance of improving retention of patients in treatment. The frst month following cessation of opioid agonist treatment is a period of increased risk of suicide and self-harm, during which additional psychosocial support is required. Funding Medical Research Council. Copyright © 2021 Elsevier Ltd. All rights reserved. Introduction Suicide is a major public health burden and the second most common cause of death among people aged 15–29 years globally. 1 People with a substance use disorder are at a greatly increased risk of suicide compared with the general population. 2 Opioids are the main substance for which people access drug treatment in England. 3 Opioids are also the most common substance involved in drug poisoning deaths in England and Wales, 4 and the UK has one of the highest rates of drug-related deaths in Europe. 5 Although suicidal intent can be difcult to determine in many opioid-related deaths, 6 there is evidence that opioid dependence is associated with a markedly increased risk of suicide. 2 Opioid agonist treatment (OAT) involves prescrip- tion of long-acting opioids, such as methadone and buprenorphine, alongside other interventions. It has wide-ranging individual, population, and societal bene- fts, particularly in relation to mortality, infectious disease, mental and physical health, and criminal activity. 7 A recommended duration of OAT is generally unspecifed, although there is evidence that retention of patients in treatment is associated with better treatment outcomes. 7,8 Despite the benefts of OAT, strong evidence has emerged in recent years showing a substantial increase in overdose and all-cause mortality risk in the frst 2–4 weeks after initiation and cessation of OAT. 9 To date, research investigating suicidal behaviour in relation to OAT has Lancet Psychiatry 2021 Published Online Month date, 2021 https://doi.org/10.1016/ S2215-0366(21)00392-8 Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK (P Padmanathan MSc, H Forbes PhD, M T Redaniel PhD, Prof D Gunnell FMedSci, Prof P Moran MD, Prof M Hickman PhD); National Institute for Health Research Applied Research Collaboration West, Bristol, UK (M T Redaniel, Prof P Moran); National Institute of Health Research Biomedical Research Centre at the University Hospitals, Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK (Prof D Gunnell, Prof P Moran, Prof M Hickman); Institute of Epidemiology and Healthcare, University College London, London, UK (D Lewer MSc); Bristol Specialist Drug and Alcohol Service, Avon and Wiltshire Mental Health Partnership NHS Trust, Bath, UK (P Padmanathan, B Watson MD); National Drug and Alcohol Research Centre, University of New South Wales Sydney, Sydney, NSW, Australia (Prof L Degenhardt PhD) Correspondence to: Dr Prianka Padmanathan, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 1UD, UK prianka.padmanathan@ bristol.ac.uk This version saved: 10:55, 09-Dec-21 21TLP2007 Ben B thelancetpsych-D-20-02007R2 S2215-0366(21)00392-8 Embargo: [add date when known] Doctopic: Primary Research OA licence TBC