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Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database

BMJ 2015; 350 doi: (Published 18 February 2015) Cite this as: BMJ 2015;350:h517
  1. Carol Coupland, associate professor and reader in medical statistics1,
  2. Trevor Hill, research statistician1,
  3. Richard Morriss, professor of psychiatry and community mental health2,
  4. Antony Arthur, professor of nursing science3,
  5. Michael Moore, professor of primary care research4,
  6. Julia Hippisley-Cox, professor of clinical epidemiology and general practice1
  1. 1Division of Primary Care, School of Medicine, University of Nottingham, University Park, Nottingham NG7 2RD, UK
  2. 2Institute of Mental Health, Jubilee Campus, Nottingham, UK
  3. 3School of Health Sciences, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK
  4. 4University of Southampton Medical School, Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, UK
  1. Correspondence to: C Coupland carol.coupland{at}
  • Accepted 30 December 2014


Objective To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression.

Design Cohort study.

Setting Patients registered with UK general practices contributing data to the QResearch database.

Participants 238 963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012.

Exposures Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables.

Main outcome measures Suicide and attempted suicide or self harm during follow-up.

Results During follow-up, 87.7% (n=209 476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79-590 days). During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants (1.80, 1.61 to 2.00). The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine (1.85, 1.61 to 2.13), trazodone (1.73, 1.26 to 2.37), and mirtazapine (1.70, 1.44 to 2.02), and significantly reduced for amitriptyline (0.71, 0.59 to 0.85). The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment.

Conclusion Rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants. Mirtazapine, venlafaxine, and trazodone were associated with the highest rates of suicide and attempted suicide or self harm, but the number of suicide events was small leading to imprecise estimates. As this is an observational study the findings may reflect indication biases and residual confounding from severity of depression and differing characteristics of patients prescribed these drugs. The increased rates in the first 28 days of starting and stopping antidepressants emphasise the need for careful monitoring of patients during these periods.


  • We thank those practices who use EMIS (Egton Medical Information Systems) and contribute to QResearch, and we thank EMIS and the University of Nottingham for expertise in establishing, developing, and supporting the database.

  • Contributors: CC, JH-C, RM, AA, and MM contributed to the overall conception and design of the study. CC wrote the first draft of this manuscript. JH-C undertook the data extraction. TH and CC carried out the statistical analyses of the study. All authors contributed to the interpretation of results and drafting of this manuscript. All authors read and approved the final manuscript. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health. CC is the guarantor.

  • Funding: This project was funded by the National Institute for Health Research (NIHR) School for Primary Care Research (project No 81). RM’s contribution to the study has been funded through the NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands (CLAHRC EM).The funding body did not play a role in the study design, writing of the manuscript, or the decision to submit the manuscript for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: financial support from NIHR for the submitted work; JH-C is director of QResearch, which is a not for profit venture between the University of Nottingham and Egton Medical Information Systems (commercial supplier of general practice clinical systems); no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The project has been independently peer reviewed and accepted by the QResearch Scientific board and has been approved in accordance with the agreed procedure with the Trent Research Ethics Committee (reference No MREC/03/4/021).

  • Data sharing: The patient level data from the QResearch are specifically licensed according to its governance framework. See for further details.

  • Transparency: The lead author (CC) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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