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Long term effect of reduced pack sizes of paracetamol on poisoning deaths and liver transplant activity in England and Wales: interrupted time series analyses

BMJ 2013; 346 doi: (Published 07 February 2013) Cite this as: BMJ 2013;346:f403
  1. Keith Hawton, professor of psychiatry and director centre for suicide research1,
  2. Helen Bergen, researcher1,
  3. Sue Simkin, researcher1,
  4. Sue Dodd, scientific assessor2,
  5. Phil Pocock, principal statistician3,
  6. William Bernal, reader in hepatology4,
  7. David Gunnell, professor of epidemiology5,
  8. Navneet Kapur, professor of psychiatry and population health6
  1. 1University of Oxford Centre for Suicide Research, Department of Psychiatry, Warneford Hospital, Headington, Oxford OX3 7JX, UK
  2. 2Post Authorisation Signal Unit, Vigilance and Risk Management of Medicines, Medicines and Healthcare products Regulatory Agency, London, UK
  3. 3Statistics and Clinical Audit, NHS Blood and Transplant, Stoke Gifford, Bristol, UK
  4. 4Liver Intensive Therapy Unit, Institute of Liver Studies, King’s College Hospital, London, UK
  5. 5University of Bristol, School of Social and Community Medicine, Canynge Hall, Bristol UK
  6. 6University of Manchester, Centre for Suicide Prevention, University Place, Manchester, UK
  1. Correspondence to: K Hawton keith.hawton{at}
  • Accepted 11 December 2012


Objective To assess the long term effect of United Kingdom legislation introduced in September 1998 to restrict pack sizes of paracetamol on deaths from paracetamol poisoning and liver unit activity.

Design Interrupted time series analyses to assess mean quarterly changes from October 1998 to the end of 2009 relative to projected deaths without the legislation based on pre-legislation trends.

Setting Mortality (1993-2009) and liver unit activity (1995-2009) in England and Wales, using information from the Office for National Statistics and NHS Blood and Transplant, respectively.

Participants Residents of England and Wales.

Main outcome measures Suicide, deaths of undetermined intent, and accidental poisoning deaths involving single drug ingestion of paracetamol and paracetamol compounds in people aged 10 years and over, and liver unit registrations and transplantations for paracetamol induced hepatotoxicity.

Results Compared with the pre-legislation level, following the legislation there was an estimated average reduction of 17 (95% confidence interval −25 to −9) deaths per quarter in England and Wales involving paracetamol alone (with or without alcohol) that received suicide or undetermined verdicts. This decrease represented a 43% reduction or an estimated 765 fewer deaths over the 11¼ years after the legislation. A similar effect was found when accidental poisoning deaths were included, and when a conservative method of analysis was used. This decrease was largely unaltered after controlling for a non-significant reduction in deaths involving other methods of poisoning and also suicides by all methods. There was a 61% reduction in registrations for liver transplantation for paracetamol induced hepatotoxicity (−11 (−20 to −1) registrations per quarter). But no reduction was seen in actual transplantations (−3 (−12 to 6)), nor in registrations after a conservative method of analysis was used.

Conclusions UK legislation to reduce pack sizes of paracetamol was followed by significant reductions in deaths due to paracetamol overdose, with some indication of fewer registrations for transplantation at liver units during the 11 years after the legislation. The continuing toll of deaths suggests, however, that further preventive measures should be sought.


  • We thank Claudia Wells at the Office for National Statistics for supplying the mortality data.

  • Contributors: KH conceived the idea for the study. KH, SS, DG, and NK designed the study. KH, DG, and NK obtained funding. SS, SD, PP, and KH obtained the data. HB conducted the analysis. KH drafted the first version of the manuscript. All authors commented on drafts and approved the final version. KH is the guarantor. All authors had full access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: This paper presents independent research commissioned by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (RP-PG-0606-1247) as part of a programme of work related to suicide prevention. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or the Medicines and Healthcare Products Regulatory Agency. The funder had no role in the study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the paper for publication. KH and DG are NIHR senior investigators. KH is also supported by the Oxford Health NHS Foundation Trust, HB by the Department of Health under the NHS Research and Development Programme (DH/DSH2008), and NK by the Manchester Mental Health and Social Care Trust.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: support from the NIHR for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; DG is a member of the Pharmacovigillance Expert Advisory Group of the MHRA; KH, NK, and DG are members of the National Suicide Prevention Strategy Advisory Group; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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