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: http://dx.doi.org/10.1136/bmj.f403 (Published 7 February 2013)
Cite this as: BMJ 2013;346:f403

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The data provided in this study is obviously very encouraging and it is clear that the limit in pack size is clearly having an effect on the number of both paracetamol poisoning deaths and liver transplant activity.

Although, interestingly there are many countries that do not have this restriction and yet still continue to show a reduction in paracetamol overdose mortality1. Subsequently it would seem prudent to explore the other factors that may contribute to this encouraging trend.

Results from a patient interview study looking at those whom had previously attempted a paracetamol overdose showed that 53.3% already had the paracetamol tablets at home2. Therefore it is possible that restriction in pack sizes would not have affected the overdose attempt.

Education is another factor that should be considered, not only to the person buying the tablets but the people selling them. One study looking at the availability of paracetamol in pharmacy and non-pharmacy outlets showed that the researcher was able to purchase paracetamol in excess of statutory limit in 81.8% of newsagents/mini-markets compared the 50.0% in pharmacies3.

Greater awareness by doctors of suicidal intent may also be playing a role in the decrease in suicide attempts. Awareness groups have more than doubled over the last twenty years and the stigma around mental health is on the decline. It is possible that these are playing an important role in patients seeking help for depression and hopelessness at a much earlier stage, therefore possibly preventing people from taking a paracetamol overdose in the first place.

In summary the evidence shown is this study is very encouraging and it seems that limiting pack size has played a key role in this. However for rates to continue to drop at a rapid rate we must take a multi-factorial approach and remember this when we treat our patients.

1) Li C, Martn BC. Trends in emergency department visits attributable to acetaminophen overdoses in the United States: 1993-2007. Pharmacoepidemiol Drug Saf.2011;20(8):810-8
2) Simkin S, Hawton K, Kapur N, Gunnell D. What can be done to reduce mortality from paracetamol overdoses? A patient interview study. QJM.2012;105(1):41-51
3) Ni Mhaolain AM, Davoren M, Kelly BD, Breen E, Casey P. Paracetamol availability in pharmacy and non-pharmacy outlets in Dublin, Ireland. Ir J Med Sci.2009;179(1):79-82

Competing interests: None declared

Mark Willis, Fourth Year Medical Student

Nicholas D. Gollop, Academic FY1 Doctor, Norfolk and Norwich University Hospital.

University of Manchester , UHSM, Southmoor Road, Manchester, M23 9LT

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Hawton and colleagues [1] illustrate the value of wise, National regulation (in this case control over the dispensing of pills widely used for self poisoning). The present Government abhors such National standards for health and now delegates mental health protection to individual councils within its Localism agenda. Key professionals within the public health workforce are in the process of moving from the NHS to local authorities. Local authorities already have statutory powers in key areas related to suicide: abuse and bullying in childhood, loss of employment within the local economy, hazardous drinking, public transport safety and homelessness.

A recent report on the inadequacy and inequality of Local Suicide Prevention Plans [2] uses one word frequently: 'Leadership'. This year 152 Directors of Public Health become responsible for health leadership in English councils. Some will inherit good suicide prevention plans and enthusiastic local champions, but for many others there is an urgent need for proactive leadership. Ensuring good quality health intelligence and identifying local community assets just might help these DPHs begin leading, in the right direction?

[1] Hawton K, Bergen H, Simkin S, Dodd S, Pocock P, Bernal W, Gunnell D, Kapur N. 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:f403

[2] All Party Parliamentary Group on Suicide and Self-Harm Prevention. The Future of Local Suicide Prevention Plans in England. London, 2013.

Competing interests: A public health advisor to the All Party Parliamentary Group on suicide prevention

Woody Caan, Editor

Journal of Public Mental Health, Hurdles Way, Duxford CB22 4PA

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We are happy to see the number of registrations for hepatic transplantation for paracetamol overdose found in SALT (study of acute liver transplantation) (1) in the UK - 63 cases in 2005-2007, i.e. 5.25 cases per quarter - was the same as that reported here.

However, we also found in the UK and in the other European countries concerned by that study a number of acute liver failures leading to registration for transplantation not related to overdoses (ALFT), in which paracetamol was used within 30 days before the first symptoms of liver injury. This represents 24 cases in the UK, 49 in France, for instance. Using exactly the same criteria as for other "known hepatotoxic agents" such as NSAIDs, we found that non-overdose paracetamol was associated with three times more ALFT than all NSAIDs pooled, or individual NSAIDs such as diclofenac or nimesulide. This is true whether the denominator is in patients-years or individual patients (2).

Maybe one might start looking into hepatotoxicity associated with paracetamol at normal doses? Does this have anything to do with chronic glutathione depletion, too, and increased risk from other toxins, as was hypothesized for asthma?

Is paracetamol like the mailman: so obviously innocuous and commonplace that it becomes invisible?

1. Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jove J, et al. Transplantation for Acute Liver Failure in Patients Exposed to NSAIDs or Paracetamol (Acetaminophen) : The Multinational Case-Population SALT Study. Drug Saf. 2013. Epub 2013/01/18.
2. Moore N, Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, et al. Choice of the denominator in case population studies: event rates for registration for liver transplantation after exposure to NSAIDs in the SALT study in France. Pharmacoepidemiol Drug Saf. 2012. Epub 2012/11/21.
3. Shaheen S, Potts J, Gnatiuc L, Makowska J, Kowalski ML, Joos G, et al. The relation between paracetamol use and asthma: a GA2LEN European case-control study. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2008;32(5):1231-6. Epub 2008/06/27.

Competing interests: The study cited was requested and approved by the European Medicines Agency and funded by Helsin Health care, which had no part in its doing, the publications or this reply.

Nicholas D Moore, Clinical pharmacologist

Ezgi Gulmez, Patrick Blin

University of Bordeaux, INSERM U657 CIC-P0005, 146 rue Leo Saignat, 33076 Bordeaux, France

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This paper makes interesting reading and strongly indicates that reducing pack sizes of paracetamol has reduced the incidence of fatal overdose. Unfortunately the discussion is marred somewhat by the suggestion of reducing the strength of paracetamol tablets to further reduce poisoning. This may well work but has about as much utility as suggesting that rope be only sold in lengths of six inches to reduce the incidence of hanging. It is possible that both actions may achieve their aim but make the products wholly unsatisfactory for its intended use.

Competing interests: None declared

Duncan j Livingstone, Hospital pharmacist

Queen Victoria hospital, East Grinstead

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We should not be surprised by the results of this research, as the intervention being studied is the application of one of Dr William Haddon’s “Ten Countermeasures” (1).

Dr Haddon was a physician and engineer and is considered to be the father of modern injury epidemiology. He developed two complementary conceptual frameworks: the Haddon Matrix and Ten Countermeasures (1,2). Both these frameworks are excellent tools for generating ideas about possible new public health interventions. They can be applied to a large variety of important topics including alcohol, smoking, obesity, and guns (3,4).

Hawton and colleagues state that significant reductions in deaths due to paracetamol overdose have already been achieved by the intervention they were studying, but that there is still a need for further preventive measures (5). Perhaps the pioneering work of Haddon should be drawn upon for potential new measures.

1 Haddon, W. Energy Damage and the Ten Countermeasure Strategies. Journal of Trauma 1973;13:321-31.
2 Haddon W. The changing approach to the epidemiology, prevention, and amelioration of trauma: the transition to approaches etiologically rather than descriptively based. American Journal of Public Health 1968;58:1431-1438
3 Runyan C. Back to the future: revisiting Haddon’s conceptualization of injury epidemiology and prevention. Epidemiol Rev 2003;25:60-4.
4 Runyan C, Baker S. Bulletin World Health Organization 2009;87:402–403
5 Hawton K, Bergen H, Simkin S, Dodd S, Pocock P, Bernal W, Gunnell D, Kapur N. BMJ 2013;346:f403

Competing interests: None declared

Michael C. Watson, Associate Professor in Public Health

Emily Clare Watson (GP Registrar, Barnsley Hospital)

University of Nottingham, Faculty of Medicine and Health Sciences, Queen's Medical Centre, Nottingham. NG7 2HA

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