We have shown that the 1998 legislation to restrict pack sizes of paracetamol was associated with a significant reduction in terms of the level and slope in deaths due to paracetamol poisoning in England and Wales over an 11 year period. A decrease was seen both when considering deaths with a coroner’s verdict of suicide and undetermined intent, and when including deaths from accidental poisoning. This effect was found in analyses with estimates based on a continuation of the pre-legislation trend, as well as more conservative estimates assuming no increasing trend in the absence of the legislation.
The downward step change was not apparent when the intervention point was moved back to the beginning of 1998. Although we saw no significant change in deaths due to poisoning with paracetamol compounds, they constituted a small proportion of paracetamol related deaths. Deaths from poisoning with drugs excluding paracetamol also showed a significant reduction between 1998 and 2009, but to a lesser extent than that found for paracetamol. These deaths did not have the step change associated with the 1998 paracetamol legislation date. When we adjusted the paracetamol analyses for underlying trends in poisoning deaths (excluding those that were paracetamol related), the findings for paracetamol deaths were largely unaltered. The 43% reduction in deaths over 11 years was equivalent to 765 fewer deaths with a suicide or open verdict, or 990 fewer deaths if accidental poisoning verdicts were included.
A significant reduction after the legislation was also found for registrations for liver transplantation due to paracetamol induced hepatotoxicity in residents of England and Wales. However, a downward step change was also apparent when the beginning of 1998 was used as the intervention point, and the change was not significant using a conservative estimate of the effect. The 61% reduction in registrations at liver units represented 482 fewer registrations. Although there was also a reduction in liver transplantations of a similar order to registrations, this finding was not significant, owing to smaller numbers.
The reduction in registrations for liver unit transplantation is particularly striking because in 2005 the criteria for registration were broadened, with a lowering of the thresholds for consideration for surgery.30
The reduction in liver transplant registrations may have, in part, resulted from improvements in the early management of patients presenting to hospital with paracetamol poisoning (including administration of the antidote N-acetylcysteine) and the increasing sophistication and success of intensive care support given to patients with acute liver failure induced by paracetamol use.31
These factors could also have accounted for some of the non-significant reduction in the numbers of paracetamol deaths observed over the study period. However, the process of change has been one of continuous evolution and would be unlikely to account for the step change seen in outcomes coincident with the introduction of sales restrictions. Importantly, there has been no decline in hospital presentations in England for non-fatal overdoses of paracetamol after the legislation32
; thus, these findings cannot be explained by fewer paracetamol overdoses.
The effect of the 1998 legislation on pack sizes of paracetamol is likely to reflect the fact that many people who intentionally overdose with paracetamol take what is available in the household,13
especially if the overdose is impulsive. Also, when people purchase drugs specifically for the purpose of an overdose, the amount of paracetamol available would have been more limited after the legislation, probably even if multiple purchases are made. We previously showed a reduction in the size of non-fatal overdoses of paracetamol after the legislation.15
Despite the apparent benefits of the 1998 legislation, there continues to be a considerable number of deaths each year due to paracetamol poisoning, averaging 121 per year (for suicide, open, and accidental verdicts) between 2000 and 2009 for paracetamol alone with or without alcohol but excluding paracetamol compounds (table 1). The benefits should therefore not lead to complacency.
Further measures might be needed to reduce this death toll. These measures might include stronger enforcement of the legislation.34
Another possibility is a further reduction in pack sizes—some commentators have suggested that the limit should have been set lower.13
Another measure might be to reduce the paracetamol content of tablets, similar to the recent reduction of paracetamol (from 500 mg to 325 mg) in prescribed compound preparations introduced by the US Food and Drug Administration.35
However, it would need to be shown that such a further reduction would have no major effect on efficacy of pain relief.
One limitation of this study was that we only used data for deaths for poisoning with paracetamol (with or without alcohol), in pure or compound form. We did not use data for deaths where paracetamol was consumed with other drugs. This approach, however, ensured that our findings were restricted primarily to paracetamol, and not substantially affected by changed availability or toxicity of other drugs or compounds.
A strength of the study was that it was based on national data for both deaths and liver unit activity. We have not been able to estimate possible substitution of paracetamol overdoses with other methods of poisoning or self harm, but the non-significant change in total suicides (by all methods) and in suicides by ingestion during the period after the 1998 legislation was downward. This non-significant decrease in all suicides probably indicates that other factors may have favourably influenced suicide rates, and hence might have contributed to the findings for paracetamol poisoning deaths.
Other changes in availability of analgesics during the study included withdrawal of co-proxamol in 200724
and cyclo-oxygenase-2 inhibitors after safety concerns in 2004.36
However, these withdrawals probably would have not influenced the results, and we took account of changes in poisoning deaths in our analyses.
What is already known on this topic
- Paracetamol poisoning, which occurs mainly through intentional overdose, is an important worldwide cause of deaths and reason for liver transplantation due to hepatotoxicity
- UK legislation implemented in 1998 to restrict pack sizes of paracetamol sold over the counter has shown initial benefits, in terms of non-fatal overdoses and liver unit activity in England and Wales
- The long term effect of the legislation has yet to be evaluated
What this study adds
- The legislation appears to have had long term benefits in terms of fewer deaths due to paracetamol poisoning, after controlling for changes in overall rates of death by self poisoning and suicide
- Less robust evidence suggested a reduction in liver unit registrations and transplantation owing to paracetamol induced hepatotoxicity
- Nevertheless, substantial numbers of deaths due to paracetamol poisoning still occur annually, and further preventive measures might be warranted