Paracetamol (acetaminophen) poisoning is the leading cause of acute liver failure in Great Britain and the United States. Successful interventions to reduced harm from paracetamol poisoning are needed. To achieve this, the government of the United Kingdom introduced legislation in 1998 limiting the pack size of paracetamol sold in shops. Several studies have reported recent decreases in fatal poisonings involving paracetamol. We use interrupted time-series analysis to evaluate whether the recent fall in the number of paracetamol deaths is different to trends in fatal poisoning involving aspirin, paracetamol compounds, antidepressants, or nondrug poisoning suicide.
Methods and Findings
We calculated directly age-standardised mortality rates for paracetamol poisoning in England and Wales from 1993 to 2004. We used an ordinary least-squares regression model divided into pre- and postintervention segments at 1999. The model included a term for autocorrelation within the time series. We tested for changes in the level and slope between the pre- and postintervention segments. To assess whether observed changes in the time series were unique to paracetamol, we compared against poisoning deaths involving compound paracetamol (not covered by the regulations), aspirin, antidepressants, and nonpoisoning suicide deaths. We did this comparison by calculating a ratio of each comparison series with paracetamol and applying a segmented regression model to the ratios. No change in the ratio level or slope indicated no difference compared to the control series. There were about 2,200 deaths involving paracetamol. The age-standardised mortality rate rose from 8.1 per million in 1993 to 8.8 per million in 1997, subsequently falling to about 5.3 per million in 2004. After the regulations were introduced, deaths dropped by 2.69 per million (p = 0.003). Trends in the age-standardised mortality rate for paracetamol compounds, aspirin, and antidepressants were broadly similar to paracetamol, increasing until 1997 and then declining. Nondrug poisoning suicide also declined during the study period, but was highest in 1993. The segmented regression models showed that the age-standardised mortality rate for compound paracetamol dropped less after the regulations (p = 0.012) but declined more rapidly afterward (p = 0.031). However, age-standardised rates for aspirin and antidepressants fell in a similar way to paracetamol after the regulations. Nondrug poisoning suicide declined at a similar rate to paracetamol after the regulations were introduced.
Introduction of regulations to limit availability of paracetamol coincided with a decrease in paracetamol-poisoning mortality. However, fatal poisoning involving aspirin, antidepressants, and to a lesser degree, paracetamol compounds, also showed similar trends. This raises the question whether the decline in paracetamol deaths was due to the regulations or was part of a wider trend in decreasing drug-poisoning mortality. We found little evidence to support the hypothesis that the 1998 regulations limiting pack size resulted in a greater reduction in poisoning deaths involving paracetamol than occurred for other drugs or nondrug poisoning suicide.
Analysis of mortality rates for paracetamol poisoning in England and Wales does not support the view that regulations limiting pack size have been responsible for a reduction in deaths.
Paracetamol—known as acetaminophen in the United States—is a cheap and effective painkiller. It is widely used to relieve minor aches and pains as well as fevers and headaches. Recommended doses of paracetamol are considered safe in humans, but overdoses are toxic and can cause liver failure and death. Because this drug is very easy to get hold of, there are many overdoses each year, either accidental or deliberate. In the UK, paracetamol poisoning is the most common cause of acute liver failure. Toward the end of 1998, new laws were introduced in the UK to try to reduce the number of paracetamol overdoses. These laws said that pharmacies could not sell packs of paracetamol containing more than 32 tablets and other shops could not sell packs with more than 16 tablets. One of the reasons behind the introduction of this law was that many suicides are not preplanned and, therefore, if it was harder for people to get hold of or keep large quantities of tablets, they might be less likely to attempt suicide or accidentally overdose.
Why Was This Study Done?
Following the introduction of these new laws, the number of deaths caused by paracetamol overdose in the UK dropped. However, it is possible that the drop in deaths came about for a variety of different reasons and not just as a result of the new laws on paracetamol pack size. For example, the suicide rate might have been falling anyway due to other changes in society and the fall in death rate from paracetamol might just have been part of that trend. It is important to find out whether the legal changes that were introduced to address a public health problem did in fact bring about a change for the better. This knowledge would also be relevant to other countries that are considering similar changes.
What Did the Researchers Do and Find?
The researchers used data from the Office of National Statistics, which holds information on drug poisoning deaths in England and Wales. These data were then broken down by the type of drug that was mentioned on the death certificate. The researchers compared death rates involving the following drugs: paracetamol; paracetamol-containing compounds (which were not subject to the new pack size laws); aspirin; antidepressant drugs; and then finally non-drug poisoning suicides. The reason for comparing death rates involving paracetamol against death rates involving other drugs, or non-drug suicide, was that this method would allow the researchers to see if the drop in paracetamol deaths followed overall trends in the poisoning or suicide rates or not. If the paracetamol death rate dropped following introduction of the new laws but the rates of other types of poisoning or suicide did not, then there would be a link between the new laws and a fall in paracetamol suicides. The researchers compared these death data within specific time periods before the end of 1998 (when the new laws on paracetamol pack size were introduced) and after.
Overall, there were nearly 2,200 deaths involving paracetamol between 1993 and 2004. The number of deaths per year involving paracetamol dropped substantially when comparing the periods of time before the end of 1998 and after it. However, the number of deaths per year involving any drug, and the non-drug suicides, also fell during this period of time. When comparing the trends for paracetamol deaths with other poisoning or suicide deaths, the researchers did not find any statistical evidence that the fall in paracetamol deaths was any different to the overall trend in poisoning or suicide death rates.
What Do These Findings Mean?
Although the paracetamol death rate fell immediately following the new laws on pack size, this study suggests the link might just be coincidence. The researchers could not find any data supporting the idea that the new laws caused a drop in paracetamol deaths. However, this was an observational study, not a true experimental one: the researchers here were clearly not able to set up equivalent “experimental” and “control” groups for comparison. It is very difficult to prove or disprove conclusively that new laws such as this are, or are not, effective.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040105
Information is available from Medline Plus about suicide
Wikipedia has an entry on paracetamol (note that Wikipedia is an internet encyclopedia anyone can edit)
Information about regulation of drugs in the UK is available from the Medicines and Healthcare Regulatory Agency
The Office for National Statistics provides key economic and social data about the UK, and is involved in many other important projects