Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study
BMJ 2001; 322 doi: https://doi.org/10.1136/bmj.322.7296.1203 (Published 19 May 2001) Cite this as: BMJ 2001;322:1203
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Yes it is true that suicides have decreased as a result of the amount
of paracetamol tablets available to be sold in one box over the counter.
But it is not solely because of this., there are also mental health crisis
teams that offer services to clients who present as suicidal or at risk of
self harm, to attempt to prevent overdose or actual suicides occuring so
clients can access the services appropiate for them. The team I work in
has seen a significant decline in suicide rates since it was first set up
2 1/2yrs ago. This team offers a diverse service, but respond to those in
mental health crisis and clients can refer themselves.
Competing interests: No competing interests
EDITOR
Hawton et al’s study1 addresses the important question: has the
legislation restricting pack size had any effect on suicidal behaviour
involving paracetamol and salicylates?
Their aims and study methods are clearly defined, but we feel there were
some flaws in their design.
The authors assumed that the purchase of paracetamol and salicylate
tablets equates to their use in self-poisoning. Since it was an ecological
study, data about individual subjects was not included. It is not known
why the tablets were bought. This is important because there are many
possible explanations other than an intention for self-poisoning. The
authors suggest that morbidity and mortality from poisoning with
paracetamol and salicylate was reduced as a result of pack size reduction.
However, we think that these conclusions must be more cautiously drawn.
Further, we feel that given the size of the problem of self-poisoning in
the UK, too few centres (5 liver units and 7 general hospitals) were
involved in the study to give accurate, widely applicable data.
Also, only one year had lapsed since the legislation was introduced and we
query whether this is sufficient time to show any significant effect – the
authors do not provide information on the longer term trend of sales of
paracetamol and salicylate.
This study paves the way for further research into this important field
perhaps with a case-control study. The past history of over-the-counter
tablet purchases of patients admitted with hepatotoxicity due to self-
poisoning could be compared to that of the general population.
Pack size reduction is logical because the impulsive act of self-poisoning
is made difficult to carry out when tablets are harder to come by.
However, conclusive evidence is yet to be provided.
Anna Freeman, Sarah Kitching, Alex Scott (3rd year Medical Students,
University of Newcastle-Upon-Tyne)
1 - Hawton, K. et al. Effects of legislation restricting pack sizes
of paracetamol and salicylate on self poisoning in the United Kingdom:
before and after study. BMJ 2001; 322:1203-1207.
Competing interests: No competing interests
EDITOR
Legislation Restricting Pack Sizes.
In view of the evidence
that restricting pack sizes of paracetamol and salicylate reduces
excessive consumption (BMJ 19 May). Should the medical profession lobby
for a reduction in pack size of cigarettes?
Rory J Shaw
Medical Director and Professor of Respiratory Medicine
Hammersmith Hospitals NHS Trust, London W12 OHS
Competing interests: No competing interests
Editor
Hawton et al (1) has claimed that restricting the pack size of
paracetamol has had substantial beneficial effects on the mortality and
morbidity associated with self-poisoning in the United Kingdom. However,
his study has used data from hospitals in England and from the Office for
National Statistics which holds information from only England and Wales.
Other studies have shown some reduction self poisoning and transplant
rates since 1998 in England, Wales and Northern Ireland (2-5).
In Scotland, our findings are not the same. The number of self-
poisonings have remained unaffected by the pack size restriction (6). The
mortality from self-poisoning with paracetamol appears to have been
reduced slightly, but more data is needed to confirm any statistical
significance. However, the mortality rates in Scotland are twice that of
England and Wales (Sheen unpublished data).
Thus it cannot be concluded that morbidity from paracetamol self-
poisoning has been reduced since the pack size restriction in 1998 for the
whole of the United Kingdom. Further studies as to why there is a
difference in Scotland are on going.
Yours Sincerely
Dr Christopher L. Sheen
Clinical RFesearch Fellow
Dr Tom M MacDonald
Professor of Pharmacoepidemiology
Medicines Monitoring Unit
Ninewells Hospital and Medical School,
Dundee
DD1 9SY
Reference List
1. Keith Hawton, Ellen Townsend, Jonathan Deeks, Louis Appleby,
David Gunnell, Olive Bennewith, and Jayne Cooper. Effects of legislation
restricting pack sizes of paracetamol and salicylate on self poisoning in
the United Kingdom: before and after study. BMJ 322 (7296):1203, 2001.
2. M. I. Prince, S. H. L. Thomas, O. F. W. James, and M. Hudson.
Reduction in incidence of severe paracetamol poisoning. Lancet 355
(9220):2047-2048, 2000.
3. J. L. Turvill, A. K. Burroughs, and K. P. Moore. Change in
occurrence of paracetamol overdose in UK after introduction of blister
packs. Lancet 355 (9220):2048-2049, 2000.
4. Denise Robinson, Alice M. J. Smith, and G. Dennis Johnston.
Severity of overdose after restriction of paracetamol availability:
retrospective study. BMJ 321 (7266):926-927, 2000.
5. Z. Atcha. Paracetamol related deaths in England and Wales, 1993-
97. Health Statistics Quarterly 07:5-9, 2000.
6. C. L. Sheen, J. F. Dillon, D. N. Bateman, K. Simpson, and T. M.
MacDonald. The Effect on Toxicity on Reducing the Size of Available
Paracetamol Pack Sizes. Gut 48:A105, 2001. (Abstract)
Competing interests: No competing interests
Paracetamol overdose is the most common cause of acute hepatic failure. Hepatocytes become sensitive to paracetamol metabolites and inflammatory mediators1-3 when intracellular glutathione (GSH) is depleted due to paracetamol metabolism4. For this reason, many clinical conditions associated with GSH depletion place patients at greater risk of paracetamol toxicity, even at therapeutic paracetamol dosings. These predisposing conditions include chronic alcohol abuse, HIV, sepsis, multi-organ system failure, chemotherapy, other types of hepatic failure, certain metabolic diseases, and chronic CNS disease. In addition, patients without predisposing disease are at risk because over-the-counter cold remedies and similar preparations frequently contain paracetamol and represent sources of potential overdose due to excessive, concomitant or chronic use.
Importantly, Hawton, Townsend, Deeks, Appleby, Gunnell, Bennewith, and Cooper now report that morbidity and mortality from paracetamol overdose decreased in the years following UK legislation to restrict the package sizes of the drug5. However, as these authors note, restricting the package size did not completely resolve the problem.
N-acetylcysteine (NAC), which provides the cysteine necessary to replenish glutathione (GSH) depleted by paracetamol, is used to treat paracetamol overdose6,7.
Intravenous NAC treatment protocols are used in some regions. However, oral treatment protocols have been shown to be highly effective. Treatment is most effective when started soon after paracetamol ingestion8,9; delays should be avoided but are still common10. Therefore, we suggest that toxicity caused by intentional or unintentional paracetamol overdoses is best treated by prevention, i.e., by formulating or packaging paracetamol with sufficient amounts of NAC to largely prevent toxicity .
NAC preserves the antipyretic and analgesic properties of paracetamol. Therefore, co-administration should not interfere with paracetamol effectiveness. Further, since NAC has been used for many years at high doses with minimal (or no) toxicity, administration at the estimated doses together with paracetamol should not pose any safety issues. The disagreeable odor and taste characteristic of some NAC formulations, particularly those used clinically in the United States, would appear to be a problem. However, the contaminants responsible for the bad taste and odor are not present in appropriately manufactured NAC formulations. Our estimates indicate that including less than 200 mg of NAC per 500 mg of paracetamol would accomplish the necessary prevention of toxicity. Therefore, we foresee no obstacles to the introduction of NAC/paracetamol products. Efficacy of such formulations for preventing morbidity and mortality should be evaluated.
James P. Andrus, MD#
Lenore A. Herzenberg, PhD+
Leonard A. Herzenberg, PhD+
Stephen C. DeRosa, MD+
Departments of Pediatric Critical Care# and Genetics+,
Stanford University School of Medicine, Stanford, CA 94305-5318
Corresponding author: James Andrus,
Andrus@darwin.stanford.edu
Citations
1. Luster MI, Simeonova PP, Gallucci RM, Bruccoleri A, Blazka ME, Yucesoy B. Role of inflammation in chemical-induced hepatotoxicity. Toxicol Lett 2001;120(1-3):317-21.
2. Laskin DL, Laskin JD. Role of macrophages and inflammatory mediators in chemically induced toxicity. Toxicology 2001;160(1-3):111-8.
3. Walsh TS, Wigmore SJ, Hopton P, Richardson R, Lee A. Energy expenditure in acetaminophen-induced fulminant hepatic failure. Crit Care Med 2000;28(3):649-54.
4. McClain CJ, Price S, Barve S, Devalarja R, Shedlofsky S. Acetaminophen hepatotoxicity: An update. Curr Gastroenterol Rep 1999;1(1):42-9.
5. Hawton K, Townsend E, Deeks J, Appleby L, Gunnell D, Bennewith O, et al. Effects of legislation restricting pack sizes of paracetamol and salicylate on self poisoning in the United Kingdom: before and after study. Bmj 2001;322(7296):1203.
6. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med 1988;319(24):1557-62.
7. Kind B, Krahenbuhl S, Wyss PA, Meier-Abt PJ. [Clinical-toxicological case (1). Dosage of N-acetylcysteine in acute paracetamol poisoning]. Schweiz Rundsch Med Prax 1996;85(31-32):935-8.
8. Donovan JW. Medical fortune-telling: predicting acetaminophen toxicity. Acad Emerg Med 1999;6(11):1079-82.
9. Smilkstein MJ, Bronstein AC, Linden C, Augenstein WL, Kulig KW, Rumack BH. Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. Ann Emerg Med 1991;20(10):1058-63.
10. McCormick PA, Casey P, Barry P, Laffoy M, Treacy J. Delays in administration of acetylcysteine in paracetamol overdose. Ir Med J 2000;93(3):77-8.
Competing interests: No competing interests
We would like to comment on the article by Hawton et al. that looks
at the effect of restricting pack size of paracetamol and salicylate on
self poisoning 1. They provide some evidence for a decrease in the
severity and incidence of paracetamol and salicylate poisoning 1.
However, they have not considered the effect on deliberate self poisoning
as a whole, or on self poisoning with other medications 1. Limiting
access to one type of medication may simply increase the incidence of
overdose with other potentially more dangerous substances. It is
important to determine if there is an increase in poisoning with other
agents 2. Although this is alluded to in the discussion 1, they only
consider the small, but significant increase in overdoses with paracetamol
compounds and paracetamol with other drugs. Using self poisoning with
paracetamol and salicylates alone, as a measure of the effect of this
legislation on self poisoning, is erroneous and potentially dangerous.
Hawton et al. have not considered the effect of the legislation on
accidental poisoning in children 1. This is a critical public health
issue and needs to be evaluated alongside deliberate self poisoning to
assess the impact of any legislation change. Data from poison information
centres would be useful to evaluate any changes in paediatric accidental
poisoning.
With only one year of data after the change of legislation to
evaluate the effects, it is concerning that the results are not
significant for the larger liver transplant units alone. Further, the
biochemical data does not support the decrease in severity, with no change
in the mean highest blood paracetamol concentration. The slight decrease
in mean highest prothrombin time (PT) is a poor measure of severity.
About 50% of patients with paracetamol poisoning, without hepatotoxicity,
will have a raised PT 3 making it a poor indicator of liver poisoning.
We are concerned that Hawton et al. conclude that the legislation has
been relatively successful 1, without properly assessing its effects on
all deliberate and accidental self poisoning.
Reference List
1. Hawton K, Townsend E, Deeks J, Appleby L, Gunnell D, Bennewith O,
et al. Effects of legislation restricting pack sizes of paracetamol and
salicylate on self poisoning in the United Kingdom: before and after
study. BMJ 5-19-1; 322:1203-1207.
2. Thomas MR, Jowett NI. Restriction has not reduced admissions with
self poisoning. BMJ 2001; 322:553
3. Whyte IM, Buckley NA, Reith DM, Goodhew I, Seldon M, Dawson AH.
Acetaminophen causes increased International Normalized Ratio by reducing
functional factor VII. Ther.Drug Monit. 2000; 22:742-748.
Competing interests: No competing interests
EDITOR -- Hawton et al’s paper (1) reports a decrease (at least over
the first year) in the number of deaths from paracetomol and salicylate
self poisoning after the introduction of legislation restricting the pack
sizes. This is certainly encouraging.
However, there remains the problem of self poisoning with prescribed
medication. Co-proxamol, a prescription only drug, is a combination of
dextropropoxyphene and paracetomol. In overdosage, the opioid component
produces respiratory depression and coma, and, in combination with
alcohol, acute cardiovascular collapse. (2)
In 1994, Farmer (3) reported that co-proxamol and paracetomol
accounted for the majority of suicides in analgesia overdosage. When
examining young suicides, Hawton et al’s study (4) found that the most
frequently used drug in overdosage was co-proxamol, and the medication had
usually been prescribed for someone other than the young person who had
committed suicide. If the number of suicides using co-proxamol is
increasing – and this was postulated at the recent Mental Health 2001
Conference in London – then action is required.
But what is effective action? Hawton et al (1) report that warnings
on packets are generally ineffective. Restricting sales is only possible
on OTC medication. Perhaps some of the responsibility rests with the
prescriber, to help limit the availability of prescribed analgesics,
particularly co-proxamol.
(1) Hawton, K., Townsend, E., Deeks, J., Appleby, L., Gunnell, D.,
Bennewith, O. et al. Effects of legislation restricting pack sizes of
paracetomol and salicylate on self poisoning in the United Kingdom: before
and after study. BMJ 2001; 322:1203-6.
(2) British National Formulary, March 2001
(3) Farmer, R.D.T. Suicide and poisons. Human Psychopharmacology
1994; 9 (suppl): S11-19.
(4) Hawton, K., Houston. K., and Shepperd, R. Suicide in young
people. Study of 174 cases, aged under 25 years, based on coroners’ and
medical records. British Journal of Psychiatry 1999; 175: 271-276.
Competing interests: No competing interests
To conclude that there has been a beneficial effect on suicide rates,
surely rate of suicide by self-harm or other drug overdose has to be
assessed? One would think that a patient intent on suicide would find
some other way of achieving their objective.
While I agree with the logic of reducing pack sizes for any toxic
drugs, I don't think that any assumption can be made with regard to
suicide rates in the wake of this legislation.
Competing interests: none.
Competing interests: No competing interests
Dear Sir,
We read with interest the paper of Hawton et al on the impact of
restricted paracetamol pack size on overdose and welcome any measure that
will effectively reduce the incidence of paracetamol poisoning.[1] This is
interesting data but there are major limitations in its interpretation,
such as the period of time studied since the legislation came into force
is too short (1 year) to fully assess its impact.[1] This is particularly
relevant in assessment of acute liver patients as the numbers are small
and there will be baseline variability.[2] The King's liver unit data
crosses the line and the Leeds, Newcastle and Royal Free data have
incidence rates close to zero. [1] Hawton et al [1] show data on blood
paracetamol concentrations and mean number of tablets taken per
paracetamol overdose, but these have not significantly changed and would
be expected to the main determinant of outcome in early paracetamol
poisoning. [3] Certainly PTR would not be expected to be a good marker,
not least because of availability of adequate treatment with N-
acetylcysteine.
For the same period of time, Donogue et al examined 2020 cases of
deliberate paracetamol poisoning and concluded there was no change in
incidence of poisoning after pack size restriction in Ireland. [4]
In addition, our own data show that the pack size legislation is not
complied with, at least in London and it possible to purchase much in
excess of the restricted numbers in pharmacies, supermarkets and corner
shops. [2]
In conclusion, pack size restrictions are not universally being
adhered to and it is too early to make any causal conclusions on their
impact either on the incidence of paracetamol poisoning in general or
acute liver failure in particular.
Yours faithfully
Paul Dargan and Alison Jones
1. Hawton K, Townsend E, Deeks J et al, Effects of legislation
restricting pack sizes of paracetamol and salicylate on self-poisoning in
the UK: before and after study. BMJ 2001; 322: 1203-1207.
2 Norman E, Dhairiwan R, Dargan PI, Wallace C, Jones AL. Paracetamol
poisoning: can it be prevented ? Proc R Coll Physicians Edinb 2001; 31: 62
-65.
3 Prescott LF, Illingworth RN, Critchley JAJH et al, Intravenous NAC:
the treatment of choice for paracetamol poisoning. BMJ 1979; 2: 1097-1100.
4 Donogue E, Tracey JA. Restrictions on sale of paracetamol in
Ireland had no impact on the number of tablets ingested in acute
deliberate overdose.[abstract Clin Tox 2000; 38: p 251.
Competing interests: No competing interests
Please can we return to normal packet sizes now?
I can see from the responses already filed that learned critics have
stated all the flaws i could see by "common sense" in this research, and
more. So it seems that this research is discredited and there is no
evidence that the reduction in pack sizes, which has inconvenienced the
entire purchasing public for several years, has had any benefit.
It has been stated today (6th December 2004) that suicides among
young moslem women are three times the national average; this implies that
an astonishing 75% of the UK's suicides are young moslem women; and this
cause is now being examined in detail. It appears that someone is at last
barking up the right tree.
So please can whoever had this daft idea now stop blaming suicide on
the size of asprin packets, and let us return to normal packet sizes, for
everyone's convenience and economy ?
Competing interests:
None declared
Competing interests: No competing interests