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Paracetamol Self-Poisoning Characteristics, Prevention and Harm Reduction


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Paracetamol is now the most common drug used for self-poisoning in the UK and is associated with potentially fatal liver damage. Patients admitted to hospital because of paracetamol overdoses were studied in order to determine their characteristics and factors which might have deterred them from taking paracetamol or reduced the dangers of the overdose. Eighty patients were studied in hospital using a structured interview schedule, measures of depression and suicidal intent, information collected through the Oxford Monitoring System for Attempted Suicide, and the results of liver function tests. Acute liver dysfunction (25 patients) was associated with consumption of more than 25 tablets (odds ration 4.46, 95% CI 1.31 to 17.41, P = 0.014). The proportionate use of tablets from blister packs (60%) and loose preparations (46%; 5 patients using both types) reflected their general availability. More of those who took tablets from a loose preparation consumed 25 or more tablets (69%) than those who used a blister-pack preparation (40%; odds ratio = 3.0, 95% CI 1.12 to 9.95, P = 0.028). Only 20 patients thought that any type of warning label would have deterred them from taking a paracetamol overdose. Establishing a maximum number of tablets (e.g. 25) that can be available in individual preparations is likely to reduce the dangers of paracetamol self-poisoning. The potential effects of other measures are uncertain.
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10.1192/bjp.168.1.43Access the most recent version at doi:
1996 168: 43-48 The British Journal of Psychiatry
K Hawton, C Ware, H Mistry, J Hewitt, S Kingsbury, D Roberts and H Weitzel
Paracetamol self-poisoning. Characteristics, prevention and harm
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British Journal of Psychiatry(1996), 168, 43-48
A steady increasein paracetamoloverdoses sincethe
mid-1970s has meant that paracetamol has now
become the substance used most frequently in
deliberate self-poisoning in the UK (Hawton &Fagg,
1992a). In Oxford, for example, 47.8°loof all over
doses in 1993involved paracetamol or paracetamol
containing drugs (unpublished data). It is especially
common in overdoses by adolescents (Hawton &
Fagg,1992b).Thisphenomenon isnotconfinedto
the UK, having also been reported from Denmark
(Ott et a!, 1990) and Germany (Augustin &
Schmoldt, 1991). Hepatic toxicity (Bray, 1993)is the
main reason for concern about paracetamol self
poisoning and why methods of prevention or harm
reduction need to be found. Paracetamol liver
damage accounts for over half of all cases referred
to liver units because of fulminant liver failure, is
the definite cause of at least 150 deaths per year in
the UK (Spooner & Harvey, 1993), and has now
become a common reason for liver transplantation
(O'Grady et a!, 1991).
While a study of paracetamol self-poisoners
admitted to a tertiary referral centre for patients with
liverproblemsinthe 1970srevealedthatmost patients
did not know that paracetamol was dangerous in
overdose (Gazzard eta!, 1976), we have found that
paracetamol self-poisoners today are mostly aware
of the dangers, and the main reason they take
paracetamol is its ready availability (Hawton et a!,
1995). We report on the characteristics of
the overdoses and their effects, and examine the
potential effectiveness of possible measures to reduce
the likelihood or dangers of paracetamol self
The subjects were 80 consecutive self-poisoning
patients who were admitted to the John Radcliffe
Hospital in Oxford between September 1992 and
March 1993, having taken overdoses of paracetamol
or paracetamol-containingcompounds, or both, and
who consented to participate in the research
interview. The patients had first undergone a full
psychosocial assessment (Hawton & Catalan, 1987),
following which members of the research team
approached them to seek their permission for
inclusion in the study. Eighteen other patients refused
the research interview. A further 20 patients left
hospital before their consent could be obtained and
five were not invited to participate because they were
confused or too ill. There were no significant age or
sex differences between the included and excluded
Paracetamol Self-Poisoning
Characteristics, Prevention and Harm Reduction
Background.Paracetamolis now the most commondrugusedfor self-poisoningin the UK
andisassociatedwith potentiallyfatal liverdamage.Patientsadmittedto hospitalbecause
of paracetamoloverdoseswerestudiedinorderto determinetheircharacteristicsandfactors
which might have deterredthem from taking paracetamolor reducedthe dangersof the
Method.Eightypatientswerestudiedin hospitalusinga structuredinterviewschedule,
Systemfor Attempted Suicide,and the resultsof liverfunctiontests.
Results.Acuteliverdysfunction(25 patients)was associatedwith consumptionofmorethan
25 tablets(oddsratio4.46,95% Cli .31 to 17.41, P=0.Oi 4). Theproportionateuseoftablets
fromblisterpacks(60%) andloosepreparations(46%; 5 patientsusingbothtypes)reflected
theirgeneralavailability.Moreof thosewhotooktabletsfroma loosepreparationconsumed
25 or more tablets (69%) than those who used a blister-packpreparation(40%; odds
ratio = 3.0,95% CI 1.12 to 9.95, P= 0.028). Only 20 patients thought that any type of warning
label would have deterred them from taking a paracetamol overdose.
ConclusIons. Establishing a maximum number of tablets (e.g. 25) that can be available in
individualpreparationsis likelyto reducethe dangersof paracetamolself-poisoning.The
potentialeffects of other measuresare uncertain.
There were eight researchinterviewers, all psy
chiatristsor membersof the psychiatricconsultation
service in the general hospital who were familiar with
interviewing self-poisoning patients.
The research questionnaire contained questions
regarding details of previous overdoses (including
whether paracetamol was used and treatment
received), and of the current overdose (including
substances used, extent of premeditation and alcohol
use before and with the overdose). Specific questions
about paracetamol use (including paracetamol
compounds) in the current overdose concerned
where the paracetamol was originally obtained,
where it was kept in the house, and the form
of paracetamol (loose tablets or blister-pack
preparation). Enquiry was then made about factors
which might have affected the patient's decision
to take an overdose of paracetamol. These included
full knowledge of its dangers, specific warnings
on the paracetamol container, blister packaging,
availability of smaller amounts, and being available
only on prescription. The final 42 subjects in
the study were also asked how their decision to
take the paracetamol preparation might have been
influenced if they had known it to have included
an antidote which would reduce its dangers. Patients
were asked for their responses to statements
presented on typed cards about the anticipated
dangers of paracetamol self-poisoning and about
possible specific warnings on labels of containers
of paracetamol which might deter them from taking
it in overdose. The warnings included the following:
“¿Anoverdose of paracetamol can kill―,“¿Due
to the addition of an antidote, exceeding the stated
dose may cause vomiting―,“¿Thisdrug is dangerous
in overdosage―, “¿Donot exceed the stated dose―,
and “¿Itmay be harmful to exceed the stated
dose―. Findings from further questions about
why paracetamol was chosen, the effects expected
by the patient, and knowledge about the dangers of
paracetamol self-poisoning, including the anticipated
timing of any adverse effects, are reported elsewhere
(Hawton et a!, 1995).
In each case the research interviewer assessed the
patient's suicidal intent using the Suicidal Intent
Scale (SIS; Beck et a!, 1974), which includes items
about the circumstances of the overdose and the
patient's response to questions concerning pre
meditation, intent, and so on, and the level of
depression by means of the Montgomery—Asberg
Depression Rating Scale (MADRS; 1979). The
clinical assessor for each case was asked to indicate,
from a list of motives (Bancroft eta!, 1979), the likely
reasons for the overdose, and whether or not in their
opinion the patient had wanted to die when taking
the overdose. The inter-rater reliability of the
measures was not investigated.
The information collected in the study was
combined with data routinely collected on each
patient by the Oxford Monitoring System for
Attempted Suicide (Hawton & Fagg, 1992a). This
provided details concerning each patient's current
problems (e.g. alcohol abuse).
We reviewed the results of the physical investigations
that had been conducted in order to ascertain whether
the patients had any signs of acute liver dysfunction.
Evidence of dysfunction was defined as an INR
(International Normalised Ratio), based on a pro
thrombin coagulation test, of greater than 1.2 which
had risenfrom or fallento a baselinevalue(usually 1.0).
We also noted whether or not the liver function tests
were abnormal. In defming a cut-off point with regard
to the number of tablets taken, weused the mid-point
(25 tablets) of the range of 20—30500-mg tablets
(10-15 g) that has been estimated as the threshold dose
for liver toxicity (Mitchell eta!, 1974; Prescott, 1983).
Statistical methods
The differences in proportions (odds ratios and 95%
confidence intervals (CIs)) were calculated using the
EPI-INFO program (Dean et a!, 1990). The signifi
cance of differences between the means of con
tinuous variables were assessed by the t-test.
The 80 paracetamol self-poisoners included more
females than males, and were predominantly relatively
young (Table 1). According to their MADRS scores,
Age: years
36 +
0-6 (low)
21+ (very high)
Table 1
Subjects included in the study
No. (%) of
53 (66)
27 (34)
32 (40)
32 (40)
16 (20)
42 (53)
38 (47)
17 (21)
27 (34)
5 (6)
38 (48)
23 (29)
(%) of
gainrelieffroman unbearablestateof mind53
findif someonecaredforthe person13
showhow muchthepersonlovedsomeone9
In mostcasesmorethanonemotivewasattributed.
38 were in the moderately or more depressedrange
(22 or more). Fourteen patients were in the severely
depressed range (35 or more). Nearly half had had
previous episodes of deliberate self-harm, and more
than a quarter had taken at least one previous
paracetamol overdose.
The index overdose
Of the overdoses, 56 (70%) included paracetamol
only, 16(20°lo)paracetamol-containing compounds
only, and eight (10°lo)both paracetamol and
paracetamol-containing compounds. Of those who
took paracetamol-containing compounds, 11(69%)
said they had not known they contained paracetamol,
but all but one of them said that if they had known
they would still have used the preparation for self
poisoning. Twenty patients took other substances in
addition to paracetamol, including antidepressants
(six), major tranquillisers (three), other prescribed
drugs (six), and salicylates (two). In addition, 18
patients consumed alcohol as part of the overdose
and 29 had been drinking during the six hours
beforehand.The numbersof paracetamol/compound
tablets taken were 1—25(35 patients), 26—50(27
patients), more than 50 (15 patients), or were not
known (three patients). Twenty-seven patients said
they took all the tablets (or capsules) available, 28
more than half, and 24 half or less (1 did not know).
The tablets had been contained loose in a tub or
bottle in 37 (46%) cases and in a blister pack in 48
(60°lo)cases (five patients having taken both types
of preparation). Significantly more of those who
used only tablets from a loose preparation pack
(22/32, 69%) took more than 25 tablets compared
with those who used tablets from a blister-pack
preparationalone (16/40,40%; odds ratio 3.0,95%
CI 1.12 to 9.95, P=0.028). On the other hand,
somewhat more of those who used a blister-pack
preparationalone said that they had taken more than
half of the tablets available (33/42, 79°lo)compared
with those who used a loose preparation (19/32,
59%; odds ratio=2.51, 95% CI 0.81 to 7.91,
P= 0.125). While patients who used a blister-pack
preparation did not differ in their premeditation or
suicidal intent from those who used loose tablets,
those who took more than 25 tablets (of either
type of preparation) had higher suicidal intent
(mean 13.3, s.d. 6.2) than those who took 25 or
less (mean 9.1, s.d. 4.4; t=3.49, P<0.01). In
the patients who took 25 tablets or less, there
was no difference between the mean suicidal
intent scores of those who used a blister-pack
preparation and those who took tablets from a
loose preparation.
Source of the tablets
The most frequentsourceof the tabletswas a chemist
(32, 40%), followed by some other type of shop (19,
24%), a family member (10, 13%), and the general
practitioner (9, 11%). Thirty-three patients (41%)
had obtained the tablets less than an hour before
taking the overdose, 11 (14%) between 1 and 24
hours beforehand, seven(9%)! to 7 days beforehand,
and 25 (31%) more than a week beforehand (four
did not know when they had obtained the tablets).
In42 cases, the tabletshad been obtained specifically
for the purpose of taking an overdose, whereas the
remaining 38 patients had initially obtained them for
some other reason, usually pain relief. In 43 cases
the tablets had a usual location in the house - for
18this was the kitchen, nine the bedroom, seven the
bathroom, and nine some other location.
Premeditation and motivation
The overdoses were often taken impulsively, 33
patients (41%) having seriously contemplated taking
the overdose for less than one hour beforehand, 26
(33%) for between 1and less than 3 hours, five (6%)
for between 3 and 24 hours, and 16(200lo)for more
than a day. The tablets were usually taken rapidly,
36 (45%) having taken the overdose in less than 5
minutes, 27(34%) in between 5 minutes and an hour,
and 17 (21%) in more than an hour.
The clinical assessors regarded escape from a
difficult situation or state of mind as the most
frequent explanation, followed by communication
of distress,help-seekingand interpersonalcommuni
cation (Table 2). With regard to suicidal intent, the
clinical assessors thought that 31 (39%) patients had
wanted to die, 20(25%) had not wanted to die, and
29(36%) did not mind eitherway. In 32(40%) cases,
Table 1
The motives chosen by the clinical assessors to explain
the overdoses
(%) of patients
>25 tablets19/24
(79)23/50 (46)Odds
ratio=4.46 (95% Cl 1.31 to17.41)P=0.01Abused
ratio=0.43 (95% Cl 0.09 to1.64)P=O.29Mean
(s.d.)MADRSscore21.5 (10)23.2
(6)10.7 (6)(=0.12NS
Associations with liver damage following paracetamol self-poisoning
the suicidal intent scores recorded by the research
interviewers were in the high range (Table 1).
Liver dysfunction
Twenty-four (31%) out of 77 patients (notes
unobtainable in three cases) had evidence of acute
liver dysfunction), 17 having abnormal INR values
alone and seven abnormal INR and liver function
test values. Transfer to a specialised liver unit was
considered for four of the latter patients but
eventually proved unnecessary. Liver dysfunction
was associated with consumption of more than 25
tablets in the overdose (Table 3). No association was
found with evidenceof alcohol problems, depression
or suicidal intent scores.
Factors which might have deterred patients from
taking paracetamol overdoses
Danger. After being told that paracetamol overdoses
can cause death even when treatment has been
instigated, 53 (66%) patients said they would still
have taken paracetamol in spite of knowing this (ten
patients were uncertain).
De!ay in effects. When told that if a paracetamol
overdose causesharmthe personusuallyis not aware
of this for several days, during which time he or she
is likely to remain conscious, only 28(35%) patients
said they would have taken paracetamol despite this
(eight subjects were uncertain).
Warning on labe!. The rank order in which
patients allocated cardsshowing specific wording of
possible warning labels on paracetamol containers
indicated that the simple statement “¿Anoverdose
of paracetamol can kill―was likely to have been the
most off-putting, 58 of 74 patients (78°/a)having
given this warning the highest rank. However, only
20(25%) patients thought that any type of warning
on the container would have stopped them taking
an overdose.
B!ister packs. When the 32 patients who had not
used tablets from a blister-pack preparation for the
overdose were asked what they would have done if
only blister-pack preparations were available, 21
(660/a)said they would still have taken a paracetamol
overdose (five patients were uncertain).
Limited number of tab!ets. The 68 patients who
had taken more than 12 tablets of paracetamol in
their overdoses were asked what they would have
done if paracetamol had been available only in small
packets (of 12tablets). Forty-seven (69%) said they
would still have taken a paracetamol overdose,
although 12(180/a) said that they would have taken
a smaller amount. Thirteen (19%) said they would
not have taken an overdose at all, and five (70/,)that
they would have taken some other substance (three
were uncertain). Thus 25 (37%) out of 68 patients
said that they would either have taken a smaller
paracetamol overdose or no overdose at all.
Paracetamo!availableonly on prescription. The
patients were also asked what they would have done
if paracetamol had been available only on pre
scription from a general practitioner (n = 71;
excluding patients who obtained paracetamol from
general practitioners). Fourteen (20°!.)said they
would still have taken a paracetamol overdose, 24
(34%) that they would have taken something else in
overdose, 4 (60/a)that they would have used some
other means of self-harm, and 25 (350/a)that they
wouldnot havetakenanoverdose(sixwereuncertain).
Antidote preventing liver damage. The fmal 42
patients included in the study were asked if they
would still have taken a paracetamol overdose if
paracetamolcontained an antidote which would stop
the harmful effects of an overdose. Twenty-seven
(640/.) said that they would not have done and 13
(310/.) that they would have (two were uncertain).
The prevention of paracetamol self-poisoning, or at
least of its consequences, is a complex issue.
Paracetamol is a useful minor analgesic and
antipyretic, and in considering prevention one must
consider how it can remain available, yet either be
used less for self-poisoning or made more safe if
taken in overdose. A methodological issue relevant
to interpretation of our findings concerns the
representativeness of the sample. Unfortunately, we
were unable to interview approximately a third of
the potential sample. While the excluded patients did
not differ from those interviewedin termsof sex and
age, we cannot saythatthey might not havediffered
in termsof other factors relevantto the focus of the
It appears that warningson paracetamol containers
might deteronly a minority of patients from taking
paracetamol in overdose, with a blunt warning that
“¿Anoverdose of paracetamol can kill―being the
most off-putting of those shown to the patients in
this study. The impulsive nature of many of the
overdoses also suggests that warningson containers
might have little effect. Thereis the furtherriskthat
they might make paracetamol more attractive to
patients with high suicidal intent.
might reduce the likelihood that would-be self
poisoners would choose paracetamol for self
poisoning (Gazzard eta!, 1976). Our fmdings do not
support this hypothesis, as 600/aof patients had used
tablets from blister-pack preparations in their
overdoses, a figure which is similar to the current
salesof blisterpacks (54.90/a)as a percentageof sales
of all preparations of paracetamol in the UK
(Paracetamol Information Centre). Secondly, of
those who took tablets from a loose preparation,
two-thirds said they would still have taken an
overdose of paracetamol even if it was available
only in blister-pack form. Blister packs were,
however, associatedwith fewertabletsbeingtakenin
overdose. Thus significantly fewer of the patients
in this study who used this type of preparation in
contrast to those who used pills from a loose
container took more than 25 tablets. This was not
due to any difference in premeditation or suicidal
intent. Nor did it reflect a tendency for those using
tablets from a blister pack to consume a smaller
proportion of the availabletablets; therewas in fact
a tendencyfor the reverseto be true.The blisterpack
itself seems unlikely to be the key factor, but more
the fact that blister packs in general contain fewer
tablets. On average they contain less than half the
number of tablets found in loose preparations
(Paracetamol Information Centre). In patients who
took 25 tablets or less, one might have expected that
those who used a blister-pack preparation would
have had somewhat higher suicidal intent than
those who used a loose preparation, but this was
not found.
Limiting availability
It appears that limiting the overall number of
paracetamol tablets available for sale in each pack
mightpreventsome patientstakingan overdose, and
could mean that others would still make a para
cetamol overdose but use fewer tablets. This strategy
might, therefore, reducethe morbidityand mortality
associated with paracetamol self-poisoning. In order
to avoid the risk of patients turning to other over
the-counter medication for self-poisoning, which can
be at leastas dangerousas paracetamol(e.g. aspirin),
it would be sensible if this strategy were applied to
similar preparations.
Ifparacetamolwereavailableonlyon prescription,
it appears that this would be likely to prevent a
sizeable proportion of patients from taking an
overdose, although an equally large number said
they would have taken something else instead of
paracetamol. It would also mean that paracetamol
would be less readily available for its intended
use as a minor analgesic. Were all paracetamol
preparations to contain an antidote to liver damage
(e.g. methionine) this might reduce the incidence of
hepatic toxicity following paracetamol self-poisoning.
However, lackof knowledgeabout whetherthereare
any adverse effects of long-term use of methionine
in regularusers, possible toxicity of a large dose of
methionine, fears that knowledge of the antidote
might deter regular users of paracetamol, and
increased costs, limit the relevance of this strategy
at this stage. The majority of patients indicated that
knowledge of the presence of an antidote in
paracetamol tablets would put them off taking them
in overdose but, paradoxically, most patients said
that warnings of any kind on containers would not
prevent them taking an overdose.
Highlighting the delay before the effects of a
paracetamol overdose become apparent seems to be
important, since the majority of patients said they
would not havetakenparacetamolif theyhadknown
this. Perhaps this information could be imparted
through the media. It could also be given to patients
recovering from paracetamol self-poisoning, perhaps
supplemented by an information sheet, in the hope
of preventing repetition. Any method of reducing
the frequency of paracetamol self-poisoning is
associated with the problematic question of what
patients might do instead. One risk is that some
might use another dangerous method of self-harm,
particularly with an increasing range of drugs being
available in over-the-counter preparations.
Our overall conclusion is that limiting the
number of tablets available in all over-the-counter
paracetamol (and other similar) preparations (to 25
or perhaps fewer tablets) is the most pragmatic
initial approach to the problem of paracetamol
self-poisoning. Other approaches, except making
paracetamol available only on prescription, are
unlikely to succeed in view of the considerable
impulsiveness associated with most paracetamol
overdoses, the low likelihood that warnings on the
container will influence the behaviour and possible
effects on regular users of paracetamol. It should
become apparent relatively soon whether or not a
reduction in the number of tablets per container
would have the desired effect in terms of reduced
morbidity and mortality from paracetamol self
poisoning. If it did, this could contribute to the
achievement of the government's Health of the
Nation general suicide target (Secretary of State for
Health, 1992), especially in young people.
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Keith Hawton, DM,Christopher Ware, MRCPsych,Stephen Kingsbury, MRCPsych,University Department
of Psychiatry, Warneford Hospital, Oxford; Hamant Mistry, MRCGP, Jonathan Hewitt, MRCPsych, Dave
Roberts, RMN, Heather Weitzel, RMN, Barnes Unit, Department of Psychological Medicine, John Radcliffe
Hospital, Headington, Oxford
Correspondence: Dr K. Hawton, University Department of Psychiatry, Warneford Hospital, Oxford 0X3 7JX
(First received 23 January 1995, final revision 18 May 1995, accepted 19 May 1995)
... Среди суицидентов эти показатели во многих случаях были выше: доля осведомлённых о возможности повреждения печени при передозировке парацетамола -от 31 [31] до 80,0% [47], его высокой токсичности -55% [31], высокой вероятности смерти и необратимого повреждения -88,3% [47]. Эти цифры можно расценить как свидетельство целенаправленного интереса данной категории лиц к токсическим качествам препарата, но две трети (68%) тех же опрашиваемых сообщали, что не читали предупреждение на пакетах [31], а каждый четвёртый из совершивших самоотравление парацетамолом, отметили, что любой тип предупреждающей надписи удержал бы их от выбора препарата [51]. Тем не менее, исследователями отмечается, что предупреждения на пачках не имеют большого сдерживающего эффекта [47]. ...
... Among suicide attempters, these indicators were mostly higher: the percentage of those aware of the possibility of liver damage in case of paracetamol overdose ranged from 31 [31] to 80.0% [47], 55% were aware of its high toxicity [31], and 88.3% knew of high probability death and irreversible damage [47]. These figures can be regarded as evidence of the deliberate interest of this category of people in the toxic qualities of the drug, but two-thirds (68%) of the same respondents reported that they did not read the warning on the packages [31], and every fourth of those who committed self-poisoning with paracetamol, noted that any type of warning label would deter them from choosing the drug [51]. Nevertheless, the researchers noted that warnings on packs do not have a large deterrent effect [47]. ...
... Moreover, previously published studies did not distinguish between accidental overdoses and deliberate self-harm, the latter being the impetus for the legislated restrictions on package sizes, given the often impulsive nature of deliberate overdoses. 44 We focused specifically on accidental overdoses, the prevention of which would be the likely goal of labelling changes intended to promote safe use of acetaminophen. ...
Background: Accidental acetaminophen overdoses are associated with substantial morbidity and health care costs. In Canada, updated labelling standards were implemented in October 2009 and September 2016, with the intent of communicating risks of overdose and facilitating product identification and safe use, respectively. Full compliance with the 2016 standards was expected by March 2018. We sought to explore whether these changes affected rates of hospital admission for accidental acetaminophen overdose. Methods: We conducted a population-based study of hospital admissions for accidental acetaminophen overdose in 9 Canadian provinces and 3 Canadian territories between Apr. 1, 2014, and Mar. 31, 2020. We used interventional autoregressive integrated moving average (ARIMA) models to evaluate the impact of the updated labelling standards on rates of hospital admission for accidental acetaminophen overdose. In secondary analyses, we studied intensive care unit (ICU) admissions and hospital admissions for accidental acetaminophen overdose involving opioids. Results: Monthly rates of hospital admission for accidental acetaminophen overdose were essentially unchanged over the study period (0.21 and 0.22 cases per 100 000 population in April 2004 and March 2020, respectively). We found no association between changing labelling standards and trends in rates of hospital admission for accidental acetaminophen overdose (October 2009 p = 0.2, September 2016 p = 0.7 and March 2018 p = 0.2). Similarly, labelling changes did not have an impact on admissions involving ICU admission and concomitant opioid poisoning. Interpretation: Modifications to product labels did not reduce the rate of acetaminophen-related harm. Additional measures to reduce the burden of accidental acetaminophen overdose are required.
... [11,16]. Suicidal ideation was declared by 39% of patients in a study by Hawton et al. [17], as compared with 41% in our study. The most frequent symptoms on admission, such as nausea, vomiting, and abdominal pain, were also typical for this clinical condition [5]. ...
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Background and Objectives: Over-the-counter availability and a good safety profile make paracetamol one of the most common analgesics in developed countries but also the leading cause of liver failure due to overdose. The objectives of the study were to identify modifiable risk factors for severe hepatotoxicity following paracetamol overdose in adults. Materials and Methods: A retrospective cohort study involved the consecutive adult patients hospitalized in a toxicological center over a period of seven years due to paracetamol overdose. Complete medical datasets of laboratory and anamnestic variables were analyzed and validated by means of logistic regression model. Results: A total of 185 patients entered the study, including 25 individuals who developed severe hepatotoxicity (plasma aminotransferases levels above 1000 UI/L) and 31 individuals with mild to moderate liver injury (plasma aminotransferases levels above upper normal range, but below 1000 UI/L). In the univariable analysis, significant hepatotoxicity risk factors were male gender, alcohol abuse, an ingested paracetamol dose, and a timespan from ingestion to hospital admission. The later one was the only significant risk factor in the multivariable model (adjusted odds ratio 1.08; 95%CI: 1.03–1.12). Conclusions: A delay in hospital admission, resulting in a delayed administration of disease-specific treatment outweighs any other known risk factors of paracetamol-induced hepatotoxicity.
... In 1998, the British Houses of Parliament passed legislation limiting package size and using blister packs to deter impulsive behavior. [50][51][52] Whether this has proved effective has been a subject of continued debate. 53,54 Over the past three decades, little specific progress has been made in curbing these unfortunate events, other than prompt use of NAC. ...
... The person's own prescription medicines are a common source of substances for ISP [15]. Paracetamol may be chosen due to ease of access, and because people have a limited understanding of its effects in overdose [16,17]. In adults, acute paracetamol overdoses of 10 g or more may be associated with acute liver injury and are therefore of concern, and overdoses above 30 g may necessitate enhanced management such as the use of higher doses of the antidote [18]. ...
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Background Intentional self-harm is a common cause of hospital presentations in New Zealand and across the world, and self-poisoning is the most common method of self-harm. Paracetamol (acetaminophen) is frequently used in impulsive intentional overdoses, where ease of access may determine the choice of substance. Objective This cross-sectional study aimed to determine how much paracetamol is present and therefore accessible in urban New Zealand households, and sources from where it has been obtained. This information is not currently available through any other means, but could inform New Zealand drug policy on access to paracetamol. Methods Random cluster-sampling of households was performed in major urban areas of two cities in New Zealand, and the paracetamol-containing products, quantities, and sources were recorded. Population estimates of proportions of various types of paracetamol products were calculated. Results A total of 174 of the 201 study households (86.6%) had at least one paracetamol product. Study households had mostly prescription products (78.2% of total mass), and a median of 24.0 g paracetamol present per household (inter-quartile range 6.0–54.0 g). Prescribed paracetamol was the main source of large stock. Based on the study findings, 53% of New Zealand households had 30 g or more paracetamol present, and 36% had 30 g or more of prescribed paracetamol, specifically. Conclusions This study highlights the importance of assessing whether and how much paracetamol is truly needed when prescribing and dispensing it. Convenience of appropriate access to therapeutic paracetamol needs to be balanced with preventing unnecessary accumulation of paracetamol stocks in households and inappropriate access to it. Prescribers and pharmacists need to be aware of the risks of such accumulation and assess the therapeutic needs of their patients. Public initiatives should be rolled out at regular intervals to encourage people to return unused or expired medicines to pharmacies for safe disposal.
Since the dawn of humankind, humans have relied on plant-based medicines for the majority of their health and disease needs. The rapid and increasing rise in the worldwide use of herbal medicines in recent decades suggests botanical medicines, both traditional and modern, fulfill a therapeutic niche not adequately addressed in modern health care delivery systems. At the same time, there is a propensity, predominantly in developed, but also developing nations, to develop herbal medicines in the same manner as modern chemically characterized drugs. This trend is driven partly by a belief that the same regulatory requirements that are applied to modern pharmaceuticals should be applied to herbal medicines and partly by economics, a subject not often discussed.
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Objectives : To study characteristics and risk factors for severe hepatotoxicity among paracetamol overdose patients who were treated at Ramathibodi Hospital from 2007 to 2016. Methods : This is a retrospective descriptive study of patients who were diagnosed with “paracetamol overdose” (ICD-10: T391) between 1 January 2007 and 31 December 2016. Data were collected from Patients’ Record and Medical Informatics Division, Ramathibodi Hospital. Results : A total 105 patients were diagnosed with paracetamol overdose. The majority of patients were female students between the age of 21–39 with non-marital status and holding a bachelor’s degree or higher. The motivation for paracetamol overdose was to commit suicide and self-harm (49.42%), driven by relationship problems (67.44%) and most of them had suicidal attempts before (66.67%). Most overdoses were impulsive attempts (91.95%) with no previous history of psychiatric illnesses (84.95%). 58.25 percent of them were diagnosed with adjustment disorders. Laboratory tests indicating severe hepatotoxicity were AST, ALT, PT, PTT and INR, whereas ALP played insignificant role. Paracetamol blood level did not correlate with the severity of hepatotoxicity. The major risk for hepatotoxicity is the time between paracetamol ingestion and visiting the emergency room. Patients who visited the emergency room later than 8 hours after paracetamol ingestion had a 20.9 time higher risk for hepatotoxicity compared to those who visited earlier (95% CI 5.476-79.682, p-value < 0.001). The hospitalization period of patients with severe hepatotoxicity is significantly higher than those without severe hepatoxicity. Conclusion : Most cases of paracetamol overdose were impulsive acts of self-harm. The chance of developing severe hepatotoxicity is low if patients came earlier after drug ingestion. It is crucial to promote social awareness of the importance of receiving prompt treatment after paracetamol overdose as this helps reduce the rate of severe hepatoxicity. It will also reduce unnecessary uses of resources, including expenses, time, and medical personnel.
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Objective: To determine whether non-pharmaceutical retail outlets are aboding to the current Medicines and Healthcare products Regulatory Agency (MHRA) national guidelines for over-the-counter (OTC) sales of aspirin and paracetamol. Methods: Stages 1 and 2 of the study deployed eight and four medical students, respectively, to undertake a mystery shopper style investigation. Stage 1: eight medical students attempted to buy ≥96 tablets/ capsules aspirin or paracetamol in one transaction in 62 shops. Stage 2: four medical students attempted to purchase 32 paracetamol 500 mg along with a 'flu remedy preparation also containing paracetamol, in 54 shops. Results: Stage 1 data revealed that 58% and 57% retailers sold more than the MHRA guidelines recommended for paracetamol and aspirin, respectively. We observed that 23% and 28% retailers were willing to sell ≥96 tablets of paracetamol or aspirin with no questions asked. Stage 2 results showed that 57% retailers sold 32×500 mg paracetamol in conjunction with a paracetamol-containing 'flu preparation; while 98% shops sold 16×paracetamol 500 mg along with a paracetamol-containing 'flu remedy, with no questions asked of the shopper or advice given.
Drug-induced liver injury caused by acetaminophen (acetyl-para-aminophenol [APAP]) is the main cause of acute liver failure and liver transplantation in several Western countries. Whereas direct toxicity exerted by APAP metabolites is a key determinant for early hepatocytes injury, the recruitment of cells of innate immunity exerts a mechanistic role in disease progression, determining the clinical outcomes. GPBAR1 is a G protein-coupled receptor for secondary bile acids placed at the interface between liver sinusoidal cells and innate immunity. In this report, using genetic and pharmacological approaches, we demonstrate that whereas Gpbar1 gene deletion worsens the severity of liver injury, its pharmacological activation by 6β-ethyl-3a,7b-dihydroxy-5b-cholan-24-ol rescues mice from liver injury caused by APAP. This protective effect was supported by a robust attenuation of liver recruitment of monocyte-derived macrophages and their repolarization toward an anti-inflammatory phenotype. Macrophage depletion by gadolinium chloride pretreatment abrogated disease development, whereas their reconstitution by spleen-derived macrophage transplantation restored the sensitivity to APAP in a GPBAR1-dependent manner. RNA sequencing analyses demonstrated that GPBAR1 agonism modulated the expression of multiple pathways, including the chemokine CCL2 and its receptor, CCR2. Treating wild-type mice with an anti-CCL2 mAb attenuated the severity of liver injury. We demonstrated that negative regulation of CCL2 production by GPBAR1 agonism was promoter dependent and involved FOXO1. In conclusion, we have shown that GPBAR1 is an upstream modulator of CCL2/CCR2 axis at the sinusoidal cell/macrophage interface, providing a novel target in the treatment of liver damage caused by APAP.
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Liver diseases form a heterogenous group of acute and chronic disorders of varying etiologies. Not only do they result in significant morbidity and mortality, but they also lead to a marked reduction in quality of life, together with a high socioeconomic burden globally. A better understanding of their global distribution is necessary to curb the massive health‐care and socioeconomic burden that they entail. Notable differences and similarities have been described between common liver disease conditions occurring in Asia and the West (Europe and North America), giving rise to the need for an updated collective appraisal of this subject. In this review, the epidemiological differences of common liver conditions, specifically acute liver failure, drug‐induced liver injury, acute‐on‐chronic liver failure, hepatocellular carcinoma, and non‐alcoholic fatty liver disease, between Asia and the West are discussed. The epidemiology of common liver conditions is different between Asia and the West. The predominance of viral hepatitis in Asia results in differences in etiology and prognosis of acute liver failure, acute‐on‐chronic liver failure, and hepatocellular carcinoma from that in the West. Etiological differences in drug‐induced liver injury (DILI) between Asia and the West may lead to a difference in prognosis
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To review trends in deliberate self poisoning and self injury (attempted suicide) over 15 years (1976-90) on the basis of general hospital referrals. Prospective data collection by computerised monitoring system. Teaching general hospital. All patients aged 15 and over (n = 9605) referred to the hospital after episodes (n = 13,340) of deliberate self poisoning or self injury. Rates based on population of Oxford city; changes in substances used for self poisoning; history and repetition of attempts; and rates of admission to the hospital and of referral to the psychiatric service. Attempted suicide rates for women declined during the late 1970s and early 1980s but increased again during the late 1980s. Those for men remained relatively steady throughout the period. Highest mean annual rates occurred in women aged 15-19 (711/100,000) and in 20-34 year old men (334/100,000). The proportion of overdoses with paracetamol increased from 14.3% (125/873) in 1976 to 42% (365/869) in 1990 (chi 2 for trend = 481, p less than 0.01). Throughout the period the proportions of referred patients admitted to hospital and of those attempting suicide for the first time (over two thirds) did not decrease. Annual rates of repetition of attempts by women declined from 15.1% (257/1700) in 1976-8 to 11.9% (161/1356) in 1987-9 (chi 2 for trend = 7.8, p less than 0.01). Lower repetition rates occurred in women admitted to hospital and referred to the psychiatric service (431/4585, 9.4%) than in those not referred (42/235, 17.9%; chi 2 = 17.2, p less than 0.0001). Rates of attempted suicide declined in the 1970s and early 1980s, in women, but there are probably at least 100,000 hospital referrals a year in England and Wales because of this problem. Prevention of paracetamol self poisoning requires urgent attention, and psychosocial assessment should be conducted with as many of those who attempt suicide as possible.
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To evaluate the role of liver transplantation after paracetamol overdose. Prospective study of consecutive candidates for transplantation and performance of transplantation over 18 months. Liver unit, King's College Hospital, London. Fulfilment of indicators of poor prognosis, selection for transplantation, transplantation, survival. 30 of 37 patients considered to have a reasonable prognosis with intensive medical care survived. Of 14 of 29 patients considered to have a very poor prognosis and registered for urgent liver transplantation, six received liver transplants, four of whom survived, while seven died and one survived without a transplant. Three of 15 patients with poor prognostic indicators but not selected for transplantation survived. Liver transplantation will have a definite but limited role in the management of fulminant hepatic failure induced by paracetamol.
Describes a phenomenological approach to the study of personality factors in drug abuse, emphasizing the problem of compulsion, symptom equivalence, and their effects on life-style. The question of whether certain personality traits are indicative of a predisposition to drug addiction (e.g., object dependency or affect defense), the long-range effects of drugs on personality, and implications for treatment are also examined. (67 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inter-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
A representative sample of 41 cases of self-poisoning was studied in depth. In each case ‘reasons’ for taking the overdose, both stated spontaneously and chosen from a presented list, were recorded. The commonest spontaneous reason was the ‘wish to die’. Nearly one-third indicated some non-suicidal purpose early in the interview and consistently denied suicidal intent subsequently. Apart from suicidal intent, reasons chosen from the list bore little resemblance to reasons that had been offered earlier in the interview and are therefore of uncertain relevance. Three psychiatric judges attributed reasons for each case based on common-sense criteria. Several reasons were seldom or never chosen by them; four were chosen frequently with good agreement, i.e. communicating hostility, influencing others, relieving a state of mind and suicidal intent. The first two were the most frequently chosen, attributed to 71 per cent and 54 per cent of cases respectively. They were the reasons chosen least frequently by the self-poisoners themselves. Of 23 (56 per cent) subjects indicating suicidal intent, 12 (29 per cent) were judged to be suicidal by psychiatrists. These were not clearly distinguishable on the basis of their original interviews, except that those judged suicidal tended to indicate suicidal intent early in the interviews. The clinical and research implications of these findings are discussed.
A questionnaire to assess motives for choosing paracetamol as a suicidal agent was completed by 107 patients admitted after an overdose of the drug. None of the 48 patients interviewed would have chosen paracetamol had they known that there would be an interval of two to three days before the onset of serious symptoms. Only five of the patients had obtained the drug on prescription, but the remainder had obtained it easily from a retail pharmacy. There was no apparent reason for the preference for paracetamol. It would be difficult to restrict the availability of paracetamol, and educating the public about the effects of an overdose would be more appropriate.
In Oxford during the late 1970s and early 1980s a decline in rates of deliberate self-poisoning and self-injury in older female teenagers was followed by a steady increase between 1986 and 1989. Rates for male adolescents and young female adolescents remained relatively stable throughout 1976-89. Applying the Oxford rates to England and Wales suggest a total of 18,000-19,000 hospital-referred cases per year. While self-poisoning with minor tranquillisers and sedatives has declined, there has been a marked increase in paracetamol self-poisoning, such that by 1988-89 it was involved in 48.3% of overdoses. Relationship difficulties were the most frequent problems faced by these adolescents, especially the females, with unemployment and alcohol and drug problems also being common, especially in males, but psychiatric disorders relatively rare. Substantial proportions of the adolescents, especially the males, were not living with either relatives or friends, and had a history of violence or a criminal record. The annual rate of repetition of attempts, which was 8.9% overall, was higher in adolescents not admitted to the general hospital, and in females not referred to the hospital psychiatric service. Adolescent attempted suicide clearly continues to be a major health problem for which both effective preventive and therapeutic strategies are badly needed.
During the period 1978-1986, annual sales of paracetamol in Denmark increased from 1 million defined daily doses (DDD) (3 g) to 47 million DDD, while the number of admissions and deaths from overdose increased from 26 to 202 and from 1 to 3-4, respectively. The corresponding figures for salicylates are a decrease in sales from 113 to 94 million DDD, an increase in admissions from 282 to 595, and an increase in deaths from 5 to 22. From 1 January 1984 paracetamol became available on an over-the-counter basis. The figures for 1983 and 1984 were an increase in sales from 14 to 28 million DDD, an increase in admissions from 114 to 198, and an increase in deaths from 0 to 4. The number of deaths from opioid overdose remained constant at a value of about fifty during this period, the mortality per dose being about 20-fold higher than for paracetamol and salicylates. Dextropropoxyphene-related deaths increased twofold to 121 in 1986, with unchanged sales figures. A campaign launched by the National Board of Health resulted in a reduction in the number of deaths from dextropropoxyphene to 66 in 1987. The main effect of over-the-counter release of paracetamol was a dramatic increase in sales, without the epidemic of deaths observed a decade ago in the UK. It is suggested that the higher mortality of paracetamol poisonings in the UK compared to Denmark is related to the dextropropoxyphene content of the combination product, which is not available in Denmark. From an epidemiological toxicological viewpoint such combinations are not justified.
Recent studies o f acetaminophen-induced liver damage in animals indicate that acetaminophen is converted in the liver to a chemically reactive arylating agent that normally is detoxified by conjugation with glutathione. When the dose of acetaminophen is large enough to deplete hepatic glutathione, however, there is extensive arylation of hepatic macromolecules and cell death. This paper presents evidence that administration of glutathione-like nucleophiles, such as cysteamine, protects mice from arylation of hepatic macromolecules, hepatic necrosis, and death caused by the reactive acetaminophen metabolite. Additional studies indicate that glutathione may serve a similar protective function in man as in other animals. Thus, logical treatment of patients overdosed with acetaminophen might be based on cysteamine or other nucleophiles.