UK legislation on analgesic packs: before and after study of long term effect on poisonings
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《英国医生杂志》
1 Centre for Suicide Research, University of Oxford Department of Psychiatry, Warneford Hospital, Headington, Oxford OX3 7JX, 2 Centre for Statistics in Medicine, University of Oxford, Oxford OX3 7LF, 3 Centre for Suicide Prevention, University of Manchester, Manchester M13 9PL, 4 Mental Health Resource Centre, Derbyshire Royal Infirmary, Derby DE1 2QY, 5 Department of Hepatology, St James's University Hospital, Leeds LS9 7TF, 6 Institute of Liver Studies, King's College Hospital, London SE5 9RS, 7 Liver Laboratories, Queen Elizabeth Hospital, Birmingham B15 2TH, 8 Liver Unit, Freeman Hospital, Newcastle upon Tyne NE7 7ND, 9 Royal Free Hospital, London NW3 2QG, 10 Department of Medicine, University of Edinburgh, Royal Infirmary, Edinburgh EH3 9YW
Correspondence to: K Hawton keith.hawton@psych.ox.ac.uk
Abstract
Legislation to limit the size of packs of analgesics (paracetamol, salicylates, and their compounds) sold over the counter was introduced in the United Kingdom on 16 September 1998 to try to reduce the mortality and morbidity associated with deliberate overdoses, especially with paracetamol. The increasing problem of paracetamol overdoses had been highlighted for several years in the United Kingdom and elsewhere.1-9 The legislation reduced the previously unrestricted sale limit for pharmacies to a maximum of 32 tablets and for other retail outlets from 24 to 16 tablets.10 The main aim of the legislation was to reduce household stocks of analgesics and the associated danger of overdoses from these supplies.11 12
We previously showed noticeable declines in numbers of large overdoses, deaths from paracetamol and salicylate overdose, and paracetamol related liver transplants in the year after the legislation was introduced.4 Other evidence largely supported these findings.13-16 We have now assessed the legislation's longer term effect and investigated possible substitution of overdose method with the non-steroidal anti-inflammatory drug ibuprofen, which was not included in the legislation.17
Methods
Deaths due to paracetamol and salicylate overdoses
Compared with the two years before the legislation, significant decreases in deaths in the year after the legislation involving either paracetamol alone (-29%, 95% confidence interval -13% to -41%) or salicylates alone (-46%, -8% to -68%) were sustained in the subsequent two years (table 1). Findings were similar for paracetamol or salicylates taken with other drugs (including in compounds).
Table 1 Deaths related to paracetamol and salicylates among people aged 12 years and over in England and Wales, trends in deaths from poisoning 1993-2001, and change associated with legislation
Between September 1993 and September 2001 there were underlying non-significant upward trends in deaths due to paracetamol overdose and downward trends in deaths due to salicylate overdose. Allowing for these trends, we found clear evidence of downward step changes in deaths from overdoses of both paracetamol and salicylates, either taken alone or with other drugs, which corresponded to the timing of the legislation (see table 1).
Analysis of all deaths due to poisoning also showed a downward step change corresponding to the timing of the legislation (see table 1). The change was much smaller, however, than those for the drugs covered by the legislation. All findings were similar when restricted to suicides and open verdicts (data not shown).
On the basis of mortality during 1993-8, 199 deaths were avoided in the three years after the legislation—118 involving paracetamol and 81 involving salicylates.
Deaths due to ibuprofen overdose
Few deaths involved ibuprofen: four accidental deaths and seven open verdict or suicide deaths occurred in the five years before the legislation and four and nine deaths occurred, respectively, in the subsequent three years. All these deaths also involved other drugs. The increased annual incidence of all deaths represented a 2.2-fold rise (95% confidence interval 0.95 to 4.94) and of open verdicts and suicides a 2.1-fold rise (0.80 to 5.75).
Admissions to liver units and numbers of liver transplants
We found reductions of around 30% in numbers of people admitted to liver units because of paracetamol induced hepatotoxicity, those listed for liver transplant, and actual transplantations in both the first (1998-2000) and second (2000-2) periods after the introduction of the legislation (table 2). A different pattern for one unit produced significant heterogeneity in number of admissions for paracetamol poisoning during 2000-2.
Table 2 Annual numbers and relative incidence rates for admissions for liver transplants, listings, and transplantations due to paracetamol poisoning. Values are incidence rate ratios (95% confidence intervals) unless stated otherwise
Mean annual admissions for paracetamol poisoning decreased from 349 in the two years before the legislation to 230 in the four years afterwards, listings for liver transplantation decreased from 43 to 30, and transplants decreased from 32 to 21.5.
Non-fatal self poisonings
Overall, there was a 15% (9% to 21%) reduction in presentations to hospital for paracetamol overdoses in the year after the legislation, but no reduction in subsequent years. Numbers of salicylate overdoses did not significantly change, whereas the numbers of ibuprofen overdoses increased by 27% (11% to 44%) in the second and third years (table 3).
Table 3 Annual numbers of non-fatal self poisonings (Oxford, Manchester, and Derby combined) due to specific drug categories, and percentage change in number of overdoses. Values are percentage change in numbers (95% confidence intervals) unless stated otherwise
Numbers of tablets taken in paracetamol and salicylate overdoses significantly decreased in the three years after the legislation (table 4). Reductions in the second and third years after the legislation were significantly larger than in the first year for overdoses involving paracetamol and salicylates, but not for overdoses with paracetamol alone. We found no major change for overdoses with ibuprofen alone, although the mean number of tablets in overdoses that involved ibuprofen decreased during the second and third years after the legislation.
Table 4 Numbers of tablets taken during overdose in non-fatal self poisonings (Oxford, Manchester, and Derby combined). Values are percentage change in geometric mean numbers (95% confidence intervals) unless stated otherwise
Only large (more than 32 tablets) paracetamol overdoses decreased significantly in the year after the legislation (table 5). Significant decreases in large overdoses of paracetamol alone and of any paracetamol and salicylates occurred in the second and third years after the legislation. Numbers of large ibuprofen overdoses did not change significantly.
Table 5 Numbers of non-fatal self poisonings with more than 32 tablets (Oxford, Manchester, and Derby combined). Values are percentage change in numbers (95% confidence intervals) unless stated otherwise
Sales data
Mean pack sizes decreased significantly between 1996-7 and 1998-9 for paracetamol (35 to 24 tablets per packet) and aspirin (61 to 25 tablets per packet), although they subsequently increased slightly (see figure on bmj.com). The sales of paracetamol rose after the legislation, so overall there was little effect on total numbers of tablets sold (520 million in 1996-7, 580 million in 2001-2). Sales data for paracetamol compounds followed a similar pattern. The sales of aspirin remained almost constant (11 million packs in 1996-7, 12 million packs in 2001-2) whereas the number of tablets sold was approximately halved.
Discussion
Hawton K, Fagg J, Simkin S, Bale E, Bond A. Trends in deliberate self-harm in Oxford, 1985-1995. Implications for clinical services and the prevention of suicide. Br J Psychiatry 1997;171: 556-60.
Bialas MC, Reid PG, Beck P, Lazarus JH, Smith PM, Scorer RC, et al. Changing patterns of self-poisoning in a UK health district. QJM 1996;89: 893-901.
O'Grady J. Acute liver failure. Medicine 1999;27: 80-2.
Hawton K, Townsend E, Deeks JJ, Appleby L, Gunnell D, Bennewith O, et al. Effects of legislation restricting pack sizes of paracetamol and salicylates on self poisoning in the United Kingdom: before and after study. BMJ 2001;322: 1203-7.
Ott P, Dalhoff K, Hansen PB, Loft S, Poulsen HE. Consumption, overdose and death from analgesics during a period of over-the-counter availability of paracetamol in Denmark. J Int Med 1990;227: 423-8.
Borna P, Ekedahl A, Alsén M, Traskman-Bendz L. Self-poisonings with drugs by adolescents in the Lund catchment area. Nord J Psychiatry 2001;55: 325-8.
Laffroy M, Scallan E, Byrne G. Paracetamol availability and overdose in Ireland. Ir Med J 2001;94: 212-4.
Ostapowicz G, Fontana RJ, Schi?dt FV, Larson A, Davern TJ, Han SHB, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002;137: 947-54.
Buckley NA, Whyte IM, Dawson AH, McManus PR, Ferguson NW. Self-poisoning in Newcastle, 1987-1992. Med J Aust 1995;162: 190-3.
Committee on Safety of Medicines Medicines Control Agency. Paracetamol and aspirin. Curr Probl Pharmacovigilance 1997;23: 9.
Hawton K, Ware C, Mistry H, Hewitt J, Kingsbury S, Roberts D, et al. Why patients choose paracetamol for self poisoning and their knowledge of its dangers. BMJ 1995;310: 164.
Hawton K. United Kingdom legislation on pack sizes of analgesics: background, rationale, and effects on suicide and deliberate self-harm. Suicide Life Threat Behav 2002;32: 223-9.
Turvill JL, Burroughs AK, Moore KP. Change in occurrence of paracetamol overdose in UK after introduction of blister packs. Lancet 2000;355: 2048-9.
Robinson D, Smith AMJ, Johnston GD. Severity of overdose after restriction of paracetamol availability: retrospective study. BMJ 2000;321: 926-7.
Prince MI, Thomas SHL, James OFW, Hudson M. Reduction in incidence of severe paracetamol poisoning. Lancet 2000;355: 2047-8.
Office for National Statistics. Deaths related to drug poisoning: results for England and Wales, 1997-2001. Health Statistics Q 2003;17: 65-71.
Sheen CL, Dillon JF, Bateman DN, Simpson KJ, MacDonald TM. Paracetamol pack size restriction: the impact on paracetamol poisoning and over-the-counter supply of paracetamol, aspirin and ibuprofen. Pharmacoepidemiol Drug Safety 2002;11: 329-31.
Smolinske SC, Hall AH, Vandenberg SA, Spoerke DG, McBride PV. Toxic effects of nonsteroidal anti-inflammatory drugs in overdose. An overview of recent evidence on clinical effects and dose-response relationships. Drug Safety 1990;5: 252-74.
Office for National Statistics. Series DH2 No 29 Mortality statistics: cause. London: ONS, 2003.
Hawton K, Cole D, O'Grady J, Osborn M. Motivational aspects of deliberate self-poisoning in adolescents. Br J Psychiatry 1982;141: 286-91.
Hawton K, Ware C, Mistry H, Hewitt J, Kingsbury S, Roberts D, et al. Paracetamol self-poisoning. Characteristics, prevention and harm reduction. Br J Psychiatry 1996;168: 43-8.
Gunnell D, Hawton K, Murray V, Garnier R, Bismuth C, Fagg J, et al. Use of paracetamol for suicide and non-fatal poisoning in the UK and France: are restrictions on availability justified? J Epidemiol Community Health 1997;51: 175-9.
Prescott LF. Paracetamol overdosage: pharmacological considerations and clinical management. Drugs 1983;25: 290-314.(Keith Hawton, professor o)
Correspondence to: K Hawton keith.hawton@psych.ox.ac.uk
Abstract
Legislation to limit the size of packs of analgesics (paracetamol, salicylates, and their compounds) sold over the counter was introduced in the United Kingdom on 16 September 1998 to try to reduce the mortality and morbidity associated with deliberate overdoses, especially with paracetamol. The increasing problem of paracetamol overdoses had been highlighted for several years in the United Kingdom and elsewhere.1-9 The legislation reduced the previously unrestricted sale limit for pharmacies to a maximum of 32 tablets and for other retail outlets from 24 to 16 tablets.10 The main aim of the legislation was to reduce household stocks of analgesics and the associated danger of overdoses from these supplies.11 12
We previously showed noticeable declines in numbers of large overdoses, deaths from paracetamol and salicylate overdose, and paracetamol related liver transplants in the year after the legislation was introduced.4 Other evidence largely supported these findings.13-16 We have now assessed the legislation's longer term effect and investigated possible substitution of overdose method with the non-steroidal anti-inflammatory drug ibuprofen, which was not included in the legislation.17
Methods
Deaths due to paracetamol and salicylate overdoses
Compared with the two years before the legislation, significant decreases in deaths in the year after the legislation involving either paracetamol alone (-29%, 95% confidence interval -13% to -41%) or salicylates alone (-46%, -8% to -68%) were sustained in the subsequent two years (table 1). Findings were similar for paracetamol or salicylates taken with other drugs (including in compounds).
Table 1 Deaths related to paracetamol and salicylates among people aged 12 years and over in England and Wales, trends in deaths from poisoning 1993-2001, and change associated with legislation
Between September 1993 and September 2001 there were underlying non-significant upward trends in deaths due to paracetamol overdose and downward trends in deaths due to salicylate overdose. Allowing for these trends, we found clear evidence of downward step changes in deaths from overdoses of both paracetamol and salicylates, either taken alone or with other drugs, which corresponded to the timing of the legislation (see table 1).
Analysis of all deaths due to poisoning also showed a downward step change corresponding to the timing of the legislation (see table 1). The change was much smaller, however, than those for the drugs covered by the legislation. All findings were similar when restricted to suicides and open verdicts (data not shown).
On the basis of mortality during 1993-8, 199 deaths were avoided in the three years after the legislation—118 involving paracetamol and 81 involving salicylates.
Deaths due to ibuprofen overdose
Few deaths involved ibuprofen: four accidental deaths and seven open verdict or suicide deaths occurred in the five years before the legislation and four and nine deaths occurred, respectively, in the subsequent three years. All these deaths also involved other drugs. The increased annual incidence of all deaths represented a 2.2-fold rise (95% confidence interval 0.95 to 4.94) and of open verdicts and suicides a 2.1-fold rise (0.80 to 5.75).
Admissions to liver units and numbers of liver transplants
We found reductions of around 30% in numbers of people admitted to liver units because of paracetamol induced hepatotoxicity, those listed for liver transplant, and actual transplantations in both the first (1998-2000) and second (2000-2) periods after the introduction of the legislation (table 2). A different pattern for one unit produced significant heterogeneity in number of admissions for paracetamol poisoning during 2000-2.
Table 2 Annual numbers and relative incidence rates for admissions for liver transplants, listings, and transplantations due to paracetamol poisoning. Values are incidence rate ratios (95% confidence intervals) unless stated otherwise
Mean annual admissions for paracetamol poisoning decreased from 349 in the two years before the legislation to 230 in the four years afterwards, listings for liver transplantation decreased from 43 to 30, and transplants decreased from 32 to 21.5.
Non-fatal self poisonings
Overall, there was a 15% (9% to 21%) reduction in presentations to hospital for paracetamol overdoses in the year after the legislation, but no reduction in subsequent years. Numbers of salicylate overdoses did not significantly change, whereas the numbers of ibuprofen overdoses increased by 27% (11% to 44%) in the second and third years (table 3).
Table 3 Annual numbers of non-fatal self poisonings (Oxford, Manchester, and Derby combined) due to specific drug categories, and percentage change in number of overdoses. Values are percentage change in numbers (95% confidence intervals) unless stated otherwise
Numbers of tablets taken in paracetamol and salicylate overdoses significantly decreased in the three years after the legislation (table 4). Reductions in the second and third years after the legislation were significantly larger than in the first year for overdoses involving paracetamol and salicylates, but not for overdoses with paracetamol alone. We found no major change for overdoses with ibuprofen alone, although the mean number of tablets in overdoses that involved ibuprofen decreased during the second and third years after the legislation.
Table 4 Numbers of tablets taken during overdose in non-fatal self poisonings (Oxford, Manchester, and Derby combined). Values are percentage change in geometric mean numbers (95% confidence intervals) unless stated otherwise
Only large (more than 32 tablets) paracetamol overdoses decreased significantly in the year after the legislation (table 5). Significant decreases in large overdoses of paracetamol alone and of any paracetamol and salicylates occurred in the second and third years after the legislation. Numbers of large ibuprofen overdoses did not change significantly.
Table 5 Numbers of non-fatal self poisonings with more than 32 tablets (Oxford, Manchester, and Derby combined). Values are percentage change in numbers (95% confidence intervals) unless stated otherwise
Sales data
Mean pack sizes decreased significantly between 1996-7 and 1998-9 for paracetamol (35 to 24 tablets per packet) and aspirin (61 to 25 tablets per packet), although they subsequently increased slightly (see figure on bmj.com). The sales of paracetamol rose after the legislation, so overall there was little effect on total numbers of tablets sold (520 million in 1996-7, 580 million in 2001-2). Sales data for paracetamol compounds followed a similar pattern. The sales of aspirin remained almost constant (11 million packs in 1996-7, 12 million packs in 2001-2) whereas the number of tablets sold was approximately halved.
Discussion
Hawton K, Fagg J, Simkin S, Bale E, Bond A. Trends in deliberate self-harm in Oxford, 1985-1995. Implications for clinical services and the prevention of suicide. Br J Psychiatry 1997;171: 556-60.
Bialas MC, Reid PG, Beck P, Lazarus JH, Smith PM, Scorer RC, et al. Changing patterns of self-poisoning in a UK health district. QJM 1996;89: 893-901.
O'Grady J. Acute liver failure. Medicine 1999;27: 80-2.
Hawton K, Townsend E, Deeks JJ, Appleby L, Gunnell D, Bennewith O, et al. Effects of legislation restricting pack sizes of paracetamol and salicylates on self poisoning in the United Kingdom: before and after study. BMJ 2001;322: 1203-7.
Ott P, Dalhoff K, Hansen PB, Loft S, Poulsen HE. Consumption, overdose and death from analgesics during a period of over-the-counter availability of paracetamol in Denmark. J Int Med 1990;227: 423-8.
Borna P, Ekedahl A, Alsén M, Traskman-Bendz L. Self-poisonings with drugs by adolescents in the Lund catchment area. Nord J Psychiatry 2001;55: 325-8.
Laffroy M, Scallan E, Byrne G. Paracetamol availability and overdose in Ireland. Ir Med J 2001;94: 212-4.
Ostapowicz G, Fontana RJ, Schi?dt FV, Larson A, Davern TJ, Han SHB, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002;137: 947-54.
Buckley NA, Whyte IM, Dawson AH, McManus PR, Ferguson NW. Self-poisoning in Newcastle, 1987-1992. Med J Aust 1995;162: 190-3.
Committee on Safety of Medicines Medicines Control Agency. Paracetamol and aspirin. Curr Probl Pharmacovigilance 1997;23: 9.
Hawton K, Ware C, Mistry H, Hewitt J, Kingsbury S, Roberts D, et al. Why patients choose paracetamol for self poisoning and their knowledge of its dangers. BMJ 1995;310: 164.
Hawton K. United Kingdom legislation on pack sizes of analgesics: background, rationale, and effects on suicide and deliberate self-harm. Suicide Life Threat Behav 2002;32: 223-9.
Turvill JL, Burroughs AK, Moore KP. Change in occurrence of paracetamol overdose in UK after introduction of blister packs. Lancet 2000;355: 2048-9.
Robinson D, Smith AMJ, Johnston GD. Severity of overdose after restriction of paracetamol availability: retrospective study. BMJ 2000;321: 926-7.
Prince MI, Thomas SHL, James OFW, Hudson M. Reduction in incidence of severe paracetamol poisoning. Lancet 2000;355: 2047-8.
Office for National Statistics. Deaths related to drug poisoning: results for England and Wales, 1997-2001. Health Statistics Q 2003;17: 65-71.
Sheen CL, Dillon JF, Bateman DN, Simpson KJ, MacDonald TM. Paracetamol pack size restriction: the impact on paracetamol poisoning and over-the-counter supply of paracetamol, aspirin and ibuprofen. Pharmacoepidemiol Drug Safety 2002;11: 329-31.
Smolinske SC, Hall AH, Vandenberg SA, Spoerke DG, McBride PV. Toxic effects of nonsteroidal anti-inflammatory drugs in overdose. An overview of recent evidence on clinical effects and dose-response relationships. Drug Safety 1990;5: 252-74.
Office for National Statistics. Series DH2 No 29 Mortality statistics: cause. London: ONS, 2003.
Hawton K, Cole D, O'Grady J, Osborn M. Motivational aspects of deliberate self-poisoning in adolescents. Br J Psychiatry 1982;141: 286-91.
Hawton K, Ware C, Mistry H, Hewitt J, Kingsbury S, Roberts D, et al. Paracetamol self-poisoning. Characteristics, prevention and harm reduction. Br J Psychiatry 1996;168: 43-8.
Gunnell D, Hawton K, Murray V, Garnier R, Bismuth C, Fagg J, et al. Use of paracetamol for suicide and non-fatal poisoning in the UK and France: are restrictions on availability justified? J Epidemiol Community Health 1997;51: 175-9.
Prescott LF. Paracetamol overdosage: pharmacological considerations and clinical management. Drugs 1983;25: 290-314.(Keith Hawton, professor o)