UOA04-06: Withdrawal of Co-Proxamol: A Successful International Suicide Prevention Initiative
Submitting InstitutionUniversity of Oxford
Unit of AssessmentPsychology, Psychiatry and Neuroscience
Summary Impact TypePolitical
Research Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Public Health and Health Services
Summary of the impact
Research led by Professor Keith Hawton in Oxford starting in 2003 showed
that the painkiller co- proxamol (`Distalgesic') was the most common drug
used for fatal self-poisoning in the UK. The findings led to its complete
withdrawal in the UK by 2008, and further research demonstrated that this
was followed by a reduction in deaths from suicide and accidental
poisoning. The findings were instrumental in the European Medicines Agency
decision in 2010 to recommend withdrawal of the toxic component of
co-proxamol, dextropropoxyphene, in all EU countries. This has also
occurred in the USA, Canada, and several other countries. The withdrawal
of co-proxamol is estimated to have led to approximately 600 fewer deaths
by 2012 in the UK alone.
- Co-proxamol (`Distalgesic') is a combination of an opiate,
dextropropoxyphene, plus paracetamol. It was a prescription-only
painkiller, widely prescribed in the 1980s and early 1990s.
- In a study of local suicides between 1993 and 1997, Hawton and
colleagues at the Oxford Centre for Suicide Research noted that
co-proxamol was involved in approximately 20% of overdose deaths. Then,
using national data on suicide deaths, and local data based on the
team's Oxford Monitoring System for Attempted Suicide, Hawton and
colleagues showed in a key paper published in the British Medical
Journal in 2003 that: (a) co-proxamol was the most common drug
used for suicide in England and Wales (18%; 766 out of 4162 fatalities),
and (b) the risk of death following an overdose of co-proxamol was 28
times greater than that for paracetamol (Hawton, Simkin and Deeks,
2003). It was this study which prompted the Medicines and Healthcare
Products Regulatory Agency (MHRA) and the Committee for the Safety of
Medicines (CSM) to investigate the safety of co-proxamol in 2004.
- In parallel, the Hawton research team conducted a study in 24
coroners' jurisdictions of 123 people who died from co-proxamol overdose
to determine the characteristics of these individuals and the
circumstances of their suicidal acts (Hawton, Simkin et al.,
2005). This showed that in over 80% of cases the co-proxamol had been
prescribed for the individual (rather than someone else) and that death
sometimes resulted from relatively small overdoses. The team also
conducted a review of the international research literature on
co-proxamol poisoning (Simkin, Hawton et al., 2005). This showed
that the majority of deaths occurred before individuals reached
hospital. Based on the data, they proposed that `complete withdrawal
[of co-proxamol] should be considered'. This was the first time
that this course of action had been proposed.
- The Oxford team contributed to the MHRA/CSM review of the benefits and
risks of co-proxamol mentioned above, both by giving evidence and
participating as advisors. The conclusion of the review was that the
MHRA recommended to the CSM that co-proxamol should be withdrawn in the
UK. This recommendation was implemented: there was an initial withdrawal
phase between 2005 and 2007 when no new patients were prescribed
co-proxamol, followed by full withdrawal of the drug in 2008.
- Hawton and colleagues showed that as prescriptions for co-proxamol
markedly declined during the withdrawal phase (2005-7), there was a
corresponding reduction in deaths due to poisoning with the drug
(Hawton, Bergen et al., 2009) and also fewer non-fatal poisonings
(Hawton, Bergen et al., 2011). Encouragingly, there was no
substantial increase in poisoning deaths involving other analgesics used
in place of co-proxamol.
- More recently the research team have evaluated the longer-term impact
of the initiative, including following full withdrawal of co-proxamol
from 2008 to 2010 (Hawton, Bergen et al., 2012). This showed a
similar picture, with a further decrease in deaths due to co-proxamol
poisoning, such that over the six-year period from the beginning of the
initial withdrawal there were about 600 fewer deaths, with again no
indication that deaths due to overdoses with other analgesics increased
References to the research
Hawton K, Simkin S, Deeks JJ. Co-proxamol and suicide: a study of
national mortality statistics and local non-fatal self-poisonings. BMJ.
2003;326:1006-8. DOI: 10.1136/bmj.326.7397.1006
Demonstrated the extent to which co-proxamol contributed to suicide
poisoning deaths and toxicity of co-proxamol relative to other drugs
used for self-poisoning. 42 citations.
Hawton K, Simkin S, Gunnell D, Sutton L, Bennewith O, Turnbull P, et al.
A multicentre study of co- proxamol poisoning suicides based on coroners'
records in England. Br J Clin Pharmacol. 2005;59(2):207-12. DOI:
Identified characteristics of people dying by suicide using co-proxamol
poisoning, including fact that death could result from relatively small
overdoses. 26 citations.
Simkin S, Hawton K, Sutton L, Gunnell D, Bennewith O, Kapur N.
Co-proxamol and suicide: a review to inform initiatives to prevent the
continuing toll of overdose deaths. Q J Med 2005;98:159- 70. DOI:
Highlighted international problems and concerns regarding co-proxamol
poisoning. 17 citations.
Hawton K, Bergen H, Simkin S, Brock A, Griffiths C, Romeri E, et al.
Effect of withdrawal of co- proxamol on prescribing and deaths from drug
poisoning in England and Wales: time series analysis. BMJ.
2009;338:b2270. DOI: 10.1136/bmj.b2270
Showed large initial beneficial impact of withdrawal of co-proxamol on
poisoning suicides and accidents, without compensatory increase in
deaths involving other analgesics. 28 citations.
Hawton K, Bergen H, Waters K, Murphy E, Cooper J, Kapur N. Impact of
withdrawal of the analgesic co-proxamol in the UK on non-fatal
self-poisoning. Crisis. 2011;32(2):81-7. DOI:
Demonstrated similar benefits regarding non-fatal poisonings. 4
Hawton K, Bergen H, Simkin S, Wells C, Kapur N, Gunnell D. Withdrawal of
co-proxamol in England and Wales: time-series investigation of impacts on
prescribing and deaths during the six years after the withdrawal. PLoS
Medicine. 2012;9: e1001213. DOI:10.1371/journal.pmed.1001213
Showed longer-term benefits of withdrawal of co-proxamol on suicidal
and accidental poisoning deaths. 4 citations.
Professor Hawton led research in Oxford on suicide prevention throughout
this period, in his role as Director of the Centre for Suicide Reseach at
Oxford University. He is also an honorary consultant psychiatrist. Key
colleagues on the research included Sue Simkin, Helen Bergen, and John
Deeks, and collaborators Nav Kapur (Manchester) and David Gunnell
Details of peer reviewed grants and fellowships that supported this
Hawton (PI) 2003-2008 Department of Health (£379,421) Oxford
Monitoring System for Attempted Suicide
Hawton (PI) 2002-2004 Department of Health (£122,055)
Coroner-based Investigation of Specific Methods of Suicide
Hawton (PI) 2004-2010 Department of Health (£1,757,022)
Multicentre Study of Self-harm in England
Hawton (PI) 2007-2011 National Institute for Health Research
(£897,994) A multicentre programme of clinical and public health research
in support of the National Suicide Prevention Strategy for England
Hawton NIHR Senior Investigator Award (fellowship award from NIHR 01/4/09
Details of the impact
- As highlighted above, the research of Hawton and colleagues was
instrumental in leading to the withdrawal of co-proxamol (and its toxic
component dextropropoxyphene) in the UK from 2005 onwards (Section 5,
- The resulting benefits were shown during the initial three year
withdrawal phase (2005-7) in terms of a major reduction in deaths, both
suicidal and accidental, from co-proxamol poisoning and absence of
significant increases in deaths involving other analgesics likely to
have been prescribed instead of co-proxamol. (See Hawton et al, 2009,
2011, cited in Section 3).
- More recently the long-term benefits of this initiative have been
demonstrated through evaluation of its impact during the six years 2005
- 2010, including the three years following full withdrawal. This has
indicated about 600 fewer deaths in the UK from co-proxamol poisoning
and again no major substitution of deaths from fatal poisoning with
other analgesics. (See Hawton et al, 2012, cited in Section 3).
- This initiative has been one of most important contributions to the
success of the National Suicide Prevention Strategy for England (see
Section 5, Sources 1-3).
- This initiative did not stop in the UK. Following presentation of the
Oxford team's findings by Hawton to the European Medicines Agency
(EMEA), the EMEA recommended to the European Union (EU) that
non-prescribing of dextropropoxyphene should become policy throughout
the EU. The decision was endorsed in June 2010. (Section 5, Source 6).
- The UK and EU initiative prompted the US Food and Drug Administration
to take action in 2010 to withdraw dextropropoxyphene in the USA.
(Section 5, Source 7).
- In 2010 Health Canada did likewise in Canada, as did the equivalent
authorities in New Zealand, Singapore and Taiwan (Section 5, Sources
8-10). Thus it is anticipated that the work of Hawton and his team will
contribute to the saving of lives in many countries, not just in the UK.
Sources to corroborate the impact
- Letter from MHRA Director, Dr June Raine, in August 2012, confirming
importance of Hawton's research in the decision to withdraw co-proxamol.
Includes the statements: `Your research team's contribution has been
pivotal' and `...one of the most significant public health
actions of the last decade...' Available on request.
- Letter from Professor Louis Appleby, former Director of Mental Health
for England, and Chair of the National Suicide Prevention Strategy Group
for England, confirming importance of Hawton's research on co-proxamol
(and his other research on suicide prevention). Includes the statements:
`His work on suicide by co-proxamol overdose has led to the
withdrawal of this drug and a substantial reduction in suicides by
this method, without a compensatory increase in suicide using other
analgesics...' and `...findings from Prof Hawton's research
have been and remain highly influential.' Available on request.
- The renewed National Suicide Prevention Strategy (2012) states (page
38): `Significant progress has been made in reducing access to
medications associated with suicide attempts, including the phased
withdrawal of co-proxamol...,' citing the Hawton et al. 2012 PLoS
Medicine paper (cited in Section 3 above) to support this conclusion.
- Medicines and Healthcare products Regulatory Agency. Withdrawal of
co-proxamol products and interim updated prescribing information
CEM/CMO/2005/2. 2005 [updated 2008/07/09/02/03/2005];
[Accessed 4/11/13]. Highlights the Hawton et al. 2003 BMJ paper (cited
in Section 3 above) as being the evidence behind the decision.
- Committee on Safety of Medicines. Withdrawal of co-proxamol
(Distalgesic, Cosalgesic, Dolgesic). Current Problems in
- European Medicines Agency (EMEA) recommends withdrawal of
dextropropoxphene- containing medicines (including co-proxamol).
(http://www.mhra.gov.uk/NewsCentre/CON049300 [Accessed 4/11/13]). This
announcement highlights Hawton's research.
- FDA U.S. Food and Drug Administration. Xanodyne agrees to withdraw
propoxyphene from the U.S. market. 2010 [updated 01/12/201015/05/2011];
- Health Canada. Darvon-N (dextropropoxyphene) - Recall and Withdrawal
in Canada - For the Public. 2010 [cited 2011 11/05/2011]; Available
- Withdrawal in New Zealand:
- Withdrawal in Singapore: