Methadone increases death risk in first four weeks of treatment for opioid dependence

Patients who start treatment for dependence on
opioids are five times as likely to die in the first four weeks when they are
prescribed the most commonly used treatment, methadone, than with an
alternative treatment, buprenorphine, a study by researchers at the University
of Bristol, King’s College London and the National Drug and Alcohol Research
Centre at UNSW in Australia has found.

The study, published on 16 September in the
Lancet Psychiatry, reviewed the records of 32,033 patients who had started
treatment with methadone or buprenorphine between 2001 and 2010. Patients who
started treatment with buprenorphine were less likely to die from any cause,
including drug-related causes, in the first four weeks of treatment. However,
after four weeks there was little difference in risk of death between methadone
and buprenorphine.

Around 50,000 Australians (and over 100,000
people in the UK) currently receive opioid pharmacotherapy treatment for
dependence on heroin or other opioids. Around two thirds of these are being
treated with methadone with the remainder on buprenorphine, according to
figures from the Australian Institute of Health and Welfare. Buprenorphine is
considered to be safer as it is less likely to cause respiratory depression
(problems breathing), but patients are more likely to drop out of treatment
than with methadone. Both treatments are endorsed by the World Health
Organisation.

Dr Jo Kimber, one of the study’s lead author’s
and a researcher at the National Drug and Alcohol Research Centre UNSW and
King’s College London, said:

“Clinicians providing opioid substitution
treatment face an important dilemma: which is more likely to reduce patient
risk, buprenorphine or methadone?

“Buprenorphine is argued to have a superior
safety profile to methadone but a higher drop-out rate. Our data suggests at
least at the beginning of treatment for heroin use that buprenorphine has clear
benefits over methadone in reducing mortality risk.”

Professor Louisa Degenhardt at the National Drug
and Alcohol Research Centre and one of the study’s authors added:

“The findings
support a stepped approach to treatment. Opioid substitution therapy is proven
to be a cost effective and safe treatment for opioid dependence. It not only
reduces risk of death but also involvement in crime and imprisonment.”

Professor Matthew Hickman, Professor in Public
Health and Epidemiology at the University of Bristol and a Director for the Addictions Health Integration Team, said:

“These findings are
of importance to GPs treating patients with drug-dependency problems, one way
to reduce risks might be to commence treatment on buprenorphine for the first
four weeks and then switch to methadone at a later stage without increased
risk.”

Paper

‘Mortality risk of opioid substitution therapy with methadone versus buprenorphine: aretrospective cohort study’ by Jo Kimber, Sarah Larney, Matthew Hickman,
Deborah Randall, Louisa Degenhardt in Lancet Psychiatry 16 September 2015.