11:11am Wednesday 11 December 2019

New study on risk of death during and after opiate substitution therapy

The annual mortality rate was 0.7 per cent during treatment and 1.3 per cent off treatment; 5.3 and 10.9 times higher respectively than the mortality rate in the general population. Opiate using men had approximately twice the risk of mortality of women.

Opiate substitution therapy (OST), where patients with a substance abuse diagnosis are prescribed methadone or buprenorphone, is central to the prevention of drug-related deaths.  OST is effective also in improving physical and mental health and decreasing illicit drug use, criminal activity and the risk of HIV infection.  In the UK, in the last decade, opiate prescription has more than doubled while the number of deaths involving methadone have declined.  However, the overall number of opiate overdose deaths has not decreased.   

The researchers studied 5,577 patients prescribed OST between 1990-2005 to investigate whether the risk of death was greater in the first few weeks of treatment and in the period immediately after treatment.  They also projected how different durations of OST impact on drug related deaths. 

A total of 178 (three per cent) of patients died either on treatment or within a year of their last prescription; of these 63 (35 per cent) died while on treatment.  The mortality rate was raised in the first four weeks of treatment, being 3.1 times higher in the first two weeks, and 2.3 times higher in weeks 3-4.  The mortality rate was also raised substantially in the period immediately after treatment, being over eight times higher in the first month after treatment.

This could be because opiate tolerance falls after OST so, if a patient relapses, they are more likely to precipitate a fatal heroin overdose in the first few weeks after ending treatment when tolerance has yet to be re-established.  Starting OST, especially methadone, also poses risks in terms of overdose if the initiation dose is too high or if patients continue to use street opiates as well.

Professor Matthew Hickman, co-author of the study, said: “In the UK, OST provision has substantially increased but the total number of opiate overdose deaths has remained stable and national targets to reduce their number have not been met.

“The elevated risk of death in the first month of treatment and especially in the month after treatment may negate any protective effect of OST, unless duration of treatment is prolonged.  Further research is required to test this hypothesis and investigate the impact of average OST duration on drug related deaths.”


Risk of death during and after opiate substitution therapy in primary care: a prospective observational study in the UK General Practice Research Database by Rosie Cornish, John Macleod, John Strang, Peter Vickerman, Matt Hickman BMJ

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