Opioid Substitution Therapy (OST) implicated deaths and prescribing: evidence review

This paper summarises current knowledge of trends around methadone and buprenorphine related deaths and changes to prescribing practice in Scotland.

2. Role of OST in drug-related deaths

Scotland continues to have a high level of drug-related deaths (DRDs). The annual figure for 2020 increased from the previous year by 4.6% to 1,339, the highest number ever recorded.[12] In addition there has been a similar increase in deaths where an OST drug (methadone or buprenorphine) was implicated. These are explored separately below.

2.1 Methadone implicated in drug-related deaths

Both the number and percentage of methadone-implicated deaths has increased over time. In 2020 methadone was implicated in 708 deaths, an increase of 25% on 2019 (567) and following a long term increase over the last twenty years (Figure 1).

Figure 1: Number of drug-related deaths in Scotland: in total and for which any opiate or opioid, heroin/morphine, and methadone are implicated, 2009-2020
Line graph, showing steep incline in all drug-related deaths and deaths implicating any opiate/opioid; heroin/morphine and methadone, particularly from 2013. The line for any opiate/opioid closely parallels all drug-related deaths. Heroin/morphine declined slightly between 2019 and 2020, while methadone increased sharply in this period.

Source: NRS 2021

In 2020, methadone was implicated in 53% of all drug-related deaths. This is the highest percentage since records began, and continues a general upward trend with some fluctuations (Figure 2).

Figure 2. Percentage of drug-related deaths where methadone was implicated, 2000-2020
Line graph showing steep rise in methadone implicated deaths over the time series, with some fluctuation. In 2000, methadone was implicated in 19% of all DRDs, rising to 27% in 2003 before decreasing to 21% in 2007; rising continually again to 47% in 2011 before sharply decreasing to 35% in 2014. Deaths implicating methadone rose to 47% in 2017 and 2018, decreasing to 44% in 2019, before reaching 53% in 2020.

Source: NRS 2021

Figure 3 below shows methadone-implicated deaths in 2020 broken down by local authority area. Although Glasgow City had the highest absolute number of methadone-implicated deaths (177 of 291 DRDs), the highest percentage of methadone deaths relative to DRDs were in Perth & Kinross (73.5%, 25 of 34 DRDs) and Dumfries & Galloway (68.2%, 15 of 22 DRDs). A full table of deaths by local authority and NHS Health Board is available in Appendix 1.

Appendix 2 provides charts showing the change over time of the percentage of drug-related deaths where methadone was implicated, by health board area. Areas which have seen distinct upward trends in the percentage of DRDs where methadone was implicated are Fife, Greater Glasgow and Clyde, Lanarkshire and Tayside. Smaller health board areas with fewer DRDs present a more fluctuating picture.

Figure 3. Methadone deaths as a proportion of all DRDs by local authority area 2020*
Heat map of scotland. Darkest areas, indicating highest propoertion of methadone-implicated deaths relative to DRDs, are Peth and Kinross and Dumfries and Galloway. Second darkest areas include Moray, Stirling, Fife, Aberdeen City, West Dunbartonshire, Glasgow City, South Lanarkshire. The lighest areas belong to Clackmannanshire and West Lothian, followed by Highland.

*Figures for LAs with fewer than 5 drug-related deaths have been suppressed

2.1.1 By age and sex

As with overall DRDs, the greatest number of methadone-implicated deaths in absolute terms in 2020 occurred in males, and those aged 35-54 (Table 1). The age distribution of methadone deaths is slightly older than the average for all DRDs, with 45.3% of all methadone-implicated deaths being among those aged over 45, compared with 43% of all DRDs. However, methadone-implicated deaths were proportionally more common among females than males, accounting for 59% and 51% of all DRDs, respectively. This is in line with evidence which suggests older age groups and women are more likely to be in treatment.[13]

Table 1. Methadone-implicated deaths by gender and age, 2020
Methadone-implicated deaths All DRDs Percentage of all DRDs implicated by methadone
Gender Male 492 973 51
Female 216 366 59
Age Under 25 19 80 24
25-34 118 260 45
35-44 249 418 60
45-54 249 419 59
55 and over 73 162 45
All 708 1,339 53

(Source: NRS 2021)

2.1.2 Drugs implicated in death

96.5% (685)of methadone deaths had more than one drug implicated, while only 23 methadone-implicated deaths had only one substance implicated. It is important to note that in cases where an OST is identified in toxicology results it is almost always thought to be implicated in death, rather than just present at death, and it is not possible to determine from the NRS data the relative contribution of different substances to the cause of death.

Figure 4. Substances most often implicated in methadone-implicated DRDs
Line graph showing broad rise for most substances (detailed further in text). Benzodiazepines have, with some minor fluctuation before 2016, steadily been most often implicated. Line for heroin/morphine begins to noticeably diverge around 2016, where the number was 237, rising gradually to 298 in 2020. Gapabentin/pregabalin rise steadily in line with the increase in methadone-implicated deaths, becoming second most commonly implicated after benzodiazepines in 2020. Amphetamines and buprenorphine had no noticeable increase and remained below 15 until 2019, before both rose to 24 in 2020.

Source: NRS 2021

Figure 4 above shows that the most common combinations of substances in methadone-implicated deaths were:

  • Benzodiazepines: implicated in 86% (609) of methadone-implicated DRDs. Illicit 'street' benzodiazepines accounted for the majority of cases (566 deaths, 80%).
  • Gabapentinoids: implicated in 49% (345) of methadone-implicated DRDs.
  • Heroin/Morphine: implicated in 42% (298) of methadone-implicated DRDs.
  • Cocaine: implicated in 34% (241) of methadone-implicated DRDs.

2.2 Buprenorphine implicated in drug-related deaths

In 2020 there were 97 deaths where buprenorphine was implicated, accounting for 7% of all DRDs. This represents an 18% increase on 2019 (82 deaths). There has been a general upward trend over time, with a 169% increase since 2017 (36 deaths).[14] Due to the smaller number of buprenorphine-related deaths, data is available at a less granular level and it is not possible to robustly determine the geographic or demographic breakdown of buprenorphine-related deaths.

The number of buprenorphine deaths is smaller than the number of methadone-implicated deaths. However, far fewer individuals are prescribed buprenorphine and it is therefore less available than methadone. Patient estimates suggest the number of people prescribed methadone is approximately four times higher than the number prescribed buprenorphine.[15]

While numbers remain small, the percentage of all drug deaths where buprenorphine was implicated has increased dramatically, from 0.6% of all DRDs in 2010 to 7% in 2020. This is a greater increase than with methadone, and is partly a result of the increase in buprenorphine prescribing over the period.

Figure 5. Number of buprenorphine-implicated deaths, 2010-2020
Line graph showing broad rise in numbers, with sharpest rise occurring between 2017 and 2018. 2018-2019 shows a slight decrease from 90 to 82, before rising to peak of 98 in 2020.

Source: NRS 2021

2.3 OST implicated deaths: quarterly trends

Figure 6 below presents methadone and buprenorphine implicated deaths by quarter and calendar year from 2016 to 2020. The chart shows the overall increasing trend is evident at the quarterly level over the time series, with quarter two of 2020 having the highest deaths from both substances over this time series.

Figure 6. Methadone and Buprenorphine-implicated deaths, Q1 2016 to Q4 2020
Line graph showing methadone implicated deaths have been prone to more fluctuation than buprenorphine, which has remained relatively steady (though still increased gradually) over the times series. In quarter 1 of 2016, methadone implicated deaths were 84, compared with 128 in quarter 1 of 2020. Between Q1 and Q2 methadone sharply rose to 217, before decreasing to 192 in Q3 and 173 in Q4. Between Q1 and Q2 buprenorphine rose from 20 to 30, before decreasing to 26 in Q3 and 22 in Q4.

Source: NRS 2021

2.4 Source of OST implicated in death

While it is clear that there has been an increase in deaths where methadone and/or buprenorphine was implicated it is not possible to determine from NRS data alone whether the decedent was prescribed the OST or whether they obtained it illicitly.

The National Drug Related Deaths Database provides more detail around the background and circumstances of DRDs.[16] The most recent analysis uses data from 2015/2016 and shows that over one third of people who died from a DRD (37%) were prescribed an OST drug (mainly methadone) at the time of death. The percentage of people prescribed an OST at the time of death has steadily increased since 2009. Contributing factors to this rise include the ageing cohort of problem drug users and an overall increase in the number of problem drug users (particularly older drug users) in treatment.


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