Vol. 7 Methadone deaths in the first Covid-19 lockdown

The deaths were largely in those not prescribed.

Methadone and buprenorphine-related deaths among people prescribed and not prescribed Opioid Agonist Therapy during the COVID-19 pandemic in England. Aldabergenov D, Reynolds L, Scott J, et al. International Journal of Drug Policy 2022;:103877. doi:10.1016/j.drugpo.2022.103877

This paper does some interesting things. Chiefly, it shines a bit more of a light on a group of people where we know far too little — those not in treatment. That reflects a problem with research (if not life generally) where we tend to measure and take notice of the things we can see rather than other factors hiding just around the corner out of sight. 

Key points on the paper

This was a retrospective post-mortem toxicology study of deaths related to opiate agonist therapy (OAT).¹ They took a narrow window of three months (23 March - 22 June) and they looked at deaths in that period for the five years from 2016-2020. They used the National Programme on Substance Abuse Deaths (NPSAD) which is a database for drug-related deaths. It’s essential to have a denominator and the best they could come up with is the unofficial estimates provided through NDTMS data. That was then figured into the statistical modelling. 

First off, let’s get buprenorphine out of the way. When the numbers were crunched they found no difference in death associated with buprenorphine. So, onto methadone… Overall, the authors estimate that methadone-related deaths in 2020 (n=157) increased by 64% compared with 2019 (n=96). The researchers looked at whether they were prescribed or not when they died. There was a 22% increase in methadone deaths in people prescribed but this was “only marginally higher than would haver been anticipated”. The model estimated 44 deaths and there were 55 deaths. However, in the non-prescribed group there was a 74% rise in methadone-related deaths. The model estimated 43 deaths and there were 80 deaths. This is the most stark finding from this paper. 

The authors were also able to report on post-mortem blood concentrations of methadone and they noted levels were quite a bit lower in people who died who were not prescribed methadone. But these differences were not statistically significant. There was no difference in the average number of drugs co-prescribed with methadone in 2020. And there was no differences in the number of cases where benzos were involved — interesting, given recent concerns around the role of benzodiazepines in overdose deaths. 

What does this all mean?

In short, more people died from methadone-related deaths in 2020 but it was almost entirely in the group of people who were not prescribed methadone.

The very brief summary of the results I’ve given skates blithely over a whole lot of complexity in the analysis. The timeframe makes perfect sense given the aim is to investigate deaths related to methadone and buprenorphine during the first Covid-19 lockdown. Did the natural experiment of the pandemic offer us any insights into how we might approach future policy for pick ups for methadone and buprenorphine? 

There are a number of ways to cut this up and I think the discussion in the paper itself is reasonably balanced. It would be very easy to rush headlong into this paper, let one’s inner bias demons rage, and draw a whole set of conclusions.

Firstly, we should note again that this study could not detect any difference in buprenorphine-related deaths. That can’t just be dismissed as a non-finding, a confirmation of the null hypothesis, and we all just move on. It is important in itself. There were some pretty wild shifts in clinical practice during that first lockdown and I can still remember the bum-squeakiness of signing off on 14 day pick ups. Despite this there was no detectable difference in deaths. We always thought that buprenorphine was safer and this has been one hell of a test of that. All other things being equal, this evidence supports a move towards reduced pick ups with buprenorphine.

Is this all about methadone diversion? Has the more liberal approach to supervision in this period resulted in methadone being diverted to people not in treatment? It is plausible that people shared out their methadone to help those who, for whatever reason, couldn’t access their usual opiates. And, the evidence does suggest, including findings around co-detection of other opioids in people who died in 2020, that there was reduced availability and disruption to normal supplies of heroin. 

The problem with sharing methadone is that it is inherently risky as it tends to be intermittent. That irregular dosing is particularly hazardous with methadone given its pharmacological profile. A few days here and there creates all sorts of fluctuations, with serum levels rising and dropping at unpredictable intervals. Even experienced people, those that have been on methadone many times before, will have a hell of a job balancing risks of using drugs when faced with intermittent methadone at variable doses and intermittent illicit drug availability.

As far as Covid-19 and deaths go, much of this might be unknowable but it raises a lot of future issues around supervision of methadone and the excruciating challenge of balancing safety with stigma. That, for me, is where we need to return here. Daily supervision, even daily collection at the pharmacy, is stigmatising and painful for people. It just can’t be under-estimated. Yet as a prescriber I am painfully aware that methadone is a medication where the risks need to be balanced and some of that responsibility to prescribe is also about the wider consequences of prescribing.

We don’t know that diverted methadone was the key factor in the deaths in the first lockdown — more research is needed to unpick this. Of course, the need for prescribing prudence with supervision or daily collection is also about the wider system and it is not hard to see how that grinds the gears of the people being made to feel like shit in a pharmacy queue. (I know many pharmacies are warm, welcoming places of support for people who use drugs.) 

1. I’m finding the capitalisation of opiate agonist therapy in the title of this paper slightly weird. But I find use of Title Case a Bit Odd at the Best of Times. There is a whole set of rules for it. I’m not going there.