From the Editor

Methadone was invented in the 1930s. The first legal injection site opened its doors nearly two decades ago. Yet our challenges with opioids seem to have only worsened with time. Consider, for example, that in a new, two-year study, the authors found that opioid-related deaths rose almost 600% between 2015 and 2017 in Canada.

What can we do? This week, we consider two selections.

In the first, Thomas Santo Jr (of the University of New South Wales) and his co-authors do a systematic review and meta-analysis for opioid agonist treatment for those with opioid dependence. They write in JAMA Psychiatry: “Our findings suggest a potential public health benefit of OAT, which was associated with a greater than 50% lower risk of all-cause mortality, drug-related deaths, and suicide and was associated with significantly lower rates of mortality for other causes.” We consider the big paper and its implications.


And in the other selection, Benedikt Fischer (of the University of Toronto) and his co-authors weigh the recent interest in decriminalizing illicit drug use. In a new Canadian Journal of Psychiatry commentary, they note their hesitation, writing: “while ‘decriminalization’ proposals for illicit drug use are popular and largely well-intended, their overall merits require cautious analysis and scrutiny.”



Selection 1: “Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis”

Thomas Santo Jr, Brodie Clark, Matt Hickman, et al.

JAMA Psychiatry, 2 June 2021 Online First


Opioid dependence is increasing in many countries, particularly in North America, where there have been substantial increases in opioid-related health harms, specifically overdose. In the US during the COVID-19 pandemic, opioid overdoses have increased in some states by up to 30% in 2020 compared with those in 2019. Population-level increases in ‘deaths of despair,’ including suicides, injuries, and liver disease, have also been observed. People with opioid dependence are at an elevated risk of a range of causes of death beyond deaths of despair, including other acute and systemic causes such as unintentional opioid and suicide-related death, and all liver-related, alcohol-related, cancer-related, chronic respiratory-related, digestive-related, HIV-related, influenza- and pneumonia-related, and injection-related injuries.

Methadone and buprenorphine are classified by the World Health Organization as essential medicines for opioid agonist treatment (OAT) for opioid dependence. There is robust evidence from a recent systematic review that during OAT, overdose and all-cause mortality are reduced among people with opioid dependence. That review also found that people who cease OAT are at the highest risk of all-cause and overdose mortality in the first 4 weeks after treatment cessation and that risk of mortality is elevated in the first 4 weeks of OAT compared with the remainder of time receiving OAT.

So begins a paper by Santo et al.

Here’s what they did:

  • They conducted a systematic review and meta-analysis, and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.
  • They drew papers from 3 databases (Medline, Embase, and PsycINFO); the search terms included “opioid dependence” and “OAT.”
  • “Eligible studies had to report mortality data for people with opioid dependence during and out of OAT…”
  • Both observational studies and RCTs were included.
  • “Two reviewers independently reviewed the titles and abstracts identified in the search and retrieved articles to determine eligibility; full texts were also independently reviewed…” Information was extracted.
  • Statistical analyses were done.

Here’s what they found:

  • “Of the 7980 studies identified, 72 publications fulfilled inclusion criteria … A total of 15 RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were eligible for analysis.”
  • RCT characteristics: Eight of 15 RCTs (53%) were conducted in North America and at single clinics. Buprenorphine was studied in 7 of 15 of the RCTs (47%).
  • Cohort characteristics: Cohorts ranged from 110 to 306 786 participants and included people from Europe (20 of 36 studies, or 58%), Australia (6 studies, or 17%), and North America (5 studies, or 14%).
  • Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47). (!) This association wasn’t affected by gender, age, geographic location, and HIV status. (!!)
  • Associations were not different for methadone (RR, 0.47) vs buprenorphine (RR, 0.34).
  • There was lower risk of suicide (RR, 0.48), cancer (RR, 0.72), drug-related (RR, 0.41) mortality during OAT.


“We synthesized 36 observational cohort studies that assessed mortality risk during and out of OAT, which represented a 3-fold increase from a previous review of all-cause mortality that included 19 cohorts. Our findings suggest a potential public health benefit of OAT, which was associated with a greater than 50% lower risk of all-cause mortality, drug-related deaths, and suicide and was associated with significantly lower rates of mortality for other causes.”

A few thoughts:

  1. This is a good paper.
  1. Wow.
  1. The findings are big. All-cause mortality, drug-related deaths, and suicide were all reduced with OAT.
  1. Also, new wasn’t necessarily better: methadone matched the buprenorphine results.
  1. Interestingly, the RCTs were less than impressive. As the authors note: “Our results suggest that RCTs of OAT were underpowered to examine mortality risk.” In seven of them, no deaths were reported.
  1. Like all studies, there are limitations. The authors note: “The current evidence base in general was unrefined, lacking detail on clinical characteristics of patient history, intervention delivery, and consistent measures of confounders. For example, most cohorts did not specify whether treatment ceased because of dropout or completion.”
  1. Are there implications for public policy? The authors certainly think so. “Despite this positive association, access to OAT remains limited in many settings, and in the US and globally, coverage for this type of treatment is low.”
  1. Obviously, stigma about opioids and OAT is part of the problem. But the prescribing of opioid agonist treatment is heavily regulated in North America, and across the west. If this sort of care is life-saving, are we being too cautious? A just-published scoping review in The American Journal of Psychiatry finds the potential of office-based prescribing: “Limited research suggests that office-based methadone treatment and pharmacy dispensing could enhance access to methadone treatment for patients with opioid use disorder without adversely affecting patient outcomes and, potentially, inform modifications to federal regulations.” Here’s the link:
  1. Would further public policy changes help? What about decriminalization? See the next selection for a cool reception to an idea that seems very hot right now.

The full JAMA Psychiatry paper can be found here:


Selection 2: “Proposals for Decriminalization of Illicit Drug Use: Considering a Combination of déjà-vu, Diversion and Devil-with-many-details for Health-oriented Policy Reform”

Benedikt Fischer, Neil Boyd, Serge Brochu

The Canadian Journal of Psychiatry, 26 May 2021 Online First


In February 2021, the Liberal government tabled Bill C-22, a bill proposing to purge mandatory minimum penalties (MMP) for multiple criminal offences in Canada, including several of the Controlled Drugs and Substances Act’s drug supply offences. Furthermore, the government announced for the bill to include provisions that will ‘require police and prosecutors to consider alternatives to laying charges in simple [drug] possession cases, such as diversion to treatment […towards] leeway to use conditional sentence orders in cases where an individual is not a public safety threat.’

Little of the proposed reforms is new or innovative. The MMPs proposed for deletion were introduced by a previous (Conservative) government, thus reverting to an earlier status quo. Moreover, ‘conditional sentencing’ is a dated (1996) justice reform vehicle towards increasing use of ‘alternative punishments’ to mainly keep non-violent offenders from incarceration, to improve sentencing and to reduce costs. The C-22 initiative, however, fits within a currently popular chorus promoting ‘decriminalization’ of illicit drug use in Canada including leading stakeholder voices from health, legal, and other sectors. Its volume has been amplifying, especially in the face of the unrelenting ‘opioid crisis’ and related overdose-mortality, yet persistent lack of soundly effective solutions. Several countries have implemented decriminalization approaches for illicit drug use, which vary widely in design and operations. But beyond these variations, and while many Canadians agree with the general concept of ‘decriminalization’ of illicit drug use, decriminalization is a complex construct with potential for multiple – some hidden – pitfalls or unintended adverse consequences.

So begins a paper by Fischer et al.

The authors forward five arguments; three are summarized here.

Many criminal justice-initiated alternatives to punishment involve institutionalized “discretion,” for example, by police or prosecutors, as to whether diversion approaches should be used.

They argue: “These decisions rely on mostly subjective judgements of individual or behavioural characteristics of the offender, while in practice commonly translate into expressions of socio-racial biases, stigma, or outright discrimination. While many justice system authorities prefer to use punitive over alternative or ‘soft’ approaches, almost any user of illicit drugs may indicate some (subjective) reason possibly viewed as a possible ‘public safety’ threat. ‘Discretion’ is a well-recognized, universally tricky challenge in justice system operations. Its enactment precariously positions police or prosecutors as ‘judges’ ruling on the ‘deservingness’ of drug use offenders for alternatives to punishment.”

With “decriminalization” aiming to reduce the reach and severity of legal punishments for illicit drug users, its application to personal drug possession offences-only misses the mark by design.

They argue: “Especially among users intensively involved with addictive (e.g., opioids/psychostimulants) drug use, law-breaking by circumstance is rarely limited to drug possession-specific offences. As long as the drugs of consumption are illegal and can only be sourced from illegal (e.g., ‘black market’) sources, most users inevitably are involved with ‘drug supply’ offences – illegal drug purchasing, trading or ‘trafficking’ – on a regular basis. Moreover, many ongoing, and especially socially marginalized (e.g., homeless) users, are continuously involved with other illegal activities including theft, fraud/forgery, burglaries, or sex work necessary towards supporting and funding their illicit drug use needs.”

“Decriminalization” approaches offer little sustained advancement towards shifting fundamental reforms of “drug use” control from a criminal to a genuinely health-based and health-focused matter.

They argue: “Under most ‘decriminalization’ frameworks, the predominant logic remains that of drug use as ‘crime’ and ‘deviance’ principally governed by justice-based norms, authorities and consequences. Those measures and experts to supposedly serve the health or therapeutic interests of drug users/offenders come in only secondarily or ‘at the mercy’ of justice-based provision. Crucially, ‘decriminalization’ reinforces the hegemony of crime control over public health for illicit drugs; this largely means stalemate rather than progress for fundamental and sustained policy reform.”

The authors go on to suggest more sweeping changes:

“Rather, fundamentally more genuine and sounder reform concepts are needed – and especially given the extreme volatility and harm arising from currently prevalent illicit/synthetic opioid (fentanyl) use and supply – to genuinely move ‘drug use’ from a crime to a public health issue in Canada. This, as has been conceptually accepted for cannabis, will inevitably require consideration of legalization and regulation frameworks.”

A few thoughts:

  1. This is a good commentary.
  1. The paper is very timely. Obviously, the discussion about decriminalization isn’t confined to the Liberal government. Others have embraced this idea, including the Canadian Association of Chiefs of Police.
  1. Are the authors persuasive? You can draw your own conclusions. But Fischer et al. make an important point about the limits of transferring a public policy idea from one jurisdiction to another. “In many current decriminalization discussions, reference to the ‘Portugal model’ as a guiding blueprint for decriminalization is made. While Portugal’s decriminalization reforms for illicit drug use implemented in the early 2000s have been associated with some (limited) reductions in problematic drug use and related criminal justice burden while increased treatment uptake, it is rightly observed that decriminalization options fundamentally depend on social-cultural and structural system contexts involved.” Fair point.

The full CJP paper can be found here:


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.