Commentary on Young <i>et al</i> .: Clinical guidance is required for stimulant co‐prescription with opioid agonist therapy

Young et al.'s [1] large Canadian cohort study showed no association between prescribed stimulants and opioid overdose among people on opioid agonist therapy, despite low rates of co-prescription, highlighting a need for clinical guidance on the management of coexisting opioid use disorder and attention-deficit hyperactivity disorder and/or stimulant use disorder. Young et al. [1] present new findings on the lack of a relationship between prescribed stimulants and opioid overdose from a Canadian cohort of people on opioid agonist therapy (OAT). The authors drew from a linked database of fatal and non-fatal opioid overdose in the province of British Columbia from 2015 to 2020. The authors found no association between stimulant co-prescription and overdose. Importantly, as the authors point out, the incidence of fatal overdose was low (1/500/year) [1], testimony to the protective role of OAT [2] and underscoring the importance of community access to effective OAT. Promoting effective initiation onto [3] and retention in [2] OAT is increasingly important in face of the rise of potent synthetic opioids and co-use with synthetic stimulants [4]. Stimulant prescription among people on OAT is an emerging therapeutic area that may have additional benefits over OAT alone. Prescription stimulants are first line pharmacotherapy for adults with attention-deficit hyperactivity disorder (ADHD) [5], which coexists with an important proportion of people with opioid use disorder (recent meta-analytic data suggest 20% [6]) and is associated with more severe opioid dependence and psychiatric comorbidity [7]. Young et al. [1] reported 4.4% of the 9395 participants had an ADHD diagnosis recorded; of those, 31% (212 participants) were prescribed a stimulant. Consistent with the literature [8], these data suggest a likely under-recognition and under-treatment of ADHD in an OAT population. Treatment of ADHD may improve retention in OAT [9]. Although the study was not designed to assess reasons for or patterns of stimulant prescription, more work is needed to explore the role of effective treatment of ADHD among people with opioid use disorder. Diagnosis of ADHD in adults with coexisting opioid use disorder (with or without concomitant non-prescribed stimulant use) is complicated by overlap in symptoms and lack of validated screening measures for substance use disorder populations. Consensus guidelines recommend routine screening and prompt diagnosis and treatment in people presenting with substance use disorder [10]. Emerging evidence suggests there may be a role for stimulant prescription for the management of stimulant use disorder at doses higher than for ADHD [11]. Co-use of stimulants with opioids is implicated in rising fatalities in North America, suggesting coexisting stimulant use disorder with opioid use disorder may be increasing at least in those countries. Yet only 38 people (0.4%) of the sample of 9395 people Young et al. [1] report on were noted to have a stimulant use disorder diagnosis, and only six (0.9%) of those prescribed a stimulant had a stimulant use disorder diagnosis. Indeed, the presence of a stimulant use disorder may preclude access to OAT [12]. Recent consensus guidelines for stimulant use disorder released by the American Society of Addiction Medicine and the American Academy of Addiction Psychiatry recommend consideration of off-label prescription of stimulants for the treatment of stimulant use disorder [13]. However, in the face of limited evidence for the treatment of coexisting opioid and stimulant use disorder, there are as yet no consensus OAT guidelines that comprehensively address concurrent treatment of stimulant use disorder. The Young et al. [1] data are drawn from administrative datasets and as such it is unclear whether the apparent low prevalence of ADHD and stimulant use disorder is an artefact of the data. It is difficult to interpret the rationale for stimulant prescription in this cohort, perhaps reflecting a lack of consistency, clarity and a regulatory framework for prescription of stimulants to people prescribed OAT. The study highlights the need to explore the role of stimulant co-prescription for both the treatment of stimulant use disorder and for the treatment of ADHD at the relevant doses for each of these conditions. New research from Norway exploring dexamfetamine prescription for amphetamine dependence among people on OAT may provide additional evidence [14] as will emerging evaluation data from Canadian safer supply measures that allow for prescription psychostimulants for the purposes of reducing harm from illegal stimulant use [15]. Context is outpacing evidence [3]. The manuscript of Young et al. [1] serves as a timely reminder of the need for consensus treatment guidelines for opioid use disorder that make recommendations for treatment of coexisting stimulant use disorder and other conditions such as ADHD. Nadine Ezard: Conceptualization (lead); project administration (lead); writing—original draft (lead); writing—review and editing (lead). Krista J. Siefried: Conceptualization (supporting); writing—original draft (supporting); writing—review and editing (supporting). Brendan Clifford: Conceptualization (supporting); writing—original draft (supporting); writing—review and editing (supporting). The authors have no financial interests to declare. The National Centre for Clinical Research on Emerging Drugs receives funding from the Australian Department of Health and Aged Care. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

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