In this issue, Caplin and Fraser1 review the potential future role of the Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs) in the treatment of substance use disorders (SUDs). GLP-1RAs may offer a novel mechanism to reduce the appetitive desire of substances, facilitating improvements in SUD treatment. While there is interest and speculation about their use, the data is preliminary. Most compelling effects are seen in those with alcohol use disorder (AUD) with comorbid type 2 diabetes mellitus and/or obesity paired with weekly cognitive behavioral therapy (CBT) for AUD. More research is needed before these agents could be considered as an adjunctive treatment for SUDs. Like other pharmacotherapies, some patients respond well, while most see limited or no benefit without follow-up and evidence-based behavioral therapies. GLP-1RAs also have notable side effects2 that may be equal or greater in people with SUDs with or without type 2 diabetes mellitus or obesity. GLP-1RAs represent a promising but unproven avenue; time will tell if they play a role in SUD treatment. There is a significant need to develop new pharmacotherapies for SUDs.3 Only a few medications are formally indicated for SUDs, limited to only 3 substance classes: alcohol (naltrexone, acamprosate, disulfiram), nicotine (NRT, varenicline, bupropion), and opioids (methadone, buprenorphine).4–6 Slow-release oral morphine is also used for opioid use disorders, alongside topiramate and gabapentin for AUD; however, data are limited, and they remain off-label.5,6 No pharmacotherapies are currently indicated for cannabis or stimulant use disorders.3 Expanding pharmacotherapy options is long overdue. However, despite there being few indicated evidence-based pharmacotherapies, there has been a marked increase in the prescribing for AUD and opioid use disorders.7 Co-prescribing also appears to be increasing for opioid and stimulant use disorders.8 Moreover, one in five Canadians aged 40 to 79 currently consumes five or more medications, illustrating a broader trend towards heightened prescribing practices.9 The concern with SUDs is that it seems that there is a trend to increasing off-label prescribing in clinical practice, often based on “signals,” “promising results,” and other optimistic takes from usually very small studies with limited follow-up or simply from anecdotal experiences. The prescribing also seems to occur without the evidence-based psychotherapies and weekly follow-up used in almost all SUD treatment trials, making their likelihood of benefit increasingly doubtful. Although in some ways then, it is good that prescribing is happening, as it may suggest that stigma towards the SUDs is less stemming from the expanding understanding of the underlying neurobiology contributing to SUDs and increased interest in providing care for people with SUDs.3 The risk, however, is that prescribing may be happening for other reasons that are not beneficial to the people we see. Prescribing sometimes occurs to manage practitioner feelings of helplessness yet wanting to help, where writing a prescription represents doing something rather than reflecting on the inability to help the person with a SUD change and the discomfort with this.10 It also, at times, seems to potentially come with briefer consultations potentially related to billing practices11 rather than working to engage people with SUDs longitudinally, following up with them frequently, and working with their ambivalence to change. Recent guidelines, which tend to prioritize pharmacological prescribing over psychological interventions, may further exacerbate this trend.5,6 SUDs are frequently characterized as chronic and relapsing disorders requiring comprehensive treatment approaches addressing not just their neurobiological aspects but also their often multifaceted psychological and social dimensions.3,4 GLP-1RAs introduce a novel mechanism that warrants further research, but, like all pharmacotherapies for the SUDs, they need to be seen as potential adjuncts to comprehensive treatment for SUDs, rather than as stand-alone treatments. Short of a medication selectively ablating the reward associated with the use of a particular substance and the memories of that use, there will likely not be a medication that will address SUDs on its own. Support, learning how to change behavior, developing skills to not return to substances, and addressing the social determinants of health remain the foundation of treatment and recovery coming from personal engagement and frequent follow-up.
Crockford et al. (Tue,) studied this question.