This Week in the ASAM Weekly

As each wave of the opioid crisis has taught us something, the fourth wave is telling us that it’s about more than just opioids. High-potency synthetic opioids and novel drug supplies continue to challenge the clinical approaches born out of prior waves. In response, ASAM assembled a group of OUD experts to provide much-needed, updated considerations for buprenorphine treatment (Journal of Addiction Medicine). Unfortunately, large-scale increases in buprenorphine prescribing did not occur after removal of the X-waiver training, but this may have less to do with opioids and more to do with engagement and utilization (JAMA Health Forum). Or maybe we just need a little more time.

Stimulants helped define the fourth wave while underscoring the significance of poly-substance use and comorbidities. Contingency management will therefore be an essential part of addiction treatment going forward (Preventive Medicine), and latent-class analysis could help us better understand the sub-groups within polysubstance addiction (iScience). But contrary to what many might reasonably assume, appropriately prescribed amphetamines may actually improve buprenorphine retention and reduce overdose risks in certain individuals with co-occurring psychiatric disorders (BMJ Mental Health).

What the fourth wave is telling us may be that we’re reaching a point in defining waves that can no longer be confined to any particular substance(s). Stress and social pressures are likely closing the gender gap in alcohol-related deaths (JAMA Network Open) while deaths of despair are driving declines in life expectancy but possibly contributing to the hopefulness underlying psychedelic medicine (JAMA Psychiatry).

Or maybe the fourth wave is telling us that the drivers underlying it are less tangible but more enduring than the substances themselves.

Thanks for reading,

Nicholas Athanasiou, MD, MBA, DFASAM
Editor in Chief

with Co-Editors: Brandon Aden, MD, MPH, FASAM, Debra R. Newman, PA-C, MSPAS, MPH, Jack Woodside, MD, John A. Fromson, MD

Lead

ASAM Clinical Considerations: Buprenorphine Treatment of Opioid Use Disorder for Individuals Using High-potency Synthetic Opioids 🔓

Journal of Addiction Medicine

This clinical considerations document is based on a narrative literature review and expert consensus and addresses considerations for changes to the clinical practice of treatment of opioid use disorder (OUD) with buprenorphine for individuals using high-potency synthetic opioids (HPSOs). Broadly, it suggests that individualized strategies for buprenorphine initiation may be needed. The experience of opioid withdrawal negatively impacts the success of buprenorphine treatment, and attention to withdrawal management before and during buprenorphine initiation should be proactively addressed. Buprenorphine dose and dosing frequency should be individualized based on patients’ treatment needs, the possibility of novel components in the drug supply should be considered during OUD treatment, and all forms of opioid agonist treatment should be offered and considered for patients.

Research and Science

Trends in Alcohol-Related Deaths by Sex in the US, 1999-2020 🔓

JAMA Network Open

This cross-sectional study used CDC data to explore sex differences in alcohol-related mortality from 1999-2020. Age-adjusted mortality rates from 2018-2020 increased by 12.5% (95% CI, 6.4%-19.1%) per year among males and 14.7% (95% CI, 9.1%-20.5%) for females during the same period. Females were also noted to experience a higher rate of increase compared to males with regard to race/ethnicity, age, cause, and region. With regard to age, the rate of change was higher for women compared to males 65 years and over; it was also higher for non-Hispanic White, non-Hispanic Black, and American Indian or Alaska Native women. These results emphasize the need for further research to understand factors specific to women, and to target treatment accordingly.

Polysubstance addiction patterns among 7,989 individuals with cocaine use disorder 🔓

iScience

To characterize polysubstance addiction (PSA) patterns of cocaine use disorder (CoUD), this study used a latent class analysis (LCA) in 7,989 participants with a lifetime DSM-5 diagnosis of CoUD. This analysis identified three PSA subgroups among CoUD participants (i.e., low, 17%; intermediate, 38%; high, 45%). While these subgroups varied by age, sex, and racial-ethnic distribution, there was no difference with respect to education or income. After accounting for sex, age, and race-ethnicity, the CoUD subgroup with high PSA had higher odds of antisocial personality disorder, agoraphobia, mixed bipolar episode, posttraumatic stress disorder, antidepressant medication use, and sexually transmitted diseases than the low-PSA CoUD subgroup. These findings underscore the importance of modeling PSA severity and comorbidities when examining the clinical, molecular, and neuroimaging correlates of CoUD.

Characteristics and Prescribing Patterns of Clinicians Waivered to Prescribe Buprenorphine for Opioid Use Disorder Before and After Release of New Practice Guidelines 🔓

JAMA Health Forum

The educational requirement for a Drug Addiction Treatment Act (DATA) waiver was eliminated in 2021. The study compares providers who obtained the waiver prior to the change (prior DATA waiver), after the change but fulfilled the educational requirement (concurrent DATA waiver), or after the change and did not fulfill the educational requirement (practice guidelines). A significant minority of all three groups never prescribed buprenorphine and reported significant barriers to access to psychiatry and addiction specialists. The practice guideline group was more likely to work in urban areas and emergency departments (ED). They were also more likely to report prescribing to 0 or 1-4 patients in the prior month than the other 2 groups and less likely to utilize other interventions and monitoring strategies such as in-person counseling.

Prescription amphetamines in people with opioid use disorder and co-occurring psychostimulant use disorder initiating buprenorphine: an analysis of treatment retention and overdose risk 🔓

BMJ Mental Health

This study examined the effect of prescription amphetamines (PA) in patients with OUD treated with buprenorphine. Data were obtained from Medicaid records from all 50 states for 90,269 people with OUD receiving buprenorphine; of these, 14,735 also received PA. Treatment retention was greater in those receiving PA (158 days with PA, 139 days without PA, P<0.001). This was also true for people with an additional diagnosis of psychostimulant use disorder, (114 days with PA, 97 days without PA, P<0.001). A second analysis of SUD related emergency admissions and drug-related poisonings found no increase in these events associated with receiving PA. The authors conclude that “patients with OUD on buprenorphine should receive treatment with a PA when indicated.”

Learn More

The fourth wave of the overdose crisis: Examining the prominent role of psychomotor stimulants with and without fentanyl

Preventive Medicine

This article describes the fourth wave of the overdose crisis being fueled by fentanyl combined with stimulants. The preceding waves involved (1) prescription opioids, (2) heroin, and (3) fentanyl. In 2021, 32% of overdose deaths involved both fentanyl and stimulants, similar to the 34% from fentanyl alone. In addition, 18% of overdose deaths involved stimulants alone. In the Midwest, West, and South, methamphetamine was most prevalent, while in the Northeast and Great Lakes, cocaine was most common. Although there are no FDA approved medications for stimulant use disorder, contingency management (CM) has considerable evidence of efficacy. A meta-analysis has demonstrated long-term efficacy superior to established treatments such as CBT. Among the barriers discussed is a SAMHSA limit of rewards to $75/pt/year, well below the amount used in research studies. The authors conclude that expanding CM is a priority in addressing this fourth wave of the overdose crisis.

Psychedelics as Therapeutics—Potential and Challenges

JAMA Psychiatry

In the context of the history of marijuana use as medicine and its rapid legalization, the authors discuss the potential future of psychedelics for treatment of psychiatric and substance use disorders. Authors note there is limited evidence to suggest that psychedelics may offer benefit, but there are essential research questions to be answered. First, if the subjective experiences that occur with psychedelics are intrinsic to or separate from their potential benefits. Second, currently there are not standardized protocols and research needs to establish therapeutic thresholds, including dosing, timing and what if any contextual components are needed. In addition, improved understanding about the mechanisms of action that produce benefit could lead to alternate treatments modalities that could provide similar benefits.

Achieving integrated treatment: a realist synthesis of service models and systems for co-existing serious mental health and substance use conditions

The Lancet Psychiatry

Integrating care for persons with co-occurring mental health disorders is complex. In the UK, uncertainty exists on how to best employ systems of care for persons with these conditions. This article discusses theories that could increase understanding of how these services might work in the UK, for whom, and in what circumstances. This realist synthesis highlights that comprehensive workforce training, supervision, and policy change are needed to provide integrated care. This will require committed leadership and clear expectations, as well as solid care-coordination to be successful.

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