PURPOSE OF REVIEW: This review provides an update on recently published literature on the rise of illicit fentanyls, risks for overdose, combinations with other substances, e.g. stimulants, consequences, and treatment. RECENT FINDINGS: Overdose due to illicit synthetic opioids (e.g. fentanyl and fentanyl analogs) continues to rise in the US both preceding and during the COVID-19 pandemic. Fentanyl-related overdose is rising in new geographic areas e.g. the western USA. Stimulant-related overdose is also increasing nationwide driven by methamphetamine and cocaine. Polysubstance use, e.g. the use of a stimulant along with an opioid is driving stimulant-related overdose. Other medical consequences of injection drug use are rising including HIV and hepatitis C infections. Medication approaches to treating opioid use disorder remain the standard of care and there are new promising pharmacological approaches to treating methamphetamine use disorder. SUMMARY: A 'fourth wave' of high mortality involving methamphetamine and cocaine use has been gathering force in the USA. Availability and use of illicit fentanyls are still the major drivers of overdose deaths and the current rise in stimulant-related deaths appears entwined with the ongoing opioid epidemic.

The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis.

Importance Medication treatment for opioid use disorder (MOUD) is efficacious, but comorbid stimulant use and other behavioral health problems often undermine efficacy. Objective To examine the association of contingency management, a behavioral intervention wherein patients receive material incentives contingent on objectively verified behavior change, with end-of-treatment outcomes for these comorbid behavioral problems. Data sources A systematic search of PubMed, Cochrane CENTRAL, Web of Science, and reference sections of articles from inception through May 5, 2020. The following search terms were used: vouchers OR contingency management OR financial incentives. Study selection Prospective experimental studies of monetary-based contingency management among participants receiving MOUD. Data extraction and synthesis Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 3 independent investigators extracted data from included studies for a random-effects meta-analysis. Main outcomes and measures Primary outcome was the association of contingency management at end-of-treatment assessments with 6 clinical problems: stimulant use, polysubstance use, illicit opioid use, cigarette smoking, therapy attendance, and medication adherence. Random-effects meta-analysis models were used to compute weighted mean effect size estimates (Cohen d) and corresponding 95% CIs separately for each clinical problem and collapsing across the 3 categories assessing abstinence and the 2 assessing treatment adherence outcomes. Results The search identified 1443 reports of which 74 reports involving 10 444 unique adult participants met inclusion criteria for narrative review and 60 for inclusion in meta-analyses. Contingency management was associated with end-of-treatment outcomes for all 6 problems examined separately, with mean effect sizes for 4 of 6 in the medium-large range (stimulants, Cohen d = 0.70 [95% CI, 0.49-0.92]; cigarette use, Cohen d = 0.78 [95% CI, 0.43-1.14]; illicit opioid use, Cohen d = 0.58 [95% CI, 0.30-0.86]; medication adherence, Cohen d = 0.75 [95% CI, 0.30-1.21]), and 2 in the small-medium range (polysubstance use, Cohen d = 0.46 [95% CI, 0.30-0.62]; therapy attendance, d = 0.43 [95% CI, 0.22-0.65]). Collapsing across abstinence and adherence categories, contingency management was associated with medium effect sizes for abstinence (Cohen d = 0.58; 95% CI, 0.47-0.69) and treatment adherence (Cohen d = 0.62; 95% CI, 0.40-0.84) compared with controls. Conclusions and relevance These results provide evidence supporting the use of contingency management in addressing key clinical problems among patients receiving MOUD, including the ongoing epidemic of comorbid psychomotor stimulant misuse. Policies facilitating integration of contingency management into community MOUD services are sorely needed.

/pdf/contingency-management-for-patients-receiving-medication-for-pwok7llrm4.pdf

Contingency Management for Patients Receiving Medication for Opioid Use Disorder: A Systematic Review and Meta-analysis.

The fourth wave of the US opioid epidemic and its implications for the rural US: A federal perspective.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/wps.21056

The future of psychopharmacology: a critical appraisal of ongoing phase 2/3 trials, and of some current trends aiming to de‐risk trial programmes of novel agents

In the early 2000s, increasing prevalence of psycho-stimulant (e.g., crack/cocaine, methamphetamine) use and related harms, including severe adverse health outcomes, was observed among - mostly marginalized - populations of persons using illicit drugs in North America, underscoring an urgent need for interventions options towards improved prevention and treatment. By about 2010, however, the ‘opioid crisis’, featuring unprecedented use and public health burden, had accelerated into full force in North America, largely muting attention to the psycho-stimulant issue until recently. Recent surveillance data on drug use and related mortality/morbidity from the present decade has documented a marked resurgence of psycho-stimulant use and harms especially in at-risk populations, commonly in direct combination with opioids, across North America, resulting in a ‘twin epidemic’ comprised of opioids and psycho-stimulants We briefly review select epidemiological data indicators for these developments from the United States and Canada; in the latter jurisdiction, related evidence has been less prevalent and systematic but corroborating the same trends. Evidently, the (widely ongoing) focus on the ‘opioid epidemic’ as a ‘mono-type’ drug problem has become an anachronism that requires urgent and appropriate correction. We then briefly consider existing, evidence-based options for – prevention and treatment – interventions targeting psycho-stimulant use and harms, which are substantially more limited and/or less efficacious than those available for problematic opioid use, while presenting major gaps and challenges. The observed resurgence of psycho-stimulants may, indirectly, relate to recent efforts towards curtailing (medical) opioid availability, thereby accelerating demand and supply for both illicit opioids and psycho-stimulants. The presently unfolding ‘twin epidemic’ of opioids and psycho-stimulants, combined with limited intervention resources, presents an acute challenge for public health and may crucially undermine actively extensive efforts to reduce opioid-related health harms in North America.

/pdf/resurgent-twin-or-silent-epidemic-a-select-data-overview-and-4c7kwqpcju.pdf

‘Resurgent’, ‘twin’ or ‘silent’ epidemic? A select data overview and observations on increasing psycho-stimulant use and harms in North America

Background The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. Methods We conducted this multisite, double-blind, two-stage, placebo-contr...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2020214

Sidarth Wakhlu

Papers

Bupropion and Naltrexone in Methamphetamine Use Disorder