Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine has been shown to be effective at retaining people in treatment programs, decreasing illicit opioid use, decreasing rates of hepatitis B, and reducing all cause and overdose mortality. Unfortunately, barriers exist in accessing these lifesaving medications: users wishing to start buprenorphine therapy require a waivered provider to prescribe the medication, while some states have no methadone clinics. As such, users looking to wean themselves from opioids or treat their opioid dependence will turn to alternative agents. These agents include using prescription medications, like clonidine or gabapentin, off-label, or over the counter drugs, like loperamide, in supratherapeutic doses. This review provides information on the pharmacology and the toxic effects of pharmacologic agents that are used to treat opioid use disorder. The xenobiotics reviewed in depth include buprenorphine, clonidine, kratom, loperamide, and methadone, with additional information provided on lofexidine, akuamma seeds, kava, and gabapentin.
IMPORTANCE Opioid-reduction policies have been enacted by US states to address the opioid epidemic. Evidence of an association between policy implementation and decreased rates of pediatric opioid poisoning provides further justification for expanded implementation of these policies.OBJECTIVE To examine the association of 3 state-level opioid-reduction policies with the rate of opioid poisoning in children and adolescents. DESIGN, SETTING, AND PARTICIPANTSThis interrupted time series analysis used data from the National Poison Data System (NPDS), a database of poisoning information reported to poison control centers across the US. Individuals younger than 20 years who experienced poisoning associated with 1 or more prescription opioids from January 1, 2005, to November 30, 2017, were included. The analysis focused on 3 widespread policy interventions: the prescription drug monitoring program (PDMP), pain clinic legislation, and opioid prescribing guidelines. Data analysis was performed from January 30, 2020, to March 30, 2020.EXPOSURES Any opioid poisoning in individuals younger than 20 years that was reported to the NPDS. MAIN OUTCOMES AND MEASURESOpioid poisoning rates per million person-months before and after implementation of each of the 3 policies, overall and stratified by age (Յ4 years, 5-9 years, 10-14 years, and 15-19 years).RESULTS A total of 338 476 opioid poisoning incidences in children and young adults were reported to the NPDS within the study period. Of this study population, the mean (SD) age was 9.74 (7.15) years, and 179 011 (52.9%) were female. The implementation of a PDMP was associated with a reduction in the monthly rate of opioid poisoning in children and adolescents (-0.07 per million person-months; 95% CI, -0.09 to -0.04) in the postimplementation period. This reduction was observed for all age groups except for the 10-to 14-year age group (−0.03 per million person-months; 95% CI, −0.05 to 0.00). Pain clinic legislation was associated with an immediate reduction in opioid poisoning (-6.22 per million person-months; 95% CI, -8.98 to -3.47). This association was statistically significant across all ages except for the 4 years or younger group. Analysis of the association of implementation of opioid prescribing guidelines was limited because of insufficient follow-up data and did not show an immediate or monthly change in the rate of opioid poisoning. CONCLUSIONS AND RELEVANCEResults of this study suggest that certain state-level opioid-reduction policies were associated with decreases in pediatric opioid exposures across age groups. Further examination of the underlying mechanisms of these associations, including age group-specific outcomes, may expand and strengthen policies that reduce opioid poisoning, misuse, and overdoses in children and adolescents.
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