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Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity

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Abstract

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.

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Abbreviations

AAPCC NPDS:

American Association of Poison Control Centers’ National Poison Data System

ADHD:

Attention-deficit hyperactivity disorder

BUP:

Buprenorphine and buprenorphine/naloxone

CNS:

Central nervous system

COWS:

Clinical Opiate Withdrawal Scale

CYP:

Cytochrome P450

DEA:

Drug Enforcement Agency

ECG:

Electrocardiogram

EDDP:

2-Ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine

FDA:

Food and Drug Administration

GABA:

γ-Amino butyric acid

hERG:

Human ether-a-go-go-related gene

I-1:

Imidazoline-1

IKr :

Potassium rectifier channel

IV:

Intravenous

MAT:

Medication-assisted treatment

MME:

Morphine milligram equivalents

OUD:

Opioid use disorder

QTcF:

Fridericia rate-corrected QT

P-gp:

P-glycoprotein

RADARS:

Researched Abuse, Diversion, and Addiction-Related Surveillance

TdP:

Torsades de pointes

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Authors and Affiliations

  1. Harvard Medical Toxicology Program, Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA

    Michael S. Toce, Peter R. Chai, Michele M. Burns & Edward W. Boyer

  2. Division of Emergency Medicine, Department of Medicine, Boston Children’s Hospital, Boston, MA, USA

    Michael S. Toce, Michele M. Burns & Edward W. Boyer

  3. Division of Medical Toxicology, Department of Emergency Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Peter R. Chai & Edward W. Boyer

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Dr. Boyer is supported by the National Institutes of Health 1K24DA037109.​ Dr. Chai is supported by the National Institutes of Health K23DA044874. Dr. Burns is the Pediatric Toxicology Section Editor for UpToDate®. No funding was provided for the production of this manuscript.

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Toce, M.S., Chai, P.R., Burns, M.M. et al. Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity. J. Med. Toxicol. 14, 306–322 (2018). https://doi.org/10.1007/s13181-018-0685-1

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  • DOI: https://doi.org/10.1007/s13181-018-0685-1

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