Do abuse deterrent opioid formulations work?

Richard C. Dart, MD, PhD; Janetta L. Iwanicki, MD; Nabarun Dasgupta, PhD; Theodore J. Cicero, PhD; Sidney H. Schnoll, MD, PhD

doi:10.5055/jom.2017.0415

Authors

Richard C. Dart, MD, PhD
Janetta L. Iwanicki, MD
Nabarun Dasgupta, PhD
Theodore J. Cicero, PhD
Sidney H. Schnoll, MD, PhD

DOI:

https://doi.org/10.5055/jom.2017.0415

Keywords:

hydrocodone, morphine, oxycodone, drug abuse, prescription drug abuse, abuse-deterrent formulation, misuse, FDA, systematic review

Abstract

Objective: We performed a systematic review to answer the question, “Does the introduction of an opioid analgesic with abuse deterrent properties result in reduced overall abuse of the drug in the community?”

Design: We included opioid analgesics with abuse deterrent properties (hydrocodone, morphine, oxycodone) with results restricted to the metasearch term “delayed onset,” English language, use in humans, and publication years 2009-2016. All articles that contained data evaluating misuse, abuse, overdose, addiction, and death were included. The results were categorized using the Bradford-Hill criteria.

Results: We included 44 reports: hydrocodone (n = 7), morphine (n = 5), or oxycodone (n = 32) with Food and Drug Administration-approved Categories 1, 2, or 3 abuse deterrent labeling. The data currently available support the Hill criteria of strength (effect size), consistency (reproducibility), temporality, plausibility, and coherence. There was insufficient or no information available for the criteria of biological gradient, experiment, and analogy. We also assessed confounding factors and bias, which indicated that both were present and substantial in magnitude.

Conclusions: Our analysis found that only oxycodone extended release (ER) had information available to evaluate abuse deterrence in the community. In Australia, Canada, and the United States, reformulation of oxycodone ER was followed by marked reduction in measures of abuse. The precise extent of reduced abuse cannot be calculated because of heterogeneous data sets, but the reported reductions ranged from 10 to 90 percent depending on the measure and the duration of follow-up.

Author Biographies

Richard C. Dart, MD, PhD

Director, Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, Colorado; Professor, Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Janetta L. Iwanicki, MD

Associate Medical Director, Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, Colorado; Assistant Professor, Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, Colorado

Nabarun Dasgupta, PhD

Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, Colorado

Theodore J. Cicero, PhD

Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri

Sidney H. Schnoll, MD, PhD

Vice President, Pharmaceutical Risk Management Services, Pinney Associates, Bethesda, Maryland

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