Safety and efficacy considerations due to misuse of extended-release formulations of stimulant medications

ABSTRACT

Amphetamine or methylphenidate are first-line options for treating attention-deficit/hyperactivity disorder (ADHD). Deviations from suggested routes of administration such as crushing, chewing, intravenous administration, or snorting stimulant medication may alter the release rate, absorption, and bioavailability of the active drug. Additionally, the pharmacokinetic (PK) profiles of extended-release formulations of certain medications (e.g., some opioids) are known to be dangerously altered when consumed with alcohol; specifically, there is an unintended, rapid release of a significant portion of the drug (dose dumping). In vitro data suggest some extended-release stimulants dose dump in the presence of alcohol, which is of concern because the ADHD patient population is at risk for alcohol abuse. This article reviews the available scientific literature concerning modifications to routes of administration that may alter PK properties of stimulant-based medication for treating ADHD. These modifications are of clinical interest because they may pose safety hazards and affect efficacy. Electronic databases were searched for appropriate studies using relevant search terms. The misuse and abuse potential for stimulants and the efforts to prevent misuse are also discussed. Future research should be focused on determining the PK ramifications of stimulant misuse, along with developing new formulations with abuse-deterrent properties.

KEYWORDS:

• Attention-deficit/hyperactivity disorder
• stimulant
• controlled-release
• modified-release
• misuse
• dose dumping

Declaration of interest

Writing and editorial support was provided by Jennifer Tyson, PhD; and Liqing Xiao, PhD; of AlphaBioCom, LLC, and funded by Neos Therapeutics, Inc. J Stark reports employment by Worldwide Clinical Trials. R Jain reports research support from Eli Lilly and Company and Shire; and speaker’s bureau fees from Eli Lilly and Company, Shire, Rhodes Pharmaceuticals, and Neos Therapeutics Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This article was funded by Neos Therapeutics Inc.