title: 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.
authors.affiliation: a Department of Psychiatry , Texas Tech Health Sciences Center Medical School at Permian Basin , Midland , TX , USA.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Jain
authors.affiliation: b Division of Early Phase Services, Worldwide Clinical Trials , Austin , TX , USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Stark
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004304:Dosage Forms; D004339:Drug Compounding / Q000379:methods; D004335:Drug and Narcotic Control / Q000379:methods / Q000458:organization & administration; D006801:Humans; D008774:Methylphenidate / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000517:prevention & control*
chemical_list: D000697:Central Nervous System Stimulants; D004304:Dosage Forms; D008774:Methylphenidate; D000661:Amphetamine
keywords: Attention-deficit/hyperactivity disorder; controlled-release; dose dumping; misuse; modified-release; stimulant