October 18, 2023
Modified release (MR) formulations of ADHD stimulant medications simplify adherence over immediate-release (IR) formulations, by only requiring a single dosing per day. They are also intended to reduce diversion to nonmedical usage and the development of drug abuse or dependency. Is there evidence they deliver on this promise?
There are 55 poison control centers distributed throughout the United States, and they all report through the National Poison Data System (NPDS).
A pair of researchers used the NPDS to obtain all 15,796 single-substance MR ingestion and single-substance 23,418 IR ingestion reported to poison control centers over the eleven years from January 1, 2007, through December 31, 2017. The medications were either amphetamine or methylphenidate-based.
IR ingestion was more commonly associated with more serious outcomes than were MR ingestion. No deaths were reported from MR stimulant ingestion, versus three deaths (a rate of one in 7,800 reports) from IR stimulant ingestion. While there were no observed differences between youth MR and IR ingestion about admission to critical care units, adult IR ingestion was more commonly admitted to a critical care unit than was adult MR ingestion. Moreover, adults were more commonly admitted to critical care units for both MR and IR ingestion than were youths.
Among youths, the vast majority of MR ingestion was unintentional, with only one in eleven attributed to intentions of suicide. Among adults, however, almost half were intentional, with just over a quarter attributed to intentions of suicide, and another one in six to intentional misuse.
Turning to IR ingestion, the vast majority were again unintentional among youths, with less than one in twelve attributed to suspected suicide attempts. But among adults, the majority were intentional, with almost one in three attributed to suspected suicide attempts, plus another one in five to intentional misuse.
More than four out of five IR ingestion among both youths and adults were of amphetamine medications. For MR ingestion, methylphenidate was most common in youths and amphetamine medications in adults, but only by slight margins.
The most commonly reported symptoms in adults and youths alike for both IR and MR ingestion were agitation, abnormally rapid heart rates, and high blood pressure.
The authors concluded, "More serious outcomes were associated with advancing age, intentional ingestion, and IR preparations. Higher rates of hyperadrenergic symptoms (tachycardia, agitation, and hypertension) were observed with IR ingestion."
On balance, this suggests MR formulations are safer, but both formulations are subject to abuse by a small minority of users.
Michael A. Darracq and Stephen L. Thornton, "Sustainedstimulation? Characteristics of modified release and immediate releasestimulant exposures reported to the national poison data system," ClinicalToxicology (2020), https://doi.org/10.1080/15563650.2020.1787428.