Long-acting stimulants: development and dosing.
Year: 2005
Type: article
Abstract: Until relatively recently, the choices of stimulant medications for children were limited. Amphetamines and immediate-release methylphenidate (MPH) have been used for several decades, but in their native “immediate release” (IR) formulations, both have rapid onsets and short durations of action, and must therefore be given at least twice daily for optimal clinical efficacy throughout the day. The challenge to the clinician using short-acting preparations was to find the optimum dosing regimen for each child—and dosing requirements could vary as much as sixfold between individual children.
After a morning dose of MPH, peak concentration (Cmax) is reached about 2 hours after dosing, and concentrations have declined by half approximately 2 hours later (T1/2). Higher doses will produce higher Cmax values, but do not affect the time of the peak (Tmax) or onset or T1/2. For several decades, it was assumed that the clinician merely had to find the Cmax that would produce the optimal clinical response 1 to 2 hours after dosing, and keep this constant throughout the day. Smaller doses were therefore used toward the end of the day; these were the “sculpted” dosing regimens of the early 1990s. For example, children in the MTA study who were treated with an average MPH dose received MPH 10 mg in the morning, 10 mg at noon, and 5 mg in the afternoon. However, after the 14-month treatment phase, compliance with drug treatment worsened considerably, in part because medicated children suffered teasing at the hands of their peers when called to the principal’s office to take noontime medication doses. The longer formulations then available included Ritalin SR® and Dexedrine® spansules. Neither medication provided coverage for the whole day, and the reasons for this were a mystery. Several manufacturers therefore embarked on the development of more effective once-daily medications in collaboration with investigators at the University of California at Irvine laboratory school (analogue classroom) using surrogate measures of drug efficacy.
Source: PubMed
Author: James M Swanson
Institution: University of California, Irvine
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W17113556