Adverse events were less frequent during the randomized classroom phase of a lisdexamfetamine trial than during its preceding dose-optimization phase. That pattern does not, by itself, prove that adverse effects disappeared with time.
The human trial enrolled children aged 6–12 years with ADHD. Four weeks of open-label dose optimization preceded a randomized, double-blind crossover comparing optimized lisdexamfetamine with placebo. Of 117 randomized participants, 111 completed the study.
During optimization, decreased appetite was reported in 47% and insomnia in 27%. Their reported frequencies during the crossover were 6% and 4%, respectively. These percentages belong to different phases, exposure periods and treatment conditions.
Participants reaching randomization had already experienced treatment and dose selection. Differences in who remained, the duration of observation and adjustment of doses can influence adverse-event frequencies. The phase comparison did not randomize participants to develop tolerance or establish its mechanism.
The crossover demonstrated improvements over placebo on classroom behavior and math measures at scheduled postdose assessments. Those efficacy comparisons are stronger evidence for their specific question than an uncontrolled comparison of adverse-event percentages across phases.
The study was industry funded and involved a selected pediatric ADHD population. It cannot estimate uncommon long-term harms or show that an event absent during a brief phase cannot occur later. An optimized regimen is also different from unrestricted nonmedical use.
The useful safety conclusion preserves both periods: appetite and sleep complaints were common during optimization, while fewer events were reported during the shorter crossover. These observations concern clinical reporting, not measured blood amphetamine levels or an individual impairment threshold.
See benefit and tolerability in another pediatric amphetamine trial.
A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. doi:10.1186/1753-2000-3-17.