A laboratory-classroom trial found symptom and math-task benefits for a formulation containing equal proportions of d- and l-amphetamine. Because it compared the complete formulation with placebo, it did not isolate the contribution of either enantiomer.
Childress and colleagues enrolled 107 children aged 6–12 years with ADHD. After eight weeks of open-label dose optimization, 97 were randomized to receive racemic amphetamine sulfate and placebo in opposite sequences during a two-week double-blind crossover phase.
The usual regimen included two daily doses, but only the morning dose was given on laboratory-classroom assessment days. This detail matters when interpreting the observed duration: the classroom findings concern those single-morning-dose test days, rather than direct observation of every ordinary day on the usual regimen.
The primary outcome was the combined classroom-behavior rating at two hours after dosing. It significantly favored racemic amphetamine. Ratings also favored active treatment at every scheduled postdose assessment, from 45 minutes through ten hours. Math problems attempted and correctly completed likewise improved relative to placebo.
These results establish benefit on the measured scales and tasks under the study conditions. The first and last assessment times delimit the observation window; they do not identify the exact moment effects began or ended for each child. Significant findings at group level also do not imply identical duration in every participant.
Neither isolated d-amphetamine nor isolated l-amphetamine was a treatment arm. The results therefore cannot determine that the enantiomers contribute equally, that either alone would produce the same duration, or that another amphetamine formulation is equivalent.
Prior open-label optimization and exclusion of substantial comorbidities restrict generalization. Common open-label adverse events included appetite loss, abdominal pain, irritability and headache. The study was industry funded. This therapeutic classroom evidence is distinct from analytical identification of amphetamine isomers in a specimen and from evaluation of driving impairment.
Read our analysis of racemic methamphetamine and simulated driving.
The Efficacy and Safety of Evekeo, Racemic Amphetamine Sulfate, for Treatment of Attention-Deficit/Hyperactivity Disorder Symptoms: A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled Crossover Laboratory Classroom Study. doi:10.1089/cap.2014.0176.