“Better than placebo” and “better than the same morning’s predose score” are different comparisons. A 2009 lisdexamfetamine laboratory-school study reported both, with different late-day results. The distinction helps prevent a time-course finding from becoming an overstated claim about continuous improvement.
How the study was organized
Children aged 6–12 with ADHD first underwent four weeks of open-label oral dose optimization at 30, 50 or 70 mg/day. The trial then used two one-week crossover periods of optimized lisdexamfetamine and placebo.
Of 129 enrolled children, 117 were randomized, 113 entered the intention-to-treat efficacy population and 111 completed the study. Safety observations came from the 129 exposed during optimization. These denominators serve different purposes and should not be interchanged.
The placebo-adjusted result
Classroom observers rated deportment and attention. Children also completed an individualized mathematics task measuring attempted and correct responses. Assessments occurred before dosing and at specified times from 1.5 through 13 hours afterward.
Lisdexamfetamine separated significantly from placebo on the primary deportment scale at all postdose assessments, including 13 hours. Mathematics outcomes also favored treatment at all assessed postdose times. The first sampled time was 1.5 hours; the study did not establish effects before that observation.
The predose comparison
In a post hoc analysis within the lisdexamfetamine condition, deportment improved significantly from predose at earlier observations. At 12 and 13 hours, scores were numerically worse than predose but not significantly different.
The placebo condition worsened from its predose score across the day. Consequently, an active-treatment score can resemble its own predose level and still be better than the placebo score measured at the same late time. These findings are compatible rather than contradictory.
Why the design limits interpretation
The late comparison does not establish a plasma amphetamine concentration, a pharmacokinetic cutoff or a universal 13-hour effect in every child. It reflects group behavior under a structured classroom protocol after dose optimization.
Adverse events were more common during optimization than the crossover phase; decreased appetite and insomnia were prominent. Some participants discontinued before randomization, meaning the crossover sample had already passed a treatment-selection stage.
How to state the conclusion
This historical trial supports placebo-adjusted classroom benefits through the final assessed time in its selected ADHD sample. It does not show that every outcome remained better than predose, that benefits continued after 13 hours or that the same timeline applies to driving. A careful description names the outcome, time and reference condition.
Scientific source
Wigal SB, Kollins SH, Childress AC, Squires L, for the 311 Study Group. A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. Child and Adolescent Psychiatry and Mental Health. 2009;3:17. doi:10.1186/1753-2000-3-17. Original commentary on the supplied paper.
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