A study can find no deterioration on selected tests without establishing that a medicine carries no cognitive risk. Coghill and colleagues’ 2018 report is a useful example: its primary purpose was cognitive monitoring during prolonged lisdexamfetamine exposure, while its design could not isolate treatment benefits.
Who was followed?
The study enrolled 314 children and adolescents aged 6–17 with ADHD. All received open-label, dose-optimized oral lisdexamfetamine dimesylate, 30, 50 or 70 mg/day, for up to 104 weeks. Lisdexamfetamine is a prodrug of d-amphetamine; the reported milligram doses refer to the prodrug formulation.
Only 191 participants, 60.8%, completed the study. Withdrawal by participants and adverse events were prominent reasons for discontinuation. About 39.5% had participated in a previous lisdexamfetamine study, so the cohort was not wholly treatment-naive.
Which cognitive outcomes were measured?
Four computerized CANTAB tasks assessed delayed matching, spatial working memory, stopping responses and reaction time. The investigators prospectively defined key variables and treated group mean percentage changes exceeding 5% as potentially clinically significant.
No key variable showed potentially clinically significant deterioration under that rule. Some measures improved: spatial working-memory between-search errors declined by 22.8% at six months, while stop-signal reaction time declined by 18.9%. These are changes in test performance, not percentages of children cured or protected from harm.
Why the last assessment is not always a two-year result
The report also used the last on-treatment assessment. That observation may precede week 104 for a participant who leaves early. It should not be described as a complete two-year examination of all 314 children.
Attrition can affect which participants contribute later results. Group averages can also conceal individual deterioration, and four tasks cannot cover every cognitive, emotional or functional outcome.
Did the medicine cause improvement?
There was no placebo or untreated comparison group. Development over two years, repeated-test familiarity, changing symptoms and treatment selection could contribute to score changes. The authors specifically identified the difficulty of separating treatment effects from maturation and practice.
The study therefore supports the narrower historical conclusion that the monitored group did not show the predefined pattern of deterioration on these selected measures. It does not establish risk-free use, enhancement in people without ADHD or an individual’s fitness to drive. The work was industry sponsored, a relevant feature when evaluating the overall evidence.
Scientific source
Coghill DR, Banaschewski T, Bliss C, Robertson B, Zuddas A. Cognitive Function of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate. CNS Drugs. 2018;32:85–95. doi:10.1007/s40263-017-0487-z. Original commentary on the supplied paper.
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