Lisdexamfetamine improved a repeated workplace-style math-performance measure in adults with ADHD across tested times from two to fourteen hours after dosing. That finding concerns a selected clinical population and a defined task, rather than unrestricted enhancement in healthy workers.
Wigal and colleagues first used four weeks of open-label dose optimization with 30–70 mg daily lisdexamfetamine. Participants then entered a two-week randomized, double-blind, placebo-controlled crossover phase. The medication is a prodrug that supplies active d-amphetamine.
Of 127 randomized participants, 105 were included in the intention-to-treat population and 103 completed the study. The distinction between those denominators is important when reporting the trial.
The Permanent Product Measure of Performance combined the number of math problems attempted and answered correctly. Lisdexamfetamine produced significantly higher average post-dose total scores than placebo, with a least-squares mean difference of 23.4 and a 95% confidence interval of 15.6–31.2.
Differences were significant at the measured post-dose times from two through fourteen hours. Those endpoints establish benefit at sampled times. They do not locate the exact onset before two hours or the exact offset after fourteen hours.
A simulated workplace provides standardized demands, but it does not reproduce every real job, interpersonal task or safety-critical activity. Prior dose optimization also means the randomized comparison followed an initial treatment-selection period rather than testing an unselected first dose in all applicants.
During optimization, common treatment-emergent events included reduced appetite, dry mouth, headache and insomnia. Low event frequencies in the later crossover phase do not negate those earlier observations or establish universal tolerability.
The trial demonstrates a measured therapeutic effect under its protocol. It does not establish that any positive amphetamine result indicates either impairment or improved functioning. Medication history, actual task demands and case-specific observations remain necessary.
Related reading: Selected performance improvements in human methamphetamine experiments.