Differential working memory changes following methylphenidate in medication-naive and medication-experienced adults...

The long-term impact of pharmacological treatment on cognitive function in adults with attention-deficit/hyperactivity disorder (ADHD), particularly whether benefits persist after treatment discontinuation, is not well understood. This study aimed to investigate whether prior medication history is associated with different patterns of cognitive change following methylphenidate (MPH) administration.

Thirty-six adults with ADHD (17 medication-naive, 19 medication-experienced) were assessed on five cognitive tasks, the multitasking test (MTT), reaction time (RTI), rapid visual processing (RVP), stop signal task (SST), and spatial working memory (SWM), from the Cambridge Neuropsychological Test Automated Battery baseline and following a period of clinically stable MPH treatment (Post). We used mixed-design ancovas to test for Time × Medication history interactions.

We found a significant interaction in the SWM task (6-box condition; q = 0.044). A sensitivity analysis excluding atomoxetine-experienced participants showed a preserved effect size but trend-level significance (q = 0.061). Post hoc analyses revealed that the medication-naive group's SWM performance significantly improved from baseline to Post, whereas the medication-experienced group, who exhibited a significantly better baseline performance, showed no change. Exploratory analyses suggested similar trends across the other SWM difficulty levels. No significant interactions were found for other tasks.

Two groups showed differential trajectories of change in the SWM task. Rather than reflecting a purely pharmacological effect, these patterns may involve a combination of baseline cognitive differences, learned cognitive strategies, and pre-existing individual characteristics. These preliminary findings highlight the importance of considering treatment history in clinical practice and research.