Electroencephalographic Signatures of Methylphenidate in ADHD: A Systematic Review and 10 Recommendations for Future Research.

Objective

Methylphenidate is the first-line treatment for ADHD, yet its neurocognitive mechanisms remain incompletely understood. Electroencephalography (EEG) has been used to examine methylphenidate's effects on brain function and has been proposed as a potential tool for monitoring treatment response. This systematic review addressed whether EEG can (a) clarify methylphenidate's neurocognitive mechanisms and (b) serve as a biomarker of treatment response.

Methods

A PRISMA-compliant systematic review (PROSPERO: CRD42024538039) searched six databases for English-language studies published after 1994. Included studies involved individuals with ADHD, used within-subject designs with acute methylphenidate administration, and collected resting-state or task-based EEG. Assessment of study quality and risk of bias assessment was conducted.

Results

Forty-four studies were included. The most consistent finding was an increase in P3 amplitude following methylphenidate administration, observed in eleven of twenty P3 studies. In contrast, there was little evidence to support effects on early sensory processing, movement planning or response monitoring event-related potentials. Findings from quantitative EEG and event-related spectral perturbation analyses were limited, with either no effect observed, or a paucity of studies in some frequency bands.

Discussion

Methylphenidate reliably increased P3 amplitude across tasks, suggesting an improvement in higher order cognitive functioning. However, the P3 does not meet criteria for a pharmacodynamic or surrogate endpoint biomarker in this context, and the current evidence does not support EEG as a treatment-response biomarker for MPH in ADHD. Based on our findings, we make 10 recommendations for future research in this area.