Systematic Review: Medication Effects on Brain Intrinsic Functional Connectivity in Patients With Attention-Deficit/Hyperactivity Disorder

Objective: Resting-state functional magnetic resonance imaging (R-fMRI) studies of the neural correlates of medication treatment in attention-deficit/hyperactivity disorder (ADHD) have not been systematically reviewed. Our objective was to systematically identify, assess and summarize within-subject R-fMRI studies of pharmacological-induced changes in patients with ADHD. We critically appraised strengths and limitations, and provide recommendations for future research.

Method: Systematic review of published original reports in English meeting criteria in pediatric and adult patients with ADHD up to July 1, 2020. A thorough search preceded selection of studies matching prespecified criteria. Strengths and limitations of selected studies, regarding design and reporting, were identified based on current best practices.

Results: We identified and reviewed 9 studies (5 pediatric and 4 adult studies). Sample sizes were small-medium (16-38 patients), and included few female participants. Medications were methylphenidate, amphetamines, and atomoxetine. Wide heterogeneity was observed in designs, analyses and results, which could not be combined quantitatively. Qualitatively, the multiplicity of brain regions and networks identified, some of which correlated with clinical improvements, do not support a coherent mechanistic hypothesis of medication effects. Overall, reports did not meet current standards to ensure reproducibility.

Conclusion: In this emerging field, the few studies using R-fMRI to analyze the neural correlates of medications in patients with ADHD suggest a potential modulatory effect of stimulants and atomoxetine on several intrinsic brain activity metrics. However, methodological heterogeneity and reporting issues need to be addressed in future research to validate findings which may contribute to clinical care. Such a goal is not yet at hand.