Brain activity predicts response to Ritalin in ADHD

Jul 29, 2018 - neurocare group

Results from the large multicenter iSPOT-A study have been published which not only suggest gender differences in brain activity in ADHD but also activity which may or may not respond to Psychostimulants

Today results from the large multicenter iSPOT-A study were published in European Neuropsychopharmacology, demonstrating that brain activity can assist in predicting response to Ritalin in male adolescents with ADHD. In addition, this study clearly demonstrated gender differences in brain activity, where brain activity only predicted Ritalin response in males and not in females with ADHD. No differences in brain activity were found between children with and without ADHD, further demonstrating the value of brain imaging in prognosis rather than diagnosis.An international group of researchers including researchers from Research Institute Brainclinics, Brainresource, University of Sydney, Utrecht University, Stanford School of Medicine, Westmead Hospital and Radboud University Nijmegen published results from the international multicenter iSPOT-A study (international Study to Predict Optimized Treatment in ADHD). This study recruited 336 children and adolescents with ADHD who were subsequently treated with methylphenidate and 158  children and adolescents without ADHD, and is the largest brain imaging study in ADHD focused on predicting response to Ritalin.

Researchers measured brain electrical activity, also called EEG or QEEG before treatment and clinical measures before and after treatment. When looking at differences in brain activity between participants with and without ADHD, no differences  in brain activity were found. However, a clear difference was found between adolescents that did and did not  respond to treatment with methylphenidate, albeit only for males, suggesting sex specific differences in the etiology of ADHD.

Predicting Ritalin response in ADHD

The main aim of the study was to investigate if brain-based ‘biomarkers’, such as measured with QEEG, could predict treatment response. This study demonstrated that a single biomarker – namely Alpha Peak Frequency (APF) – was able to predict treatment response to methylphenidate for male adolescents. This study replicates and extends an earlier pilot-study that already suggested that this biomarker could predict treatment non-response (Arns et al., 2008).

“… the most striking aspect of the outcome of the study is that no difference in brain activity a measured using EEG was found between patients with and without ADHD, whereas brain activity was clearly different between male adolescents with ADHD that did and did not respond to methylphenidate, further demonstrating that brain imaging is better used for ‘prognosis’ and not for ‘diagnosis’. This finding offers hope and can prospectively be used to develop new treatments that are specifically aimed at this biomarker…’ said Martijn Arns, first author on the study.

This biomarker – possibly used in conjunction with other biomarkers identified in the iSPOT studies – could help assist in a future of Personalized Medicine or Precision Medicine, where biomarkers are used to objectively guide patients to the optimal treatment and can aid in discovery of new treatments aimed at this subgroup.


Arns, M., Vollebregt, M.A., Palmer, D., Spooner, C., Gordon, E., Kohn, M., Clarke, S., Elliott, G., Buitelaar J.K. (2018).
Electroencephalographic biomarkers of methylphenidate response in Attention- Deficit/Hyperactivity Disorder.

European Neuropsychopharmacology. doi: 10.1016/j.euroneuro.2018.06.002Arns, M., Gunkelman, J., Breteler, M., & Spronk, D. (2008). EEG phenotypes predict treatment outcome to stimulants in children with ADHD. Journal of Integrative Neuroscience, 7(3), 421-38.

Click here to view the press release


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