Predicting acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder: data from quantitative electroencephalography, event-related potentials, and a continuous-performance test

Geir Ogrim,^1–3 Knut A Hestad,^3,4 Jan Ferenc Brunner,^3,5,6 Juri Kropotov<sup>3,7,8

1</sup>Neuropsychiatric Unit, Østfold Hospital Trust, Fredrikstad, Norway; ²National Resource Center for ADHD, Tourettes' Syndrome and Narcolepsy, Oslo, Norway; ³Institute of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; ⁴Division of Mental Health, Innlandet Hospital Trust, Brumunddal, Norway; ⁵Department of Physical Medicine and Rehabilitation, St Olav's Hospital, Trondheim, Norway; ⁶Department of Neuroscience, NTNU, Trondheim, Norway; ⁷Institute of the Human Brain, Russian Academy of Sciences, Saint Petersburg, Russia; ⁸Department of Neuropsychology, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland

Background: The aim of this study was to search for predictors of acute side effects of stimulant medication in pediatric attention deficit/hyperactivity disorder (ADHD), emphasizing variables from quantitative electroencephalography (QEEG), event-related potentials (ERPs), and behavior data from a visual continuous-performance test (VCPT).
Methods: Seventy medication-naïve ADHD patients aged 7–16 years were tested with QEEG, including a go/no-go task condition (VCPT) from which behavior data and ERPs were extracted, followed by a systematic trial on stimulant medication lasting at least 4 weeks. Based on data from rating scales and interviews, two psychologists who were blind to the QEEG/ERP test results independently rated the patients as having no or small side effects (n = 37) or troublesome side effects (n = 33). We determined if the side effects were related to sex, age, IQ, ADHD subtype, comorbidities, clinical outcome, and variables in QEEG, ERPs, and VCPT.
Results: There was a moderate negative correlation between clinical outcome and side effects. Three variables were significantly associated with side effects in a multivariate logistic regression analysis. In the ERP independent component – contingent negative variation – which reflected action preparation and time evaluation, patients with high amplitudes (close to normal values) experienced more side effects than patients with lower amplitudes. A faster-than-normal reaction time in VCPT was associated with side effects, as was a high amplitude in an early ERP component (early visual independent component), reported to be influenced by attention, perceptual sensitivity, and anxiety.
Conclusion: The group with troublesome side effects had normal action-preparation electrical brain activity, a faster-than-normal reaction time, and an increased level of anxiety (measured by ERP) compared with the no side-effects group.

Keywords: ADHD, stimulants, side effects, QEEG, ERP, go/no-go test