The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial
Ludger Tebartz van Elst1, Simon Maier1, Stefan Klöppel1
1From the Section for Experimental Neuropsychiatry, Clinic for Psychiatry and Psychotherapy, University Freiburg Medical Center, Hauptstr, Freiburg, Germany (Tebartz van Elst, Maier, Klöppel, Killius, Rump, Perlov); Freiburg Brain Imaging, University Freiburg Medical Center, Freiburg, Germany (Tebartz van Elst, Maier, Klöppel, Killius, Rump, Ebert, Berger); the Department of Neurology, University Freiburg Medical Center, Freiburg, Germany (Klöppel); the Clinical Trials Unit, University Freiburg Medical Center, Freiburg, Germany (Graf); the Central Institute for Mental Health, Mannheim, Germany (Sobanski); the Clinic of Psychiatry and Psychotherapy, University Freiburg Medical Center, Freiburg, Germany (Ebert, Berger, Matthies, Philipsen); the Department for Child and Adolescent Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany (Warnke); and the Department of Psychiatry and Psychotherapy, Karl Jaspers Clinic, Faculty of Medicine and Health Sciences, European Medical School, Carl von Ossietzky University Oldenburg, Oldenburg, Germany (Philipsen).
Background:
Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease.
Methods:
We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra.
Results:
We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase.
Limitations:
Detecting possible neurotoxic effects of methylphenidate might require a longer observation period.
Conclusion:
There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.
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