title: The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Detecting possible neurotoxic effects of methylphenidate might require a longer observation period.
  
  
  
  There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD.
authors: From 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).
authors: Ludger
authors: L
authors: Tebartz van Elst
authors: From 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).
authors: Simon
authors: S
authors: Maier
authors: From 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).
authors: Stefan
authors: S
authors: Klöppel
authors: From 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).
authors: Erika
authors: E
authors: Graf
authors: From 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).
authors: Carola
authors: C
authors: Killius
authors: From 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).
authors: Marthe
authors: M
authors: Rump
authors: From 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).
authors: Esther
authors: E
authors: Sobanski
authors: From 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).
authors: Dieter
authors: D
authors: Ebert
authors: From 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).
authors: Mathias
authors: M
authors: Berger
authors: From 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).
authors: Andreas
authors: A
authors: Warnke
authors: From 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).
authors: Swantje
authors: S
authors: Matthies
authors: From 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).
authors: Evgeniy
authors: E
authors: Perlov
authors: From 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).
authors: Alexandra
authors: A
authors: Philipsen
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000628:therapy*; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000627:therapeutic use*; D009929:Organ Size; D011613:Psychotherapy; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate