Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence |
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| Authors: | Cleo L. Crunelle Wim van den Brink Dick J. Veltman Katelijne van Emmerik-van Oortmerssen Geert Dom Robert A. Schoevers Jan Booij |
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| Affiliation: | 1. Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;2. Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;3. Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium;4. Department of Psychiatry, Vrije Universiteit Medical Center, Amsterdam, The Netherlands;5. Arkin Mental Health and Addiction Treatment Centre, Amsterdam, The Netherlands;6. Department of Psychiatry, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands;1. Laboratory of the Limbic System, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw, Poland;2. Department of Animal and Human Physiology, University of Gdansk, 59 Wita Stwosza St., 80-308 Gdansk, Poland;1. Inserm, U1061, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier F-34093, France;2. Université Montpellier1, Montpellier F-34000, France;3. Cancer & Disease Epigenetics, Murdoch Children''s Research Institute, Flemington Road Parkville, 3052 Victoria, Australia;4. Inserm, U897, Université Bordeaux 2, Bordeaux F-33000, France;5. CHRU Dijon, Centre Mémoire Ressources et Recherche, Dijon F-21033, France;6. Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom;7. Inserm U1018, Université Paris Sud 11, UMRS 1018, F-94807 Villejuif, France;1. Hadassah Medical School, Hebrew University, Jerusalem, Israel;2. Research and Psychiatry Departments, Ezrath Nashim–Herzog Memorial Hospital, Jerusalem, Israel;1. Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;2. Psychiatry Research Unit, Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;3. Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel;4. Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel;5. Institute of Drug Research, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel;1. Centre for Psychiatric Research, Aarhus University Hospital, Denmark;2. Protein Laboratory, Rigshospitalet University Hospital, Denmark;1. Department of Psychology, University of Bern, 3000 Bern, Switzerland;2. National Institute of Mental Health, Magnetic Resonance Spectroscopy Core, National Institutes of Health, Bethesda 20892, USA;3. Salt Lake City Veterans Affairs Medical Center and Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, USA;4. National Institute of Mental Health, Section on Magnetic Resonance Spectroscopy, National Institutes of Health, Bethesda, MD 20892, USA;5. Psychiatric University Hospital, University of Bern, Bolligenstrasse 111, 3000 Bern 60, Switzerland |
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| Abstract: | Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [123I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients.This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127. |
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| Keywords: | Attention deficit hyperactivity disorder Cocaine addiction Dopamine transporter Methylphenidate SPECT Substance use disorder |
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