Iron and attention deficit/hyperactivity disorder: what is the empirical evidence so far? A systematic review of the literature

Samuele Cortese Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, Child Study Center of the NYU Langone Medical Center, New York, NY, USA. [email protected]; Child Neuropsychiatry Unit, G. B. Rossi Hospital, Department of Life Science and Reproduction, Verona University, Verona, Italy; UMR_S INSERM U 930, ERL 3106, François-Rabelais University, Child Psychiatry Centre, University Hospital, Tours, France; Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, Child Study Center of the NYU Langone Medical Center, New York, NY, USA. [email protected]; Child Neuropsychiatry Unit, G. B. Rossi Hospital, Department of Life Science and Reproduction, Verona University, Verona, Italy; UMR_S INSERM U 930, ERL 3106, François-Rabelais University, Child Psychiatry Centre, University Hospital, Tours, France

Marco Angriman Child Neurology and Neurorehabilitation Unit, Department of Pediatrics, Central Hospital of Bolzano, Italy; Child Neurology and Neurorehabilitation Unit, Department of Pediatrics, Central Hospital of Bolzano, Italy

Michel Lecendreux Pediatric Sleep Center, National Reference Network for Orphan Diseases-Narcolepsy and Idiopathic Hypersomnia, CHU Robert-Debré, Paris VII University, Paris, France; Pediatric Sleep Center, National Reference Network for Orphan Diseases-Narcolepsy and Idiopathic Hypersomnia, CHU Robert-Debré, Paris VII University, Paris, France

Eric Konofal Pediatric Sleep Center, National Reference Network for Orphan Diseases-Narcolepsy and Idiopathic Hypersomnia, CHU Robert-Debré, Paris VII University, Paris, France; AP-HP, Child and Adolescent Psychopathology Unit, Robert Debré Hospital, Paris VII University, Paris, France; Pediatric Sleep Center, National Reference Network for Orphan Diseases-Narcolepsy and Idiopathic Hypersomnia, CHU Robert-Debré, Paris VII University, Paris, France; AP-HP, Child and Adolescent Psychopathology Unit, Robert Debré Hospital, Paris VII University, Paris, France

Abstract

The authors systematically reviewed evidence on iron status, as well as studies of iron supplementation, in individuals with attention deficit/hyperactivity disorder (ADHD). PubMed, Ovid, EMBASE and Web of Knowledge were searched on 4 July 2012. Quantitative appraisal of trials was performed using Jadad’s score. Most (n = 20) of the retrieved studies assessed an index of peripheral iron status (i.e., serum ferritin), with overall mixed results – that is, both significant and nonsignificant association between ADHD symptoms and serum ferritin levels. One MRI study reported significantly lower indices of thalamic iron in ADHD versus comparison subjects. Two trials, an open-label and a pilot randomized placebo-controlled study with high Jaded score (4), showed improvement in some but not all measures of ADHD symptoms. Three studies showed that children with ADHD plus sleep disorders, in particular restless legs syndrome, are at risk of iron deficiency. Finally, two studies suggested that iron deficiency might decrease the effectiveness of psychostimulant treatment. The authors discussed how the field could move from initial research mainly focused on serum ferritin towards a more comprehensive and translational investigation of iron in ADHD, with the potential to inform clinical practice in terms of screening and treating iron deficiency in individuals with ADHD.

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Financial & competing interests disclosure

S Cortese served as scientific consultant for Shire Pharmaceuticals from June 2009 to December 2010. He received support to attend meetings from Eli Lilly and Co. in 2008 and from Shire in 2009–2010. M Lecendreux has received consulting fees, has been on advisory boards and has been a speaker for Cephalon, UCB, Shire and Eli Lilly. In the past year, E Konofal has received consulting fees and has been on advisory boards for Pierre Fabre, Shire, UCB, Janssen-Cilag and Pharmacosmos. In previous years, E Konofal has received consulting fees, has been on advisory boards and has been a speaker for UCB, Janssen-Cilag, GlaxoSmithKline and Vifor. M Angriman reports no competing interests.

No writing assistance was utilized in the production of this manuscript.

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Iron and attention deficit/hyperactivity disorder: what is the empirical evidence so far? A systematic review of the literature

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