Attention Deficit Hyperactivity Disorder (ADHD) is considered to be the most prevalent
psychiatric disorder of childhood, affecting 3% to 5% of school-aged children around
the world (
Goldman et al., 1998
). In 1998, the National Institute of Mental Health (NIMH) and the National Institute
on Drug Abuse (NIDA) were the lead organizations to sponsor an National Institutes
of Health (NIH) Consensus Conference on ADHD (
National Institutes of Health, 1998
), which highlighted controversies about diagnosis and treatment. Controversies were
especially noted regarding the use of stimulant medications (methylphenidate and amphetamine),
which have been the mainstay of clinical treatment for more than 50 years. Specifically,
since methylphenidate (MPH) and amphetamine have reinforcing effects (
Kollins et al., 2001
), there was some concern that chronic stimulant medications may induce changes in
the brain that may predispose individuals to drug abuse (
National Institutes of Health, 1998
). Though the literature, with over 150 randomized-controlled trials (
Spencer et al., 1996
) including some that are long-term trials such as the multimodal treatment study
of ADHD (MTA) (
MTA Cooperative Group, 1999
), demonstrates robust efficacy and safety of the stimulants when taken as prescribed,
there are still questions about adverse neural or behavioral consequences of long-term
psychostimulant treatment in children. In such a situation, preclinical studies may
play an important role in directing inquiries about the long-term safety of clinical
treatments. However, most preclinical studies in the literature have used very large
doses of stimulants (10-50 mg/kg, intraperitoneal [IP]) that have questionable relevance
to clinical treatment (.3-1.0 mg/kg, oral [PO]) and most have been done in adult animals
precluding an assessment of effects on the developing brain.To read this article in full you will need to make a payment
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© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
