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CNS Stimulants: Methylphenidate (Ritalin)
and Dextroamphetamine (Dexedrine; Adderall)
Although methylphenidate has demonstrated efficacy (Barkley et al. 1991; MTA 1999a, 1999b), there is evidence that children with mental retardation have an increased number of side effects with
methylphenidate, compared to normal-IQ children with ADHD. These side effects are worse at higher doses, and they include an increase in irritability, a decrease in verbalizations, social withdrawal, or an increase in stereotypic
behavior, such as finger picking (Gadow and Pomeroy 1990; Handen et al. 1991; Arnold 1993; Gadow et al. 1992; Handen et al. 2000).
The two stimulants that are most commonly used are methylphenidate (Ritalin) and dextroamphetamine (Dexedrine; Adderall). Adderall is a mixture of four different dextro- and levoamphetamine salts that
have a longer half-life than methylphenidate and less of a rebound when the medication wears off (Swanson et al. 1998; Pelham et al. 1999). Controlled studies have demonstrated efficacy in treatment of ADHD, and once-a-day dosing
with Adderall is comparable to twice-a-day dosing with short-acting methylphenidate (Manos et al. 1999; Pliszka et al. 1996).
Experience in FXS is limited and includes a double-blind crossover trial of methylphenidate and dextroamphetamine compared to placebo in 15 prepubertal boys with FXS (Hagerman et al. 1988). Ten were
clinical responders to stimulants with improvements in attention span and socialization skills. Seven were improved on methylphenidate, and two were improved on dextroamphetamine. A subsequent trial of Adderall in children with FXS
demonstrated only a 50% response rate because of side effects, including irritability and an increase in anxiety (Riley et al. 2000). Pemoline (Cylert) is an alternative long-acting stimulant medication (fig. 8.1) and has been
associated with less irritability and rebound than has methylphenidate or dextroamphetamine in anecdotal experience with FXS (Hagerman 1996), but reports of rare liver failure, which appears to be an autoimmune process, have
curtailed its use (Rosh et al. 1998).
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This article is not intended to give medical advice for individual cases. Any change in medical treatment
should be done in consultation with appropriate medical personnel. This article is written for medical professionals. Some of the terms will be unfamiliar to those who are not trained in medical fields.
*This article is from the chapter on treatment in the 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research edited
by Randi Jenssen Hagerman, M.D. and Paul Hagerman, M.D., Ph.D., to be published May 2002. It is included with permission from The Johns Hopkins University Press. References to other chapters refer to chapters in
the book which are not included as part of this website.
The complete 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research can be ordered from the National Fragile X Foundation by calling
1-800-688-8765 or from The Johns Hopkins University Press at 1-800-537-5487.
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Medical Follow-up Pharmacotherapy Future Prospects
Outline Medications Medical Conditions
References: A, B, C, D, EF, G, H, IJ, K, L, M, NOP, QR, S, T, UVWXYZ
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