CNS Stimulants: Buproprion (Wellbutrin)

Buproprion (Wellbutrin) (fig. 8.2) is an antidepressant that has shown efficacy in treatment of ADHD in young patients in controlled trials (Barrickman et al. 1995; Conners et al. 1996), but it carries a significant risk of seizures, particularly for patients with FXS who are predisposed to seizures (chap. 1). This medication is therefore not a drug of choice for patients with FXS (Tranfaglia 2000).

CNS Stimulants: Desipramine and Imipramine

Tricyclics are antidepressant medications with known efficacy in the treatment of ADHD primarily because the reuptake of norepinephrine is blocked (Pliszka et al. 1996). Among patients with tics and ADHD, desipramine is more effective than clonidine for treatment of both problems (Singer et al. 1995). There has been one published report of the use of a tricyclic, imipramine, in a patient with FXS (Hilton et al. 1991). This patient was a six-year-old boy who had a negative response to methylphenidate, but imipramine improved his hyperactivity, insomnia, and enuresis. Berry-Kravis (2000) found that approximately 50% of children with FXS have improved ADHD symptoms with a tricyclic, usually imipramine, but it is typically tried only after failure on a stimulant.

The cardiovascular side effects, specifically prolongation of conduction, are the main impediment to use, and several cases of unexplained sudden death have been reported with desipramine (Riddle et al. 1993). Cardiovascular monitoring with electrocardiograms (EKGs) are necessary with tricyclics, as outlined by Gutgesell et al. (1999). A report by Mezzacappa et al. (1998) showed that tricyclics decrease vagal tone, which is already reduced in children with FXS compared to controls (Boccia and Roberts 2000).

CNS Stimulants: Buspirone (Buspar)

Last, buspirone (Buspar), an anxiolytic agent that is a partial agonist at 5HT1A serotonin receptors in addition to stimulating dopamine and alpha-adrenergic systems, has been shown to be helpful in an open trial for treatment of ADHD (Malhotra and Santosh 1998). It has also been shown to be effective in treatment of anxiety and irritability in children with PDD or autism (reviewed by Buitelaar et al. 1998). We have not seen efficacy in treatment of ADHD in children with FXS, but buspirone can be helpful in treatment of anxiety, although it does not seem to be as effective as selective serotonin reuptake inhibitors (SSRIs), described below, in our experience.

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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