Psychopharmacologic interventions for fragile X: Prader-Willi, Angelman's syndrome

Pediatric News, Feb, 2004 by Ben Van Houten

SAN DIEGO -- Considerable progress has been made in understanding some of the unique psychopharmacological responses in disorders such as fragile X syndrome, Prader-Willi syndrome, and others, Dr. Randi Hagerman said at a meeting sponsored by the Los Angeles Pediatric Society.

But because these disorders have multiple component problems, the use of combined psychopharmacologic intervention is common and appears to be the most efficacious for the patient.

In addition, the synergistic effect of medication with additional therapies is a fertile area for future research, said Dr. Hagerman, who holds the Tsakopoulos-Vismara Chair in Pediatrics and is the medical director of the Medical Investigation of Neurodevelopmental Disorders (M.I.N.D.) Institute at the University of California, Davis.

* Fragile X syndrome. This is the most common inherited form of mental retardation, and can cause a spectrum of cognitive and behavioral problems. Dr. Hagerman reported that guanfacine HC1 (Tenex) and clonidine (Catapres) are often used in the preschool period for the treatment of hyperactivity and hyperarousal. The dosage of clonidine is low initially, and for preschoolers is often only one-quarter of a o. 1-mg tablet twice per day. For school-aged children, that dosage can be increased

Stimulant medication can be helpful in treating hyperactivity in children with fragile X syndrome (FXS) who are younger than 5 years, although stimulants are more commonly helpful in children aged 5 or older. The response rate is typically 65%, she said.

Other stimulant medications shown to be successful are Adderall and Concerta--however, children with FXS can be extra sensitive to the side effects of stimulant medications, such as social withdrawal and a decrease in verbalizations.

Alternate medications for treatment of attention-deficit hyperactivity disorder (ADHD) in FXS include Strattera (atom-oxetine) and amantadine, an antiviral agent that stimulates the dopamine system to improve attention and concentration.

A core behavioral problem in those with FXS is anxiety, which can lead to aggression. Selective serotonin reuptake inhibitors are helpful in treating this problem. Specifically, fluoxetine (Prozac) can be helpful, said Dr. Hagerman.

* Prader-Willi syndrome. Treatment of Prader-Willi syndrome should include a multidisciplinary approach for the severe hypotonia in infancy and the hyperphagia that develops after age 2 years, she said. The most common medications used are fluoxetine or other selective serotonin reuptake inhibitors. In addition, endocrine therapy, such as growth hormone replacement, has been shown to be helpful for growth and pubertal development in patients with Prader-Willi syndrome.

* Angelman's syndrome. In this syndrome, the most significant problems are seizures, sleep disturbances, and severe hyperactivity. Valproic acid (Depakene) is helpful for seizures. Most patients with Angelman's syndrome also have sleep problems, and medications such as melatonin or clonidine can be helpful. Melatonin is helpful in improving sleep in approximately 80% of individuals with developmental disabilities, Dr. Hagerman said.

* Smith-Magenis syndrome. The use of multiple medications for Smith-Magenis is typical, due to the extreme severity of the behavioral difficulties, she said. An intensive behavioral program is recommended, along with stimulant medications, atypical antipsychotics, or mood stabilizers.