Impulsivity is also frequent. However, it is not more prevalent than in nonspecific mental retardation and significantly less prevalent than in Down syndrome (Walz and Benson 2002
). In one study, impulsivity was significantly less frequent in Angelman syndrome (27%) than in nonspecific moderate to profound mental retardation (60%) (Barry et al 2005
Distractibility and short attention span is frequent but has insufficiently been studied (Hersh et al 1981
; Pulsifer 1996
; Barry et al 2005
). It seems to be comparable with findings in moderate to profound intellectual disability (Barry et al 2005
), though one study documented shorter attention span and higher levels of distractibility in Angelman syndrome than Down syndrome, Prader-Willi syndrome, or nonspecific mental retardation (Walz and Benson 2002
). Among other factors, attention may be disrupted by seizure activity (Pelc et al 2008b
). Attention span has been noted to increase with age (Clayton-Smith 2001
Effect of management of problematic hyperactivity, impulsivity, and inattention has not been studied in patients with Angelman syndrome. Current approaches are mostly behavioral.
In some patients, neuroleptic (ie, antipsychotic) medication may be beneficial. Low dose neuroleptics (eg, risperi-done) may reduce both hyperactivity and impulsivity. Dosage varies according to the desired effect and may greatly differ from patient to patient. Neuroleptics have no significant positive effects on cognitive or attentional problems but may enhance them, particularly at higher doses. They may be associated with a number of side effects, including sedation and motor effects. In addition, propensity toward weight gain may limit the use of risperidone.
Drugs in ‘antidepressant’ classes may be useful in some patients. In our experience, tricyclic agents, such as amitriptylin, can be effective in reducing hyperactivity and impulsivity. They do not seem to improve attention. Cholinergic side effects may occur, such as dry mouth (which is usually not a problem given the spontaneous drooling) and gastrointestinal perturbations, including constipation. In a few patients, we found that selective serotonin reuptake inhibitors (we used fluoxetine) could reduce hyperactivity, impulsivity and anxiety. However, in one 6 year-old girl with a chromosome 15q11-q13 deletion, fluoxetine seemed to enhance impulsivity, hyperactivity and excitability. Potential interference with sleep quality and architecture (Pelc et al 2008b
) should be considered. The recent development of chronobiotic agents may be promising in this respect.
The effectiveness of psychostimulant drugs, such as methylphenidate, has been debated but no sound data are available. In our experience, these agents have not been useful in controlling behavioral problems or in increasing attention in patients with Angelman syndrome. In one personal case (Dan and Boyd 2005
), a 7 year-old boy with a chromosome 15q11-q13 deletion, methylphenidate precipitated a state of lethargy associated with generalized fast electroencephalographic activity (‘mu rhythm status’).
More recent drugs used in attention deficit/hyperactivity disorder, such as atomoxetin, have not been evaluated reliably in Angelman syndrome. In this context, it would appear particularly important to study medication with expected action on mood, anxiety, and attention.