Psychiatric disorders in Prader-Willi syndrome: epidemiology and management

Although people with intellectual disabilities are at increased risk for psychiatric disorders, the type and rate of these problems differ between those with different causes for their retardation. In this paper, we review behavioural and psychiatric problems in persons with Prader-Willi syndrome, a disorder caused by a paternally derived deletion at chromosome 15(q11-q13) in about 70% of affected patients, and by maternal uniparental disomy in the majority of the remaining patients. In addition to the syndrome's characteristic hyperphagia and food seeking, individuals with Prader-Willi syndrome also have increased risks of nonfood, compulsive behaviours. These include skin picking, which is highly prevalent, as well as more variable rates of hoarding, redoing and concerns with symmetry, exactness, cleanliness, ordering and arranging. Relative to others with mental retardation, persons with Prader-Willi syndrome are at a marked increased risk for developing full-blown, obsessive-compulsive disorder. In addition, many people with Prader-Willi syndrome show increased rates of tantrums, oppositionality and aggression. Recent findings suggest that they also have an increased risk of psychotic disorder or affective illness with a psychotic component, especially young adult patients and those with the maternal uniparental disomy as opposed to paternal deletion. Dietary approaches include a reduced-calorie diet and increased physical activity, as well as close supervision around food and keeping food locked away. To date, neither CNS stimulants nor anorectic agents have been effective in treating hyperphagia, in part because hyperphagia in Prader-Willi syndrome is attributed to decreased satiation as opposed to increased hunger. Treatment for compulsivity and maladaptive behaviours include: behavioural programming; a structured, predictable routine; extra help with transitions; family support; and pharmacotherapy. Although formal drug studies have yet to be conducted, SSRIs have been effective in reducing skin picking, compulsivity and aggressive episodes in some individuals with Prader-Willi syndrome. Atypical antipsychotics have also proven helpful in persons with psychotic features or extreme aggression and impulsivity. Largely on the basis of case studies, the risks and benefits of these and other drugs in Prader-Willi syndrome are reviewed. Drug trials that move beyond case studies and that assess the relative efficacy of behavioural treatments alone or in combination with pharmacotherapy are sorely needed.