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January 2008

Treating Behavioral Problems in Dementia
No drug is clearly efficacious for behavioral problems in dementia, and all are associated with significant risks.

Prolactin Elevation and Antipsychotics
Risperidone (Risperdal) seems to increase prolactin more than conventional and other second-generation antipsychotics; adjunctive aripiprazole (Abilify) may lower antipsychotic-induced hyperprolactinemia.

In Brief
Atomoxetine Effective for ADHD in Preschool Children; Excessive Body Weight Increases Risk of Dementia

Treating Adolescent Mania
Olanzapine (Zyprexa) effectively treats adolescent bipolar disorder but appears to cause harmful medical consequences in young patients.

Isotretinoin and Depression
Depression is a possible side effect of treatment with isotretinoin (Accutane and others).

In Brief

January 2008

Methylphenidate (Ritalin and others) showed modest, dose-dependent efficacy in preschool-aged children with attention deficit hyperactivity disorder (ADHD) in a large, multicenter, double-blind, controlled study (Greenhill et al. J Am Acad Child Adolesc Psychiatry 2006;45:1284-1293). During 1 year of open-label, maintenance treatment, however, it caused moderate to severe adverse events in almost one third of subjects (Wigal et al. J Am Acad Child Adolesc Psychiatry 2006;45:1294-1303). Common initial adverse events included insomnia, anorexia, weight loss, repetitive thoughts and behavior, and mood and behavioral disturbances. Insomnia and anorexia persisted duringlong-term treatment, and the other methylphenidate-related adverse effects continued to a lesser extent. There was also some evidence of growth retardation. Atomoxetine (Strattera), another medication approved by the U.S. Food and Drug Administration for treating ADHD in patients aged 6 years and older, was studied by Kratochvil and colleagues in younger children with this disorder (J Child Adolesc Psychopharmacol 2007;17:175-185). Nineteen boys and three girls, aged 5 to 6 years, received atomoxetine on an open-label basis for 8 weeks. Atomoxetine was flexibly dosed up to 1.8 mg/kg/day, and the final mean dose was 1.3 mg/kg/day. Parents were provided education on behavioral management. Subjects showed statistically significant improvements on all measures, including hyperactivity/impulsiveness, inattentiveness, total ADHD symptoms, and global assessments. The most commonly reported adverse events were mood lability, anorexia, and weight loss, which occurred in about half of atomoxetine-treated children.

Overweight and obese individuals have an increased risk of developing dementia. Whitmer and colleagues investigated whether there is a difference in the risk of developing Alzheimer's disease (AD) versus vascular dementia associated with high body weight as measured by body mass index (BMI) (Curr Alzheimer Res 2007;4:103-109). Over 10,000 participants aged 40 to 45 had a health exam between 1964 and 1968. An average of 36 years later, diagnoses of AD or vascular dementia were obtained from neurology visits. (Subjects diagnosed with general dementia from a primary care provider were excluded.) Compared with those who had a normal BMI (18.5 to 24.9) at midlife, those who were overweight (BMI ≥ 25 and < 30) had a twofold increase in risk of AD and vascular dementia. Those considered obese at midlife (BMI ≥ 30) had a 3.10-fold increase in risk of AD and a fivefold increase in risk of vascular dementia. All results were independent of age, education, race, sex, marital status, smoking, hyperlipidemia, hypertension, diabetes, ischemic heart disease, and stroke. The mechanism by which high body weight increases the risk of dementia is unknown.

Heather S. Hopkins