Methylphenidate improves weight control in childhood brain tumor survivors with hypothalamic obesity

Authors: HORNE, VINCENT - Texas Children'S Hospital; BIELAMOWICZ, KEVIN - Arkansas Children'S Hospital; NGUYEN, JESSICA - Baylor College Of Medicine; HILSENBECK, SUSAN - Baylor College Of Medicine; HOLLY, LINDSAY - Baylor College Of Medicine; SONABEND, RONA - Baylor College Of Medicine; WOOD, ALEXIS - Baylor College Of Medicine; OKCU, FATIH - Baylor College Of Medicine; SISLEY, STEPHANIE - Baylor College Of Medicine

Submitted to: Pediatric Blood and Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/14/2020
Publication Date: 5/8/2020
Citation: Horne, V., Bielamowicz, K., Nguyen, J., Hilsenbeck, S., Holly, L., Sonabend, R., Wood, A., Okcu, F., Sisley, S. 2020. Methylphenidate improves weight control in childhood brain tumor survivors with hypothalamic obesity. Pediatric Blood and Cancer. e28379. https://doi.org/10.1002/pbc.28379.
DOI: https://doi.org/10.1002/pbc.28379

Interpretive Summary: Obesity which is caused by damage to the brain after brain surgery (hypothalamic obesity) does not have any widely recommended treatment. This is unfortunate because it is unrelenting and is a significant risk for other diseases like diabetes and high blood pressure. Thus, finding a treatment which can curb weight gain would be significantly beneficial for these children. Stimulants, such as methylphenidate, are commonly used in pediatric patients with attention deficit disorder. These medications are safe in pediatrics and commonly have a side effect of decreased food intake. Thus, methylphenidate is an intriguing option for treating patients with hypothalamic obesity. Previous studies have shown that methylphenidate may be useful for treating weight gain in patients with hypothalamic obesity in the short term. However, no study has investigated the use of this medication over multiple years of therapy. In this study, we found that patients at Texas Children's Hospital with hypothalamic obesity treated with methylphenidate had less weight gain while on treatment. Additionally, we found that methylphenidate was effective up to 5 years of treatment. Half of the patients had mild side effects. Thus, our research shows that methylphenidate might be a useful first-line treatment for patients who have hypothalamic obesity. This work is important as it is the first study to show long-term effectiveness of methylphenidate to treat obesity in patients after brain surgery.

Technical Abstract: Hypothalamic obesity causes unrelenting weight gain for childhood brain tumor survivors. No single therapy has proven effective for treatment. We aimed to evaluate effectiveness of long-term methylphenidate therapy on body mass index (BMI) change in children with hypothalamic obesity. A retrospective analysis included children with a history of brain tumor and hypothalamic obesity receiving methylphenidate (10-60 mg/day) for hypothalamic obesity. Subjects were evaluated for BMI trajectory before and after methylphenidate start. Given that z-scores can be skewed in severely obese children, we calculated BMI as a percent of the BMI at the 95th percentile for the child’s age and gender (BMI% 95th). Twelve patients with hypothalamic obesity completed methylphenidate therapy for at least 6 months (median 3.1 years, range 1.0-5.8 years). All subjects had a suprasellar tumor (nine [75%] with craniopharyngioma) and pituitary dysfunction. Pretreatment median BMI percent of the 95th percentile was 125.6% (interquartile range [IQR] 25-75: 115.3-138.3%) with BMI z-score of 2.4 (IQR 25-75: 2.1-2.6). Following methylphenidate treatment, there was a 69.9% reduction in the median slope of BMI change. Eleven of 12 patients (92%) had a reduction in the slope of their BMI change on methylphenidate treatment. Post methylphenidate median BMI percent of the 95th percentile decrease to 115.2% (IQR 25-75: 103.6-121.2%) with median BMI z-score of 2.1 (IQR 25-75: 1.8-2.2). Mild side effects were noted in six patients. Methylphenidate use reduced and sustained BMI change in children with hypothalamic obesity. Stimulant therapy is an effective first-line agent for treatment of hypothalamic obesity.