Off-label use of the stimulant methylphenidate in children with genetic obesity was associated with a lower body mass index (BMI) and decreased appetite after nearly one year of treatment, a study reports.
These changes are clinically meaningful among patients who would otherwise experience rapid weight gain and subsequent complications over time, its researchers said. But the long-term safety of such use of a stimulant needs further study.
The study, “Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI‐SDS—A case series,” was published in the journal Pediatric Obesity.
Monogenic obesity — obesity due to a mutation in a single gene — accounts for 1% to 5% of all cases of severe childhood obesity. Its most common form is caused by changes in the melanocortin 4 receptor gene (MC4R). Other forms include variants in the leptin receptor gene (LEPR).
Lifestyle changes in this group of patients are the main treatment for genetic obesity, but are often unsuccessful. This calls attention to the need to develop other treatment options to prevent the progression of obesity and associated complications.
Methylphenidate (MPH) — sold under the brand name Ritalin, among others — is used to treat children with attention-deficit/hyperactivity disorder (ADHD). Reduced appetite and weight loss are among its most frequent side effects, likely due to blocking the re-entry of dopamine in nerve cells that regulate eating.
The research team in Germany previously reported that a boy with a mutation in MC4R and severe ADHD experienced a substantial decrease in BMI standard deviation score (SDS; a measure of relative weight adjusted for a child’s age and sex) within 24 months of treatment with MPH.
As such, they decided to look more closely at the affects of MPH use on weight in people with monogenic obesity.
Five patients with obesity — three due to mutations in LEPR and two with them in MC4R — were prescribed methylphenidate off-label (a common practice if a treating physician suspects benefit) as 5 mg or 10 mg pills taken two or three times, for a maximum 20 mg a day.
Eating behavior was assessed using the Child Eating Behaviour Questionnaire (CEBQ), and appetite with visual analogue scales of 0 (never) to 10 (always). Along with BMI, these parameters were analyzed at the study’s start (baseline) and again after 9 or 15 months of treatment.
Other measures of weight included BMI‐SDS, which measures changes in BMI using a standardized score for children, and %BMIP95, which refers to the percentage of patients in the 95th percentile for weight.
Results showed an average reduction in BMI of 0.7 kg/m2. BMI-SDS decreased by 0.32, and %BMIP95 by 6.6%.
Appetite and CEBQ scores for “food responsiveness” and “enjoyment of food” were also lower upon treatment.
“In conclusion, our results show that an off‐label individual treatment with MPH for 1 year may improve weight trajectory, decrease appetite, and favourably effect eating behaviour in children with LEPR/MC4R deficiency,” the scientists wrote.
Among the observed adverse effects were an increase in the self‐reported frequency of sleep problems, feeling nervous, hyperactivity, and tics.
“A decrease or even a stabilization of BMI‐SDS is highly meaningful in this group of patients, since the natural trajectory would be associated with rapid weight gain leading to obesity complications in short time,” the investigators added. “However, long‐term effects, especially on cardiometabolic risk profiles, are unknown.”