Abstract
Introduction
Case Report
A, a 7-year-and-5-month-old Caucasian boy, had the diagnosis of Asperger's disorder and ADHD per Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV-TR) (American Psychiatric Association 2000). He was referred to the clinic due to poorly controlled ADHD symptoms, despite treatment with mixed amphetamine salts, 10 mg three times a day, for over 9 months. His weight, height, and body mass index (BMI) on presentation were 32.7 kg, 128.3 cm, and 19.9, respectively. He had history of failed trials with methylphenidate. The mixed amphetamine salts were discontinued and he was placed on GXR 1 mg in the morning. He experienced somnolence and fatigue during day time but it gradually improved. After 1 week, he weighed 33.6 kg; GXR was increased to 2 mg/day. Three weeks later, his ADHD symptoms improved significantly. However, the patient's weight, height, and BMI were 42.3 kg, 129.5 cm, and 25.2, respectively. In the previous 4 months (prior to GXR initiation), the patient had only gained 1.6 kg and 2.03 cm in height.
During this period, his routine of physical activities, television watching, and eating habits remained unchanged. He was not on any other medications. GXR was decreased to 1 mg/day due to concerning weight gain. His laboratory work-up showed no disturbances in electrolytes, complete blood count, comprehensive metabolic panel, fasting blood sugar, hemoglobin A1C, lipid panel, folic acid, cyanocobalamin, thyroid hormone, parathyroid hormone, calcium, phosphorus, and growth hormone. His fasting leptin level was 17.2 ng/mL (prepubertal male reference rage=1.6 to 10.6 ng/mL). With the decrease in GXR dose he gained 1.4 more kilograms in the next 2 weeks but the ADHD symptoms worsened. He was switched to atomoxetine 18 mg/day twice daily. Eight weeks after GXR discontinuation, he had lost 1.8 kg and his BMI decreased to 23.6.
Discussion
Severe weight gain in our case was unexplained by his growth pattern and laboratory work-ups for other reasons for obesity were negative. Circulating leptin concentrations closely parallel body fat stores, such that a rise in adiposity increases leptin production (Oswal and Yeo 2010). The score on Naranjo adverse drug reaction scale was 7, indicating that his weight gain was a probable adverse drug reaction (Naranjo et al. 1981). The phase-3 GXR drug trials had revealed that children receiving GXR for at least 12 months in open-label studies gained an average of 8 kg in weight and 8 cm in height (Biederman et al. 2008a, 2008b; Sallee et al. 2009b). Their growth rate and BMI percentile remained stable over 12 months in these studies compared with when they began receiving GXR. Sallee et al. (2009a) conducted a long-term, open-label, flexible-dose safety continuation study of 259 GXR-treated children (mean exposure 10 months) and found weight gain in 7% of patients. The study reported a mean weight gain of 7 kg (which was expected for that population of growing children over a 24-month period), and the mean increase in height was 6.85 cm. The mechanism of GXR-induced weight gain is not clear. Previous animal studies (Sillence 1992; Gazzola 1995) have hypothesized that guanfacine lowers resting energy expenditure through a decrease in sympathetic tone (noradrenaline release) but failed to show a significant weight gain. More research is needed to determine the effect of GXR on the weight in short-term and long-term therapeutic trials. We suggest prescribers to exercise caution and carry-out close monitoring of weight and growth of children on GXR.
Footnotes
Disclosures
Drs. Khan, Jain, Soltys, and Takahashi have no conflicts of interests to report.