Methylphenidate and Growth: Demonstration of a Growth Impairment and a Growth-Rebound Phenomenon

Abstract

Methylphenidate (MPH), the drug of choice in the treatment of attention deficit disorder with hyperactivity (ADD/H), has been shown to reduce the body stature of some patients. The present study was undertaken to determine if MPH suppresses growth in rats, and whether the clinical observation of a growth rebound phenomenon could be experimentally demonstrated. Our results demonstrate that neonatal rats treated with MPH show a reduction in femur length and a reduction in thyroid, pituitary, testis, adrenal gland, and brain weights immediately following drug cessation. However, a growth- rebound phenomenon occurs such that there are no differences between treated and control groups within 30 days of the last drug exposure. These data, along with those from the clinical literature, suggest that growth impairment is most likely a result of the acute effects of the drug. Further, these data suggest that when administered at therapeutic doses which avoid significant weight loss in the patient. MPH is not likely to cause growth impairment in children.

Chronic exposure to methylphenidate impairs appendicular bone quality in young rats

“…These findings are in general agreement with prior studies showing that MP treatment of neonatal and adolescent rats results in dose dependent inhibition of weight gain [18,19,20]. In addition, the rapid normalization of both body weight and skeletal growth upon MP cessation is also in agreement with previous reports [19, 20].…”

“…In addition, the rapid normalization of both body weight and skeletal growth upon MP cessation is also in agreement with previous reports [19, 20]. However, our results extend the basic findings of these prior studies by providing significantly more detailed measures of bone size, as well as densitometric and biomechanical data that reveal the extent to which MP treatment impairs skeletal development.…”

“…The persistence of MP induced growth suppression following treatment cessation has also been evaluated. In a pair of studies, treatment of neonatal rats with MP reduced body weight and femoral length when assessed immediately post-treatment [19,20]. However, when assessed after a 30-day recovery period, these differences were no longer present; leading the authors to conclude that MP induced growth suppression is an acute problem that is compensated for by a ‘rebound’ in growth following MP cessation.…”

Juvenile toxicity assessment of d,l‐methylphenidate in rats

“…Body weights were comparable to concurrent controls at 5 weeks after cessation of dosing. A reduction in growth during dosing and growth-rebound phenomenon with cessation of MPH administration has been reported previously in juvenile rats (Pizzi et al, 1986(Pizzi et al, , 1987.…”

Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats

“…However, in children, it is well documented that MPH can cause anorexia and delayed growth (for review see [32]). Both animal and clinical studies have shown that the growth suppressing effects of MPH are acute and reversible after drug administration has stopped [29;30;33]. Even after individuals “catch up” on growth after discontinuation of MPH, our results on weight gain or arterial blood pressure point towards long-term effects on their reactivity to stressors.…”