Bodyweight gain and anticonvulsants - A comparative review

Bodyweight gain is a common and frequent undesirable effect associated with the use of anticonvulsant drugs. This has been observed for many years wit h valproic acid (sodium valproate) and carbamazepine, and also, more recent ly, with some of the newer anticonvulsants such as vigabatrin and gabapenti n. Very often bodyweight gain in children, adolescents and adults with epileps y taking such anticonvulsants results in cosmetic adverse effects. On the o ther hand, bodyweight gain is disturbing to general health, with a possible increase in the risk of diabetes mellitus or heart disease. Other potentia l adverse effects, such as the association of obesity with polycystic ovari es, have been reported with the use of valproic acid. Potential mechanisms of anticonvulsant-associated bodyweight gain are not y et clear and differ between drugs used. The involvement of lowered blood gl ucose level, which may stimulate eating through an effect on the hypothalam us, constitutes one of the possible mechanisms. Lowered blood glucose level s may result from a competition between the binding of the drug and long ch ain fatty acids. An increased availability of the latter stimulates insulin production and lowers the serum glucose levels. Another possible explanati on for lowered blood glucose may be a deficiency in carnitine directly caus ed by the drug, that would result in a reduction of fatty acid metabolism a nd an increase in glucose consumption. An enhancing effect of gamma -aminob utyric acid-mediated neurotransmission may increase appetite for carbohydra tes and reduce! energy expenditure. An antidiuretic hormone-like effect or effects on norepinephrine (noradrenaline) or serotonin-mediated neurotransm ission are more rarely considered. Many studies on anticonvulsant-associate d bodyweight gain illustrate how we could better define the risk factors fo r the development of anticonvulsant-induced bodyweight gain and uncover the mechanisms behind it.