Bodyweight Gain and Anticonvulsants

Abstract

Bodyweight gain is a common and frequent undesirable effect associated with the use of anticonvulsant drugs. This has been observed for many years with valproic acid (sodium valproate) and carbamazepine, and also, more recently, with some of the newer anticonvulsants such as vigabatrin and gabapentin. Very often bodyweight gain in children, adolescents and adults with epilepsy taking such anticonvulsants results in cosmetic adverse effects. On the other hand, bodyweight gain is disturbing to general health, with a possible increase in the risk of diabetes mellitus or heart disease. Other potential adverse effects, such as the association of obesity with polycystic ovaries, have been reported with the use of valproic acid. Potential mechanisms of anticonvulsant-associated bodyweight gain are not yet clear and differ between drugs used. The involvement of lowered blood glucose level, which may stimulate eating through an effect on the hypothalamus, constitutes one of the possible mechanisms. Lowered blood glucose levels may result from a competition between the binding of the drug and long chain fatty acids. An increased availability of the latter stimulates insulin production and lowers the serum glucose levels. Another possible explanation for lowered blood glucose may be a deficiency in carnitine directly caused by the drug, that would result in a reduction of fatty acid metabolism and an increase in glucose consumption. An enhancing effect of gamma-aminobutyric acid-mediated neurotransmission may increase appetite for carbohydrates and reduce energy expenditure. An antidiuretic hormone-like effect or effects on norepinephrine (noradrenaline) or serotonin-mediated neurotransmission are more rarely considered. Many studies on anticonvulsant-associated bodyweight gain illustrate how we could better define the risk factors for the development of anticonvulsant-induced bodyweight gain and uncover the mechanisms behind it.

Modification in body weight associated with antiepileptic drugs

“…With regard to type of medication, as in other studies, weight gain appeared to be more related to carbamazepine and valproate 3,5,14 . Here, weight gain was found in 66.7% of patients on monotherapy with carbamazepine, as well as in 60% of patients on monotherapy with valproate.…”

“…Weight gain associated with AED is frequent, particularly with drugs such as valproate and carbamazepine as well as with gabapentine. The mechanism that causes weight gain varies according to the drug used, dose, sex, age, etc [2][3][4] . These mechanisms are still not completely clear; among them are resistance to insulin leading to hyperinsulinemia in the case of valproate 5 , and in the case of carbamazepine, increased appetite favoring the deposition of fat by a mechanism still not well understood 3 .…”

“…The mechanism that causes weight gain varies according to the drug used, dose, sex, age, etc [2][3][4] . These mechanisms are still not completely clear; among them are resistance to insulin leading to hyperinsulinemia in the case of valproate 5 , and in the case of carbamazepine, increased appetite favoring the deposition of fat by a mechanism still not well understood 3 . Increase in weight is an undesirable effect that can interfere negatively with treatment, since it may reduce compliance to treatment by lowering self-esteem as well as favoring and aggravating diseases such as hypertension and insulin resistance [2][3][4][5] .…”

“…These mechanisms are still not completely clear; among them are resistance to insulin leading to hyperinsulinemia in the case of valproate 5 , and in the case of carbamazepine, increased appetite favoring the deposition of fat by a mechanism still not well understood 3 . Increase in weight is an undesirable effect that can interfere negatively with treatment, since it may reduce compliance to treatment by lowering self-esteem as well as favoring and aggravating diseases such as hypertension and insulin resistance [2][3][4][5] . The aim of this study was to determine the status of appetite and body weight associated with the most frequent AED used by patients on mono-or polytherapy for epilepsy in an outpatient epilepsy clinic in a public hospital (Southeast Brazil), over a period of six to eight months.…”

Physical Growth and Endocrinal Disorders during Pubertal Maturation in Girls with Epilepsy

“…VPA was associated with obesity due to increased appetite by stimulating the hypothalamus (2). This may occur through lowering blood glucose level, or through an enhancing effect of γ -aminobutyric acid (GABA)-mediated neurotransmission, which may increase appetite for carbohydrates and reduce energy expenditure (18). Decreased sensitivity to leptin may be another factor that is partly responsible for VPA-induced weight gain (19).…”