سدیم والپروات وزن بدن در بیماران مبتلا به صرع را در دوران کودکی افزایش می دهد؛ مکانیسم های بیماری زا و کارآزمایی بالینی رفتار درمانی دوسویه باز

Objectives Excessive weight gain associated with valproate sodium (VPA) may predispose patients with epilepsy to other health problems such as insulin resistance. The purpose of this study was to examine the changes in body weight and several biochemical parameters in children receiving VPA treatment. The effects of behavior therapy for epileptic children with VPA-induced weight gain are discussed. Methods Fifteen patients newly diagnosed with epilepsy were included in the study. The following parameters were measured: body weight, body mass index (BMI), serum glucose, serum insulin, serum VPA concentration and serum free carnitine. In addition, behavior therapy was introduced at the initiation of VPA therapy, and lasted at least for 2 years. Results After 6 months of follow-up, there were eight (53%) patients in whom weight gain was demonstrated. Significant increases in the serum insulin level and the insulin/glucose ratio were observed in the weight gain group (p < 0.01). All patients with significant weight gain showed increased appetite. However, BMI stopped increasing with intensive behavior therapy. Conclusions These findings suggest that an increase in serum insulin and insulin/glucose levels may cause weight gain, possibly by stimulating appetite, and that weight changes seem to be reversible with intensive behavior therapy without discontinuation of VPA.

Valproate sodium (VPA) is a broad-spectrum anticonvulsant. VPA is not a sedative and it is associated with fewer cognitive or behavioral effects than other drugs such as phenobarbital.1 On the other hand, VPA causes numerous side effects.2 Patients with chronic epilepsy treated with VPA did not self-report any improvement in health-related quality of life.3 Moreover, use of VPA in patients with epilepsy is associated with an increase in body weight that can interfere with treatment compliance. Weight gain is a well-known adverse effect of VPA treatment, occurring in 40% of children.4 Weight gain is the most common reason for patients to discontinue VPA treatment.5, 6 and 7 In a recent study, 38% of VPA-treated patients gained more than 10% of their body weight compared with 8% of patients treated with lamotrigine.8 Further, weight gain associated with VPA seems to be appetite-related and not metabolic.9 Although there has been recent interest in weight gain accompanying VPA therapy, the pathogenic mechanisms of this adverse effect remain unclear. In the study by Isojarvi et al., hyperandrogenism and polycystic ovaries were associated with weight gain, elevated fasting serum insulin levels, and serum low insulin-like growth factor-binding protein 1 (IGFBP-1) levels in women taking VPA for epilepsy.10 These findings suggest that the weight gain can be progressive and is associated with hyperinsulinemia and low serum IGFBP-1 levels, which may lead to hyperandrogenism and polycystic ovaries. Thus, hyperinsulinemia may cause weight gain in patients taking VPA. Many adverse health effects generally associated with adult obesity are now being seen in obese adolescents.11 and 12 Behavior therapy is a psychological treatment based on the theory that the problem in question is maintained by certain dysfunctional cognitions and beliefs.13 and 14 Basic components of behavior therapy are changing a child's eating habits, providing a moderate exercise program, implementing self-regulation skills and providing parental and peer support.15 Excessive weight (e.g., obesity) is a complex interplay of environmental, social, economic, and behavioral factors, acting on the background of genetic susceptibility. Therefore, weight-control interventions are multifaceted and excessive weight or weight gain not simply treatable with behavior therapy. However, successful weight management may be possible without strict diet prescriptions.16 and 17 The purpose of this study was to examine the changes in body weight and several biochemical and endocrine parameters in older children and adolescents receiving VPA treatment. In addition, the effect of behavior therapy on VPA-induced weight gain is discussed.

These findings suggest that an increase in serum insulin and insulin/glucose levels may cause weight gain, possibly by stimulating appetite, and that weight changes may be reversible with behavior therapy without discontinuation of VPA.