Body Mass Index and Serum Lipid Changes During Treatment with Valproic Acid in Children with Epilepsy

Pediatric Neurology Section, Department of Pediatrics, Obstetrics, Gynecology and Reproductive Medicine, University of Siena, Siena, Italy.
Annals of Pharmacotherapy (Impact Factor: 2.06). 01/2009; 43(1):45-50. DOI: 10.1345/aph.1L414
Source: PubMed


Valproic acid is the drug of choice for a wide variety of epileptic seizures and syndromes because of its broad spectrum of activity and because, in most patients, it is well tolerated. Although weight gain is a well-known adverse effect of valproic acid therapy, only a few studies have addressed weight gain associated with it in children aged 2-8 years.
To evaluate valproic acid-associated changes in the body mass index (BMI) z-scores and to assess changes in serum triglyceride, cholesterol, and fasting glucose levels in young children receiving valproic acid treatment.
Eighty-seven patients (39 females, 48 males) receiving valproic acid therapy for at least 3 months were included in the retrospective longitudinal study. Mean +/- SD age at initiation of therapy was 4.8 +/- 0.8 years. Changes in BMI z-scores as well as serum triglyceride, total cholesterol, and fasting glucose levels were evaluated as continuous variables and analyzed by longitudinal methods for all patients.
The average change from baseline in BMI z-scores was 0.80 (p = 0.001) at 3.1 years of follow-up. No significant change in triglyceride, cholesterol, and serum fasting glucose levels was observed over the same period. The percentage of overweight children at baseline was 6.9% and rose to 16% by the final visit (p = 0.081).
Valproic acid-associated weight gain may occur in young children. However, only 16% of patients were categorized as overweight at the end of the study; this percentage overlaps the percentage of overweight healthy young Italian children. The BMI z-scores significantly increased during the first 16 months of therapy, then appeared to level off. These observations may influence clinical practice and decision-making regarding suspending the drug due to weight gain in children in whom seizure control has been achieved.

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    • "Probably, the increase in thickness of CCA IMT in patients treated with PHT or CBZ may be related to total cholesterol and LDLs (Chuang et al., 2012; Sonmez et al., 2006; Tomoum et al., 2008). Instead, the effects of VPA on changes in lipid profiles and lipoproteins remains controversial (Eirìs et al., 1995; Geda et al., 2002; Nikolaos et al., 2004; Pylvänen et al., 2006; Abaci et al., 2009; Grosso et al., 2009; Lopinto-Khoury and Mintzer, 2010; Chuang et al., 2012): some studies (Geda et al., 2002; Nikolaos et al., 2004; Chuang et al., 2012) found no effect on plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, or its components, whereas others demonstrated significant changes in lipids, lipoproteins, and apolipoproteins (Demircioglu et al., 2000; Voudris et al., 2006; Abaci et al., 2009; Grosso et al., 2009; Verrotti et al., 2010); in particular, Abaci et al. found a significant increase in total cholesterol and LDLs after 12 months of VPA treatment , but triglycerides and HDLs levels did not change. High serum triglyceride concentrations and low HDL were found in patients on VPA treatment which have developed the MS, and there were no significant differences by gender (Verrotti et al., 2010). "
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    ABSTRACT: Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA. The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy.
    Full-text · Article · Sep 2013 · Epilepsy research
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    • "Recent research has found that children with epilepsy who were treated with valproate tend to be shorter in stature and have higher body mass index (BMI) than children who had not taken valproate [112] [113]. In a different series of studies with a similar approach, valproate use in children with epilepsy was associated with increased weight gain [114] [115] [116] [117] [118] [119] [120] [121] [122]. "
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    ABSTRACT: Epilepsy affects approximately 1% of children under the age of 15, making it a very common neurological disorder in the pediatric population (Russ et al., 2012 [1]). In addition, ~0.4-0.8% of all pregnant women have some form of epilepsy (Hauser et al., 1996a,b; Borthen et al., 2009; Krishnamurthy, 2012 [2-5]). Despite the potential deleterious effects of antiepileptic drugs (AEDs) on the developing brain, their use is still required for seizure control in pregnant women (Krishnamurthy, 2012 [5]), and they represent the standard approach for treating children with epilepsy (Chu-Shore and Thiele, 2010; Quach et al., 2010; Verrotti et al., 2011 [6-8]). Even when AEDs are effective, there are potential side effects, including cognitive and affective changes or altered sleep and appetite. The consequences of AED exposure in development have been studied extensively (Canger et al., 1999; Modi et al., 2011a,b; Oguni, 2011 [9-12]). Despite intensive study, there is still debate about the long-term consequences of early life AED exposure. Here, we consider the evidence to date that AED exposure, either prenatally or in early postnatal life, has significant adverse effects on the developing brain and incorporate studies of laboratory animals as well as those of patients. We also note the areas of research where greater clarity seems critical in order to make significant advances. A greater understanding of the impact of AEDs on somatic, cognitive and behavioral development has substantial value because it has the potential to inform clinical practice and guide studies aimed at understanding the genetic and molecular bases of comorbid pathologies associated with common treatment regimens. Understanding these effects has the potential to lead to AEDs with fewer side effects. Such advances would expand treatment options, diminish the risk associated with AED exposure in susceptible populations, and improve the quality of life and health outcomes of children with epilepsy and children born to women who took AEDs during pregnancy. This article is part of a Special Issue entitled "Translational Epilepsy Research".
    Full-text · Article · Jan 2013 · Epilepsy & Behavior
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    • "VPA has also been associated with weight gain and with changes in serum triglycerides, cholesterol, and fast glucose, but studies into these effects have shown only slight impacts of treatment upon weight gain in young children or teenagers [127, 128]. Body mass index scores tend to increase during the first 16 months of treatment and then tend to stabilize, resulting in an increase in the proportion of young children in the clinically overweight category from 6.9% to 16%. "
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    ABSTRACT: Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.
    Full-text · Article · Jul 2010 · BioMed Research International
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