Valproate side effects, sodium drug, valproic acid use for seizure disorder by Ray Sahelian, M.D.
January 1, 2017

 

Valproate sodium is a prescription medication anticonvulsant used to control certain types of in the treatment of epilepsy. Valproate sodium may be used alone or with other seizure medicine. Valproate is also prescribed by some doctors as a mood stabilizing agent.

 

Valproate sodium products
Name brand products for valproate sodium include Depakene  made by Abbott Laboratories and Convulex by Pfizer in the UK.

 

Valproate side effects
Expert Rev Clin Pharmacol. Jan 22 2014. Evidence for a potential protective effect of carnitine-pantothenic acid co-treatment on valproic acid-induced hepatotoxicity. Valproic acid is approved for treatment of seizures and manic episodes of bipolar disorder, and continues to be one of the most commonly prescribed antiepileptic drugs in the world. Hepatotoxicity is a rare but serious side effect resulting from its use, particularly in young patients. This adverse effect does not display normal dose-response curves and can be lethal in children. A review of the purported mechanisms of action suggest hepatotoxicity results from increased oxidative stress, caused by a reduction in beta-oxidation and an increase in activation of certain metabolizing enzymes. There is also evidence that both carnitine and pantothenic acid are involved in the regulation of valproic acid-induced hepatotoxic processes, and clinical evidence has shown that treatment with either compound shows protective effects against hepatotoxicity. These results suggest a potential increase in protective effects with cotreatment of carnitine and pantothenic acid.

 

Seizure. 2016. Metabolic syndrome and anticonvulsants: A comparative study of valproic acid and carbamazepine.

 

BMJ Case Rep. 2015. Reversible weakness and encephalopathy while on long-term valproate treatment due to carnitine deficiency. We describe a case of a 35-year-old woman who presented with bilateral leg weakness and encephalopathy while on long-term valproate therapy. She was diagnosed with valproate-induced encephalopathy due to carnitine deficiency. Clinical improvement occurred with oral carnitine supplementation. Our case report highlights the importance of considering carnitine deficiency in patients presenting with unexplained neurological signs while on long-term valproate treatment.
 

Valporate and Pregnancy, pregnant women

Roughly 20 percent of epileptic women who take the antiseizure drug valproate during pregnancy will have a fetus with a serious adverse outcome, almost twice the rate associated with phenytoin, the next most problematic antiepileptic drug. The rate of serious adverse outcomes, which includes congential malformation and fetal death, is 20 percent for valproate, 10 percent for phenytoin, 8 percent for carbamazepine, and 1 percent for lamotrigine. Several years ago, the American Academy of Neurology and other groups issued guidelines for treating epileptic women during pregnancy. Since antiepileptic drugs, in general, have been linked to adverse fetal outcomes, the strategy was to optimize treatment before conception, using a single antiepileptic drug if possible, at the lowest effective dose. These guidelines did not, however, differentiate between the various drugs for their potential to cause birth defects. Valproate use is associated with congenital malformations, including skull deformities, heart structural abnormalities, kidney swelling due to backup of urine; and cleft palate, a birth defect in which the mouth or lip tissues don't properly form during development; and several others. Neurology, August 8, 2006.

 

Neurochem Res. Jan 31 2014. Valproic Acid: A New Candidate of Therapeutic Application for the Acute Central Nervous System Injuries. Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are common causes of human disabilities and deaths, but the pathophysiology of these diseases is not fully elucidated and, thus, effective pharmacotherapies are still lacking. Valproic acid (VPA), an inhibitor of histone deacetylation, is mainly used to treat epilepsy and bipolar disorder with few complications. Recently, the neuroprotective effects of VPA have been demonstrated in several models of acute CNS injuries, such as stroke, TBI, and SCI. VPA protects the brain from injury progression via anti-inflammatory, anti-apoptotic, and neurotrophic effects. In this review, we focus on the emerging neuroprotective properties of VPA and explore the underlying mechanisms. In particular, we discuss several potential related factors in VPA research and present the opportunity to administer VPA as a novel neuropective agent.

 

Relation to acetyl l-carnitine and carnitine levels
Biomed Res Int. 2016. Carnitine and/or Acetylcarnitine Deficiency as a Cause of Higher Levels of Ammonia. Blood carnitine and/or acetylcarnitine deficiencies are postulated in the literature as possible causes of higher ammonia levels. The aim of this study was to investigate if the use of valproic acid, the age of the patients, or certain central nervous system pathologies can cause carnitine and/or acetylcarnitine deficiency leading to increased ammonia levels. Three groups of patients were studied: (A) epileptic under phenytoin monotherapy; (B) with bipolar disorder under valproic acid treatment; (C) elderly. Plasma valproic acid and blood carnitine and acyl carnitine profiles were determined. Blood ammonia concentration was determined using an enzymatic automated assay. Higher ammonia levels were encountered in patients under valproic acid treatment and in the elderly. This may be due to the lower carnitine and/or acetylcarnitine found in these patients. Patients with controlled seizures had normal carnitine and acetylcarnitine levels. Further studies are necessary in order to conclude if the uncontrolled bipolar disorder could be the cause of higher carnitine and/or acetylcarnitine levels.