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A New Look At An Old Epilepsy Drug Yields Treatment Clue

About one-third of people with epilepsy aren't helped by existing drugs. But a commonly prescribed medicine used for almost 50 years to treat the disorder has revealed new information about how the disorder works that could lead to improvements in treatments.

That drug, valproic acid, is used to treat epilepsy, migraines and bipolar disorder. It's the active ingredient in drugs like as Depakote or Depakon, among other names. Doctors often don't know why a particular drug works, and they didn't know why valproic acid helped prevent seizures.

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Articles of Interest

A Life Saving Drug-Drug Interaction

Valproic acid is a broad-spectrum antiepileptic medication used to treat bipolar disorder, focal (partial) onset, and generalized onset seizures. While standard therapy in overdose involves the use of activated charcoal and levocarnitine, the interaction between carbapenem antibiotics and valproic acid has been effective in quickly reducing serum VPA levels.

Concerns around sodium valproate

Research has shown that sodium valproate can cause serious problems in a developing baby. Of babies whose mothers take sodium valproate during pregnancy, up to 1 in 10 (10%) are at risk of having a birth defect, and up to 4 in 10 children (up to 40%) have problems with development and learning as they grow.

Depakene vs Depakote: What’s the Difference?

Depakene (valproic acid) and Depakote (divalproex sodium) are two very similar medications used to treat seizures. When talking about them together, healthcare professionals call these medications valproate products.

Mood Stabilizer Toxicities

Most of the unique aspects of valproate toxicity focus on its diagnosis and treatment. In the setting of acute intentional overdose of valproate, one of the most important things for emergency physicians to be aware of is that there can be a delay of peak valproic acid level. There are cases of patients presenting to an emergency department with stated valproate ingestion, initial negative level, then repeat level hours later being in the toxic range. So I recommend serial valproate levels until both down-trending and non-toxic.

Risk of Valproic Acid-Related Tremor: A Systematic Review and Meta-Analysis

VPA-related tremors are usually action or postural tremors, but sometimes they are rest tremors.

Therapeutic drug monitoring with valproate–Why product selection is an important factor

There is a modest collection of literature describing the pharmacokinetic and clinical differences between the extended-release form of divalproex sodium (Depakote ER®) and the delayed-release form (Depakote®). Published articles are quick to espouse the extended-release formulation, especially in the setting of seizure control.

TOXCard: Valproic Acid Toxicity

Check serial valproic acid levels to make sure it is downtrending. CNS effects (e.g. somnolence, confusion) are most common. Valproic acid induced hyperammonemia encephalopathy may be seen even without hepatotoxicity or elevated VPA levels. Supportive care is key, though L-carnitine may be helpful.

Valproic Acid and the Antidote

Valproic Acid (Depakote) is a drug that uniquely has the ability to raise serum ammonia concentrations. It is able to do this without raising liver er enzymes and it can occur in overdose or at therapeutic levels. Do not think of this in the context of hepatic encephalopathy. This a metabolic derangement caused by VPA.

Valproic Acid Intoxication

A normal valproic acid level upon admission doesn't exclude severe valproic acid toxicity. If suspicion for a significant ingestion exists, repeat levels are needed.

Valproic Acid Pathway, Pharmacokinetics

VPA is available in oral, rectal and injectable dosage forms. It is widely used in pediatric epilepsy because of its multiple mechanisms of action and acceptable safety profile. The dose requirements for VPA are highly variable...

Valproic Acid: A Summary of Indian Epilepsy Society-Consensus Document

Valproic acid (VPA) is a well established anticonvulsant drug for the last 40 years and is now a part of more than 130 national health care programmes. Since 1988, it has regularly featured as an anticonvulsant in the WHO Model List of Essential Medicines. The current NICE Guidelines recommend Valproic Acid as the first-line of treatment for Idiopathic Generalized Epilepsies (IGEs) in children, young people and adults but should be used with caution in pregnant women.

Why Are We Still Using Valproic Acid (Depakote) in Women of Childbearing Age?

There have long been concerns regarding the use of the anticonvulsant valproate (Depakote) during pregnancy. First trimester use of valproate has been associated with a 3-5% risk of neural tube defects, as well as an increased risk of other malformations affecting the heart, limbs, and genitals. Prenatal exposure to valproate may also result in lower IQ and increased risk of autism spectrum disorders in the offspring. Despite these significant risks, women of reproductive age continue to be treated with valproic acid.

Resources

Depakote

Depakote has been prescribed since 1983. Depakote is one of the first generation of a class of medications called antiepileptic drugs (AEDs). Depakote is used to treat complex partial seizures, simple and complex absence seizures, as well as acute manic symptoms in patients with bipolar disorder.

Batten Disease

It is not entirely understood how valproic acid reduces seizures. However, the medicine has been shown to inhibit GABA degradation. GABA is a neurotransmitter, a signaling molecule in the brain, that inhibits the activity of brain cells, or neurons.

Epilepsy.com

When you read about valproic acid, you will also see the word valproate (val-PRO-ate). This is the name of valproic acid after it has changed into the form that actually works in the body. A few other seizure medicines also are changed into valproate, so they work in the same way as valproic acid. The best-known valproate medicine in the United States is brand-name Depakote.

NAMI

Valproate is a mood stabilizer medication that works in the brain. It is approved for the treatment of mania associated with bipolar disorder (also known as manic depression), seizures (epilepsy), and migraine headaches.

StatPearls

Valproic acid is an anticonvulsive and mood stabilizer medication. It is extensively used in the adult population to treat convulsions, migraines, and bipolar disorders.

WikEM

Common Trade Names: Depacon; Depakene; Depakote; Depakote ER; Depakote Sprinkles; Stavzor.