Valproic Acid: What Is It and What Is It For?

Valproic acid is a medication used to prevent and treat seizures. Want to know more? Keep reading the following article.

Written and verified by el médico Diego Pereira.

Last update: 28 March, 2023

Valproic acid or valproate acts as an anticonvulsant and mood stabilizer in some psychiatric conditions. Its regular consumption isn’t associated with many adverse effects, despite the fact that there are several absolute contraindications.

Its chemical structure is different from that of the rest of the medicines for epilepsy, as it’s formed from a fatty acid. Its properties were discovered accidentally several decades ago, making it one of the best-studied drugs of its kind.

What is valproic acid?

Also called valproate, it’s one of the most prescribed anticonvulsant drugs today. Partly because it has several mechanisms of action to prevent and lessen the intensity of seizures.

In addition, its activity as a mood stabilizer has also been evaluated in some psychiatric conditions. It can be used in both children and adults, although the dosage is different.

It has the particularity of being metabolized almost entirely within the liver. This implies that those patients who have some type of previous condition (such as liver cirrhosis, active hepatitis, and liver cancer) should be cautious.

It’s considered one of the most widely used drugs as monotherapy in the management of epilepsy. This means that it’s generally prescribed in isolation. However, in those cases in which it is required to combine it with another drug, various interactions may occur.

When administered by any route (either orally or intravenously), valproic acid binds to a plasma protein called albumin, which favors its transport to nervous tissue. This may be due to the chemical structure of valproate, which is very similar to that of fatty acids.

Mechanism of action

Like other neurotropic drugs, valproic acid is capable of modulating the electrical activity of neurons. Several mechanisms are involved in this, but the most striking is the regulation of gamma-aminobutyric acid (GABA) levels in neurons.

This is the main inhibitory substance of the central nervous system. We know that when GABA interacts with its receptors in a neuron, it induces the opening of some channels that allow the passage of small electrically charged atoms. Therefore, when GABA inhibits neurons, an electrochemical phenomenon known as hyperpolarization occurs.

In this case, chloride ions enter the cell, while potassium ions leave. All this occurs in very small fractions of a second, causing a chain reaction due to the extensive neural connections. GABA concentrations increase due to the stimulation of an enzyme called glutamic acid decarboxylase.

It’s also possible that the drug interacts with the membrane of neurons and decreases the capacity for excitement. If this happens, the foci that generate epileptic seizures could be counteracted or, at least, decrease in intensity.

Indications regarding valproic acid

The drug is limited to the treatment of some neuropsychiatric conditions, especially epilepsy and bipolar disorder.

Absence seizures

This is a very common type of seizure in childhood, although it can happen in adults. In this last group, diagnosis can represent a real challenge for specialists.

It’s noteworthy that, from a clinical point of view, patients don’t usually have abrupt and uncontrolled movements. In fact, in most cases, they can go unnoticed. It’s considered an epileptic seizure without evidence of common seizures.

Affected patients are usually performing a daily activity when symptoms begin. At that moment, they enter a state of absorption or disconnection with the environment, in which they lose consciousness for a few seconds.

Typical absence seizures may be accompanied by clonic movements of small muscles, such as those involving the eyelids. Sometimes automatisms occur, which are repetitive movements with no apparent purpose.

Partial and tonic-clonic seizures

These types of seizures are more recognizable than those of absence. The main difference between partial and tonic-clonic seizures is that the former doesn’t include loss of consciousness.

Partial seizures tend to involve a specific part of the body and, depending on the cause, spread to other regions before stopping. They don’t last long.

In the case of the tonic-clonic ones, they never go unnoticed. As their name indicates, they’re events with two well-defined phases. The first includes a kind of state of muscle rigidity that can be accompanied by changes in skin color and heart or respiratory rate. After a short period of time, affected patients begin to exhibit sudden, uncontrolled, and involuntary movements of all extremities.

When the seizures are repeated without recovery of consciousness between them or when they occur for a long time, a clinical picture called convulsive status develops. It has a worse prognosis and requires a different treatment. Intravenous valproic acid, according to some reviews, is a suitable medication.

Bipolar disorder

This is a psychiatric condition that’s characterized by mood disorders that fluctuate over a prolonged period of time. Patients often alternate between depressive and manic periods between months or years.

Due to the persistence of the disease and the difficult diagnosis, as it usually affects young or adult patients, it tends to greatly reduce the quality of life. There are two main types of the disease (type I and II disorder), although other entities known as cyclothymia and non-specific bipolar disorder may also be included.

The therapeutic arsenal for this condition includes mood stabilizers, anticonvulsants, antipsychotics, and antidepressants, among others. In addition to lithium, which is the best-known drug in this field, valproic acid is also quite effective.

Its positive effects may be related to the decrease in dopamine in brain tissue, a different mechanism than the one that explains its anticonvulsant action. It’s usually indicated in patients who have rapid mood swings and a history of substance abuse.

Contraindications and adverse effects of valproate

Regular use of valproate isn’t recommended under the following conditions:

• Acute or chronic hepatitis
• Liver failure
• Allergy to valproic acid or any of the excipients

Most of these contraindications are due to the fact that the drug is metabolized in the liver. This would imply an overload of work for an organ that is already damaged, which could trigger negative consequences.

The side effects of this drug are very varied, although they’re not serious. Some of them are the following:

• Hematologic disorders: Anemia and thrombocytopenia
• Weight gain
• Hair loss: Also known as alopecia
• Problems achieving concentration

Valproic Acid Interactions

The list of drugs that valproic acid can interact with is long. Although it’s usually indicated as monotherapy in epileptic patients, it’s likely that they also have comorbidities. In any case, the doctor will assess the risk/benefit ratio and the appropriate doses for each case.

Some of these drugs with interaction are the following:

• Antidepressants
• Benzodiazepines, such as alprazolam
• Other anticonvulsants, such as carbamazepine, phenobarbital, lamotrigine, and phenytoin
• Acetylsalicylic acid (aspirin)
• Rifampicin
• Topiramate, also used as a mood stabilizer

Can it be administered during pregnancy and lactation?

Valproic acid is a teratogenic drug, which means that it’s capable of inducing fetal malformations. Some authors consider it the most dangerous during pregnancy, so it’s not usually used as a treatment for women of childbearing age.

Some of the malformations that can appear are spina bifida and craniosynostosis. The first is characterized by a defect in the formation of the spinal cord and vertebral column, which despite being more or less frequent, requires surgical treatment.

On the other hand, craniosynostosis is a group of defects in which one of the spaces that join the bones of the skull of babies closes prematurely. This leads to obvious deformities that may require surgical correction.

In mothers who consume high doses of this drug, a set of facial malformations known as fetal valproate syndrome may occur. A flat nose bridge, squint, and a small upper lip are some of its characteristics.

Valproic acid is available only by prescription

Valproate is a widely used medication throughout the world, but it should only be taken under medical indication. Epileptic syndromes and some psychiatric illnesses such as bipolar disorder are some of the conditions in which its use is justified.

Due to its high teratogenic potential, it should be avoided in sexually active women of childbearing age, unless they have a contraceptive method. The specialist doctor who usually prescribes this medication is the neurologist or psychiatrist, as appropriate.