Valproic Acid- The Can’t With, Can’t Without Drug for the Epileptologist.

Introduction

The synthesis of valproic acid from the valerian plant was described by the scientist Beverly S Burton in 1882. It was believed to be pharmacologically inert and was a very good solvent. Almost a century later, in 1963, scientists Meunier and Carraz discovered the anticonvulsant properties of sodium valproate by a fortunate chance.

Today, sodium valproate (also known by its brand name Depakote®) is one of the most widely used antiseizure drugs. It is also used to prevent headaches and is an excellent mood stabilizer. Moreover, it is cheap and can be used by both children and adults. Despite these benefits, valproate has many side effects leading to a love-hate relationship with most epileptologists.

How Does Valproate Work?

Sodium valproate works on multiple targets:

1. It inhibits the enzyme that breaks down the main inhibitory neurotransmitter in our brain, GABA. As result, it increases the GABAergic neurotransmission which yields a net inhibitory effect in brain activity.

2. It blocks voltage-gated sodium channels and reduces the high-frequency firing of neurons.

3. It blocks T-type calcium channels which are responsible for absence seizures.

This makes it a strong antiepileptic.

What Types of Epilepsy Does Valproate Treat?

Valproate considered a broad-spectrum antiepileptic, treats all types of seizures (focal, generalized, absence) and status epilepticus. It is usually used in adults and kids older than 2-3 years as it causes liver problems in children below 2 years.

What Other Conditions are Treated by Valproate?

Valproate is used for:

• Migraine prophylaxis (to avoid the headache before its’ onset).

• Status migrainosus (a migraine attack that doesn’t stop. Valproate is given fast over 20 minutes).

• Manic bipolar disorder.

What is the Dose of Valproate?

The starting dose is 10-15 mg/kg/day in two divided doses, and we increase the dose by 5-10 mg/kg/day every week until we reach the target dose. Valproate is available orally as tablets, sprinkles, or capsules. 

We monitor the blood levels after two weeks before taking the next dose to make sure we get accurate and optimum blood levels of valproate. Valproate takes 3-6 months to act and prevent seizures.

What are the side effects of valproate?

Common side effects of valproate include:

• Common reactions

• Nausea and vomiting

• Hair loss

• Abdominal pain

• Sleepiness

• Dizziness

• Dysfunctional platelet production

• Diarrhea

• Worsening of tremors

• Massive weight gain

• Appetite changes

• Emotional lability

• Tinnitus 

• Blurred vision

• Nystagmus

• Photosensitivity

• Myalgia or muscle pain

• Dyspnea or shortness of breath

• Serious reactions:

• Hepatotoxicity

• Hallucinations and suicidality

• Toxic epidermal necrolysis

• Steven Johnson Syndrome

• Anaphylaxis

• Hyponatremia

• SIADH

• Pancreatitis

• Low platelets (thrombocytopenia) and low blood counts (pancytopenia) due to bone marrow suppression

• High levels of blood ammonium

• Bleeding and easy bruising

• Erythema multiforme

• Polycystic ovarian syndrome in females

• Cerebral pseudo atrophy

• Encephalopathy

• Coma

What are the Precautions to Take When on Valproate?

As Valproate causes bone marrow suppression, we need to monitor blood counts regularly.

It can also reduce platelet counts which can lead to excessive bleeding. Therefore, we need to especially monitor the platelet count as well.

In patients with liver disease, we must prescribe Valproate with caution and in lower doses. We should not give valproate to those with severe liver disease. We must also monitor liver function in patients on Valproate.

Can I Drive While on Valproate?

Driving is not recommended as soon as you start taking Valproate as it causes dizziness. You should avoid driving at least until you get used to the medication and do not feel dizzy.

Can I Consume Alcohol While on Valproate?

No, it is not recommended to take alcohol while on valproate because of the effect alcohol has on the liver.

Will Valproate Help Me Sleep?

Yes, in certain cases Valproate helps you sleep. However, in children, it can cause strange dreams affecting their sleep.

Is Valproate Safe in Pregnancy and Breastfeeding?

No, Valproate must NOT be taken during pregnancy. Valproate is teratogenic, meaning it can cause fetal malformations. It can even cause autism, and ADHD and affect the developing brain and lower IQ significantly. 

As any woman of childbearing age can get pregnant, we avoid prescribing valproate to them. If a woman is on Valproate, we must advise them not to get pregnant while on the drug or switch her to another medicine that is safe during pregnancy.

Why is Valproate not working for me?

There are many reasons:

• Missed doses- increase the risk of seizures

• Not enough time for the drug to work- needs 3- months for it to work

• Inadequate dosage- this is guided by blood levels

• You are among the 25% with drug-resistant epilepsy (your neurologist will determine this).

How to Stop Valproate?

Immediately stopping Valproate can lead to seizures. Therefore, it must be tapered off slowly over a few weeks depending on treatment circumstances and the other drugs you use.

Valproate is usually used in men with generalized epilepsy, especially juvenile myoclonic epilepsy, people with bipolar disorder, and psychiatric conditions with epilepsy.

This article is for medical information only. Always consult your neurologist for qualified medical judgment.