Uses and Side Effects of Valproate

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In addition to epilepsy, valproate has also been used for other medical conditions. It is approved for use in migraine headache prevention, for treatment of manic episodes, and for management of bipolar disorder.

It has also been studied and has been shown to be of possible benefit in the treatment of severe migraine headaches, depression, schizophrenia, and neuropathic pain, although it is not approved for these uses.

Let's explore its role in seizure prevention.

Mechanism of Action

It is believed that valproate prevents seizures by inhibiting excessive nerve activity in the brain. The exact biochemical mechanism of seizure prevention is not completely understood though.

  • Sodium channels: One of the ways that valproate may work is by inhibiting sodium channels. These channels normally allow neurons to communicate. Suppression of overactivity may help diminish the erratic brain activity that produces seizures.
  • GABA: Valproate may also enhance GABA activity. GABA is an inhibitory neurotransmitter, and augmenting its activity may work to reduce some of the irregular neuronal activity in the brain that causes seizures.
  • NMDA receptors: The effect of valproate on this subtype of glutamate receptors may act to modify the effects of glutamate, a neurotransmitter in the brain. This action may play a role in seizure prevention.

    Valproate is a medication used for a number of conditions, including seizures, bipolar disorder, and migraine headache prevention.

    Formulations

    There are several oral and IV valproate formulations that are used to control and prevent seizures.

    • Valproic acid: Depakene is available in capsule or liquid form. Stavzor is available in capsule form.
    • Divalproex sodium: Depakote is available in tablet or sprinkle form.
    • Valproate sodium: Depacon is an IV (intravenous) formulation. Because it is given IV, it can be used in emergency situations, to stop status epilepticus (recurrent or continuous seizures that do not stop on their own), or when a person with epilepsy cannot take the liquid, pill, or sprinkle forms by mouth.

    Generally, anti-seizure medications such as valproate are taken two to four times per day to maintain optimal seizure control, although there are some people who are able to attain seizure control with once per day dosing. Maintaining a regular regimen of anti-seizure medication by taking it at the same time every day is an important component to keeping a steady level, which helps to achieve seizure prevention.

    The different formulations of valproate can be used alone or in combination with other anti-seizure medications. A combination of medications may be selected when one medication alone cannot control the seizures at a tolerable dose. When more than one anticonvulsant is used, some of the side effects that are common among most anticonvulsants, such as drowsiness, sleepiness, and dizziness can be accentuated.

    Types of Seizures Used For

    Valproate, in its different forms, is more versatile than most anti-seizure medications. It can be used for prevention of several types of seizures, including:

    • Generalized tonic-clonic seizures: These are seizures that involve impairment of consciousness and involuntary movements of the body. They are often referred to as grand mal seizures.
    • Absence seizures: These are seizures characterized by impairment of consciousness without shaking or strong physical movements, often referred to as petit mal seizures. Absence seizures are accompanied by either subtle physical movements, such as rapid eyelid blinking, or no involuntary movements at all. Interestingly, individuals who experience absence seizures are generally able to maintain postures such as sitting or even standing without falling over.
    • Myoclonic seizures: These seizures are characterized by jerking movements, with or without impairment of consciousness. Myoclonic seizures can be treated with a number of medications, including valproate. Yet there are some medications that can worsen myoclonic seizures.

    Contraindications 

    Valproate, as well as other anti-seizure medications, can have harmful interactions when combined with alcohol or recreational drugs. When taking valproate, using drugs or alcohol may cause the side effects to be accentuated, may induce toxicity even at normal doses, and may trigger serious complications, including seizures.

    There are several health conditions that are associated with increased side effects or toxicity when taking valproate. The most common include:

    • Liver disease
    • Bleeding problems/low platelets
    • Pregnancy

    In certain circumstances, your doctor may consider it safest for you to take valproate even if you are pregnant or if you have one of the other contraindications to valproate. If that is the case, you will need close follow up to monitor for any complications.

    For example, some women who are pregnant may need to remain on valproate to prevent seizures. Seizures can be potentially harmful to the mother or the developing baby. The risks and benefits of complicated medical situations are considered carefully by the healthcare team to optimize outcomes.

    Side Effects

    As with all medications, valproate can produce side effects. The most common side effects of valproate include:

    Rash: A rash is a less common but potentially serious side effect. Several anti-seizure medications can cause a serious reaction that begins with a rash. While valproate is not one of the medications that are most often associated with this severe reaction, it has been reported.

    In general, you may consider a mild rash to be merely a bothersome problem. But because of the potentially serious complications that can develop, it is important for you to tell your doctor if you develop a new rash while taking valproate.

    Polycystic ovary syndrome (PCOS): An association between valproate use and PCOS has been noted for years, particularly among women with epilepsy who take valproate. But a clear link has not been established. If you are a woman taking valproate, it is generally recommended that you maintain routine follow up with a gynecologist, who should be informed that you are taking or have taken valproate.

    Toxicity

    Medication-related toxicity is different from medication side effects. Toxicity occurs when the medication dose or concentration in the body is higher than recommended. Side effects are negative outcomes that occur at the normal recommended dose.

    The most common causes of valproate toxicity include miscalculated doses, accidental overdose, or intentional overdose. A physical problem with metabolism may also result in valproate toxicity.

    Valproate toxicity can cause:

    • Dizziness
    • Confusion
    • Loss of balance
    • Hypothermia (low body temperature)
    • Hyperthermia (high body temperature)
    • Loss of consciousness
    • Rapid heartbeat
    • Breathing abnormalities
    • Death

    Valproate toxicity is a medical emergency and, if diagnosed in time, can be managed to minimize long-term consequences.

    Blood Testing

    The blood level of valproate can be measured to determine whether you have a concentration that is in the therapeutic range. While your ideal blood level may not be the same as everyone else’s, the recommended ranges are useful for determining whether your level has changed, if you have attained an adequate blood level, and also for alerting to possible toxicity.

    Discontinuation

    As with all anti-seizure medications, abruptly stopping can trigger seizures or other complications. If you are going to discontinue taking valproate, be sure to discuss a plan with your doctor first, who will either replace it with another anti-seizure medication or advise you on a schedule for gradually decreasing your dose.

    A Word From Verywell

    If you have been given a prescription for valproate, it is likely to be useful in managing your medical condition. Valproate is a medication that has been used for years, especially for seizures. Its effects, side effects, and toxicity are relatively well understood.

    Often, it takes several weeks for the anti-seizure medication to reach a stable concentration. At that point, you and your medical team can judge whether or not it is effective in reducing your seizures.

    You can determine whether you are able to tolerate the side effects of valproate within a short period of time after starting the medication. It is beneficial for you to familiarize yourself with the common side effects of your medication so that you will be able to recognize them promptly.

    Be sure to maintain communication with your medical team regarding any seizures or medication side effects. This way you will be able to receive adequate emergency care if needed and your doctor can make any necessary changes to your medication doses.

    Sources:

    Bilo L, Meo R. Polycystic ovary syndrome in women using valproate: a review. Gynecol Endocrinol. 2008;24(10):562-70. doi: 10.1080/09513590802288259.

    U.S. Food and Drug Administration. Valproate Information.