Valproic acid

What is valproic acid?

Valproic acid, and the derivative valproate, are drugs used to treat epilepsy. The anti-epileptic is used in various forms of epilepsy. Child forms of epilepsy, such as absenteeism, can also be treated with valproic acid.

In addition, valproic acid is also used in the therapy of bipolar disorders to prevent manic and depressive phases and is an effective alternative to lithium also in the treatment of acute manic phases.

Indications for valproic acid

The indications for the anti-epileptic valproic acid include epilepsy. Valproate is used to treat so-called grand mal seizures, which are seizures that affect both sides of the brain. This also includes absence epilepsy, which is particularly common in children and is characterized by states of absence lasting a few seconds. Valproic acid can also be used for partial seizures that only affect one half of the brain. Valproic acid can prevent seizures in alcohol or drug withdrawal.

In addition to epilepsies, the prophylaxis of manic and depressive states in bipolar disorder is also part of the indication of valproate. It is also used in acute mania.
Despite recommendations from the German Migraine and Headache Society, there is (still) no approval for the use of valproic acid in migraine prophylaxis or for cluster headaches.

Find out all about the topic here: Epilepsy.

epilepsy

Valproic acid belongs to the group of anticonvulsants or anti-epileptics, so it is used in the treatment of epilepsies and seizures. These include, on the one hand, generalized seizures, i.e. grand mal seizures, which are accompanied by twitching of muscle groups and loss of consciousness. Valproic acid is also used in the therapy of absence epilepsy, including the child's form. Focal epilepsies are also part of the field of application.

Valproic acid can be used as a monotherapy, i.e. the only drug used to treat the seizure disorder, in more severe forms it can also be used as part of a combination therapy with several anticonvulsants. In addition to carbamazepine, valproic acid is the first choice in the long-term therapy of epilepsy.

Also read the article: Epilepsy in the child.

depression

Valproic acid is not suitable as a therapeutic agent for unipolar depression. However, it is used as a so-called phase therapeutic in bipolar disorder for the prophylaxis of manic and depressive phases. In patients with symptoms of depression, the diagnosis of unipolar depression should be made very carefully, as these may well be symptoms of a depressive phase of bipolar disorder. Different drugs are used depending on the disease.

Patients on antidepressants who are taking valproic acid for a seizure disorder should tell their doctor about the medication they are taking. Valproic acid has numerous side effects with other drugs, such as the antidepressant fluoxetine.

For more information, read on: Therapy of a mania.

The active substance

Valproic acid and its salts, the valproates, are drugs in the group of anti-epileptic drugs or anticonvulsants. The mechanism of action of valproic acid is not fully understood. The anticonvulsant effect is probably explained by an amplification of inhibitory signals in the brain.

Valproic acid can be taken orally or administered intravenously. Valproic acid interacts with other drugs in many ways, which can weaken or increase their effects. Therefore, the attending physician should always be informed about the use of anticonvulsants.
In addition, taking valproic acid can have side effects. It is particularly important to note that valproic acid is highly teratogenic, meaning that it can severely damage the unborn child during pregnancy. Valproic acid is not recommended for women of childbearing potential. If it is used, an effective method of contraception must be used during treatment.

Find out more about the topic here: Medicines for epilepsy.

Side effects

Every medicine carries a risk of side effects, but not every user is likely to experience them. Temporary nausea, loss of appetite, including vomiting or diarrhea can occur, especially at the beginning. The appetite can also be increased. Both weight increases and decreases are possible

Common side effects also include psychological symptoms such as confusion, aggression, restlessness, and attention disorders. Therapy with valproic acid can also affect blood values, the blood count (with suppression of the bone marrow), liver values ​​and other laboratory parameters, such as an increase in the ammonium concentration in the blood. Coordination and movement disorders such as tremors or freezing and other neurological symptoms such as tiredness, headache, paresthesia and others are also common. Temporary hair loss is also possible.
Serious but rare side effects include liver damage that can lead to death, damage to the pancreas or severe skin reactions such as Stevens-Johnson syndrome.

In the event of persistent and serious symptoms, a doctor must be consulted, and detailed examinations and laboratory tests should be carried out before and during treatment. Clinically inconspicuous patients should be checked once a month at the beginning, after one year two to three medical checks per year are sufficient as long as the therapy is still well tolerated.

Further information on this topic: Side effects of valproic acid

Weight gain

Valproic acid can change appetite and lead to both weight gain and loss. Studies have shown that valproic acid has a wide range of effects on energy and hormone metabolism, depending on gender, age, duration of therapy, initial weight and other individual factors, valproic acid can actually lead to weight gain. Valproic acid even seems to influence insulin metabolism and increase the risk of the so-called metabolic syndrome, a precursor of diabetes mellitus.

Patients should be informed about the possible side effects of therapy and monitored. Simple rules for eating behavior can counteract an increase. If the body weight increases rapidly and rapidly in the first few months of treatment, a change of medication should be considered in consultation with the doctor.

interaction

Valproic acid interacts with numerous other drugs and can increase or weaken their effects, influence the effects themselves or increase the risk of possible side effects. When prescribing valproic acid, it is important to inform the doctor about the patient's medication.

The excretion of valproic acid can be increased by the following drugs and thus the anti-epileptic effect can be weakened: other anti-epileptic drugs such as phenobarbital, primidone, phenytoin and carbamazepine. This should be taken into account in multi-drug therapy for the treatment of epilepsy. The breakdown of valproic acid is also increased by mefloquine (anti-malarial drugs) and carbapenems (antibiotics); simultaneous use can lead to seizures. The concentration of valproic acid is increased by cimetidine (an anti-heartburn agent) and erythromicin (an antibiotic). Fluoxetine for the treatment of depression also changes the concentration of valproic acid, as does acetylsalicylic acid ("aspirin", ASA), which is often used for pain and inflammation.

Valproic acid also affects the concentration of other drugs and either leads to a weakened effect or an increased rate of side effects. Particular caution is required when taking other anti-epileptic drugs, benzodiazepines, neuroleptics and drugs for the treatment of depression (antidepressants, MAO inhibitors). Therapy with valproic acid can lead to an increased bleeding tendency when taking anticoagulants and antiaggregants ("blood thinners") at the same time.

When should valproic acid not be given?

Valproic acid should not be given if allergic reactions to the drug or its components are known. In addition, valproic acid must not be used for therapy if the patient or a family member is known to have liver disease. Patients with bleeding disorders should also not take medicines containing valproic acid.

The so-called hepatic porphyria, a disorder of the blood pigment metabolism, is an absolute contraindication for the intake of valproic acid. There are also numerous diseases in which valproic acid should only be used after carefully weighing the risks and benefits. These include diseases of the bone marrow, metabolic diseases, impaired kidney function and when taking anti-coagulants or acetylsalicylic acid (ASA).

Before taking valproic acid, the doctor should be fully informed about the patient's medical history and medication.

The dosage

Therapy with valproic acid must be initiated and monitored by a specialist. The dosage is individual depending on the patient and depends on age and other factors. Valproic acid is usually crept in gradually, so start with a lower dose. The dose also depends on whether other anti-epileptic drugs are used to treat the seizure disorder.

In long-term therapy, the mean daily dose for monotherapy with valproic acid for adults and adolescents is around 20 mg valproic acid per kg body weight per day, i.e. 1200 to 2000 mg. The daily dose can be divided into several single doses; the tablets should be swallowed with plenty of fluid one hour before meals.

What is the valproine level?

The effectiveness of valproic acid in the therapy of epilepsy is hardly related to the concentration of the drug in the blood. Nevertheless, the level of the drug can be determined, for example in order to adapt the patient's individual dosage or to check the patient's compliance, that is, the correct intake of the drug.

The reference range for valproic acid is approximately between 50 and 100 micrograms per milliliter. Even patients who are optimally adjusted according to Spiegel can suffer seizures, which shows the low informative value of the value. Ultimately, the decisive factor for therapy is the dose under which the patient is free from seizures.

The price

Valproic acid is a drug for the long-term therapy of seizure disorders or bipolar disorder, the dosage is individual. The usual maintenance dose in the therapy of epilepsy valproate is between 1200 and 2000 mg in adolescents and adults.
Valproic acid is available on the market in various pack sizes from different manufacturers. For example, 200 tablets of 150 mg valproate cost between 20 and 30 €, 200 tablets of 500 mg between 35 and 50 €.

Alternatives to Valproic Acid?

Valproic acid is one of the first choices in the treatment of various forms of epilepsy. The therapy is ordered and followed up by a specialist; side effects or contraindications can lead to a change to another drug. Alternatives to valproic acid are other anti-epileptic drugs, especially carbamazepine and its derivatives are shortlisted depending on the indication. There are also phenytoin and phenobarbital. Ethosuximide is of particular importance in the therapy of absence epilepsy in children.

Newer anticonvulsants include gabapentin, lamotrigine, tiagabine, topiramate, and vigabatrin. Many are suitable for combination therapy; lamotrigine, for example, is also used in monotherapy. Benzodiazepines such as diazepam and lorazepam are used in an acute attack or in so-called status epilepticus.

If valproic acid is indicated for bipolar disorder, lithium is usually used as a so-called "phase stabilizer", as are other anti-epileptic drugs such as lamotrigine or carbamazepine.

You can find more information on this topic at: How can you fight cramps?

Valproic acid and alcohol - are they compatible?

Drinking alcohol can increase the risk of liver damage from the intake of valproic acid. In general, moderate consumption of alcohol does not increase the frequency of seizures. However, it becomes problematic when a lack of sleep and irregular medication consumption are the result of alcohol consumption.

Patients with a seizure disorder should drink alcohol responsibly and in moderation, and ideally refrain from drinking it.

Also read the article: Psychiatric drugs and alcohol.

Can it be taken during pregnancy and breastfeeding?

Valproic acid must not be used during pregnancy. If the medicine is taken during pregnancy, it can cause considerable harm to the unborn child. Risks include serious birth defects that can affect the child's physical and mental development and lead to severe disabilities.
If women become pregnant unplanned during treatment with valproic acid, they should see a doctor immediately. He will weigh up the risk and benefit of the therapy and change the drug if necessary. Valproic acid should never be discontinued without consulting your doctor.

If valproic acid is taken while breastfeeding, small amounts of the active ingredient can pass into breast milk. The risk to the infant is low. Women who want to breastfeed should consult their doctor.

The effectiveness of the pill

The use of valproic acid in unplanned pregnancies can lead to serious birth defects in the child. Therefore, when taking the anti-epileptic drug in childbearing age, careful contraception should be used. Women should consult their doctor about the methods of contraception.

The effectiveness of hormonal contraceptives, the “pill”, is not reduced by taking valproic acid.