How valproic acid works
Valproic acid interferes with neuronal events at various points in brain metabolism. It blocks voltage-dependent sodium channels and T-type calcium channels. In addition, it increases the concentration of the nerve messenger gamma-aminobutyric acid (GABA) by inhibiting its degrading enzymes.
Glutamic acid, for example, is an excitatory neurotransmitter, while GABA is an inhibitory neurotransmitter in the brain.
Antiepileptic drugs such as valproic acid inhibit excitatory neurotransmitter effects on the one hand and simultaneously enhance the effect of the inhibitory neurotransmitter GABA. This attenuating mode of action of valproic acid also explains why it can attenuate manic episodes in patients with bipolar disorder.
Absorption, degradation and excretion
The active ingredient is broken down in the liver to form many different metabolites, some of which may also be effective against seizures. The metabolites are mainly excreted in the urine. About seven to 15 hours after ingestion, the concentration of the active ingredient in the blood has halved again.
When is valproic acid used?
Valproic acid is used to treat many forms of epilepsy. These include, for example:
- Generalized seizures in the form of tonic-clonic seizures (grand mal seizure with loss of consciousness, falling, cramping, and twitching of muscle groups)
- Focal seizures of complex type with disturbed consciousness
Similarly, valproic acid can be used with other agents in other forms of epilepsy.
Other indications include migraine prophylaxis and, in some countries, use for panic attacks.
Valproic acid is usually used for longer periods of time.
How valproic acid is used
Valproic acid and its more water-soluble sodium or calcium salt (often just called valproate) are available as tablets, extended-release tablets (sustained-release tablets), enteric-coated tablets, and oral and injection solutions.
Usual dosages in adults are 1000 to 1800 milligrams of valproic acid (corresponding to approximately 1200 to 2100 milligrams of sodium valproate). The total daily dose should be divided into two to four individual doses in consultation with the doctor, depending on individual tolerance. The active ingredient should be taken fasting with a glass of water about one hour before meals.
What are the side effects of valproic acid?
If such symptoms occur, therapy with valproic acid is discontinued or the dose reduced in consultation with the physician.
Of particular significance are the occasional liver injuries that occur in infants and young children receiving valproic acid therapy. These occur in a dose-dependent manner and must be treated quickly. For this reason, coagulation parameters and liver function are regularly monitored in this age group.
What should be considered when taking valproic acid?
Contraindications
Valproic acid must not be used in:
- Liver disease in own history or in family members
- Blood coagulation disorders
- Porphyria (rare metabolic disease)
- Insulin-dependent diabetes mellitus
- Urea cycle disorders
- Women of childbearing age who do not meet the conditions of the pregnancy prevention program
- Mutation at the mitochondrial enzyme polymerase gamma (POLG)
Interactions
Before using a new medication (even an over-the-counter one), you should tell your doctor or pharmacist that you are taking valproic acid.
Conversely, valproic acid can also influence the effect of other agents. For example, it partially increases the effect of other antiepileptic drugs, which is why combined treatment should be carried out by an experienced physician. Likewise, valproic acid can increase the effect of anticoagulants and thus the bleeding tendency.
Age restriction
Medicines containing the active substance valproic acid can be used to treat children aged three months and over (or under in exceptional cases).
Pregnancy and lactation
Since valproic acid is harmful to fertility, pregnant women must not be treated with valproic acid. The drug is contraindicated in pregnancy.
How to obtain medication with valproic acid
In Germany, Austria, and Switzerland, valproic acid is available by prescription in every dosage and dosage form, i.e., it is only available from pharmacies after a doctor’s prescription has been presented.
Since when is valproic acid known?
Valproic acid was first produced by the chemist Beverly Burton in 1881. Since the acid is very suitable for dissolving water-insoluble substances, it was popular in chemistry.
Valproic acid was approved in France as a treatment for epilepsy as early as 1967. Since the active ingredient is no longer patent-protected, many pharmaceutical companies have brought preparations with the active ingredient valproic acid onto the market.
