Valproate is widely used in medicine to prevent seizures in epilepsy. In addition, it is often used as a phase prophylactic in bipolar disorder and schizoaffective psychosis.
What is valproate?
Valproate is widely used in medicine to prevent seizures in epilepsy. Valproates are salts of artificially produced valproic acid, which chemically belongs to the branched carboxylic acids. In the 1960s, the antiepileptic effect of these salts was discovered by chance. Since then, they have become established in the treatment of epilepsies. Thus, valproate belongs to the so-called group of anticonvulsants, which have anticonvulsant effects and prevent epileptic seizures. Due to their special biochemical mechanism of action, valproates are also approved for the preventive treatment of bipolar disorders (alternation between mania and depression) and schizoaffective psychoses (psychoses with affective and schizophrenic elements). They are therefore also used in psychiatric practice. The background to this is that a mood-stabilizing effect of valproates can be observed due to the attenuation of excitation conductions in the brain. Thus, rapid mood changes caused by the disease, as they occur in bipolar disorder, can often be prevented. For this reason, valproate is also considered a so-called phase prophylactic, a proven mood stabilizer. In contrast to the classic mood stabilizer lithium, whose mode of action is still largely unexplored, there are valid explanations for the mode of action of valproates.
Pharmacologic action
The antiepileptic effect of valproates or valproic acid probably stems from blocking certain excitatory ion channels in the brain. This primarily affects the voltage-dependent calcium channels as well as the sodium channels, which are closed by the active substance. As a result, these can no longer enter the cell and cause an increased action potential, which is responsible for epileptic seizures. In addition, valproate is thought to act on GABA receptors in the brain. GABA (gamma-aminobutyric acid) are neurotransmitters that inhibit excitation. They are part of the brain’s natural balancing mechanism that regulates tension and relaxation. Since an overexcitation of parts of the brain can be detected in epileptic seizures as well as in pathological mood changes such as bipolar disorder, it is obvious to artificially activate the neurotransmitter GABA in order to block such phases. Just as, for example, by benzodiazepines, GABA is enhanced by valproate, which explains its acute anticonvulsant and antimanic effects. Valproate promotes the synthesis of GABA on the one hand and inhibits its degradation on the other. This results in a broad spectrum of action, which explains why valproate can be used in almost all forms of epilepsy and in some affective-colored disorders. Valproates are administered as so-called sodium valproate, whereupon conversion to the actual valproic acid takes place in the stomach. In the blood, this binds to plasma proteins. The pharmacological advantage of the active ingredient is that it can be introduced very quickly and dosed at high levels. As a result, acute phases can be intercepted quickly.
Medical application and use
The original indication for valproic acid is epileptic seizures. In the treatment of epilepsy, valproate is used for generalized seizures, focal seizures, and secondary generalized seizures, as well as for refractory epilepsies in combination with other anticonvulsants. Generalized seizures affect both hemispheres of the brain. Focal seizures originate in a specific brain region. They can spread across both hemispheres of the brain (secondary generalized seizures). Valproic acid has been shown to be very effective in preventing these forms of seizures: according to statistics, six out of ten epilepsy patients respond to valproate. The second indication for the drug is bipolar and schizoaffective disorders, and valproate is administered primarily for manias. Acute manias can be intercepted by valproate. However, it is hardly effective against depressive phases. Therefore, antidepressants are additionally prescribed for depressive-tinged psychoses.However, due to the presumed effects on unborn life, the corresponding preparations may now only be prescribed to girls and women of childbearing age if lithium is not tolerated, although valproic acid has generally been shown to be more tolerable. In bipolar and schizoaffective disorders, the drug is used as a phase prophylactic and is thought to prevent rapid mood changes. In addition to these two main indications, valproate has been found to be helpful in preventing migraine attacks. It is also said to be effective against cluster headaches (pain in the eyes, forehead, and temples). Recently, an anti-cancer effect has also been discussed. This promising potential indication area is still under investigation.
Risks and side effects
Like all drugs, the active ingredient valproate carries risks and side effects. The most common side effects are: increased appetite and weight gain (especially at the beginning of treatment), nausea, vomiting, tremors, liver damage, damage to the pancreas, elevated liver enzymes, blood clotting disorders, headache, confusional states, attention deficit disorder, Parkinson’s-like symptoms, and temporary hair loss. Liver values in particular must be carefully monitored. Prescription in the presence of known liver damage, including family history, is contraindicated. Because of its effects on unborn children (decreased IQ, malformations), valproate should be prescribed only under the strictest supervision during pregnancy. In rare cases, chronic disease of the brain (encephalopathy) with disturbances of brain function may occur. Many side effects are dose-dependent and can be alleviated or avoided if the patient is well medicated. It should be noted that the therapeutic range of valproic acid is 50 to 100 mmol (at a maximum daily dose of 2,400 mg). Blood levels must therefore be monitored regularly.
