Since ancient times, hundreds of disorders and alterations have affected human health. But among all the diseases, there is one linked to the hyperexcitability of neuronal groups that is so old and virulent that it was considered “the sacred disease”.

This is epilepsy , a condition that has been poorly understood until relatively recent times and which has important repercussions for those who suffer from it if they do not receive treatment.

Fortunately, the progress of science has allowed different types of treatment to be developed, among which we can find the use of drugs. In this sense, one of the most widely used drugs in the treatment of this condition is valproate or valproic acid , which we will discuss throughout this article.

Valproic acid or valproate: what is it?

Valproic acid is an anti-convulsive psychoactive drug , a type of substance that is useful in combating and preventing the appearance of seizures and convulsions in general. It is one of the best known drugs used in the context of epilepsy treatment, together with carbamazepine and topiramate.

Despite being an anticonvulsant, its chemical composition differs from that of the rest of the representatives in his group.

Valproate is a highly effective and potent drug (prescription only), which also has eutimizing or mood-stabilizing effects and is considered to be broad-spectrum. It can be found under various names, such as valproate, manganese valproate or sodium valproate, and some of the better known trademarks are Depakote or Depakine.

Valproic acid can be administered by two main routes, oral and intravenous . The first is the most widely marketed, in tablet or pill form, and is usually applied in outpatient treatment. The intravenous version can be found in the form of vials whose contents are injected, and is usually reserved for the hospital setting or for emergency situations.

Mechanism of action

Valproic acid exerts its effects on the organism thanks to a mechanism of action based on the agonism of gamma-aminobutyric acid or GABA , that is, on the promotion of the production and action of this neurotransmitter in the organism. In addition, it also generates a decrease in glutamate levels and alters the behavior of the sodium, potassium and calcium receptors of our neurons (reducing their conductivity).

Taking into account that glutamate is one of the exciting neurotransmitters par excellence of our brain and that GABA is the main inhibitory neurotransmitter of the nervous system, the effects of these alterations in the levels of both will generate a reduction in nerve activity, This is fundamental in the treatment of epilepsy (in which there is an overactivation of groups of neurons that have become hypersensitive, so that minor stimulation can trigger an intense response) and in other disorders in which there is an excess of neuronal activity.

Main indications for this drug

As an antiepileptic or anticonvulsant, the main indication for valproic acid is in those who suffer from epilepsy or seizures , both those that include convulsions and the so-called “absence seizures”. This drug is prescribed to both adults and children with this condition, although caution is needed with doses and monitoring of possible side effects.

In addition, valproate is the only anticonvulsant that is officially indicated for bipolar disorder, although other drugs from the same group may also be beneficial. This is due to the aforementioned euthymizing or mood-stabilizing effect.

It is not that it increases or decreases the mood itself, but that it keeps it within margins. In this sense, it is effective in the treatment and prophylaxis of manic episodes , whether used in conjunction with lithium salts or administered as monotherapy.

These are not the only indications of valproic acid. In addition to the above, is also indicated in the treatment of migraines , in adult subjects, and its possible efficacy in problems such as dementia due to HIV or muscular atrophy due to damage to the spine is explored.

Side effects and risks

Valproic acid is a valuable drug that can help treat a variety of conditions, but its use can sometimes lead to undesirable and even dangerous side effects.

Among some of the most common side effects we can find the presence of tremors, nausea or vomiting .

Other side effects may include extrapyramidal (motor) disturbances, drowsiness, involuntary eye movement, confusion, incontinence, hearing problems, transient hair loss, gum hypertrophy, mouth inflammation, abdominal pain, diarrhea, weight gain or memory problems, attention and learning, irritability, and aggression.

Also can appear parkinsonism (reversible), uncoordination or paresthesias, dysmenorrhea and pain during menstruation, infertility (in the case of men), as well as hallucinations.

More relevant and much more dangerous (in fact with a mortal potential, which is why the doses and administration of this drug has to be very controlled), although less frequent are problems such as anemia, hypothyroidism, a possible thrombocytopenia or decrease in the number of platelets, decrease in blood sodium, hemorrhages and liver lesions, pancytopenia or decrease in the main components of the blood, leukopenia or decreased white blood cells, encephalopathy, pancreatitis, osteoporosis, problems with antidiuretic hormone and decreased electrolytes, hyperandrogenism, kidney failure, vasculitis, bone marrow failure, increased chance of myelodysplastic syndrome, infertility, rhabdomyolysis, nephritis, or clotting problems

Contraindications

Despite its great usefulness in the treatment of the above-mentioned conditions, valproic acid is a very powerful drug and as we have seen can have very dangerous side effects . In this sense, there are groups and sectors of the population for whom the use of valproate is severely contraindicated.

The use of valproate is contraindicated in those who have any type of condition in the liver, pancreas or kidneys , especially in the case of renal or hepatic insufficiency. It is also relevant that it is not taken by those with some type of hematological condition.

It is also contraindicated and discouraged in the case of pregnant women , since it has been shown to increase the risk of malformations in the fetus and alterations such as spina bifida, as well as the existence of a fetal valproate syndrome. In this sense, care should be taken not only by pregnant and lactating women but also by those who are considering becoming mothers in the near future (an appointment with the doctor will be necessary to evaluate therapeutic alternatives to valproate).

It should also not be taken by people allergic to valproate or any of its excipients, or in combination with topiramate or IMAOS (as their interaction can be dangerous). They should not be taken with alcohol and caution should be exercised with the use of hormone-type contraceptives (as they may interact). If other drugs are taken, the suitability of valproic acid treatment should be discussed with the doctor.

Bibliographic references:

  • Spanish Agency for Medicines and Healthcare Products (2018). Leaflet: Information for the user. Depakine 200 mg/ml oral solution. Ministry of Health. Spain. [Online]. Available at: https://cima.aemps.es/cima/dochtml/p/48828/P_48828.html.
  • Macritchie, K. and Geddes, J.R., Scott, J., Haslam, D., De Lima, M., Goodwin, G. (2008). Valproate for acute mood episodes in bipolar disorder. Cochrane Library. [Online]. Available at: https://www.cochrane.org/es/CD004052/valproato-para-los-episodios-agudos-del-estado-de-animo-del-trastorno-bipolar.
  • US National Library of Medicine (2017). Valproic acid. MedlinePlus [Online]. Available at: https://medlineplus.gov/spanish/druginfo/meds/a682412-es.html.