What risks are associated with this drug?
On January 15, the Spanish Agency for Medicines and Health Products (AEMPS) issued a statement warning of the risk of possible changes in the neurodevelopment of children following paternal exposure to valproate in the months before conception. Who is this drug indicated for? And why can it cause such serious harm?
Valproate or valproic acid is one of the first antiepileptic drugs marketed in Spain, although today it is also used as an euthymiser (mood stabilizer) in patients with bipolar disorder. It belongs to a large family of therapeutic compounds that also includes phenytoin, carbamazepine, popular benzodiazepines, pregabalin, gabapentin, levetiracetam and topiramate.
Interesting family of drugs
All are designed to alter neuronal excitability through different molecular pathways and mechanisms of action. We are talking about a very important pharmacological group because, in addition to their effectiveness against epilepsy, they also have other therapeutic applications. For example, pregabalin and gabapentin relieve neuropathic pain, and topiramate prevents migraines.
Valproate is derived from a fatty acid whose antiepileptic effects have been known since the 1960s. It comes in various forms: gastro-resistant tablets, extended-release tablets, oral solution or injection. Although there are other newer antiepileptic drugs with better safety profiles, valproate continues to have a reputation for its benefits in patients with bipolar disorder.
These anticonvulsant and mood-stabilizing effects are mainly due to an increase in the activity of the neurotransmitter GABA in the brain, the sedative effect of which occurs by reducing neuronal activity. Its effectiveness may also be explained by another mechanism: inhibition of sodium channels, which also reduces the excitability of neurons in certain areas of the brain.
Serious fetal abnormalities
But, as we noted earlier, valproate can cause serious side effects. Despite years of its use, one of the main manufacturers and marketers of drugs based on this compound made headlines in 2022 when a Madrid court ordered it to pay a million dollars in compensation to families whose mothers used one of its brands. , during pregnancy.
The Association of Valproic Acid Syndrome Victims (Avisav) recognizes the decision as groundbreaking because it stops the use of a drug with serious consequences after in utero exposure.
Teratogenicity is the ability to cause changes in the structure or function of the fetus, and it came into the pharmacological field after the thalidomide incident in the 50s and 60s. Valproic acid is considered an active ingredient with high teratogenicity. potential (category D), with toxic effects demonstrated in both animal embryos and humans.
It is now estimated that approximately 10% of children exposed to valproic acid in utero may develop malformations such as spina bifida, cleft palate, and cardiac or genital abnormalities. And at least 30-40% will be affected by developmental abnormalities such as delayed walking, difficulties with speech, language or memory, and autism spectrum disorder.
Men should be vigilant too
What’s new is that the effects are not limited to pregnant mothers. An observational study conducted in Scandinavian countries suggests that about 5% of children whose male parents took valproate may also have changes in their neurodevelopment.
These data confirm the results of other work published in 2020. The researchers showed that the sperm of men taking valproate was of lower quality (they had fewer sperm and changes in sperm motility and morphology) than men taking antiepileptic drugs. y newer ones such as lamotrigine or levetiracetam.
AEMPS reminds that men taking valproate should be aware of these effects and take the following precautions: tell their doctor, do not donate sperm, consult a doctor about other alternatives if they want to become parents, use contraception and report whether they took this drug at the time of conception.