[7] Valproate is known to cause serious abnormalities or birth defects in the unborn child if taken during pregnancy,[7][8] and is contra-indicated for women of childbearing age unless the drug is essential to their medical condition and the person is also prescribed a contraceptive.

[10] The United States Food and Drug Administration has indicated a black box warning given the frequency and severity of the side effects and teratogenicity.

[7][13] Proposed mechanisms include affecting GABA levels, blocking voltage-gated sodium channels, inhibiting histone deacetylases, and increasing LEF1.

[19][20] Valproate or valproic acid is used primarily to treat epilepsy and bipolar disorder and to prevent migraine headaches.

[4] There is evidence that valproic acid may cause premature growth plate ossification in children and adolescents, resulting in decreased height.

[39] There is evidence that shows valproic acid may increase the chance of polycystic ovary syndrome (PCOS) in women with epilepsy or bipolar disorder.

Studies have shown this risk of PCOS is higher in women with epilepsy compared to those with bipolar disorder.

[4] Excessive amounts of valproic acid can result in somnolence, tremor, stupor, respiratory depression, coma, metabolic acidosis, and death.

In general, serum or plasma valproic acid concentrations are in a range of 20–100 mg/L during controlled therapy, but may reach 150–1500 mg/L following acute poisoning.

Monitoring of the serum level is often accomplished using commercial immunoassay techniques, although some laboratories employ gas or liquid chromatography.

[33] It may also interact with:[4][33][54] Although the mechanism of action of valproate is not fully understood,[33] traditionally, its anticonvulsant effect has been attributed to the blockade of voltage-gated sodium channels and increased brain levels of the inhibitory synaptic neurotransmitter gamma-aminobutyric acid (GABA).

By inhibition of histone deacetylase, it promotes more transcriptionally active chromatin structures, that is it exerts an epigenetic effect.

[58][59] Valproic acid has been found to be an antagonist of the androgen and progesterone receptors, and hence as a nonsteroidal antiandrogen and antiprogestogen, at concentrations much lower than therapeutic serum levels.

[60][61] Valproic acid has been found to directly stimulate androgen biosynthesis in the gonads via inhibition of histone deacetylases and has been associated with hyperandrogenism in women and increased 4-androstenedione levels in men.

[62][63] High rates of polycystic ovary syndrome and menstrual disorders have also been observed in women treated with valproic acid.

[68] The other major pathway in the metabolism of valproate is mitochondrial beta oxidation, which typically accounts for over 40% of an administered dose.

In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity.

[7] In 2012, pharmaceutical company Abbott paid $1.6 billion in fines to US federal and state governments for illegal promotion of off-label uses for Depakote, including the sedation of elderly nursing home residents.

[103][104] Some studies have suggested that valproate may reopen the critical period for learning absolute pitch and possibly other skills such as language.

A 2023 systematic review of the literature identified only one study in which valproate was evaluated in the treatment of seizures in infants aged 1 to 36 months.