Epilepsy drug valproate causes mental retardation in kids

Kids born to epileptic mothers using valproate (Depakote) are found to be having far low IQ levels.

The epilepsy drug valproate, which is commonly sold under the brand name Depakote,  can cause a serious side-effect: it can severely lower the intelligent quotient (IQ) levels of your kid, if consumed while in pregnancy.

The kids of mothers taking valproate had average IQs six to nine points lower than those whose moms took other epilepsy medicines, according to research published in New England Journal of Medicine.

Valproate is the second-most-popular antiseizure medication used for epilepsy. Earlier studies found that use during pregnancy also increased the risk of developmental delays and major malformations.

Valproate is also sold under brand names Depakene (Abbott Laboratories in U.S. & Canada), Convulex (Pfizer in the UK and Byk Madaus in South Africa), Stavzor (Noven Pharmaceuticals Inc.), Depakine (Sanofi Aventis), Epival (Abbott Laboratories U.S. & Canada), Epilex (Knoll Abbott in India), Valparin Alkaletes (Torrent) .

Physicians warned that valproate should never be the first choice for use in women of childbearing age, though exceptions may be made if a woman’s epileptic seizures cannot be controlled with other available medications.

Valproate “should not be used as a first-line drug for treatment of epilepsy,” Kimford Meador, who led the study and is a professor of neurology at Emory University in Atlanta, said. “Although it may be an appropriate drug in some women, there should be a discussion with their clinicians about what are the options and what are the risks.” 

Dr Meador and his colleagues enrolled 303 pregnant women who were each using an antiepileptic drug and were treated at 25 epilepsy centers in the United States and Britain from October 1999 to February 2004. Cognitive assessments were conducted in 258 2- and 3-year-olds born to 252 mothers, of whom 53 had taken valproate. Over all, children’s I.Q. scores were strongly related to mothers’ I.Q. scores, except among the children of mothers treated with valproate, the study found.

At age 3, children exposed to valproate in utero had a mean I.Q. of 92, compared with 101 for children exposed to lamotrigine, 99 for those exposed to phenytoin, and 98 for those exposed to carbamazepine, the study found. Some 13,000 to 21,000 babies each year are born to women with epilepsy, and the vast majority are healthy, researchers and advocates emphasized.

The average IQ for children whose mothers took valproate during pregnancy was 92. The score was 101 for offspring of mothers who took lamotrigine, 99 for phenytoin, and 98 for carbamazepine.

IQ is a number derived from standardized tests. The measure is designed to yield an average score of 100 in the general population. An IQ of 70 or below is considered an indication of retardation.

Valproate contains valproic acid (2-propylvaleric acid). Valproate  is believed to affect the function of the neurotransmitter GABA (as a GABA transaminase inhibitor) in the human brain, making it an alternative to lithium salts in treatment of bipolar disorder.In addition to blocking transamination of GABA, Valproate is believed to reverse the transamination process to form more GABA. Hence, Valproate indirectly acts as a GABA agonist. However, several other mechanisms of action in neuropsychiatric disorders have been proposed for valproic acid in recent years.

Valproic acid also blocks the voltage-gated sodium channels and T-type Calcium channels.These mechanisms make valproic acid a broad spectrum anticonvulsant drug.

Valproic acid is an inhibitor of the enzyme histone deacetylase 1 (HDAC1) hence it is a histone deacetylase inhibitor.

Abbott Laboratories, based in Abbott Park, Illinois, sells Depacon, an intravenous form of valproate, as well as Depakote, a tablet known chemically as divalproex sodium, which becomes valproate in the body.

Valproate is also sold as a generic by Abraxis Biosciences Inc based in Los Angeles, and Bedford Laboratories, a unit of Boehringer Ingelheim GmbH of Ingelheim, Germany, according to information on the Web site of the US Food and Drug Administration.