September 2010

Personalized Medicine
Even before genomic advances are ready for clinical use, "low-tech" aspects of personalized medicine can enhance psychiatric treatment.

Treating Patients with Schizophrenia: The Importance of Adherence
Antipsychotics can't work if patients don't take them. Nonadherance is a major cause of relapse among patients with schizophrenia.

Valproic Acid and Congenital Malformation
Exposure to valproic acid in the first trimester of pregnancy increases the risk of many congenital malformations in newborns.

In Brief
Bone Mineral Density Is Lower in Depressed than Nondepressed People; Few Adolescents Who Die by Suicide Have Had Recent Exposure to SSRIs

IV Ketamine Infusion Decreases Suicidal Ideation
In a study of treatment-resistant inpatients with major depressive disorder, a single IV infusion of ketamine rapidly decreased suicidal ideation.

SSRIs May Increase the Risk of Cataracts
In a pharmacoepidemiologic study, the use of selective serotonin reuptake inhibitor (SSRI) antidepressants was associated with a greater risk of cataracts among elderly patients.

Valproic Acid and Congenital Malformation

September 2010

Initially introduced for the treatment of epilepsy, valproic acid (Depakote, Depakene, and others) has been used for decades in psychiatry to treat patients with bipolar disorder. It has long been known that valproic acid can increase the risk of spina bifida if taken in the first trimester of pregnancy. Recently, Jentink and others in Europe assessed the risk of other congenital malformations in the offspring of mothers exposed to this medication.1

The authors combined data from eight published cohort studies involving 1565 pregnancies in which mothers were exposed to valproic acid. They identified 14 malformations that occurred significantly more often in the babies of women who took valproic acid during the first trimester. Investigators then assessed the association between valproic acid use during the first trimester and these 14 malformations by performing a case-control study. The entire data set comprised almost 100,000 pregnancies in 14 European countries between 1995 and 2005.

For five malformations—atrial septal defect, cleft palate, hypospadias, polydactyly, and craniosynostosis (in which one or more sutures on a baby's head closes earlier than usual and leads to an abnormally shaped head)—the risk was 2 to 7 times higher for fetuses exposed to valproic acid in the first trimester compared with controls not exposed. (Exposure to valproic acid did not increase the risk of craniosynostosis beyond that caused by other antiepileptic agents, but it did elevate the risk compared with no exposure to antiepileptic drugs.) The risk of spina bifida associated with valproic acid was 12 to 16 times greater than in control groups.

Dr Jentink's group notes that other studies have found that the risk of fetal malformations rises with higher doses of valproic acid. Their data set, however, did not include dose information.

If a woman taking valproic acid plans to become pregnant, it is best to stop this agent before she attempts to conceive to protect the fetus from malformation. However, about half of all pregnancies are unplanned, and if clinicians wait for notification and confirmation of pregnancy, the first trimester may have elapsed before the agent is discontinued. Thus, valproic acid should not be used in women of childbearing potential, unless there is compelling evidence of its benefit and of the woman's likely use of effective contraception. In addition, valproic acid may increase the risk of polycystic ovary syndrome in this population (BTP 2006;29:54).

1Jentink J, Loane MA, Dolk H, Barisic I, Garne E, Morris JK, de Jong-van den Berg LT, for the EUROCAT Antiepileptic Study Working Group: Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 2010;362:2185–2193.