There have long been concerns regarding the use of the anticonvulsant valproate (Depakote) during pregnancy. First trimester use of valproate has been associated with a 3-5% risk of neural tube defects, as well as an increased risk of other malformations affecting the heart, limbs, and genitals. Prenatal exposure to valproate may also result in lower IQ and increased risk of autism spectrum disorders in the offspring.
Because of these risks, it is recommended that all women of reproductive age taking valproic acid should use effective contraception and should also take folic acid to reduce the risk of birth defects if an unplanned pregnancy occurs. But does this really happen?
Using electronic medical record (EMR) and administrative claims data, researchers conducted a retrospective chart review which included all reproductive-aged female patients at a major medical center in the Midwest who were taking valproic acid (VPA) as treatment for their psychiatric illness (n = 190; aged from 15 to 49 years). In reviewing the charts, they asked three questions:
- Was there documentation of a discussion with the patient regarding the potential teratogenicity associated with VPA use?
- Did the patient receive a prescription for contraception?
- Was the patient taking a folic acid supplement?
The results were disappointing. Documentation of discussions related to the possible teratogenicity of VPA was rare (13.2%), as was documentation of contraception use (30%) and prescription of folic acid supplements (7.9%). Neurologists were more likely to adhere to these guidelines than psychiatrists.
Given the risks associated with the use of valproic acid during pregnancy and the poor adherence to standard guidelines observed in this study (even at an academic tertiary care center), the authors question whether valproic acid should be used at all in women of reproductive age.
Raising similar concerns, last year the European Medicine Agency (EMA)’s Pharmacovigilance and Risk Assessment Committee recommended restricting the use of valproic acid in women of reproductive age. The EMA made the following specific recommendations regarding the use of valproic acid in this population:
- If possible, an alternative to valproic acid should be used in women of reproductive age
- If valproic acid is the only option, women should use effective contraception and should be closely supervised.
- Doctors who prescribe valproic acid to women of reproductive age must review the reproductive risks associated with this drug and must clearly explain the reason for choosing valproic acid over other options.
- Women taking valproic acid should also take 4mg of folic acid daily to reduce the risk of birth defects in the setting of unplanned pregnancy.
Ruta Nonacs, MD PhD
Balon R, Riba M.
J Clin Psychiatry. 2016 Apr;77(4):525-6. Free Article
Gotlib D, Perelstein E, Kurlander J, Zivin K, Riba M, Muzik M.
J Clin Psychiatry. 2016 Apr;77(4):527-34.