Ought to Valproic Acid Be Utilized in Ladies of Reproductive Age? Consultants Disagree


The Journal of Scientific Psychiatry just lately printed a collection of articles on the usage of valproic acid in ladies of childbearing age.  All of us agree that valproic acid is a teratogen and is related to unacceptably excessive charges of main congenital malformations, together with neural tube defects, neurodevelopmental problems, and different hostile outcomes.

The place there appears to be a divergence of opinions, nonetheless, is whether or not or not valproic acid needs to be used in any respect in ladies of childbearing age.  A number of different international locations have put strict limitations on the usage of valproic acid in reproductive aged ladies; america has not.




Chittaranjan Andrade, MD, et al:

Use of Valproate in Ladies: An Audit of Prescriptions to 10,001 Psychiatry, Neurology, and Neurosurgery Outpatients

Throughout September to November 2019, researchers examined prescriptions for 10,001 consecutive outpatients seen within the Departments of Psychiatry, Neurology, and Neurosurgery on the Nationwide Institute of Psychological Well being and Neurosciences in Bangalore, India, a big, tertiary care referral heart 

A big proportion of ladies (647/3,837 or 16.9%) acquired a prescription for valproate (imply dose?=?898 mg/d).  Ladies between the ages of 15 and 45 years accounted for 71.1% of those prescriptions. Compared, 403 (10.5%) of three,837 ladies acquired a prescription for carbamazepine.  Ladies had been extra prone to obtain a prescription for valproate within the Departments of Neurology and Neurosurgery than within the Division of Psychiatry (29.1% vs 14.4%, respectively).


Camille Tastenhoye, MD et al:

Valproate Prescribing Practices in People of Childbearing Age at a Tertiary Care Ladies’s Hospital

Researchers from the College of Pittsburgh reviewed a database of digital medical data from a tertiary care ladies’s hospital and recognized ladies of childbearing age (12–52 years) who acquired valproate throughout medical admission (January 1, 2019, to December 31, 2019). They recognized 15 distinctive sufferers handled with valproate. 

Documented indications for valproate use included bipolar dysfunction (7/15), seizure problems (7/15), and migraine remedy (2/15). The house dosage of valproate was continued in 14 encounters. Six encounters had a documented adverse urine being pregnant check. Three out of 15 sufferers had been pregnant. One affected person was prescribed high-dose folate previous to admission; nonetheless, the opposite 14 sufferers had no documented folate supplementation. There have been no documented risk-benefit discussions. 

The truth is that when you deal with people of reproductive potential, you’ll find yourselves on the entrance traces of perinatal well being care. The best time to pick a psychotropic for being pregnant is effectively earlier than conception, deliberate or not. Unplanned pregnancies are widespread, and ladies with psychiatric problems could also be extra possible than the final inhabitants to have unplanned pregnancies. 

Tastenhoye and her co-authors argue that valproic shouldn’t be utilized in ladies of reproductive age, and that physicians would profit from further schooling concerning the dangers of valproate use in ladies of childbearing age.


Joseph F. Goldberg, MD

Residing in a Pharmacologically Imperfect World

On this commentary, Dr. Goldberg argues that on the subject of treating ladies of childbearing age, valproic acid is however one imperfect remedy choice on a listing of different imperfect choices.  He notes that second technology atypical antipsychotic drugs carry a danger of weight achieve, and a few might enhance danger for gestational diabetes.  Lithium could also be an choice, though it does carry a danger, albeit small, for cardiovascular malformations.  Whereas lamotrigine doesn’t seem to hold any teratogenic danger, it is probably not as efficient in stopping recurrent mania.  Moreover, it’s not clear whether or not ladies who reply effectively to valproic acid will reply equally effectively to those alternate options.

Actually, if and when a greater and safer various to valproate exists, it warrants most well-liked standing. Nevertheless, the danger for relapse and purposeful impairment in bipolar dysfunction stays excessive even with state-of-the-art care, making it a dangerous proposition to advise an absolute moratorium on any remedy that might assist to avert its inordinately excessive morbidity and mortality.

Thus, Dr. Goldberg  would like to depart valproic acid on the desk.


Marlene Freeman, MD:

Prescribing Guideline for Valproic Acid and Ladies of Reproductive Potential: Overlook It Exists

On this commentary, Dr.  Freeman notes that valproic acid is a recognized teratogen that may trigger a variety of main fetal malformations, together with neural tube defects, earlier than most girls are conscious they’re pregnant. She notes the well-established literature indicating that prenatal publicity to valproic acid is related to worse neurodevelopmental outcomes and up to date information that prenatal publicity to valproic acid might have transgenerational dangers, contributing to an elevated danger of malformations within the youngsters of uncovered people.  She argues that higher schooling of prescribers is solely not sufficient.  

There is no such thing as a nuance to this: Valproic acid shouldn’t be prescribed to ladies of childbearing potential for psychiatric problems. Whereas some international locations have sought to manage its use and disseminate the hazards of use throughout being pregnant extra prominently, there isn’t a adequate threading of this needle. Not immediately, when we’ve so many different choices as temper stabilizers than we did a long time in the past.

Simply neglect it exists.


Some Remaining Ideas

Whereas on the floor these might look like dramatically divergent opinions, they aren’t.  On the coronary heart of the dialogue is the conclusion that bipolar dysfunction is an usually difficult-to-treat sickness with important morbidity.  It’s commonplace for people with bipolar dysfunction to have a protracted checklist of medicines they’ve tried and failed, they usually usually wrestle to discover a routine that maintains their stability.  

Generally that routine might embrace valproic acid.  Given the dangers related to valproic acid throughout being pregnant and the excessive frequency of unplanned being pregnant, valproic acid ought to by no means be a primary alternative in a lady of reproductive age.  Somewhat, we should always contemplate remedy choices within the context of a being pregnant sooner or later, and our first line choices ought to embrace drugs which are applicable for a given medical state of affairs whereas on the similar time contemplating information on reproductive security.

Ruta Nonacs, MD PhD




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