November 30, 2022

Must Valproic Acid Be Utilized in Ladies of Reproductive Age? Mavens Disagree

The Magazine of Scientific Psychiatry not too long ago revealed a chain of articles on using 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 issues, and different antagonistic results.

The place there appears to be a divergence of evaluations, on the other hand, is whether or not or no longer valproic acid will have to be used in any respect in ladies of childbearing age.  A number of different nations have put strict barriers on using valproic acid in reproductive elderly ladies; the USA has no longer.




Chittaranjan Andrade, MD, et al:

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

Throughout September to November 2019, researchers tested prescriptions for 10,001 consecutive outpatients observed 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 middle 

A big share of girls (647/3,837 or 16.9%) won 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. When compared, 403 (10.5%) of three,837 ladies won a prescription for carbamazepine.  Ladies have been much more likely 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 Health facility

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

Documented indications for valproate use incorporated bipolar dysfunction (7/15), seizure issues (7/15), and migraine remedy (2/15). The house dosage of valproate was once persisted in 14 encounters. Six encounters had a documented adverse urine being pregnant check. 3 out of 15 sufferers have been pregnant. One affected person was once prescribed high-dose folate previous to admission; on the other hand, the opposite 14 sufferers had no documented folate supplementation. There have been no documented risk-benefit discussions. 

The truth is that should you deal with people of reproductive doable, you’re going to to find yourselves at the entrance strains of perinatal well being care. The best time to choose a psychotropic for being pregnant is definitely ahead of conception, deliberate or no longer. Unplanned pregnancies are commonplace, and girls with psychiatric issues is also much more likely than the overall inhabitants to have unplanned pregnancies. 

Tastenhoye and her co-authors argue that valproic will have to no longer be utilized in ladies of reproductive age, and that physicians would have the benefit of further training in regards to the dangers of valproate use in ladies of childbearing age.


Joseph F. Goldberg, MD

Dwelling in a Pharmacologically Imperfect International

On this observation, Dr. Goldberg argues that in terms of treating ladies of childbearing age, valproic acid is however one imperfect remedy possibility on an inventory of alternative imperfect choices.  He notes that 2nd technology abnormal antipsychotic medicines raise a threat of weight achieve, and a few would possibly build up threat for gestational diabetes.  Lithium is also an possibility, even if it does raise a threat, albeit small, for cardiovascular malformations.  Whilst lamotrigine does no longer seem to hold any teratogenic threat, it might not be as efficient in fighting recurrent mania.  Moreover, it isn’t transparent whether or not ladies who reply properly to valproic acid will reply similarly properly to those choices.

Indisputably, if and when a greater and more secure choice to valproate exists, it warrants most well-liked standing. Then again, the chance 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 would lend a hand to avert its inordinately excessive morbidity and mortality.

Thus, Dr. Goldberg  would favor to go away valproic acid at the desk.


Marlene Freeman, MD:

Prescribing Tenet for Valproic Acid and Ladies of Reproductive Possible: Disregard It Exists

On this observation, Dr.  Freeman notes that valproic acid is a identified teratogen that may motive a variety of main fetal malformations, together with neural tube defects, ahead of most ladies are conscious they’re pregnant. She notes the well-established literature indicating that prenatal publicity to valproic acid is related to worse neurodevelopmental results and up to date knowledge that prenatal publicity to valproic acid could have transgenerational dangers, contributing to an greater threat of malformations within the kids of uncovered people.  She argues that higher training of prescribers is just no longer sufficient.  

There’s no nuance to this: Valproic acid will have to no longer be prescribed to ladies of childbearing doable for psychiatric issues. Whilst some nations have sought to keep watch over its use and disseminate the risks of use throughout being pregnant extra prominently, there’s no enough threading of this needle. Now not as of late, when we’ve such a lot of different choices as temper stabilizers than we did many years in the past.

Simply omit it exists.


Some Ultimate Ideas

Whilst at the floor those would possibly look like dramatically divergent evaluations, they don’t seem to be.  On the center of the dialogue is the conclusion that bipolar dysfunction is an ceaselessly difficult-to-treat sickness with important morbidity.  It’s common for people with bipolar dysfunction to have an extended record of medicines they have got attempted and failed, and so they ceaselessly battle to discover a routine that maintains their balance.  

Every so often that routine would possibly come with valproic acid.  Given the dangers related to valproic acid throughout being pregnant and the excessive frequency of unplanned being pregnant, valproic acid will have to by no means be a primary selection in a girl of reproductive age.  Quite, we will have to imagine remedy choices within the context of a being pregnant one day, and our first line choices will have to come with medicines which are suitable for a given medical scenario whilst on the similar time bearing in mind knowledge on reproductive protection.

Ruta Nonacs, MD PhD




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