The Journal of Medical Psychiatry not too long ago revealed a collection of articles on using valproic acid in girls 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 adversarial outcomes.
The place there appears to be a divergence of opinions, nevertheless, is whether or not or not valproic acid must be used in any respect in girls of childbearing age. A number of different international locations have put strict limitations on using valproic acid in reproductive aged girls; the US 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 girls acquired a prescription for carbamazepine. Ladies have 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:
Researchers from the College of Pittsburgh reviewed a database of digital medical data from a tertiary care girls’s hospital and recognized girls 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 issues (7/15), and migraine therapy (2/15). The house dosage of valproate was continued in 14 encounters. Six encounters had a documented unfavorable urine being pregnant take a look at. Three out of 15 sufferers have been pregnant. One affected person was prescribed high-dose folate previous to admission; nevertheless, the opposite 14 sufferers had no documented folate supplementation. There have been no documented risk-benefit discussions.
The fact is that if you happen to deal with people of reproductive potential, you’ll find yourselves on the entrance strains of perinatal well being care. The best time to pick out a psychotropic for being pregnant is nicely earlier than conception, deliberate or not. Unplanned pregnancies are widespread, and girls with psychiatric issues could also be extra doubtless than the final inhabitants to have unplanned pregnancies.
Tastenhoye and her co-authors argue that valproic shouldn’t be utilized in girls of reproductive age, and that physicians would profit from extra training concerning the dangers of valproate use in girls of childbearing age.
Joseph F. Goldberg, MD
On this commentary, Dr. Goldberg argues that on the subject of treating girls of childbearing age, valproic acid is however one imperfect therapy choice on a listing of different imperfect choices. He notes that second era atypical antipsychotic drugs carry a danger of weight achieve, and a few could improve 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 might not be as efficient in stopping recurrent mania. Moreover, it isn’t clear whether or not girls who reply nicely to valproic acid will reply equally nicely to those options.
Actually, if and when a greater and safer various to valproate exists, it warrants most popular 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 therapy that would assist to avert its inordinately excessive morbidity and mortality.
Thus, Dr. Goldberg would favor to depart valproic acid on the desk.
Marlene Freeman, MD:
On this commentary, Dr. Freeman notes that valproic acid is a identified 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 could have transgenerational dangers, contributing to an elevated danger of malformations within the youngsters of uncovered people. She argues that higher training of prescribers is just not sufficient.
There isn’t any nuance to this: Valproic acid shouldn’t be prescribed to girls of childbearing potential for psychiatric issues. Whereas some international locations have sought to control its use and disseminate the hazards of use throughout being pregnant extra prominently, there isn’t a enough threading of this needle. Not at present, when now we have so many different choices as temper stabilizers than we did many years in the past.
Simply neglect it exists.
Some Last Ideas
Whereas on the floor these could look like dramatically divergent opinions, they don’t seem to be. On the coronary heart of the dialogue is the belief 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 listing of medicines they’ve tried and failed, they usually usually wrestle to discover a routine that maintains their stability.
Typically that routine could 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 selection in a girl of reproductive age. Slightly, we must always take into account therapy choices within the context of a being pregnant sooner or later, and our first line choices ought to embrace drugs which are acceptable for a given medical state of affairs whereas on the identical time contemplating information on reproductive security.
Ruta Nonacs, MD PhD