[SSRI-Research] MedPage - Depakote Has High Birth Defects Rate Among Antiepilept

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[sSRI-Research] MedPage - Depakote Has High Birth Defects

Rate Among Antiepileptics

 

 

 

 

*Here is more information about the anticonvulsant- birth defect link.

Depakote and Lamictal**is are labeled for the treatment of certain

phases associated with bipolar disorder. Tegretol has no labled

psychiatric uses, but is sometimes prescribed offlabel for these

patients, or sometimes to control the iatrogenics of other meds.*

*

Vince

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*

 

http://www.medpagetoday.com/Neurology/Seizures/tb/3884

 

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*Depakote Has High Birth Defects Rate Among Antiepileptics

*

By Neil Osterweil, Senior Associate Editor, MedPage Today

Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of

Pennsylvania School of Medicine.

<http://www.medpagetoday.com/reviewer.cfm?reviewerid=30>

August 08, 2006

Also covered by: Forbes

<http://www.forbes.com/forbeslife/health/feeds/hscout/2006/08/08/hscout534268.ht\

ml>

, LA Times

<http://www.latimes.com/news/printedition/asection/la-sci-epilepsy8aug08,1,29599\

03.story?coll=la-news-a_section>

 

* GAINSESVILLE, Fla., Aug. 8 -- When it comes to antiepileptic drugs for

pregnant women with epilepsy, Depakote (valproate) should be at the

bottom of the list, according to the Neurodevelopmental Effects of

Antiepileptic Drugs study group.*

 

* *

 

*Major congenital malformations and fetal deaths were significantly more

common in pregnancies of women taking Depakote compared with other

antiepileptic drugs, and the effect of Depakote was dose-dependent,

Kimford J. Meador, M.D., and colleagues, reported in the Aug, 8 issue of

/Neurology/. *

 

* *

 

*The findings come from a prospective observational study comparing

Depakote monotherapy in pregnant women with Lamictal (lamotrigine),

Tegretol (carbamazepine), and Dilantin (phenytoin). *

 

* *

 

*The study was performed because pregnancy outcomes following in utero

exposure to antiepileptic drugs are uncertain, leaving clinicians with

no evidence-based approach to selection of these drugs for pregnant

women. *

 

* *

 

* " These results combined with several recent studies provide strong

evidence that valproate poses the highest risk to the fetus, " the

investigators wrote. " For women who fail other antiepileptic drugs and

require valproate, the dose should be limited if possible. " *

 

* *

 

*Of the agents studied, the four most commonly used antiepileptic drugs,

Lamictal appeared to pose the lowest risk to the fetus, but this finding

has not been seen in other studies, and needs to be confirmed through

additional studies, the authors noted. *

 

* *

 

*The report was part of an ongoing prospective observational study at 25

epilepsy centers in the United States and United Kingdom. The study was

designed to determine whether there are differential long-term cognitive

and behavioral neurodevelopmental effects for the offspring of pregnant

women with epilepsy. *

 

* *

 

*The investigators looked at a total of 333 mother and child pairs for

in utero exposures to monotherapy with either Tegretol (110 pairs),

Lamictal (98 pairs) Dilantin (56 pairs), or Depakote (69 pairs). *

 

* *

 

*The outcomes of pregnancies for all women in the study were monitored,

and the principal investigators at each of the centers reviewed and

classified adverse events. A board-certified medical geneticist was

consulted to determine whether major malformations in the fetuses or

infants could be attributable to antiepileptic drugs. *

 

* *

 

*The authors also controlled for a variety of potentially confounding

factors, including maternal IQ, education, race, seizure type and

frequency, antiepileptic drug dosages and compliance, and socioeconomic

status. *

 

* *

 

*They also controlled for use of folate prior to conception; use of

tobacco, alcohol or other drugs during pregnancy; history of prior

pregnancy abnormalities, complications during current pregnancy,

gestational age at enrollment, and birth weight. *

 

* *

 

*They found that 20.3% of women taking Depakote had pregnancies with

serious adverse outcomes, compared with 10.7% of those taking Dilantin,

8.2% of those on Tegretol, and 1.0% of those on Lamictal. *

 

* *

 

*The distribution of serious adverse outcomes differed significantly

across the agents studied, and could only be explained by differences in

in utero exposure, the investigators reported. *

 

* *

 

*There were 12 serious adverse events in the Depakote group, including

brachycephaly, coarctation of the aorta, hypoplastic right heart, atrial

septal defects, hydronephrosis, undescended testes, hypospadias, cleft

palate, dysplastic ribs, hand malformations, and pulmonary stenosis. *

 

* *

 

*Tegretol was associated with five adverse events, including absent

kidney, duplicate renal pelvis, two cases of hypospadias, and an

inguinal hernia. The hypospadias and hernia required surgical repair. *

 

* *

 

*There were four adverse events in the Dilantin group, including

agenesis of the corpus callosum, ventricular septal defect,

hydronephrosis with extra renal pelvis, and undescended testicle

requiring surgery. *

 

* *

 

*The single event occurring in patients in the Lamictal group was a

ventricular septal defect. *

 

* *

 

*The investigators found that there was a dose-dependent effect of

Depakote on total serious adverse outcomes. *

 

* *

 

* " The rate of serious adverse outcomes was 24.2% for valproate when

doses were at or above the median first trimester dose (i.e., 900

mg/day) and was 9.1% for doses below the median, " they wrote. " The mean

(range) dose for those with serious adverse outcomes was 1,268 mg/day

(200 to 2,750 mg/day) and for those without malformations was 844 mg/day

(200 to 2,000 mg/day). " *

 

* *

 

*The findings suggest that pregnant women with epilepsy should be

maintained whenever possible on antiepileptic drugs other than Depakote,

or if their seizures are controlled only on Depakote, that they take the

lowest possible effective dose, the investigators recommended. *

 

*Additional Seizures Coverage

<http://www.medpagetoday.com/Neurology/Seizures/indexC.cfm>

Primary source: Neurology

Source reference:

Meador KJ et al. " In utero antiepileptic drug exposure: Fetal death and

malformations. " <http://www.neurology.org/cgi/content/abstract/67/3/407>

/Neurology/ 2006;67:407-412 *