Registry Releases Polytherapy Findings

TOPICS ON THIS PAGE: Winter 2010 Newsletter
WINTER 2010 NEWSLETTER - Online Edition

Registry Releases Polytherapy Findings

The North American Antiepileptic Drug Pregnancy Registry is pleased to announce findings on the comparative safety of some combinations of anticonvulsant drugs. We have previously published our findings regarding phenobarbital, carbamazepine, valproate and lamotrigine taken alone as monotherapy. Since we have analyzed the rate of malformations in infants for each of these specific drugs when taken alone, we wanted to investigate the effect they might have on the prevalence of major malformations when taken in combination.

A common perception in prescribing anticonvulsant drugs during pregnancy is that the combination of two or more drugs harbors a greater risk of major malformations. As a result, monotherapy is more frequently recommended as an ideal treatment even though a woman’s condition may be better controlled with multiple antiepileptic drugs (AEDs), which is referred to as polytherapy. However, we predicted that the risk of malformation associated with a drug combination is a function of the specific drugs used in that polytherapy treatment, and therefore some combinations may be less harmful to the fetus than others.

As part of our ongoing research, we looked at combinations of the drugs we have already studied as monotherapy. Since its inception in 1997, 6,690 women have enrolled in the Registry. Among these participants, the most common drug therapies have been lamotrigine (Lamictal®) and carbamazepine (Tegretol®). We found that the rate of major malformations for lamotrigine taken as monotherapy was 1.2% and the rate of major malformations for carbamazepine taken as monotherapy was 2.5%. In comparison with these two anticonvulsant monotherapy treatments, we found that prenatal exposure to valproate has a considerably higher fetal risk. When taken as monotherapy, valproate had a 10.7% rate of major malformations. These results are compared with an external control group for which the rate malformation is 1.6%.2

When lamotrigine and carbamazepine were taken together as polytherapy, the rate of major malformation was 3.2%. We then looked at each of those drugs combined with valproate. The rate of malformation for those taking lamotrigine and valproate as polytherapy was 10.2%. The rate of malformation for those taking carbamazepine and valproate was 6.9%. The risk associated with both of these valproate polytherapy combinations was much higher than the risk of taking lamotrigine and carbamazepine combined as polytherapy. These results suggest that polytherapy treatments containing valproate result in a considerable increase of malformations. The combination of lamotrigine and carbamazepine was associated with a lower risk of malformations.




This graph demonstrates our findings in comparison with two separate studies that also evaluated the “safety” of certain combinations of anticonvulsants. The UK Epilepsy and Pregnancy Register3 and the International Lamictal Registry4 also found that polytherapy treatments that contain valproate increase the rate of major malformations. Because these three separate pregnancy registries have comparable rates, our findings are strengthened. The general trend illustrates that the fetal risks for malformations vary for the specific drugs used in polytherapy.

The findings of all three pregnancy registries suggest that we should not necessarily be concerned about polytherapy, but rather the specific combination of drugs used as polytherapy treatment. When taken by itself, valproate generates an increased risk of malformations. Additionally, when valproate is taken in combination with another AED, high rates of major malformations are found. These findings demonstrate that there are “safer” options for pregnant women who require treatment with more than one anticonvulsant drug.

In order to continue to explore the safest treatment options, we need your continued participation. We need more women to enroll so that we can provide accurate and useful information on other monotherapy and polytherapy treatments to health care providers and the women they treat. With your continued dedication and support, we can continue to seek answers to the difficult questions facing pregnant women taking antiepileptic medications. We would like to thank everyone who has contributed thus far; we are excited to have you on board as the Registry continues to grow. Please continue to encourage any woman currently taking AEDs for any reason to call us toll free at 1-888-233-2334 to enroll in the Registry.

REFERENCES:
1 Holmes L.B., et al. Birth Def Res (Part A) 2009; 85:465.
2 Nelson K., et al. N Engl J Med 1989; 320:19-23.
3 Morrow J., et al. J Neurol Neurosurg Psych 2006; 77:193-198.
4 Cunnington M., et al. Neurology 2005; 64:955-960.

http://www2.massgeneral.org/aed/winter2010.htm#poly

Web Survey for Women With Epilepsy
Please visit www.WomenWithEpilepsy.org to participate in a survey for Women With Epilepsy (WWE) who have already completed one or more pregnancies to term. The purpose of this survey is to gather information about the experiences of WWE who had seizures/epilepsy related events during pregnancy. The results of this survey will be compiled in order to give WWE who are considering pregnancy information that may help resolve some of their concerns and fears by learning from the experiences of other WWE. For more information, contact info@womenwithepilepsy.org.



Valproate study needs your help

The Genetics Unit of the MassGeneral Hospital for Children is looking for children who were exposed to the anticonvulsant drug, valproate, before birth. There has been some concern that prenatal exposure to this drug increases the risk for Autism Spectrum Disorders (ASDs) in some children. We are studying whether the effects of exposure to valproate during pregnancy depend on the child’s genetic makeup (the presence of certain genes).

To participate in this study, the children must be at least 2 years of age. The research study would require only a one-day visit as an outpatient free of charge. For some children, the visit would be shorter than an entire day. Participants will receive $100 for his/her participation, and travel expenses will be reimbursed. If you are interested in participating or would like more information, please contact Uma Deshmukh by calling 617-724-1252 or by e-mail at udeshmukh@partners.org. You can also call us at our toll-free number 1-866-354-1523.




Statistics Update

Enrollment:
7,242 participants as of November 2009

Participants:
Gravidity:
1st Pregnancy: 38%
2nd Pregnancy: 30%
3rd Pregnancy: 16%
4th + Pregnancy: 15%

Education:
Some high school or less: 20%
Some college: 24%
College: 35%
Post-graduate: 21%

Ethnicity:
White: 86%
Black: 4%
Hispanic: 6%
Other: 4%

Health Insurance
Some form of insurance: 97%

Drugs Taken:
25 different monotherapies and 197 different polytherapy combinations



Control Group Raffle

We enroll two different groups of women at the AED Pregnancy Registry. One group is case participants, who are pregnant women taking one or more anti-epileptic drugs. The other group is control participants, pregnant women not taking any AEDs. It is very important for our analyses to have a control group to compare with the women who are taking AEDs in order to better determine the risks of taking AEDs during pregnancy.

If you know of someone who can serve as a control, please ask her to call us TOLL FREE at 1-888-233-2334. As a token of our appreciation, each participant who refers a friend or family member that enrolls as control with the Registry will be entered into a drawing to win a $400 American Express Gift Card. In addition, control group members will be entered into a separate drawing to win their own $400 American Express Gift Card. You both have a chance to win! For every woman you refer as a control, you get one raffle entry. The more women you refer, the more chances you have to win the raffle!
EMAIL: info@aedpregnancyregistry.org
TOLL FREE: 1-888-233-2334
WEB: http://www.aedpregnancyregistry.org