Topamax Linked to Cleft Palate, Cleft Lip and Other Birth Defects

New research indicates that the use of the epilepsy and migraine drug Topamax, either on its own or in combination with other epilepsy drugs, may increase the risk of birth defects when it is used during pregnancy. A small study found much higher than expected incidences of babies born with cleft lips, cleft palates, genital defects or other birth malformations among women using the drug.

The findings are reported in the July 22, 2008 issue of Neurology, the medical journal of the American Academy of Neurology (AAN). Researchers at the Royal Group of Hospitals in Belfast, Northern Ireland, followed 203 women who were pregnant while taking topiramate, which is available as a generic or under the brand name Topamax.

Women included in the study were epileptics taking either Topamax alone or Topamax in combination with another epilepsy drug. Of the 178 babies born, 16 had major birth defects. Mothers of three of these infants were taking only Topamax while in the remaining 13 cases the mothers were taking Topamax along with other epilepsy drugs.

Four of the babies were born with cleft lips or palates, which is a rate 11 times higher than what would be expected in the general population. Cleft lip and palate is a congenital deformity caused by abnormal facial development during gestation, where cartilage does not fuse correctly. Often the birth defect can be treated with surgery, but it may cause problems with feeding, ear disease, speech problems and difficulty with socialization as the child ages.

Four of the male babies born to women in the study were found to have genital defects, which is a rate 14 times higher than what would be expected in the general population. Two of these babies were diagnosed with hypospadias, in which the opening of the urinary tract is not at the tip of the penis.

Topamax is manufactured by Ortho-McNeil Neuologics, a subsidiary of Johnson & Johnson. When it was first introduced, it was only approved by the FDA for treatment epilepsy, which is a neurological disorder characterized by recurrent uncontrolled seizures. In 2004, the FDA approved Topamax for an additional use of treating severe headaches known as migraines. It is also used off-label by many doctors to treat bipolar disorder. Generic forms of the drug began to appear in 2006.

“More research needs to be done to confirm these results, especially since it was a small study,” said John Craig, MRCP, of the Royal Group of Hospitals. “But these results should also get the attention of women with migraine and their doctors, since topiramate is also used for preventing migraine, which is an even more common condition that also occurs frequently in women of childbearing age.”

Although the study only involved women with epilepsy, it does raise concerns about the overall risk of Topamax birth defects. Topamax has become one of the most widely prescribed migraine medications in the United States, and women generally suffer from migraines three times more often than men.