Treatment with valproate during the first trimester of pregnancy is associated with a 1–2% risk of neural tube defects including spina bifida. In addition, an increased incidence of cardiovascular, orofacial, and digital abnormalities has been noted. Finally, cognitive impairment in offspring has been reported.
These observations must be strongly considered in the choice of drugs in women of child-bearing potential.
Topiramate is a broad-spectrum antiseizure drug whose chemical structure is that of a sulfamate-substituted monosaccharide derived from d-fructose. It is used in the treatment of focal seizures, primary generalized seizures, and seizures in the Lennox-Gastaut syndrome. Topiramate is also commonly used for migraine headache prophylaxis.
Mechanism of Action
Topiramate likely acts through several cellular targets, which may account for its broad-spectrum activity in epilepsy and migraine. Possible sites of action relevant to its clinical activities are (1) voltage-gated sodium channels; (2) GABAA receptor subtypes; and (3) AMPA or kainate receptors. The drug is a weak inhibitor of carbonic anhydrase isoenzymes II and IV, but this is not thought to account for its antiseizure effects. In rare cases, the inhibition of carbonic anhydrase may cause metabolic acidosis of clinical importance.