Discussion Questions

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  Why is this study question important?

  
  
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  When and how were exposures identified?

  
  
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  How was the analysis carried out?

  
  
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  What were the results?

  
  
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  What were the study’s strengths and weaknesses?

  
  
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  How can we put this study in context?

Topiramate was approved in the United States in 1996 for the treatment of generalized tonic-clonic and partial seizures. An indication for migraine prophylaxis was added in 2004. The drug has been used on an off-label basis for eating, sleep, and psychiatric disorders. Recently, a combination of phentermine and topiramate was approved for chronic weight management in overweight or obese adults with a weight-related disorder. Margulis and colleagues, noting that some of these conditions are particularly prevalent among women of child-bearing age, looked for a link between topiramate use in pregnancy and cleft lip with or without cleft palate in offspring.

A problem worth solving

Journal Club participants felt that the study question was very important. First, use of antiseizure drugs is common in women of reproductive age. This population includes the estimated 0.5% of pregnant women in the United States who have epilepsy. Thus, the question of medication safety for this indication comes up very often in routine clinical practice. Second, some of the older antiseizure medications, such as valproate and phenytoin, have a well-characterized risk for a constellation of congenital abnormalities. As practitioners, we may look at newer drugs and assume they are safer than older alternatives, when, in fact, data to support this idea have yet to be generated. Topiramate is a relatively new anticonvulsant. Consider, for example, that phenobarbital has been available for about 100 years; phenytoin, for more than 70. As a drug’s use expands, we continue to learn more about it. Third, postmarketing studies have suggested that use of this drug during pregnancy might be associated with clefting, although the actual mechanism is not clear. But based on this prior data, the authors were wise to focus on cleft lip with or without cleft palate. Lastly, cleft lip and palate are serious conditions, and understanding risk factors for their occurrence is important.