Commentary on Ohtahara

Dr. Ohtahara’s discussion addressed the results of a postmarketing study of adverse events reported by Japanese patients treated with zonisamide monotherapy and polytherapy. The 1512 study participants included both adults and children with partial and generalized seizures and no previous zonisamide treatment. Adverse effects were reported and categorized by each participating physician and ranked, according to a predetermined scale. The adverse effects and teratogenicity were compared with the results from the zonisamide developmental trial. Because of the benzisoxazole-based chemical structure of zonisamide, adverse effects similar to other currently used antiepileptic drugs may be expected. However, Dr. Ohtahara did not anticipate the adverse effects of zonisamide therapy to be more severe than those noted in other antiepilepsy drugs. This expectation was supported in the postmarketing study in which 476 (31.5%) participants reported 1089 adverse effects. This rate was lower than the 51.3% adverse effect rate reported in the premarketing trial. The most frequently reported adverse effects in Dr. Ohtahara’s study included psychiatric, gastrointestinal, central and peripheral neurological symptoms, and hypohidrosis. However, it is the documented cases of teratogenicity that stand out as warranting concern and