The value of adding a second antiepileptic drug in intractable epilepsy with complex-partial seizures was studied in a long-term prospective trial in 30 adult patients who failed to respond to the maximum use of carbamazepine, phenytoin, phenobarbital or primidone as the first drug. Based on the individual previous history of one-drug treatment, the most promising antiepileptic drug (carbamazepine, clobazam, clonazepam, phenobarbital, phenytoin, primidone, valproic acid) was added, if necessary until clinical toxicity occurred. A reduction of the seizure frequency by more than 75% was seen in only four patients (13%) exposed to a second drug in the event of failure of optimum one-drug treatment. The remaining majority of patients (87%) did not benefit from the second drug; in three patients the seizure frequency increased by more than 100%. The common practice of adding another drug in difficult-to-treat cases may need to be reconsidered until further evidence is presented that two drugs are more beneficial than one drug in the treatment of intractable epilepsy.
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