BOSTON – A Veterans Affairs cooperative study of epilepsy in the elderly has found that two newer agents are as effective as carbamazepine at controlling seizures but are far less likely to cause unpleasant side effects in this age group than the old standby antiepileptic agent.
The newer antiepileptic drugs (AEDs), gabapentin (Neurontin) and lamotrigine (Lamictal), were matched against the enzyme inducer, carbamazepine, in an 18-center randomized double-blind study of 593 patients that lasted 1 year, said A. James Rowan, M.D., a professor of neurology at Mount Sinai School of Medicine, New York.
Of the two newer drugs, lamotrigine was significantly superior to gabapentin in terms of patient retention over the length of the study. Neither of the newer agents was significantly better than carbamazepine in preventing seizures, said Dr. Rowan, who was codirector of the VA study.
The trial also found that optimal doses of AEDs may be lower in elderly patients, he reported at a meeting on epilepsy in the elderly sponsored by Boston University. The mean plasma levels of all three drugs were low “but that seems to be enough for this population,” he said.
The patients were 60 years or older (mean age 72.8 years) with a history of one or more seizures and no previous AED therapy, or inadequate therapy. Aside from patients with medical conditions that suggested they would not survive for a year, “we took all comers, with multiple illnesses and multiple medications–the real world,” Dr. Rowan said.
The patients were titrated to the target doses: 600 mg for carbamazepine, 1,500 mg for gabapentin, and 150 mg for lamotrigine. Clinicians had the flexibility to titrate further for tolerability, and after 12 months the mean doses were 582 mg for carbamazepine, 1,614 mg for gabapentin, and 152 mg for lamotrigine. “It was very much like office practice,” he said.
At the end of 12 months, “carbamazepine had significantly more side effects than lamotrigine or gabapentin,” which led to earlier termination of therapy, according to Dr. Rowan.
In the nursing home world, he added, adverse side effects and drug interactions, which are often promptly noted and reported in younger epilepsy patients, may be unnoticed or underreported among the elderly.
Of the 197 original carbamazepine patients, 72 finished the study (37%). That compared with 95 of 193 gabapentin patients (49%) and 114 of 197 patients in the lamotrigine arm (58%).
Among the neurologic side effects, carbamazepine led to sedation for 51% and cognitive symptoms for 32%. In the gabapentin arm, 46% of patients reported sedation and 29% had cognitive symptoms. Of lamotrigine patients, 40% reported sedation and 23% cognitive symptoms.