Perampanel. Just another anticonvulsant for partial epilepsy: no progress

Nearly a dozen antiepileptic drugs have been shown to prevent attacks in patients with partial epilepsy, whether used alone, or in combination when successive single-agent well-conducted treatments have failed. Perampanel (Fycompa, Eisai) an AMPA glutamate receptor antagonist, has been granted marketing authorisation in the European Union and United States, for use in combination with other antiepileptic drugs in patients aged 12 years or older with partial epilepsy. Perampanel has not been compared with other antiepileptic drugs in clinical trials. Its evaluation is based on three comparative, double-blind, placebo-controlled trials, in which perampanel was added to other antiepileptic drugs considered to be inadequately effective. In these trials, after 19 weeks of treatment, its efficacy was only modest: the response rate was at best only about 20% higher than with placebo. Indirect comparison, albeit inherently unreliable, suggests that perampanel is no better than other antiepileptic drugs. Perampanel has frequent and often dose-dependent adverse effects; they mainly include irritability, aggression, impaired alertness and coordination, and weight gain. Cardiac disorders were observed during a long-term trial of perampanel. This possible adverse effect requires further study. Perampanel led to stunted growth in experimental animals. It is not known whether adolescents are also at risk. Perampanel does not appear to be a potent inducer or inhibitor of the cytochrome P450 enzyme system, but its drug interaction profile requires further evaluation. In animal studies, perampanel exposure resulted in increased perinatal mortality. In practice, there is no evidence that perampanel represents a therapeutic advance for patients with partial epilepsy. In addition to its known adverse effects, there are concerns over possible long-term cardiac toxicity and a deleterious effect on growth. Other acceptable solutions, based on better-known drugs, should be discussed with epileptic patients.