Since our review, we found a published meta-analysis (Neurol Sci 2022;43:889-897), an open-label trial (Muscle Nerve 2021;64:504-508) and a small randomized double-blind placebo-controlled trial. The trials showed no benefits from Perampanel; in fact, patients in the controlled trial progressed faster on the drug than those on placebo. Adverse events were very common in the trials, with the open-label trial being stopped prematurely due to the high frequency of these. In the controlled trial, 27% of patients on 4mg had serious adverse events, 48% of patients on 8mg had serious adverse vents and 14% of patients on placebo had adverse events. Taken together, this new data warrants a change in our TOE Trials grade to F, and a change in our Risks grade to F. Our overall conclusion is unchanged: we cannot recommend Perampanel for the treatment of ALS.
Key Information
Perampanel is a drug currently used to treat seizures which has a mechanism of action that theoretically could be useful in treating patients with ALS. A single flawed study in a mouse model of ALS showed some benefits of perampanel, but data from humans with ALS is quite limited. Due to the lack of data in PALS, the failure of the closely related drug talampanel in ALS clinical trials, and several serious safety concerns, including an increased fall risk and serious psychiatric adverse effects, we cannot recommend off-label use of perampanel for ALS at this time. We look forward to the results of the on-going clinical trials of perampanel in ALS and we will update our TOE grades accordingly when these results become available.
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