The epilepsy drug phenytoin may be neuroprotective for optic neuritis commonly observed in patients with multiple sclerosis (MS), according to findings published in the March 2016 issue of Lancet Neurology.1
In the randomized, placebo-controlled, double-blind phase 2 trial, researchers investigated the potential neuroprotective effects of phenytoin via sodium-channel inhibition in patients with acute demyelinating optic neuritis presenting at 2 academic hospitals in the UK. The sample of 86 participants aged 18-60 years had onset of optic neuritis within the previous 2 weeks, which is the window at which experimental studies suggest neuroprotection should be initiated.2 Preclinical studies have shown voltage-gated sodium-channel inhibitors to be neuroprotective at therapeutic concentrations.3,4,5
“A number of other drugs inhibit voltage-gated sodium channels, including the epilepsy drugs carbamazepine and lamotrigine, but unlike phenytoin, they can’t be loaded rapidly to achieve therapeutic concentrations,” study co-author Raj Kapoor, MD, a consultant neurologist at University College London Hospitals, told Neurology Advisor. In an earlier trial6 reported in Lancet Neurology in 2010, Dr Kapoor and colleagues investigated the effects of lamotrigine, another sodium channel inhibitor, but did not find evidence of slowed brain atrophy with treatment. “That trial was therefore negative for its primary outcome, but we did report that treatment over 2 years halved the rate at which the speed of walking deteriorated, when compared with placebo,” he said
In the current study, patients were randomly assigned to oral phenytoin or placebo for a period of 3 months and were followed-up with at 6 months. The primary outcome of the study was mean retinal nerve fiber layer (RNFL) thickness in the affected eye compared with baseline RNFL thickness in the unaffected eye, the latter of which had not been accounted for in previous trials. RNFL thickness was measured at baseline and 6 months via high-resolution spectral domain optical coherence tomography (OCT), using identical protocols at both hospitals. Since the lesion on the optic nerve leads to retrograde degeneration of the retinal nerve fiber layer (RNFL), “RNFL thickness provides a plausible biomarker of axonal loss” that can be measured non-invasively using OCT, the authors wrote. “Reduction of RNFL thickness is also associated with visual loss in patients with acute optic neuritis and with greater general disability in patients with multiple sclerosis, suggesting that it might provide information about treatment response that is clinically relevant.”
In the phenytoin group, the mean 6-month RNFL thickness in the affected eye was 81.46 μm (SD 16.27), representing a mean reduction of 16.69 μm (SD 13.73) compared with baseline thickness in the unaffected eye. In the placebo group, the mean 6-month RNFL thickness was 74.29 μm (SD 15.14), indicating a mean reduction of 23.79 μm (SD 13.97) from baseline.