Submitted by: Francisco E. Gomez, MD
Edited by: Clark W. Pinyan, MD, MPH
de Greef BTA, Hoeijmakers JGJ, Geerts M, Oakes M, Church TJE, Waxman SG, Dib-Hajj SD, Faber CG, Merkies ISJ. Lacosamide in patients with Nav1.7 mutations-related small fibre neuropathy: a randomized controlled trial. Brain
, Volume 142, Issue 2, 1 February 2019, Pages 263–275.
Small fiber neuropathy (SFN) is a condition often encountered in the outpatient setting, preferentially affecting Aδ and unmyelinated C fibers. First line treatment for SFN includes tricyclic antidepressants, SSRIs, SNRIs, gabapentin and pregabalin or combinations, which are not always satisfactory.
Voltage gated sodium channels mediate membrane depolarization and are found in dorsal root ganglia neurons. Gain of function mutations in these channels are described in patients with neuropathic pain. Specifically, 15% of SFN cases are associated with mutations in the SCN9 gene coding for NaV1.7. Lacosamide binds to these channels; thus, the authors theorized this antiepileptic may prove effective for SFN.
Authors conducted the Lacosamide Efficacy and Safety in SFN Study, a randomized placebo controlled double blinded crossover study perfomed in a single center, the Maastricht University Medical Center. A total of 25 patients were randomized to lacosamide versus placebo then crossed over. The primary endpoint was a 1 or more point decrease in self-reported daily pain and improvement in sleep interference scales. Fifty to 60% of patients reported some improvement as defined in the primary outcome measures, more marked in patients with a known NaV1.7 mutation. Patients did not alter their pre-existing medication regimens, so the authors conclude that Lacosamide is a potential add-on medication with few intolerable interactions or side effects.
Having another effective medication for SFN would be of great interest for clinicians treating this common disease. The limitations to this study are not only its size but also the emphasis on NaV1.7 mutations, which are not tested as routine clinical practice.