As a treatment for small fiber neuropathy (SFN), lacosamide decreased pain and had a positive effect on sleep quality with minimal adverse events in patients with mutations in the gene SCN9A that encodes the voltage-gated sodium channel Nav1.7, according to a randomized, placebo-controlled, double-blind, crossover-design study published in.
“This is the first study that investigated the efficacy of lacosamide [Vimpat] in patients with SFN,” wrote lead author, of Maastricht University Medical Center, the Netherlands, and her coauthors. “Compared with placebo, lacosamide appeared to be safe to use and well tolerated in this cohort of patients.”
Lacosamide, which is approved in the United States to treat partial-onset seizures in people aged 4 years and older, has been shown to bind to and inhibit Nav1.7.
The investigators randomized 25 Dutch patients with Nav1.7-related SFN into the Lacosamide-Efficacy-’N’-Safety in SFN (LENSS) study to receive lacosamide followed by placebo, or vice versa. The patients were recruited between November 2014 and July 2016; 1 patient dropped out before treatment and another after the first treatment period, leaving 24 patients who received lacosamide and 23 patients who received placebo. They went through a 3-week titration period, an 8-week treatment period, a 2-week tapering period, and a washout period of at least 2 weeks, after which they switched to the other treatment arm and repeated the same schedule.
Through the daily pain intensity numerical rating scale and the daily sleep interference scale (DSIS), among other questionnaires, the investigators sought to determine if lacosamide reduced pain and thereby improved sleep quality. Lacosamide treatment led to a decrease in mean average pain by at least 1 point in 50.0% of patients, compared with 21.7% in the placebo group (odds ratio, 4.45; 95% confidence interval, 1.38-14.36; P = .0213). In addition, 25.0% of the lacosamide group reported at least a 2-point decrease in mean average pain versus 8.7% in the placebo group. There was also a notable difference in pain’s impact on sleep quality between the two, with the lacosamide period seeing a DSIS median value of 5.3, compared with 5.7 for the placebo period.
According to the patients’ global impression of change questionnaire, 33.3% felt better while using lacosamide versus 4.3% who felt better while using placebo (P = .0156). Six serious adverse events occurred during the study, though only two occurred during the lacosamide period. The most common adverse events for patients taking lacosamide included dizziness, headache, and nausea, all of which were comparable with adverse events in patients taking placebo.
Dr. de Greef and her colleagues noted the study’s potential limitations, including a carryover effect that could have confounded direct treatment effects (which they attempted to mitigate via a lengthier washout period) and a small cohort that was limited to very specific patients. However, the authors chose this particular cohort because “our aim was to demonstrate proof of-concept, which can be used for future studies involving larger groups of patients diagnosed with SFN.” They observed that their response rates were slightly lower than expected, but they noted that “lacosamide appears to be as effective as currently available neuropathic pain treatment.”
The study was funded by the Prinses Beatrix Spierfonds. Some of the authors reported receiving grants, personal fees, funding for research, and/or honoraria from foundations, pharmaceutical companies, life sciences companies, and the European Commission.
SOURCE: de Greef BTA et al. Brain. 2019 Jan 14.