Loss of Smell Related to COVID-19 Not Significantly Improved by Gabapentin

While some earlier studies suggested that gabapentin showed promise for treating olfactory dysfunction related to COVID-19, a recent double-blinded, placebo-controlled randomized clinical trial wasn’t able to confirm that. Find out why the researchers had thought the antiepileptic medication, which is also used for diabetic neuropathy and postherpetic neuralgia, was a good candidate, even though the results were disappointing.

LOUIS — Late last year, a small study from the University of Alabama Birmingham suggested that the medicationgabapentin provides “at least subjective improvement” in a distorted sense of smell, parosmia, related to SARS-CoV-2 infection.

“Although this was a small sample size, this is the first study to suggest that gabapentin could be helpful in the treatment of COVID19‐related parosmia,” the researchers wrote. 

A more recent double-blinded, placebo-controlled randomized clinical trial recommends, however, that oral gabapentin should not be considered as a potential therapeutic agent for COVID-19–induced olfactory dysfunction (OD) because no significant effect was identified.

Reporting in JAMA Otolaryngology–Head and Neck Surgery, researchers from Washington University School of Medicine in St Louis and colleagues said they found “no clinically meaningful or statistically significant difference between the gabapentin and placebo groups throughout the trial.”

Gabapentin, which is an antiepileptic medication used for diabetic neuropathy and postherpetic neuralgia, works by binding voltage-gated calcium channels, which play an important role in neuronal synaptic transmission. Its neuroregenerative properties and ability to enter the central nervous system made the drug a possibly effective treatment for OD, according to the authors of the recent study.

Their research found that, after an 8-week fixed-dose phase, positive response was 44.4% and 46.2% for the gabapentin and placebo treatment groups, respectively.
“Changes in odor identification and olfaction-related quality of life were not significantly different between the 2 treatment groups,” the study team points out.

The COVID-19 pandemic became a primary cause of OD in many patients, but “no interventions with definitive clinical utility exist,” according to the researchers, who sought to evaluate the efficacy of oral gabapentin on olfactory function and olfaction-related quality of life in patients with COVID-19–induced OD.

Their trial made sense, even those results weren’t favorable, according to the authors, because “due to its neuroregenerative properties and ability to enter the central nervous system, gabapentin represents an effective treatment option for COVID-19–induced OD.”

The pilot study was conducted at Washington University School of Medicine in St Louis from Jan. 7, 2022, to Feb.3, 2023. Included in the trial were adults with at least 3 months of OD after COVID-19 infection. Participants – 75% women, 82% white and with a mean age of 43, were randomized 1:1 to oral gabapentin or placebo.

All 68 patients underwent titration to a maximum tolerable dose, which was maintained during an 8-week fixed-dose (FD) phase then tapered off. Monitoring continued for 4 weeks passed the cessation of medication.

“Of the 18 participants in the gabapentin group, 8 (44%) were responders and of the 26 participants in the placebo group, 12 (46%) reported response to treatment (percent difference, 1.7%; 95% CI, −31.6% to 28.2%),” the researchers advise. “Mixed-model analysis of all secondary outcome measures demonstrated no clinically meaningful or statistically significant difference between the gabapentin and placebo groups throughout the trial. There were no serious adverse events.”

Background information in the articles notes that about 85% of patients infected with SARS-CoV-2 have reported some degree of olfactory dysfunction. It adds that COVID-19–induced OD might be due to direct damage to olfactory receptor neurons (ORNs).

The study notes that most patients recover their sense of smell just weeks after COVID-19 infection, although others with persistent OD don’t regain their olfactory function for months or never fully recover.