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Treatment with oral gabapentin did not improve olfactory dysfunction that remained 3 months after a COVID-19 infection, the randomized GRACE trial showed.

Of 44 patients who completed the 8-week fixed-dose phase, 44% of those who received gabapentin reported response to treatment on the Clinical Global Impression of Improvement (CGI-I) compared with 46% of those in a placebo group (percent difference 1.7%, 95% CI -31.6 to 28.2), reported Jay F. Piccirillo, MD, of Washington University School of Medicine in St. Louis, and co-authors.

"Changes in subjective olfactory function, objective odor identification, and olfactory-related quality of life were neither clinically meaningful nor statistically significant," the group wrote in .

"Further research is warranted to identify effective treatments for COVID-19-induced OD [olfactory dysfunction] and efforts should target novel therapeutic agents," they added.

Post-COVID has been reported by about 85% of patients, which includes an estimated 100 million people, noted Piccirillo and colleagues. Evidence suggests that COVID-induced olfactory dysfunction may be due to direct damage to olfactory receptor neurons.

"Although there is a growing body of literature that suggests promising treatments for OD including , , and , none of these treatments have been definitively proven to be clinically effective," they wrote.

Gabapentin's "lipophilic properties allow it to cross the blood-brain barrier and treat central nervous system disorders, such as chronic pain and ," they explained.

This is the first time the effect of gabapentin on COVID-induced olfactory dysfunction has been assessed in a published randomized controlled trial, Piccirillo told 名媛直播. "I was not really surprised that gabapentin didn't show any effect -- disappointed, yes."

For the , which was conducted virtually, 68 adult residents of Missouri or Illinois with at least 3 months of objectively identified olfactory dysfunction after COVID infection were assigned 1:1 to oral gabapentin or placebo from January 2022 to February 2023. Mean age was 43, 75% were women, and 82% were white.

The researchers used the University of Pennsylvania Smell Identification Test (UPSIT) -- a 40-question multiple-choice odor identification test that classifies patients' degree of olfactory dysfunction -- to identify eligible participants.

Olfactory dysfunction was defined as an UPSIT score between 6 and 33 for men and between 6 and 34 for women. Participants with other known causes of olfactory dysfunction or contraindications to gabapentin were excluded.

After 4 weeks of titration, patients received the maximum tolerable dose for an 8-week fixed-dose phase, then were tapered for up to 9 days, and monitored for 4 weeks after treatment cessation. All participants were titrated to a maximum dose of 3,600 mg/day, "regardless of any benefit achieved at lower doses," Piccirillo and team noted.

Gabapentin was well-tolerated overall, but 48% of patients were unable to tolerate the maximum dose of 3,600 mg and had their dose decreased during the trial.

There were higher rates of dizziness, brain fog, and weight gain in the gabapentin group. Rates of fatigue, the most common adverse event, were similar in the two groups. Neither group experienced any serious adverse events.

Both groups had comparable secondary outcomes, which included changes in Olfactory Dysfunction Outcome Rating, NASAL-7, Clinical Global Impression of Severity, and Clinical Global Impression of Parosmia scores after the fixed-dose phase and 4 weeks after taper.

Limitations acknowledged by the study authors included a predominance of women and white participants in both treatment groups. In addition, "the absence of an in-person screening visit limited the ability to identify any potential causes of OD on physical examination," they wrote.

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