Gabapentin flops for managing COVID-19 induced Olfactory Dysfunction: GRACE trial

In this double-blinded, placebo-controlled pilot RCT, the rate of response as determined by the Clinical Global Rating of Improvement (CGI) after an 8-week fixed-dose phase for the gabapentin and placebo treatment groups was 44.4% and 46.2%, respectively, with non-significant changes in odor identification and olfaction-related quality of life between groups.

COVID-19 is a dominant etiology of OD. Intranasal theophylline and corticosteroids have proven clinically ineffective in OD management. A 2022 prospective cohort study by Garcia et al. reported subjective improvement in parosmia following three weeks of gabapentin. However, the study had limitations. Considering this background, researchers evaluated whether oral gabapentin improves olfactory function and olfaction-related quality of life in COVID–19–induced OD patients.

Adults of median age 45 years with COVID-19 olfactory dysfunction of at least three months were included. Sixty-eight patients were randomized to oral gabapentin/Active intervention (Gabapentin titration to max dose maintained during the eight-week fixed-dose phase, then tapered off) or placebo (26 controls, Oral lactose placebo).

The primary outcomes were response scores on the 7-point CGI-I scale after the fixed-dose phase of much better, somewhat better or slightly better were considered responders.

Key points of the study summary are:

• Seven participants in the gabapentin group withdrew before starting the medication.
• Forty-four participants completed the FD period, and 20 reported response to treatment.
• In the gabapentin and placebo group, 8/18 and 12/26 participants constituting 44% and 46 %, respectively were responders with a percent difference of 1.7%.
• Serious adverse events were not reported.
• 48% could not tolerate the maximum dose of 3600 mg, and their dosage was reduced during the trial.
• The Gabapentin group had higher dizziness, brain fog, and weight gain rates.

There could be an improvement in olfaction with gabapentin taken for longer than the eight weeks studied, they noted.

The study demonstrated gabapentin to be non-efficacious in managing COVID-19–induced OD.

The study's limitations were female predominance, Ethnicity predominance (White), absence of an in-person screening visit, and duration differences.

Further reading:

Mahadev A, Hentati F, Miller B, et al. Efficacy of Gabapentin For Post–COVID–19 Olfactory Dysfunction: The GRACE Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. Published online September 21, 2023. doi:10.1001/jamaoto.2023.2958