Gabapentin improves parosmia after COVID‐19 infection

1. INTRODUCTION

Postviral olfactory dysfunction (PVOD) has significantly increased in incidence since the rise of coronavirus disease 2019 (COVID‐19), resulting in anosmia (complete loss), hyposmia (partial loss), phantosmia (dysfunction of smell in the absence of an odor), or parosmia (distorted perception of smell) with limited evidence for proposed treatments. ¹ , ² Olfactory disorders have been linked with a negative impact on emotions, interpersonal relationships, and overall health, as well as increased mortality. ³ , ⁴ Parosmia, typically a foul or rotten odor, can be significantly distressing and dangerous as patients may no longer enjoy or tolerate previously pleasant or innocuous scents that they regularly encounter. This results in loss of appetite or even mistaking noxious odors as benign. This appears to be a long‐term sequela, as recent literature notes an incidence of continued parosmia in 25% to 43.2% of patients 6 months after infection. ⁵ , ⁶ Parosmia has been the least studied of the PVODs but has been treated with antipsychotics, antiseizure medications, topical cocaine, and antimigraine medications with variable results. ³ This study aims to analyze the therapeutic potential of gabapentin for parosmia after COVID‐19 infection.

2. METHODS

This study was approved by the Institutional Review Board of the University of Alabama at Birmingham. The medical records of patients visiting a single provider (DYC) in the University of Alabama Smell and Taste Clinic between August 2021 and February 2022 were reviewed. The University of Pennsylvania Smell Identification Test (UPSIT) was used to detect olfactory dysfunction (OD), and parosmia was identified through the patient's history. ⁷ Patients included those with parosmia and at least a 6 month history of OD with abnormal UPSIT scores following COVID‐19 infection. The titration schedule started with 100 mg daily for 7 days, followed by 200 mg daily for another 7 days. Based on symptomatic improvement and tolerance, the dosage was increased by 100 to 300 mg weekly, if necessary, up to 600 mg daily. All subjects were instructed to perform daily budesonide (0.5 mg/2 ml suspension) sinus irrigation and olfactory training (OT) with four essential oils (lemon, rose, eucalyptus, clove). Phone interviews were performed after a minimum of 3 weeks of treatment at the maximal tolerable dosage (MTD). Responsiveness to treatment was assessed by a patient‐reported scale of no, mild, moderate, or significant improvement via phone interviews.

3. RESULTS

A total of 85 new patients with PVOD visited the Smell and Taste Clinic during the study period. Of those 85 patients, 14 patients (16.5%, male to female = 1:13, mean age 41.2 [16–67] years, mean pretreatment UPSIT score = 20.9 ± 7.5) identified parosmia as a major complaint after COVID‐19 infection. Gabapentin was prescribed to 12 patients as two decided to postpone treatment. Of those 12 patients, two did not tolerate the medication due to side effects (drowsiness) during titration, and one patient (male) was excluded as the treatment was less than 3 weeks at MTD. Four patients (44.4%) were already on daily budesonide irrigation and OT before starting gabapentin. Of the nine patients who took more than 3 weeks of treatment at MTD, an improvement was noticed in eight patients (88.9%) (Table 1). All nine patients confirmed their compliance with daily budesonide irrigation and OT during the phone interview. Significant improvement was noticed in six patients (66.7%) who had foul smell as the nature of parosmia. This cohort indicated improvement was noticed within 3 weeks of treatment at MTD. One patient who expressed an altered smell (other than foul) did not demonstrate improvement. Posttreatment UPSIT assessment was only available in three patients from this cohort, who had no or minimal improvement in their scores yet reported significant improvement in parosmia. When two of these three patients tried to taper the dosage, they noted a significant worsening of their parosmia. A total of 50% of responsive patients currently remain on MTD with excellent benefits. Moreover, the short duration of action, where all patients who responded had subjective improvement within several days of starting the medication, indicates the mitigation of parosmia was likely from gabapentin.

TABLE 1.

Demographics and characteristics

No.	Age	Gender	Duration of OD (months)	Nature of parosmia	Pre‐ & posttreatment UPSIT score	Gabapentin dosage (duration of treatment)	Outcome	Pre‐gabapentin BI & OT
1	41	F	11	Foul	17, 19	300 mg BID (6 months)	Significant	No
2 a	30	F	6	Altered	25, 25	200 mg daily (3 weeks)	No improvement	No
3	30	F	10	Sour	27, NA	200 mg daily (2 months)	Mild	Yes
4 a	29	F	10	Foul	21, NA	200 mg daily (2 months)	Significant	Yes
5 a	27	F	15	Foul	15, NA	200 mg daily (1 month)	Significant	No
6 a	54	F	11	Foul	24, NA	200 mg daily (1 month)	Significant	No
7	50	F	7	Foul	13, 14	300 mg BID (6 months)	Significant	Yes
8	33	F	12	Foul	35, NA	300 mg daily (6 months)	Significant	Yes
9 a	16	F	14	Altered	14, NA	200 mg daily (3 weeks)	Mild	No

Pre‐Gabapentin BI & OT: Application of budesonide irrigation (BI) and olfactory training (OT) before starting gabapentin.

Abbreviations: BID = twice daily; NA, not available; OD, olfactory dysfunction; UPSIT, University of Pennsylvania Smell Identification Test.

^a No longer on gabapentin.

4. DISCUSSION

In the present study, we investigated the effects of titrating gabapentin on patients with parosmia after COVID‐19 infection. Our data suggest that gabapentin provides at least subjective improvement in parosmia after 3 weeks of treatment in eight out of nine patients with parosmia, which was even more significant when all odors smelled foul/rotten. 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. Overall, the medication was well tolerated, with only one major adverse effect: daytime drowsiness. About 50% of patients could taper off within 2 months at MTD without a return of parosmia.

The qualitative smell changes associated with COVID‐19 may significantly impact the patient's overall emotional, mental, and physical health. Lerner et al. ⁸ recently demonstrated that those with COVID19‐related parosmia have significantly decreased olfactory‐related quality of life scores. Therefore, treatment options aimed at these qualitative changes, notably parosmia, have an important role in future research.

The limitations of this study include a single provider cohort of patients with a short follow‐up, a homogenous patient population, and limited objective data to determine the degree of improvement. Future directions will include a larger, more diverse patient population with objective data from pre‐ and posttreatment olfactory tests. Additionally, a randomized controlled study is necessary to prove efficacy. Many posttreatment UPSITs were unavailable due to no‐shows on follow‐up visits or a lack of UPSIT kits due to a supply crisis. Overall, gabapentin appears to be a well‐tolerated potential treatment option for parosmia in those infected with COVID‐19.

CONFLICT OF INTEREST

Bradford A. Woodworth, MD, is a consultant for Cook Medical, Smith and Nephew, and Medtronic. The authors whose names are listed other than Bradford A. Woodworth certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.

Garcia JAP, Miller E, Norwood TG, et al. Gabapentin improves parosmia after COVID‐19 infection. Int Forum Allergy Rhinol. 2022;1‐3. 10.1002/alr.23117