Gabapentin improves parosmia after COVID‐19 infection

García, Jaime; Norwood, Timothy G.; Dorin, Natalie A; Grayson, Jessica W.; Woodworth, Bradford A.; Cho, Do‐Yeon

doi:10.1002/alr.23117

Cited by 5 publications

(8 citation statements)

References 8 publications

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“…A 2022 prospective cohort study by Garcia et al reported subjective improvement in parosmia in 8 of 9 patients after 3 weeks of gabapentin. The limited sample size, lack of blinding, and absence of a placebo group are serious weaknesses of this prospective cohort study.…”

Section: Discussionmentioning

confidence: 99%

“…Gabapentin is an antiepileptic medication used for diabetic neuropathy and postherpetic neuralgia, which has been reported to improve COVID-19-induced parosmia. 12 Gabapentin works by binding voltage-gated calcium channels, which play an important role in neuronal synaptic transmission. More specifically, gabapentin acts an inhibitor of the α2δ2 subunit leading to neuronal regeneration and function.…”

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confidence: 99%

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Efficacy of Gabapentin For Post–COVID-19 Olfactory Dysfunction

Mahadev,

Hentati,

Miller

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceThe COVID-19 pandemic affected millions of people and has become a dominant etiology of olfactory dysfunction (OD). No interventions with definitive clinical utility exist. Gabapentin represents a potential therapy for COVID-19–induced OD.ObjectiveTo evaluate the efficacy of oral gabapentin on olfactory function and olfaction-related quality of life in patients with COVID-19–induced OD.Design, Setting, and ParticipantsThis pilot double-blinded, placebo-controlled randomized clinical trial (RCT) was conducted at Washington University School of Medicine in St Louis from January 7, 2022, to February 3, 2023. Adults with at least 3 months of OD after COVID-19 infection were eligible for inclusion. Participants with a history of other causes of OD or contraindications to gabapentin were excluded.InterventionPatients were randomized 1:1 to oral gabapentin or placebo. All patients underwent titration to a maximum tolerable dose, which was maintained during an 8-week fixed-dose (FD) phase then tapered off. Participants were monitored for 4 weeks following cessation of study medication.Main Outcomes and MeasuresOutcomes were assessed following the 8-week FD phase and 4 weeks after taper completion. The primary outcome measure was the response rate determined by subjective improvement in OD on the Clinical Global Impression of Improvement (CGI-I) after the FD phase. Other subjective and objective measures of olfactory function were also assessed as secondary outcome measures.ResultsSixty-eight participants were enrolled (34 randomized to each arm), a total of 44 participants completed the FD period and 20 (45.4%) reported response to treatment with at least slight improvement in olfaction from baseline. Of those randomized, 51 (75%) were women and 56 were White (82%) with a mean (SD) age of 43 (13.5) years. Baseline demographic features including age, sex, and race and ethnicity were not significantly different between the groups. 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%). 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.Conclusions and RelevanceIn this randomized clinical trial, gabapentin was not associated with statistically significant or clinically meaningful benefit over placebo and likely is not an efficacious therapy for COVID-19–induced OD.Trial RegistrationClinicalTrials.gov Identifier: NCT05184192

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Efficacy of Gabapentin For Post–COVID-19 Olfactory Dysfunction

Mahadev,

Hentati,

Miller

et al. 2023

JAMA Otolaryngol Head Neck Surg

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“…The NASAL-7 and NASAL-3 were validated against the University of Pennsylvania Smell Identification Test (UPSIT). In the UPSIT, scores out of 40 correspond to categories of OD including normosmia (≥34 in males, ≥35 in females), mild hyposmia (30-33 in males, 31-34 in females), moderate hyposmia (26-29 in males, 26-30 in females), severe hyposmia (19)(20)(21)(22)(23)(24)(25), anosmia (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), and malingering (≤5). A cutoff of 7/14 on the NASAL-7 was optimal for classifying patients as having at least moderate hyposmia on UPSIT versus not, with 79% sensitivity (95% confidence interval [CI]: 66%-89%), 70% specificity (95% CI: 58%-80%), and area under the receiver operating characteristic curve [AUC] 0.814 (95% CI: 0.727-0.900).…”

Section: Outcome Measure Development Clinical Global Impressions (Cgi...mentioning

confidence: 99%

“…13,14 One case series identified gabapentin as a potential treatment for COVID-related parosmia. 15 In this trial, we randomized 68 patients with ≥3 months of COVID-related OD to gabapentin or placebo. Gabapentin was titrated to a maximum tolerable dose, maintained for an 8-week fixed-dose period, and then tapered for 4 weeks.…”

Section: Efficacy Of Gabapentin For Post-covid-19 Olfactory Dysfuncti...mentioning

confidence: 99%

Clinical studies in COVID‐related olfactory disorders: Review of an institutional experience

Tharakan,

Kallogjeri,

Piccirillo

2024

World j. otorhinolaryngol.-head neck surg.

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ObjectiveTo share a single institutional experience with clinical research on COVID‐related olfactory dysfunction (OD).Data Source/MethodNarrative review of published original data and ongoing clinical trials on COVID‐related OD at Washington University from 2020 to 2023.ResultsThere were three new diagnostic‐/patient‐reported outcome measures developed and tested. We report five clinical trials of interventions for COVID‐related olfactory disorders: combined Visual‐Olfactory Training (VOLT) with patient‐preferred scents versus standard olfactory training (VOLT trial), oral gabapentin versus placebo (Gabapentin for the Relief of Acquired Chemosensory Experience trial), nasal theophylline irrigations versus placebo (Smell Changes and Efficacy of Nasal Theophylline trial), stellate ganglion block (single‐arm), and mindfulness‐based stress reduction (MBSR) versus lifestyle intervention (MBSR trial).ConclusionsInitial intervention trials for COVID‐related OD have shown potential for improving subjective and objective olfactory outcomes. However, there remains no gold standard treatment that definitively outperforms placebo in controlled trials. Therefore, continued investigation of novel therapeutic strategies for COVID‐related OD is necessary to maximize olfactory outcomes for affected patients.

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“…Although not tested in a randomised or controlled trial, the use of gabapentin in a small case series of nine patients is worthy of mention because it specifically examined its use in patients with parosmia. 128 In this case series, 12 patients with parosmia consented to an empirical trial of gabapentin, with titration from 100 mg daily to a maximum of 600 mg daily. This treatment was combined with topical steroid rinse and a form of olfactory training.…”

Section: Management Of Post-viral Olfactory Dysfunctionmentioning

confidence: 99%

Post-viral olfactory loss and parosmia

Liu¹,

Vaira²,

Boscolo‐Rizzo³

et al. 2023

bmjmed

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The emergence of SARS-CoV-2 has brought olfactory dysfunction to the forefront of public awareness, because up to half of infected individuals could develop olfactory dysfunction. Loss of smell—which can be partial or total—in itself is debilitating, but the distortion of sense of smell (parosmia) that can occur as a consequence of a viral upper respiratory tract infection (either alongside a reduction in sense of smell or as a solo symptom) can be very distressing for patients. Incidence of olfactory loss after SARS-CoV-2 infection has been estimated by meta-analysis to be around 50%, with more than one in three who will subsequently report parosmia. While early loss of sense of smell is thought to be due to infection of the supporting cells of the olfactory epithelium, the underlying mechanisms of persistant loss and parosmia remain less clear. Depletion of olfactory sensory neurones, chronic inflammatory infiltrates, and downregulation of receptor expression are thought to contribute. There are few effective therapeutic options, so support and olfactory training are essential. Further research is required before strong recommendations can be made to support treatment with steroids, supplements, or interventions applied topically or injected into the olfactory epithelium in terms of improving recovery of quantitative olfactory function. It is not yet known whether these treatments will also achieve comparable improvements in parosmia. This article aims to contextualise parosmia in the setting of post-viral olfactory dysfunction, explore some of the putative molecular mechanisms, and review some of the treatment options available.

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Gabapentin improves parosmia after COVID‐19 infection

Cited by 5 publications

References 8 publications

Efficacy of Gabapentin For Post–COVID-19 Olfactory Dysfunction

Efficacy of Gabapentin For Post–COVID-19 Olfactory Dysfunction

Clinical studies in COVID‐related olfactory disorders: Review of an institutional experience

Post-viral olfactory loss and parosmia

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