Therapeutic Effects of Gabapentin on Dysgeusia after Chronic Otitis Media Surgery: A Double-Blind Clinical Trial Study

Technical Summary: Therapeutic Effects of Gabapentin on Dysgeusia after Chronic Otitis Media Surgery

Problem Statement
Dysgeusia, defined as a distortion of taste where normal sensations are perceived as unpleasant or bad, is a documented complication following tympanoplasty for chronic otitis media (COM). This condition is primarily attributed to intraoperative damage—specifically cutting or stretching—of the chorda tympani nerve (CTN), a branch of the facial nerve responsible for taste sensation in the anterior two-thirds of the tongue and parasympathetic innervation. While previous studies have suggested treatments such as zinc supplements, tricyclic antidepressants (e.g., amitriptyline), and clonazepam, there is a need for further investigation into agents that may facilitate nerve regeneration. Gabapentin, an antiepileptic drug known for its efficacy in neuropathic pain and potential role in nerve repair, had not been clinically evaluated for this specific application prior to this study.

Methodology
The authors conducted a prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial.

• Participants: 58 adult patients who developed dysgeusia following COM surgery were enrolled. Eligibility required the absence of systemic diseases, neurological or psychiatric disorders, metabolic diseases, and prior history of dysgeusia.
• Randomization: Participants were assigned in a 1:1 ratio using balanced block randomization to either the gabapentin group or the placebo group (29 patients per group). Allocation was concealed via opaque, sealed envelopes.
• Intervention:
  • Gabapentin Group: Received 600 mg of gabapentin orally once daily for 3 months.
  • Placebo Group: Received a matching placebo capsule (containing lactose) once daily for 3 months.
• Outcomes: The primary outcome was the improvement of dysgeusia at 3 months, assessed qualitatively via a structured questionnaire categorized as: 0 (no improvement), 1 (partial improvement), or 2 (complete improvement). Secondary outcomes included objective reassessment of taste modalities (salty, bitter, sour, sweet) and treatment adherence.
• Analysis: Data were analyzed using SPSS version 19.0. Continuous variables were compared via independent samples t-tests, and categorical variables via the Chi-square test. An intention-to-treat principle was applied.

Key Results

• Demographics: The two groups were comparable at baseline regarding age (mean 45.83 ± 10.59 years for gabapentin vs. 47.45 ± 10.98 years for placebo; P = 0.57), sex distribution, side of ear involvement, and intraoperative CTN status (cut, stretched, or intact).
• Primary Outcome: The rate of dysgeusia improvement was significantly higher in the gabapentin group compared to the placebo group (P = 0.032).
  • Complete Improvement: 44.8% (13/29) in the gabapentin group vs. 13.8% (4/29) in the placebo group.
  • Partial Improvement: 27.6% (8/29) in the gabapentin group vs. 48.3% (14/29) in the placebo group.
  • No Improvement: 27.6% (8/29) in the gabapentin group vs. 37.9% (11/29) in the placebo group.
• Safety: Gabapentin was well-tolerated. The most frequently reported adverse events in the gabapentin group were mild to moderate dizziness, somnolence, and fatigue. No serious adverse events occurred in either group.
• Subgroup Analysis: Treatment effects were consistent across subgroups defined by age, sex, and intraoperative CTN status, with no significant interaction effects observed.

Significance and Claims
The study concludes that the administration of gabapentin (600 mg daily for 3 months) significantly improves dysgeusia following chronic otitis media surgery. The authors posit that this improvement is likely associated with enhanced repair of the chorda tympani nerve, citing gabapentin's known neuroprotective properties and its ability to increase myelinated nerve fiber thickness and accelerate nerve regeneration in previous animal and in vitro studies.

The paper modestly frames its contribution as one of the first clinical trials to investigate gabapentin for post-tympanoplasty dysgeusia, distinguishing it from prior animal studies or studies on different nerves. The authors acknowledge that while the clinical improvement is statistically significant, a definitive statement regarding the mechanism of action requires further electrophysiological studies (specifically electro-gustatory graphy) and evaluation of nerve growth factors. They also note limitations, including the lack of nutritional pattern evaluation and the absence of objective electrophysiological data, suggesting these areas for future research.

The authors recommend that clinicians consider gabapentin as a therapeutic option for this condition but advise caution regarding patient-specific factors and underlying diseases due to potential side effects such as dry mouth and mood alterations.