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Original Article
Does dimenhydrinate delay recovery of vestibular ocular reflex in acute unilateral vestibulopathy? A retrospective comparative study
Minah Shinorcid, Chae-Young Kimorcid, Ji Eun Choiorcid, Jae Yun Jungorcid, Min Young Leeorcid
Research in Vestibular Science 2024;23(3):89-94.
DOI: https://doi.org/10.21790/rvs.2024.006
Published online: September 15, 2024

Department of Otolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Korea

Corresponding author: Min Young Lee Department of Otolaryngology-Head and Neck Surgery, Dankook University College of Medicine, 119 Dandae-ro, Cheonan 31116, Korea. E-mail: eyeglass210@gmail.com
• Received: April 10, 2024   • Revised: August 9, 2024   • Accepted: August 12, 2024

© 2024 The Korean Balance Society

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Objectives
    Acute unilateral vestibulopathy (UVP), also known as vestibular neuritis, is the third most common peripheral vestibulopathy. The acute autonomic symptoms of UVP can be controlled by the H1-receptor antagonist dimenhydrinate. Despite concerns about prolonged recovery from suppressed vestibular compensation when using dimenhydrinate, research is limited. Thus, we investigated the effect of dimenhydrinate on the recovery of UVP patients.
  • Methods
    We retrospectively analyzed patients who were diagnosed with UVP from April 2018 to April 2022. The patients were divided into those who were prescribed dimenhydrinate during admission and those who were not. Recovery from UVP was defined subjectively and objectively. Subjective recovery (SR) had occurred in a patient whose dizziness clearly subsided. Objective recovery (OR) was defined when the video head-impulse test (VHIT) or rotary chair test (RCT) no longer indicated vestibular dysfunction.
  • Results
    Dimenhydrinate was prescribed to 15 patients (19.0%) during admission. The dimenhydrinate group had smaller proportions of SR and OR at 3 months after diagnosis of UVP. In terms of VHIT, the non-dimenhydrinate group had a greater increase in gain for the 3 months than the dimenhydrinate group in the semicircular canals when measured by the VHIT. The difference in gain between the two groups was significant at 0.16 Hz during follow-up RCT.
  • Conclusions
    These results suggest that dimenhydrinate should be carefully used in UVP patients as it may have a negative effect on vestibular compensation.
  • Keywords: Vestibular neuronitis; Physiological adaptation; Dimenhydrinate
Acute unilateral vestibulopathy (UVP), also known as vestibular neuritis, is the third most common peripheral vestibulopathy after benign paroxysmal positional vertigo and Meniere disease. The pathophysiology of UVP could be various and one of the possible causes is viral infection which is commonly caused by herpes simplex virus type I [1].
UVP usually presents with vertigo, nausea, vomiting, gait disturbance, nystagmus without central neurological symptoms, and/or audiological symptoms [2,3]. UVP symptoms are thought to be relieved by the recovery of vestibular neurons and the compensation process by the central nervous system [4,5]. However, the courses and durations of recovery vary greatly possibly due to multifactorial causes. The acute autonomic symptoms of UVP are occasionally controlled by medications, such as the H1-receptor antagonist dimenhydrinate [6]. Dimenhydrinate is a pharmacologic agent which is classified as a vestibular suppressant. Vestibular suppressants are not encouraged to be used in long term in cases of peripheral vestibular diseases. In terms of UVP, there are concerns about prolonged recovery from suppressed vestibular compensation when using dimenhydrinate. But, research is limited. Notably, a recent publication has introduced animal studies that have shown that the use of medications to relieve UVP symptoms may suppress vestibular compensation [7]. Nevertheless, the effect of symptomatic treatment of UVP in humans remains unclear.
Thus, in the present study, we investigated the effect of dimenhydrinate on the recovery of UVP patients. The patients were classified into two groups (with dimenhydrinate and without dimenhydrinate) and their serial recovery by subjective and objective measures were evaluated and compared.
Ethics Statement
This study was approved by the Institutional Review Board of Dankook University Hospital (No. DKUH IRB: 2024-06-004). The study was conducted as a retrospective observational study using the medical records and vestibular function tests, with a waiver of consent.
Subjects and Methods
We retrospectively analyzed patients who were diagnosed with UVP and hospitalized at Dankook University Hospital from April 2018 to April 2022. The patients underwent vestibular function tests and were discharged after their symptoms improved. The patients were divided into those who were prescribed dimenhydrinate during admission and those who were not. The patients who were prescribed other vestibular suppressants or steroids during admission.
After discharge, the patients were followed up regularly at the outpatient clinic. Patients’ symptoms were reported and follow-up vestibular function tests including the video-assisted head-impulse test (VHIT) and the rotatory chair test (RCT) were completed. Recovery from UVP was defined subjectively and objectively. Subjective recovery (SR) had occurred in a patient whose dizziness clearly subsided. Objective recovery (OR) was used when VHIT or RCT no longer indicated vestibular dysfunction. The duration of recovery was determined from the date of admission. The recovery rate and objective changes in the vestibular ocular reflex (VOR) measured by VHIT and RCT within 3 months were compared between the two groups.
Statistical Analyses
Statistical analyses were performed using IBM SPSS Statistics ver. 29 (IBM Corp.). The durations of recovery of the dimenhydrinate and non-dimenhydrinate groups and VOR gains in the two groups were compared as well as demographic data. The Shapiro-Wilk normality test was used to determine whether the data followed a Gaussian distribution; when this assumption was met, we performed two-tailed unpaired t-tests; when this assumption was not met, we performed the Mann-Whitney U-tests. The 3-month recovery rates were analyzed using the chi-square test. VOR gains in the two groups were compared using the t-test. Fisher exact test was used for comparison of abnormality rates of VOR gains. The p-values of <0.05 were regarded as statistically significant.
Demographics
Seventy-nine patients were included in this study and dimenhydrinate was prescribed to 15 patients (19.0%) during admission. The dimenhydrinate group consisted of 11 male and four female patients. The non-dimenhydrinate group included 64 patients consisting of 37 male and 27 female patients. The mean ages of the dimenhydrinate and non-dimenhydrinate groups were 52 and 55.6 years, respectively. The demographics and rate of vestibular function test abnormality in both groups are shown in Table 1. There was no statistical difference in all data between groups.
Recovery Duration and Rate
The durations of SR and OR in the dimenhydrinate group were 131 and 120 days, respectively. The non-dimenhydrinate group took 110 days to reach SR and 76 days to reach OR. Fifty-one subjects were followed up 3 months after their diagnosis. Four of 10 patients (40.0%) in the dimenhydrinate group and 26 of 41 patients (63.4%) in the non-dimenhydrinate group reached SR 3 months after the diagnosis. Three of seven patients (42.9%) in the dimenhydrinate group and 14 of 21 patients (66.7%) in the non-dimenhydrinate group reached OR 3 months after the diagnosis. The dimenhydrinate group had smaller proportions of SR and OR and differences were detected.
Video Head-Impulse Test Gains
The VOR gains of the patients were measured using the VHIT and RCT during admission and regularly followed up during outpatient visits. Eighteen patients completed the VHIT during their admission and after discharge. The VOR gains in the VHIT were measured at the anterior, lateral, and posterior semicircular canals. Initially, 10 patients showed low gain in all semicircular canals while seven patients spared vestibular function of the lateral semicircular canal. One patient exhibited decreased gain in the posterior and lateral canal and narrowly within normal in the anterior semicircular canal. Fig. 1 shows the gains in the dimenhydrinate group (n=4) and non-dimenhydrinate group (n=14) during the initial period and approximately 3 months later in each semicircular canal. The gain of the semicircular canals in the dimenhydrinate group, which was measured using the VHIT, increased compared to the initial test (ratio of 3 months to initial: 1.67, 1.47, and 1.32). However, the gain in the lateral and posterior canal decreased in the non-dimenhydrinate group (ratio of 3 months to initial: 1.37, 0.79, and 0.85). In the anterior and the lateral semicircular canal, the gains in the dimenhydrinate group were higher than those in the non-dimenhydrinate group initially but became lower after 3 months. In the posterior semicircular canal, the initial difference in the gain between the two groups was significant, showing statistically lower gain in the non-dimenhydrinate group but became non-statistically significant at 3 months later.
Rotary Chair Test Gains
A total of 26 patients had RCT data at admission and follow-up. Eight were prescribed dimenhydrinate and 18 were not. The VOR gains of RCT were compared at frequencies of 0.01, 0.02, 0.04, 0.08, 0.16, 0.32, and 0.64 Hz. Fig. 2 shows the gains in the dimenhydrinate and non-dimenhydrinate groups at each frequency. The initial and follow-up data were compared. The dimenhydrinate group had a higher gain at 0.01 to 0.04 Hz and a lower gain at 0.08 to 0.64 Hz, but there were no statistical significances. However, that group had a lower gain at every frequency in follow-up tests. The difference in gain between the two groups was significant at 0.16 Hz during follow-up RCT.
Dimenhydrinate is often used to relieve symptoms of UVP. However, its overuse may hinder recovery from UVP. Recent animal studies have reported that symptomatic treatment of UVP may prolong disease duration. Therefore, this study aimed to determine the effect of dimenhydrinate on recovery from UVP by comparing UVP patients who did and did not use dimenhydrinate.
The recovery duration of the dimenhydrinate group was subjectively 21 days and objectively 44 days longer than in the non-dimenhydrinate group. Although the difference was not significant, it supports the idea that dimenhydrinate prolongs recovery time, resulting in a longer duration of vertigo. Additionally, the 3-month recovery rate was lower in the dimenhydrinate group. UVP is a self-limiting disease that usually resolves within 3 months. Therefore, the dimenhydrinate group showing a poorer recovery rate within 3 months suggests that the drug hinders the UVP compensation process.
The VHIT and RCT were used to objectively evaluate vestibular dysfunction in the patients. The non-dimenhydrinate group had a greater increase in gain for the 3 months than the dimenhydrinate group in the semicircular canals when measured by the VHIT. In particular, the difference in the initial gain between the two groups at the posterior semicircular canal was significant, indicating that the patients who were administered dimenhydrinate had less recovery of vestibular function of the posterior semicircular canal compared to those who were not.
A previous study showed that the posterior semicircular canal recovers less when compared to other canals because it is more susceptible to the early stage of viral infection [8]. This may explain why the initial difference in the gain at the posterior semicircular canal was significant. Therefore, dimenhydrinate may more prominently affect the vestibular function of the posterior canal.
When measured using the RCT, a higher increase in gain at every frequency was observed in the dimenhydrinate group during the 3 months. The increases were more prominent at higher frequencies. Additionally, the follow-up gain of 0.16 Hz was significantly different between the two groups.
There are several limitations of this study. Some results showed unexpected outcomes compared to previous results. Interestingly, the dimenhydrinate group had higher initial gain when assessed using the VHIT but lower gain when assessed using the RCT. This may be because different patients were tested with each test. The RCT may be preferred by physicians who would prescribe dimenhydrinate to patients due to relatively severe symptoms who would have lower initial gain. As such, since different individuals have been enrolled for different tests, selection bias can interfere with the results. Most of all, the number of patients recruited is relatively small therefore, it was difficult to determine the statistical significance of the results observed.
Dimenhydrinate is used in 19% of inpatients according to our retrospective review. The dimenhydrinate group exhibited a larger proportion of longer (3 months) subjective and objective disease duration. It also showed less recovery of gain in follow-up VHIT and RCT. These results suggest that dimenhydrinate should be carefully used in UVP patients as it may have a negative effect on vestibular compensation.

Funding/Support

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1A6A1A03043283; NRF-2021R1I1A3047407), and supported by Creative Materials Discovery Program through the National Research Foundation of Korea (NRF) funded by Ministry of Science and ICT (NRF-2019M3D1A1078943), and Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) [RS-2023-00220408].

Conflicts of Interest

No potential conflict of interest relevant to this article was reported.

Availability of Data and Materials

All data generated or analyzed during this study are included in this published article. For other data, these may be requested through the corresponding author.

Authors’ Contributions

Conceptualization, Methodology: MYL, JYJ, JEC; Data curation, Formal analysis, Investigation: MAS, CYK; Project administration, Supervision: MYL; Visualization: CYK; Writing–Original Draft: MAS; Writing–Review & Editing: All authors.

All authors read and approved the final manuscript.

Fig. 1.
The video head-impulse test (VHIT) gain difference between the groups. Averaged VHIT gain values were compared between the non-dimenhydrinate group and the dimenhydrinate group. There were no differences in anterior (A) and lateral (B) semicircular canal (SCC) at both initial and follow-up. (C) On the other hand, in the case of posterior SCC, the initial averaged gain was statistically lower in the non-dimenhydrinate group compared to the dimenhydrinate group. This statistical difference was not observed at follow-up. 0, non-dimenhydrinate; 1, dimenhydrinate. *p<0.05. Y axis: Gain 1=100 (%).
rvs-2024-006f1.jpg
Fig. 2.
The rotary chair test (RCT) gain difference between the groups. Averaged RCT gains were compared between the non-dimenhydrinate group and the dimenhydrinate group at 6 frequencies of chair rotations. Initially (A), there were no statistical differences at all frequencies. But at follow-up (B), the statistical difference was observed at 0.16 Hz which showed a statistically lower gain in the dimenhydrinate group. 0, non-dimenhydrinate; 1, dimenhydrinate; *p<0.05. Y axis: Gain 1=100 (%).
rvs-2024-006f2.jpg
Table 1.
Demographics and basic vestibular function test data
Variable Dimenhydrinate group Non-dimenhydrinate group p-value
No. of patients 15 64
Age (yr) 52.0±8.98 55.63±14.34 0.179
Sex 0.381
 Male 11 (73.3) 37 (55.2)
 Female 4 (26.7) 27 (40.3)
Initial VHIT data 11 47
 Low VHIT gain (<70) 10 (90.9) 41 (87.2) >0.999
 Low anterior 10 (90.9) 29 (61.7) 0.148
 Low lateral 9 (81.8) 31 (66.0) 0.474
 Low posterior 1 (9.1) 19 (40.4) 0.077
Initial RCT data 14 54
 Low RCT gain 14 (100) 51 (94.4) >0.999
 Abnormal asymmetry 14 (100) 45 (83.3) 0.187
 Abnormal phase 9 (64.3) 41 (75.9) 0.498

Values are presented as number only, mean ± standard deviation, or number (%).

VHIT, video head-impulse test; RCT, rotary chair test.

No statistical difference between groups in all parameters (Fischer exact test and independent t-test).

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        Does dimenhydrinate delay recovery of vestibular ocular reflex in acute unilateral vestibulopathy? A retrospective comparative study
        Res Vestib Sci. 2024;23(3):89-94.   Published online September 15, 2024
        DOI: https://doi.org/10.21790/rvs.2024.006
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      Does dimenhydrinate delay recovery of vestibular ocular reflex in acute unilateral vestibulopathy? A retrospective comparative study
      Image Image
      Fig. 1. The video head-impulse test (VHIT) gain difference between the groups. Averaged VHIT gain values were compared between the non-dimenhydrinate group and the dimenhydrinate group. There were no differences in anterior (A) and lateral (B) semicircular canal (SCC) at both initial and follow-up. (C) On the other hand, in the case of posterior SCC, the initial averaged gain was statistically lower in the non-dimenhydrinate group compared to the dimenhydrinate group. This statistical difference was not observed at follow-up. 0, non-dimenhydrinate; 1, dimenhydrinate. *p<0.05. Y axis: Gain 1=100 (%).
      Fig. 2. The rotary chair test (RCT) gain difference between the groups. Averaged RCT gains were compared between the non-dimenhydrinate group and the dimenhydrinate group at 6 frequencies of chair rotations. Initially (A), there were no statistical differences at all frequencies. But at follow-up (B), the statistical difference was observed at 0.16 Hz which showed a statistically lower gain in the dimenhydrinate group. 0, non-dimenhydrinate; 1, dimenhydrinate; *p<0.05. Y axis: Gain 1=100 (%).

      Fig. 1.

      Fig. 2.

      Does dimenhydrinate delay recovery of vestibular ocular reflex in acute unilateral vestibulopathy? A retrospective comparative study
      Variable Dimenhydrinate group Non-dimenhydrinate group p-value
      No. of patients 15 64
      Age (yr) 52.0±8.98 55.63±14.34 0.179
      Sex 0.381
       Male 11 (73.3) 37 (55.2)
       Female 4 (26.7) 27 (40.3)
      Initial VHIT data 11 47
       Low VHIT gain (<70) 10 (90.9) 41 (87.2) >0.999
       Low anterior 10 (90.9) 29 (61.7) 0.148
       Low lateral 9 (81.8) 31 (66.0) 0.474
       Low posterior 1 (9.1) 19 (40.4) 0.077
      Initial RCT data 14 54
       Low RCT gain 14 (100) 51 (94.4) >0.999
       Abnormal asymmetry 14 (100) 45 (83.3) 0.187
       Abnormal phase 9 (64.3) 41 (75.9) 0.498
      Table 1. Demographics and basic vestibular function test data

      Values are presented as number only, mean ± standard deviation, or number (%).

      VHIT, video head-impulse test; RCT, rotary chair test.

      No statistical difference between groups in all parameters (Fischer exact test and independent t-test).

      Table 1.

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