Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study

Masayoshi Kobayashi; Takaki Miwa; Eri Mori; Hideaki Shiga; Kenzo Tsuzuki; Fumino Okutani; Masaki Hayama; Hitoshi Akazawa; Yosuke Nakamura; Motohiko Suzuki; Yoshinori Matsuwaki; Eriko Ogino; Takashi Shikina; Katsuhisa Ikeda; Yukiyoshi Hyo; Takashi Kashiwagi; Kenji Kondo; Minori Shibata; Takayoshi Ueno

doi:10.1016/j.anl.2023.04.010

Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study

Auris Nasus Larynx. 2024 Feb;51(1):99-105. doi: 10.1016/j.anl.2023.04.010. Epub 2023 Apr 27.

Authors

Masayoshi Kobayashi¹, Takaki Miwa², Eri Mori³, Hideaki Shiga⁴, Kenzo Tsuzuki⁵, Fumino Okutani⁶, Masaki Hayama⁷, Hitoshi Akazawa⁸, Yosuke Nakamura⁹, Motohiko Suzuki¹⁰, Yoshinori Matsuwaki¹¹, Eriko Ogino¹², Takashi Shikina¹³, Katsuhisa Ikeda¹⁴, Yukiyoshi Hyo¹⁵, Takashi Kashiwagi¹⁶, Kenji Kondo¹⁷, Minori Shibata¹⁸, Takayoshi Ueno¹⁹

Affiliations

¹ Department of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
² Department of Otorhinolaryngology, Kanazawa Medical University, Kahoku, Japan. Electronic address: miwataka@kanazawa-med.ac.jp.
³ Dpartment of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan.
⁴ Department of Otorhinolaryngology, Kanazawa Medical University, Kahoku, Japan.
⁵ Department of Otorhinolaryngology-Head and Neck Surgery, Hyogo Medical University, Nishinomiya, Japan.
⁶ Department of Occupational Health and Otolaryngology, Kochi Medical School, Nankoku, Japan.
⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan; Department of Otorhinolaryngology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya City, Japan.
⁸ Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
⁹ Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Tottori University, Yonago, Japan.
¹⁰ Department of Otolaryngology, Head and Neck Surgery, Nagoya City University, Nagoya, Japan.
¹¹ Matsuwaki Clinic Shinakgawa, Tokyo, Japan.
¹² Kyoto ENT Surgicenter, Kyotanabe, Japan.
¹³ Senri Nose Clinic, Toyonaka, Japan.
¹⁴ Department of Otorhinolaryngology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
¹⁵ Department of Otorhinolaryngology-Head and Neck Surgery, Kawasaki Medical School, Kurashiki, Japan.
¹⁶ Department of Otorhinolaryngology-Head and Neck Surgery, Dokkyo Medical University, Shimotsuga, Japan.
¹⁷ Department of Otorhinolaryngology-Head and Neck Surgery, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
¹⁸ Department of Otorhinolaryngology-Head and Neck Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
¹⁹ Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.

PMID: 37120318
DOI: 10.1016/j.anl.2023.04.010

Abstract

Objective: To determine if tokishakuyakusan (TSS) is effective for treating post-infectious olfactory dysfunction (PIOD) compared with vitamin B₁₂ (mecobalamin).

Methods: We conducted a randomized, nonblinded clinical trial. Patients with PIOD enrolled in 17 hospitals and clinics from 2016 to 2020 were randomly divided into two groups, and we administered TSS or mecobalamin for 24 weeks. Their olfactory function was examined using interviews and T&T olfactometry. The improvement of olfactory dysfunction was assessed following the criteria of the Japanese Rhinologic Society.

Results: Overall, 82 patients with PIOD were enrolled in this study. In the TSS and mecobalamin groups, 39 patients completed the medication regimen. In the TSS and mecobalamin groups, olfactory dysfunction was significantly improved based on self-reports and olfactory test results. The improvement rate of olfactory dysfunction was 56% in the TSS group and 59% in the mecobalamin group. Early intervention within 3 months produced a better prognosis than the treatment initiated after 4 months. Furthermore, age and sex differences were not observed. Both medications produced no severe adverse events.

Conclusion: The present study showed that TSS and mecobalamin might be useful for treating PIOD.

Keywords: Mecobalamin; Post-infectious olfactory dysfunction; Self-administered odor questionnaire; T&T olfactometry; Tokishakuyakusan; Visual analogue scale.

Publication types

Randomized Controlled Trial
Multicenter Study

MeSH terms

Drugs, Chinese Herbal*
Female
Humans
Male
Olfaction Disorders* / drug therapy
Olfaction Disorders* / etiology
Prospective Studies
Smell*
Vitamin B 12 / analogs & derivatives*

Substances

mecobalamin
toki-shakuyaku-san
Drugs, Chinese Herbal
Vitamin B 12