The Efficacy of Capsaicin‐Containing Film to Prevent Dry Mouth Induced by Anticholinergics for Overactive Bladder, Multicenter Prospective Pilot Study

Overactive bladder (OAB), defined by the International Continence Society as a symptom complex including urgency with or without urinary incontinence [1], affects more than 10% of men and women aged ≥ 20 [2]. Anticholinergics are effective for OAB management but often cause significant side effects, particularly dry mouth, which occurs in a significant number of OAB patients and frequently leads to treatment discontinuation [3]. Dry mouth notably impairs QOL. Capsaicin, an agonist of the transient receptor potential vanilloid 1 (TRPV1) receptor, is known to enhance salivary secretion and improve swallowing reflexes [4]. We hypothesized that a capsaicin-containing film could relieve dry mouth symptoms associated with anticholinergic use, thus supporting better treatment adherence. We conducted a multicenter, prospective observational study from October 2019 to November 2021, approved by the ethics boards at 2 institutions and registered with UMIN Clinical Trials Registry. The study involved 20 adult OAB patients experiencing significant dry mouth from anticholinergics. Inclusion required consistent anticholinergic use for at least 1 month. The patients need to select “concerned” or “it interferes with daily life” for at least one item in the Japanese dry mouth symptom questionnaire [5]. Exclusion criteria included allergies to capsaicin or physician-assessed inappropriateness. Patients completed the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS) and General Oral Health Assessment Index (GOHAI) (Figure 1a), and a dry mouth questionnaire before and after a 2-week period. A higher score on GOHAI indicates a higher QOL [6]. They were provided 96 capsaicin-containing films (CAPFILM, Yamada Bee Company Inc. Okayama, Japan) which are commercially available as a health supplement to aid swallowing and contain at least 0.25 μg/film of capsaicin. It contains a very small amount of royal jelly, making capsaicin the primary active ingredient. The patients were instructed to use them on demand, recording usage details in a diary. The primary end-point was the adherence to anticholinergics that could be confirmed from the diary. The secondary endpoints were the differences in the answers to the questionnaires between pretreatment and 2 weeks posttreatment. Statistical analysis employed paired t-tests, with significance set at p < 0.05. Figure 1b shows the baseline characteristics. All patients used an average of 3.8 ± 1.1 capsaicin films per day while maintaining uninterrupted anticholinergics. Film usage per day was less than 2 in 2 patients, 2–4 in 8 patients, and 4 or more in 10 patients. Usage times varied: 31.5% before/after meals, 15.6% for dry mouth and 27.6% for no specific reason. Dry mouth symptom improvement was evident: those reporting “concerned” or “interfering with daily life” declined for most questionnaire items. For example, patients indicating “dry mouth” decreased from 17 to 14. GOHAI showed significant improvements in eating and speaking abilities (Figure 1c). OABSS improved significantly, with urgency decreasing from 2.7 to 2.0 (p = 0.03) and urge incontinence from 1.9 to 1.4 (p = 0.03) (Figure 1d). We defined the group that used 48 or more sheet as the “high-frequency group,” and the group that used less than 48 sheets as the “infrequent-use group”. The OABSS total score decreased by 7.7% from 7.2 to 6.1 in the infrequent-use group (n = 11), whereas the high-frequency group (n = 9) decreased by 19.5% from 8.1 to 6.3 (p < 0.01). Importantly, no adverse events related to capsaicin use were reported. Our findings demonstrate that capsaicin-containing films effectively alleviate dry mouth and may contribute to maintaining patients' adherence to anticholinergic therapy. By promoting saliva secretion through TRPV1 receptor activation, capsaicin films reduce dry mouth symptoms, as evidenced by significant improvements in GOHAI and OABSS. The frequent use before meals highlights the film's utility in improving mealtime comfort, which is crucial for oral health-related QOL. Additionally, reductions in water intake and potential capsaicin effects on bladder function, such as C-fiber desensitization [7], may explain the observed improvement in storage symptoms. Notably, the fact that the OABSS significantly improved in the group that used the film frequently suggests that the alleviation of dry mouth by the film may have contributed to maintaining adherence to anticholinergic medication. The film's formulation offers advantages over other capsaicin delivery methods: it dissolves without water, preventing increased fluid intake that could exacerbate OAB symptoms. Capsaicin-containing films present a promising approach to managing dry mouth in OAB patients on anticholinergic therapy. One of the limitations is that this study is not a placebo-controlled trial. However, this pilot study supports further research into their benefits, including a future placebo-controlled randomized trial to confirm efficacy and inform large-scale implementation. These findings highlight a potential pathway for improving OAB management by enhancing patient adherence and QOL. Yuki Kyoda: conceptualization, methodology, data curation, investigation, writing – original draft. Atsushi Takahashi: supervision. Tetsuya Shindo: supervision. Kohei Hashimoto: supervision. Ko Kobayashi: supervision. Toshiaki Tanaka: supervision. Naoya Masumori: supervision, writing – review and editing, conceptualization, methodology. The authors thank Mr. Kim Barrymore for advice on English usage in this article. No funding was provided for this work. Approval of the Research Protocol by an Institutional Review Board: The study was approved by the institutional review board of Sapporo Medical University (Institutional Review Board of Sapporo Medical University, ID: 312–12). Registry and the Registration No. of the Study/Trial: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (identifier: UMIN 000037525). Naoya Masumori and Ko Kobayashi are the Editorial Board members of the International Journal of Urology and co-authors of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. Patients provided written informed consent with guarantees of confidentiality after receiving a complete description of the study protocol. This study conformed to the provisions of the Declaration of Helsinki. The authors declare no conflicts of interest. The capsaicin-containing films were provided by Yamada Bee Company Inc.