研究者詳細 - 宮脇　卓也

論文 - 宮脇　卓也

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Intranasal Premedication With Dexmedetomidine in an Adult Patient With Intellectual Disabilities: A Case Report. 国際誌

Jotaro Tanaka, Saki Miyake, Maki Fujimoto, Yukiko Nishioka, Hitoshi Higuchi, Takuya Miyawaki

Anesthesia progress 71 ( 3 ) 147 - 148 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Recently, intranasal dexmedetomidine (DEX) has been reported to be effective as a preanesthetic medication, mostly in healthy pediatric patients. We attempted to administer intranasal DEX premedication in this case to an adult patient with intellectual disability who previously had difficulty tolerating premedication with oral midazolam. Using an intranasal atomization delivery device (MAD Nasal, Teleflex), we administered 1.5 µg/kg of DEX intranasally and were able to achieve adequate sedation, which facilitated a smooth mask induction of general anesthesia with sevoflurane. Premedication with intranasal DEX may be a useful method for enabling induction of general anesthesia in adult patients with intellectual disabilities.

DOI： 10.2344/anpr-23-0057

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Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder. 査読国際誌

Hitoshi Higuchi, Kota Miyake, Saki Miyake, Maki Fujimoto, Yukiko Nishioka, Shigeru Maeda, Takuya Miyawaki

Journal of applied research in intellectual disabilities : JARID 37 ( 4 ) e13265 2024年7月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication. METHODS: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation. RESULTS: The mean OM dose required was 0.32 ± 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis. CONCLUSION: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people.

DOI： 10.1111/jar.13265

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歯科患者を対象とした歯科用局所麻酔剤アルチカイン塩酸塩・アドレナリン酒石酸水素塩注射剤（OKAD01）の臨床用量域の検討（アルチカイン塩酸塩第Ⅱ相試験）査読

樋口仁, 飯島毅彦, 北畑洋, 藤澤俊明, 角南次郎, 深山治久, 三宅実, 鮎瀬卓郎, 丹羽均, 渡辺禎久, 三島克章, 細井宏輝, 吉田道弘, 宮脇卓也

日本歯科麻酔学会雑誌 52 ( 1 ) 26 - 36 2024年1月

上下顎骨切り術中に発生した背部褥瘡の１症例査読

佐藤理子, 三宅康太, 藤本磨希, 西岡由紀子, 三宅沙紀, 樋口仁, 宮脇卓也

岡山歯学会雑誌 42 ( 2 ) 55 - 59 2023年12月

MICRO MISTネブライザを用いて上気道の表面局所麻酔を行った意識下挿管の1症例査読

佐藤理子, 樋口仁, 西岡由紀子, 藤本磨希, 三宅沙紀, 宮脇卓也

日本歯科麻酔学会雑誌 51 ( 4 ) 123 - 126 2023年10月

Sugar signals from oral glucose transporters elicit cephalic-phase insulin release in mice 査読

Mitsuhito Takamori, Yoshihiro Mitoh, Kengo Horie, Masahiko Egusa, Takuya Miyawaki, Ryusuke Yoshida

The Journal of Physiological Sciences 73 ( 1 ) 2023年7月

掲載種別：研究論文（学術雑誌）出版者・発行元：Springer Science and Business Media LLC

Abstract

Cephalic-phase insulin release (CPIR) occurs before blood glucose increases after a meal. Although glucose is the most plausible cue to induce CPIR, peripheral sensory systems involved are not fully elucidated. We therefore examined roles of sweet sensing by a T1R3-dependent taste receptor and sugar sensing by oral glucose transporters in the oropharyngeal region in inducing CPIR. Spontaneous oral ingestion of glucose significantly increased plasma insulin 5 min later in wild-type (C57BL/6) and T1R3-knockout mice, but intragastric infusion did not. Oral treatment of glucose transporter inhibitors phlorizin and phloretin significantly reduced CPIR after spontaneous oral ingestion. In addition, a rapid increase in plasma insulin was significantly smaller in WT mice with spontaneous oral ingestion of nonmetabolizable glucose analog than in WT mice with spontaneous oral ingestion of glucose. Taken together, the T1R3-dependent receptor is not required for CPIR, but oral glucose transporters greatly contribute to induction of CPIR by sugars.

DOI： 10.1186/s12576-023-00875-3

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その他リンク： https://link.springer.com/article/10.1186/s12576-023-00875-3/fulltext.html

A survey on the safety of anesthesia management provided by dental anesthesiologists in Japan: a 5-year survey by the Japanese Dental Society of Anesthesiology 査読

Takuro Sanuki, Takuya Miyawaki, Takehiko Iijima

Clinical Oral Investigations 27 ( 9 ) 5475 - 5483 2023年7月

知的能力障害を有する成人歯科患者に対してデクスメデトミジン経鼻投与による麻酔前投薬を試みた1症例査読

田中譲太郎, 三宅沙紀, 藤本磨希, 西岡由紀子, 樋口仁, 宮脇卓也

日本歯科麻酔学会雑誌 51 ( 3 ) 69 - 71 2023年7月

Anesthetic Management Using Remimazolam in a Hemodialysis Patient. 査読国際誌

Yukiko Nishioka, Saki Miyake, Midori Hamaoka, Kota Miyake, Maki Fujimoto, Hitoshi Higuchi, Takuya Miyawaki

Anesthesia progress 70 ( 2 ) 65 - 69 2023年6月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Remimazolam, an ultra-short-acting benzodiazepine, is a new intravenous anesthetic used for sedation and general anesthesia. Because remimazolam is primarily metabolized by carboxylesterases in the liver and other tissues including the lung and has metabolites with little or no bioactivity, its anesthetic effect is not significantly influenced by renal dysfunction. Therefore, remimazolam may be considered an appropriate agent for hemodialysis patients and may have added benefits beyond midazolam and propofol. Remimazolam has also been suggested to cause less cardiac depression than propofol. This case report presents an 82-year-old female hemodialysis patient with chronic heart failure who underwent partial glossectomy for squamous cell carcinoma of the tongue under general anesthesia with remimazolam and remifentanil. Hemodynamic control was stable during the anesthetic, which was safely completed without any adverse events and resulted in a rapid, clear emergence without flumazenil. Remimazolam and remifentanil may be appropriate as first-line general anesthetic agents for hemodialysis patients with heart failure.

DOI： 10.2344/anpr-70-02-06

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Evaluation of Sedation Levels Using SedLine During Intravenous Sedation for Dental Procedures: A Case-Series Study. 招待国際誌

Kota Miyake, Hitoshi Higuchi, Saki Miyake, Yukiko Nishioka, Maki Fujimoto, Erika Kurita, Akiko Kawase, Yuka Wakasugi, Takuya Miyawaki

Anesthesia progress 70 ( 2 ) 85 - 87 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

The Patient State Index (PSI) is the numerical value of anesthesia depth as measured using a SedLine Sedation Monitor (Masimo Corporation). In this pilot study, we evaluated PSI values captured during intravenous (IV) moderate sedation for dental treatment. During the dental treatment, a dental anesthesiologist maintained the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score at 3 to 4 by adjusting the administration of midazolam and propofol while PSI values were recorded. The mean (SD) and median (25th percentile, 75th percentile) PSI values during dental treatment under IV moderate sedation were 72.7 (13.6) and 75 (65, 85), respectively.

DOI： 10.2344/anpr-70-01-01

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Taste Responses and Ingestive Behaviors to Ingredients of Fermented Milk in Mice 査読

Yamase Yuko, Huang Hai, Mitoh Yoshihiro, Egusa Masahiko, Miyawaki Takuya, Yoshida Ryusuke

Foods 12 ( 6 ) 1150 2023年3月

The clinical advantage of nasal high-flow in respiratory management during procedural sedation: A scoping review on the application of nasal high-flow during dental procedures with sedation. 査読国際誌

Shinji Kurata, Takuro Sanuki, Hitoshi Higuchi, Takuya Miyawaki, Seiji Watanabe, Shigeru Maeda, Shuntaro Sato, Max Pinkham, Stanislav Tatkov, Takao Ayuse

The Japanese dental science review 58 179 - 182 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Structured summary: Rationale: Nasal high-flow (NHF), a new method for respiratory management during procedural sedation, has greater advantages than conventional nasal therapy with oxygen. However, its clinical relevance for patients undergoing oral maxillofacial surgery and/or dental treatment remains uncertain and controversial, due to a paucity of studies. This scoping review compared and evaluated NHF and conventional nasal therapy with oxygen in patients undergoing oral maxillofacial surgery and/or dental treatment. Materials and methods: A literature search of two public electronic databases was conducted, and English writing randomized controlled trials (RCTs) of nasal high flow during dental procedure with sedation reviewed. The primary and secondary outcomes of interest were the incidence of hypoxemia and hypercapnia during sedation and the need for intervention to relieve upper airway obstruction, respectively. Results: The search strategy yielded 7 studies, of which three RCTs met our eligibility criteria, with a total of 78 patients. Compared with conventional nasal therapy with oxygen, NHF significantly reduced the incidence of hypoxemia and hypercapnia during procedural sedation. Conclusion: NHF can maintain oxygenation and possibly prevent hypercapnia in patients undergoing dental treatment. Additional RCTs are needed to clarify and confirm these findings.

DOI： 10.1016/j.jdsr.2022.05.003

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Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial. 査読

Tomoko Higashi, Naomichi Murata, Maki Fujimoto, Saki Miyake, Masahiko Egusa, Hitoshi Higuchi, Shigeru Maeda, Takuya Miyawaki

Acta medica Okayama 76 ( 2 ) 179 - 186 2022年4月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 μg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson's disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding.

DOI： 10.18926/AMO/63412

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SedLineによる歯科治療時の静脈内鎮静法の鎮静レベルの評価ケースシリーズ研究査読

三宅康太, 樋口仁, 三宅沙紀, 西岡由希子, 藤本磨希, 栗田恵理佳, 川瀬明子, 若杉優花, 宮脇卓也

日本歯科麻酔学会雑誌 50 ( 2 ) 91 - 93 2022年4月

担当区分：最終著者記述言語：日本語出版者・発行元：(一社)日本歯科麻酔学会

当院歯科全身管理室で静脈内鎮静法を行う患者で、1)20歳以上、2)米国麻酔学会術前状態分類PS-1またはPS-2の患者26名を対象として、静脈内鎮静法における至適鎮静度を示唆するPatient State Index(PSI)値を検索した。静脈路を確保後、ミダゾラム1.0～3.0mgを投与し、Target Controlled Infusionモードでプロポフォール(PF)の持続投与を開始した。歯科治療中は、適時PFの投与量を調整した。治療終了時に歯科治療中のPSI値を2秒間隔でSedLineより抽出した。PSI値の平均値は72.7±13.6、中央値は75であった。治療終了後に担当歯科麻酔医から患者にアンケートを依頼し、術中の健忘効果および静脈内鎮静法の満足度を評価した。その結果、92%の患者が鎮静に満足であると回答していた。健忘度は全く覚えていないが53.8%、あまり覚えていないが30.8%であった。

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Reply. 国際誌

Hitoshi Higuchi, Kumiko Takaya-Ishida, Saki Miyake, Maki Fujimoto, Yukiko Nishioka, Shigeru Maeda, Takuya Miyawaki

Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 79 ( 11 ) 2181 - 2182 2021年11月

Comparison of Oxygen Saturation Between Nasal High-Flow Oxygen and Conventional Nasal Cannula in Obese Patients Undergoing Dental Procedures With Deep Sedation: A Randomized Crossover Trial. 査読国際誌

Hitoshi Higuchi, Kumiko Takaya-Ishida, Saki Miyake, Maki Fujimoto, Yukiko Nishioka, Shigeru Maeda, Takuya Miyawaki

Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 79 ( 9 ) 1842 - 1850 2021年9月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

PURPOSE: In anesthetic management, it is widely accepted that obese patients are more likely to suffer airway obstructions and reductions in arterial oxygen saturation (SpO2). Therefore, it is important to take special measures to prevent oxygen desaturation during the deep sedation of obese patients. This clinical study examined whether the use of nasal high-flow systems (NHFS) keep higher SpO2 and reduced hypoxemia than conventional nasal cannula during the deep sedation of obese patients with intellectual disabilities for dental treatment. MATERIALS AND METHODS: Eighteen obese patients (body mass index: >25) with intellectual disabilities who underwent dental sedation were enrolled. In each case, sedation was induced using propofol and maintained at a bispectral index of 50 to 70. The subjects were randomly assigned to the control oxygen administration (5 L/min via a nasal cannula) or NHFS (40% O2, 40 L/min, 37 °C) arm in alternate shifts as a crossover trial. The primary endpoint was the minimum SpO2 value, and the incidence of hypoxemia during dental treatment was also evaluated. RESULTS: The mean minimum SpO2 value was significantly higher in the NHFS arm than in the control arm (95.8 ± 2.1 % vs 93.6 ± 4.1 %, P = 0.0052, 95% confidence interval: 0.608-3.947). Hypoxemic episodes (SpO2: ≤94%) occurred 3 cases (16.7%) in the NHFS arm and 11 cases (61.1%) in the control arm (P = 0.0076, odds ratio: 0.127, 95% confidence interval 0.0324 - 0.630). CONCLUSION: NHFS resulted in higher minimum SpO2 and reduced hypoxemia than nasal cannula in obese patients during deep sedation for dental treatment.

DOI： 10.1016/j.joms.2021.04.004

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歯科用局所麻酔剤アーティカイン塩酸塩(アルチカイン塩酸塩)・アドレナリン酒石酸水素塩注射剤(OKAD01)の安全性および血中薬物動態の検討(第I相、単施設、非盲検試験) 査読

樋口仁, 若杉優花, 川瀬明子, 前田茂, 宮脇卓也

日本歯科麻酔学会雑誌 49 ( 3 ) 81 - 96 2021年7月

担当区分：最終著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：(一社)日本歯科麻酔学会

緒言:アーティカイン塩酸塩(アルチカイン塩酸塩)は,歯科治療に際して世界的に広く使用されているアミド型の局所麻酔薬であるが,現在日本では薬事承認を受けていない.そこで本邦での歯科用アルチカイン製剤(OKAD01)の導入を目指し,OKAD01を日本人の口腔粘膜下に投与した際の安全性および血中薬物動態を検討するため,日本人を対象としたOKAD01の第I相試験を行った.方法:健康な日本人成人男性を対象とした.OKAD01 1カートリッジ(1.7ml)および3カートリッジ(5.1ml)を口腔粘膜下にそれぞれ6名ずつに投与した.OKAD01投与前,投与終了15,30,60分後,および2,4,12,24時間後の血漿中アルチカイン濃度の測定を行った.またOKAD01投与前,投与後に臨床検査,バイタルサインなどの測定を行い,OKAD01投与による有害事象を検討した.結果:1カートリッジ群の薬物動態パラメータ値[平均値±標準偏差(最小値-最大値)]は,最高血中薬物濃度(Cmax)が374.35±97.65(252.7-514.5)ng/ml,最高血中薬物濃度到達時間(Tmax)が0.25±0.00(0.25-0.25)hであった.また3カートリッジ群では,Cmaxが694.00±175.23(517.9-970.4)ng/ml,Tmaxが0.42±0.13(0.25-0.5)hであった.有害事象は1カートリッジ群に「頭痛」が1件認められたが,OKAD01との因果関係はなしと判断された.結論:OKAD01を日本人の口腔粘膜に投与した際のCmaxは,本治験の安全域とした5.0μg/ml未満であることが確認された.また,OKAD01に関連した有害事象は認められず,OKAD01は,20歳以上の健常日本人男性に対して忍容性が認められ,安全性に問題はないと考えられた.(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01093&link_issn=&doc_id=20210819250002&doc_link_id=%2Feq9shika%2F2021%2F004903%2F002%2F0081-0096%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Feq9shika%2F2021%2F004903%2F002%2F0081-0096%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Exosome-Based Molecular Transfer Activity of Macrophage-Like Cells Involves Viability of Oral Carcinoma Cells: Size Exclusion Chromatography and Concentration Filter Method. 査読国際誌

Yanyin Lu, Takanori Eguchi, Chiharu Sogawa, Eman A Taha, Manh Tien Tran, Toshiki Nara, Penggong Wei, Shiro Fukuoka, Takuya Miyawaki, Kuniaki Okamoto

Cells 10 ( 6 ) 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Extracellular vesicles (EV) heterogeneity is a crucial issue in biology and medicine. In addition, tumor-associated macrophages are key components in cancer microenvironment and immunology. We developed a combination method of size exclusion chromatography and concentration filters (SEC-CF) and aimed to characterize different EV types by their size, cargo types, and functions. A human monocytic leukemia cell line THP-1 was differentiated to CD14-positive macrophage-like cells by stimulation with PMA (phorbol 12-myristate 13-acetate) but not M1 or M2 types. Using the SEC-CF method, the following five EV types were fractionated from the culture supernatant of macrophage-like cells: (i) rare large EVs (500-3000 nm) reminiscent of apoptosomes, (ii) EVs (100-500 nm) reminiscent of microvesicles (or microparticles), (iii) EVs (80-300 nm) containing CD9-positive large exosomes (EXO-L), (iv) EVs (20-200 nm) containing unidentified vesicles/particles, and (v) EVs (10-70 nm) containing CD63/HSP90-positive small exosomes (EXO-S) and particles. For a molecular transfer assay, we developed a THP-1-based stable cell line producinga GFP-fused palmitoylation signal (palmGFP) associated with the membrane. The THP1/palmGFP cells were differentiated into macrophages producing palmGFP-contained EVs. The macrophage/palmGFP-secreted EXO-S and EXO-L efficiently transferred the palmGFP to receiver human oral carcinoma cells (HSC-3/palmTomato), as compared to other EV types. In addition, the macrophage-secreted EXO-S and EXO-L significantly reduced the cell viability (ATP content) in oral carcinoma cells. Taken together, the SEC-CF method is useful for the purification of large and small exosomes with higher molecular transfer activities, enabling efficient molecular delivery to target cells.

DOI： 10.3390/cells10061328

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Dexmedetomidine inhibits LPS-induced inflammatory responses through peroxisome proliferator-activated receptor gamma (PPARγ) activation following binding to α2 adrenoceptors. 査読国際誌

Maki Fujimoto, Hitoshi Higuchi, Yuka Honda-Wakasugi, Saki Miyake, Yukiko Nishioka, Akiko Yabuki-Kawase, Shigeru Maeda, Takuya Miyawaki

European journal of pharmacology 892 173733 - 173733 2021年2月

担当区分：最終著者記述言語：英語掲載種別：研究論文（学術雑誌）

Over the past decade, dexmedetomidine (DEX) has been found to possess an anti-inflammatory effect. However, the local anti-inflammatory mechanism of DEX has not been fully clarified. Some intracellular inflammatory pathways lead to negative feedback during the inflammatory process. The cyclooxygenase (COX) cascade synthesizes prostaglandins (PGs) and plays a key role in inflammation, but is known to also have anti-inflammatory properties through an alternative route of a PGD2 metabolite, 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), and its receptor, peroxisome proliferator-activated receptor gamma (PPARγ). Therefore, we hypothesized that DEX inhibits LPS-induced inflammatory responses through 15d-PGJ2 and/or PPARγ activation, and evaluated the effects of DEX on these responses. The RAW264.7 mouse macrophage-like cells were pre-incubated with DEX, followed by the addition of LPS to induce inflammatory responses. Concentrations of TNFα, IL-6, PGE2, and 15d-PGJ2 in the supernatants of the cells were measured, and gene expressions of PPARγ and COX-2 were evaluated in the cells. Furthermore, we evaluated whether a selective α2 adrenoceptor antagonist, yohimbine or a selective PPARγ antagonist, T0070907, reversed the effects of DEX on the LPS-induced inflammatory responses. DEX inhibited LPS-induced TNFα, IL-6, and PGE2 productions and COX-2 mRNA expression, and the effects of DEX were reversed by yohimbine. On the other hand, DEX significantly increased 15d-PGJ2 production and PPARγ mRNA expression, and yohimbine reversed these DEX's effects. Furthermore, T0070907 reversed the anti-inflammatory effects of DEX on TNFα and IL-6 productions in the cells. These results suggest that DEX inhibits LPS-induced inflammatory responses through PPARγ activation following binding to α2 adrenoceptors.

DOI： 10.1016/j.ejphar.2020.173733

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上顎臼歯抜去後の末梢性神経障害性疼痛が疑われミロガバリンが有効であった1症例査読

濱岡緑, 川瀬明子, 三宅沙紀, 西岡由紀子, 樋口仁, 前田茂, 宮脇卓也

日本歯科麻酔学会雑誌 49 ( 1 ) 4 - 6 2021年1月

担当区分：最終著者記述言語：日本語出版者・発行元：(一社)日本歯科麻酔学会

症例は74歳女性で、約3年前に上顎右側第一大臼歯に痛みを覚え、かかりつけ歯科医院で同歯を抜去した。しかし、抜歯後に局所麻酔効果が消失する頃から上顎右側全体に持続痛を感じるようになり、鎮痛薬を内服しても効果がなかった。痛みのコントロールができず、脳神経外科に紹介されたが頭部MRIでも異常所見が認められなかったため当科へ紹介された。触覚閾値の上昇は認めなかったこと、アロディニアが生じていること、上顎臼歯抜去後から痛みが起きていることから、当初除外していた末梢性神経障害性疼痛の可能性を再考し、ミロガバリンの投与を開始した。1週間後、上顎右側臼歯部の持続痛はやや軽減しており、副作用の有無を確認しながらミロガバリンを増量したところ、痛みは徐々に軽減していった。また、カルバマゼピンは徐々に減量していき中止した。この間、特に眠気などの副作用は認めなかった。

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