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Impact of Improvement of Sleep Disturbance on Symptoms and Quality of Life in Patients with Functional Dyspepsia

中村, 文彦 ナカムラ, フミヒコ Nakamura, Fumihiko 群馬大学

2021.04.30

概要

【背景】機能性ディスペプシア(FD)では, 睡眠障害を併発することが知られている.多くの研究で本疾患における消化器症状と睡眠障害の関連性が指摘されているが, 睡眠障害の改善によってどのように消化器症状が推移するかに関してはあまり知られていない.一方, 逆流性食道炎(GERD)や過敏性腸症候群(IBS)に加えて, 本疾患に関してもメラトニンが消化器症状の改善に寄与することが示唆されている.しかしながら, 本疾患における消化器症状と睡眠障害の関連性に関して, その他の眠剤の導入による検討報告はされていないのが現状である.このため, 本研究では, FDにおける消化器症状に対する眠剤導入の効果およびFDと睡眠障害の関連性に関して検証することを目的とした.

【方法】2018年12月から2019年7月までの間に, ピッツバーグ睡眠質問票(PSQI)にて総得点5.5点以上の睡眠障害を伴う機能性ディスペプシア症例のうち, 睡眠障害に対して睡眠導入剤を投与する方針となった20例を前向きに登録した.内服導入前と導入4週後に消化器症状とQOLに関するアンケート調査を行った.睡眠障害の評価には, PSQI, PSQI, Epworth Sleepiness Scale (ESS), アテネ不眠尺度(AIS)を用いた.消化器症状の評価には, 改訂Fスケール質問票, Gastrointestinal Symptom Rating Scale(GSRS), 日本語版Patient Assessment of Constipation Quality of Life(JPAC-QOL)を, QOL評価にはSF-36を用いた.睡眠薬投与前, 投与1ヶ月後での各アンケートスコアの推移を比較検討した.

【結果】登録された20例のうち, 16例が研究プロトコールを完遂した.本研究から脱落した症例のうち, 3例は研究承認後に眠剤の服用を拒否され, 1例は睡眠導入剤にて過眠の症状が認められ, 服用の継続が困難であった.各々の質問票における中央値(投与前/投与後)は以下であった: PSQI, 10.0/8.5; ESS, 12.5/5.0; AIS, 10.0/4.0; 改訂Fスケール, 21.0/16.0(酸逆流関連症状, 8.0/6.0, 運動不全症状, 12.0/8.5); GSRS, 44.0/31.0(酸逆流, 6.5/4.0, 腹痛, 11.0/5.0, 消化不良, 11.0/8.0); JPAC-QOL, 26.0/15.5; SF-36, 63.9/71.9(身体の痛み, 41.0/52.0).これらすべての項目で, 有意に眠剤投与後におけるスコアの改善を示した(p < 0.05).

【考察】本研究では, 睡眠障害の改善に伴ってFDにおける消化器症状の改善やそれらに伴いQOLが改善することが示された.また, GSRSやSF-36における疼痛項目の改善も認めていたが, これは眠剤導入によって内蔵知覚のコントロールも得られることが示唆された.特に, ゾルピデムやエスゾピクロンはGABAA受容体に作用し, 痛覚を抑制する効果もあることが報告されており, 睡眠障害の改善のみならず, これらの眠剤自体の作用がFDの消化器症状の改善に寄与している可能性も考えられた.
本研究では, 眠剤導入1ヶ月後も消化器症状の完全な消失には至らなかったという点にも留意する必要がある.しかしながら, 眠剤の導入および睡眠障害の改善に伴って, 消化器症状をはじめとした各症状の改善が得られている点から, 睡眠障害を伴うFDに対する治療の際は, 既存の標準治療に加えて眠剤の導入が診療の一助となる可能性が考えられた.
一方で, 腹部膨満感や心窩部痛を主とするFD症状のみならず, JPAQ-QOLのスコア改善も認められた.登録された16例のうち, 便秘型過敏性腸症候群を併存していた3例と慢性便秘症を併存していた1例のみであったが, 便秘を自覚していないいわゆる「隠れ便秘」を伴っている症例が含まれている可能性が考えられた.眠剤の服用によって便秘症状の改善が得られる可能性もあるが, 更に症例を蓄積させて検証していく必要性がある.

【結論】睡眠薬の導入による睡眠障害の改善は, 機能性ディスペプシアにおける消化器症状やQOLの改善にも繋がることが示唆された.これらの事象には, 痛覚調節の機能とも関連があるかも知れない.

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