Tapering and discontinuation of benzodiazepine receptor agonists: prospective study for depression

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07933
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Kurume University
• Principal Investigator: Habukawa Mitsunari 久留米大学, 医学部, 准教授 (40343701)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: うつ病 / 不眠 / ベンゾジアゼピン受容体作動薬 / 長期使用 / 減薬 / スボレキサント

Outline of Final Research Achievements

Patients with major depressive disorder (MDD) and comorbid insomnia often take co-prescribed benzodiazepine receptor agonists (BzRAs) as hypnotics with antidepressants (ADs) to manage persistent insomnia. However, their long-term use is associated with adverse outcomes, including dependence, falls and hip fractures, and cognitive impairments. In previous our retrospective study involving 330 MDD patients, the prevalence of long-term use of BzRAs as hypnotics was 70.3%.
In this study, we assessed the effect of additional suvorexant for tapering and discontinuation of BzRAs. 20 MDD patients started ADs with co-prescribed BzRAs as hypnotics, and then when they could not discontinue BzRAs, they received additional suvorexant as hypnotics at early stage of treatment. As a result, 15 patients (75%) discontinued BzRAs within 12 months of treatment, while 5 (25%) continued BzRAs for 12 months. We concluded that additional suvorexant might reduce long-term use of BzRAs among MDD patients.

Free Research Field

精神医学

Academic Significance and Societal Importance of the Research Achievements

不眠にベンゾジアゼピン受容体作動薬（BzRAs）が高頻度に使用されるが、BzRAsの長期使用は依存形成、高齢者での転倒・骨折、認知機能低下と関連し社会問題となっている。長期使用者の約半数はうつ病患者である。睡眠薬の減量法としては漸減法や認知行動療法が有用であるとされるが、本邦でのBzRAsの減量・休薬に関する研究は絶対的に不足している。
本研究で不眠を併存するうつ病患者20名に早期にBzRAsを中止できない場合に作用機序が異なるスボレキサントを追加することでBzRAsの1年間の長期使用を著しく減少させることができた。これはうつ病でのBzRAsの減量・休薬指針となり社会的意義が非常に大きい。