Behavioral Sleep Medicine Program, Department of Psychiatry, University of Pennsylvania, USA; Center for Sleep and Circadian Neurobiology, Department of Medicine, University of Pennsylvania, USA; School or Nursing, University of Pennsylvania, USA.
Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, USA.
Sleep Med. 2021 Nov;87:56-61. doi: 10.1016/j.sleep.2021.04.041. Epub 2021 Aug 21.
Previous research has shown that after one month of full dose nightly treatment with zolpidem (priming), subjects with chronic insomnia (CI) switched to intermittent dosing with medication and placebos were able to maintain their treatment responses. This approach to maintenance therapy is referred to as partial reinforcement. The present study sought to assess whether priming is required for partial reinforcement or whether intermittent dosing with placebos (50% placebos and 50% active medication) can, by itself, be used for both acute and extended treatment.
55 CI subjects underwent a baseline evaluation (Phase-1) and then were randomized to one of two conditions in Phase-2 of the study: one month of (1) nightly medication use with standard-dose zolpidem (QHS [n = 39]) or (2) intermittent dosing with standard-dose zolpidem and placebos (IDwP [n = 16]). In Phase-3 (three months), the QHS group was re-randomized to either continued QHS full dose treatment (FD/FD) or to IDwP dose treatment (FD/VD). Treatment response rates and Total Wake Time (TWT = [SL + WASO + EMA]) were assessed during each phase of the study.
In Phase-2, 77% (QHS) and 50% (IDwP) subjects exhibited treatment responses (p = 0.09) where the average change in TWT was similar. In Phase-3, 73% (FD/FD), 57% (FD/VD), and 88% (VD/VD) of subjects exhibited continued treatment responses (p = 0.22) where the average improvement in TWT continued with FD/FD and remained stable for FD/VD and VD/VD (p < 0.01).
These results suggest that intermittent dosing with placebos can maintain effects but do not allow for the additional clinical gains afforded by continuous treatment.
先前的研究表明，在接受为期一个月的佐匹克隆全剂量夜间治疗（诱导期）后，慢性失眠症（CI）患者改用药物和安慰剂间歇性给药，能够维持治疗反应。这种维持治疗方法被称为部分强化。本研究旨在评估诱导是否是部分强化所必需的，或者单独使用安慰剂间歇性给药（50%安慰剂和 50%活性药物）是否可同时用于急性和延长治疗。
55 例 CI 患者接受基线评估（第 1 阶段），然后在研究的第 2 阶段随机分为两种条件之一：1 个月的（1）每晚使用标准剂量佐匹克隆治疗（QHS [n=39]）或（2）标准剂量佐匹克隆和安慰剂间歇性给药（IDwP [n=16]）。在第 3 阶段（3 个月），QHS 组重新随机分为继续 QHS 全剂量治疗（FD/FD）或 IDwP 剂量治疗（FD/VD）。在研究的每个阶段评估治疗反应率和总清醒时间（TWT=[SL+WASO+EMA]）。
在第 2 阶段，77%（QHS）和 50%（IDwP）的患者表现出治疗反应（p=0.09），TWT 的平均变化相似。在第 3 阶段，73%（FD/FD）、57%（FD/VD）和 88%（VD/VD）的患者继续表现出治疗反应（p=0.22），TWT 的平均改善继续在 FD/FD 中，FD/VD 和 VD/VD 保持稳定（p<0.01）。
这些结果表明，安慰剂间歇性给药可以维持疗效，但不能获得连续治疗带来的额外临床获益。
