Clinical applications of placebo research II: Conditioning of pharmacological responses in sleep patterns in mild to moderate insomnia

期望、条件反射和医患关系是影响安慰剂反应的主要机制。我们第一个资助期的项目侧重于这些机制的临床应用，特别是优化患者期望。我们第二个资助期的项目继续致力于开发安慰剂机制的临床应用，这一次的重点是调节及其对睡眠参数的影响。从药物调节的角度来研究睡眠障碍是特别有趣的，因为睡眠质量可以通过主观评分（自评睡眠质量参数）和客观测量（通过多导睡眠图PSG评估，例如总睡眠时间、睡眠开始、睡眠结构）来定义。通过使用两种不同调节睡眠的药物（唑吡坦和阿米替林），我们计划在睡眠障碍中实现条件作用范式，分离条件作用对主观和客观睡眠参数的影响。两种药物都能积极影响客观和主观睡眠参数，而只有阿米替林能通过抑制快速眼动睡眠来调节客观评估的睡眠结构（快速眼动睡眠发作的潜伏期，快速眼动睡眠的百分比）。我们将135例轻度至中度失眠患者随机分为2个实验组和2个对照组（n=30）；另外一组15名s专门用于使调查员不知道情况。基线期后，所有组被分配到5晚的获取期，使用阿米替林或唑吡坦。在唤起过程中，两个实验组接受条件安慰剂刺激，两个对照组不接受药物治疗，不接受条件刺激。我们期望在两个实验组中服用安慰剂比不服用安慰剂能产生更好的睡眠质量。我们还预计，只有阿米替林安慰剂组在rem抑制意义上存在差异调节效应，而唑吡坦安慰剂组则没有。唤起期结束后，进行为期7天的临床应用。在这些天里，实验组的参与者每晚都会服用药物（随机分配；有效药物与安慰剂药片的比例为3:4），而对照组只服用相同数量的有效药物，但他们没有服用安慰剂。

Expectation, conditioning, and the doctor-patient-relationship are major mechanisms gearing the placebo response. Our project of the first funding period focused on the clinical applica-tion of these mechanisms, especially on optimizing patient expectation. Our project of the second funding period continues with the aim of developing clinical applications of placebo mechanisms, this time focusing on conditioning and its impact on sleep parameters. Sleep disorders are especially of interest to be investigated under the perspective of conditioning with drugs, since sleep quality can be defined both in terms of subjective ratings (self-rated sleep quality parameters) and objective measures (assessed via polysomnography PSG; e.g., total sleep time, sleep onset, sleep architecture). By using two drugs (zolpidem, amitriptyline) that modulate sleep differentially, we intend to implement a conditioning paradigm in sleep disorders dissociating conditioning effects on subjective and objective sleep parameters. Both drugs should affect objective and subjective sleep parameters positively, while only amitriptyline should modulate the objectively assessed sleep architec-ture by REM-suppression (latency of REM-sleep onset, percentage of REM-sleep). We want to investigate 135 patients with mild to moderate insomnia that are randomized to 2 experimental conditions and 2 control groups (n=30 each); an additional group of 15 Ss exclusively serves to keep the conditions blinded to the investigator. After a baseline period, all groups are assigned to an acquisition period of 5 nights, using either amitriptyline or zolpidem. During evocation, the two experimental groups receive the conditioned placebo stimulus, while two control groups receive no medication and no conditioned stimulus. We expect the placebo application in both experimental groups to result in better sleep quality than no pill application. We also expect a differential conditioning effect in the sense of REM-suppression only in the amitriptyline placebo application, but not in the zolpidem placebo ap-plication. After the evocation period, seven days of clinical applications follow. During these days, participants of the experimental groups will receive pills every night (randomized; ratio 3:4 of active versus placebo pills), while the control groups only receive the same amount of active drug applications, but instead of placebo pills, they receive no pill treatment.