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。我们的第一个资助期的项目集中在这些机制的临床应用，特别是优化患者的期望。我们第二个资助期的项目继续以开发安慰剂机制的临床应用为目标，这次重点是条件反射及其对睡眠参数的影响。睡眠障碍在药物调节的角度下特别值得研究，因为睡眠质量可以根据主观评级（自我评定的睡眠质量参数）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）。通过使用两种药物（唑吡坦，阿米替林），调节睡眠的差异，我们打算实施一个条件反射范式在睡眠障碍解离条件反射的影响，主观和客观的睡眠参数。两种药物均能积极影响客观和主观睡眠参数，而只有阿米替林能通过REM抑制（REM睡眠起始潜伏期，REM睡眠百分比）调节客观评估的睡眠结构。我们想研究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（每组n=30）;另外一组15名Ss专门用于对研究者保持条件盲态。在基线期后，所有组被分配到5个夜晚的采集期，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，而两个对照组不接受药物和条件刺激。我们希望在两个实验组中使用安慰剂会比不使用药丸导致更好的睡眠质量。我们还预期，在REM抑制意义上，仅在阿米替林安慰剂应用中存在差异性条件作用，而在唑吡坦安慰剂应用中不存在。在唤起期之后，接下来是七天的临床应用。在这些天里，实验组的参与者每晚都会接受药丸（随机化;活性药丸与安慰剂药丸的比例为3：4），而对照组只接受相同数量的活性药物应用，但不是安慰剂药丸，他们没有接受药丸治疗。

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.