Ballou Sarah, Iturrino Johanna, Rangan Vikram, Cheng Vivian, Kelley John M, Lembo Anthony, Kaptchuk Ted J, Nee Judy
Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center.
Program in Placebo Studies, Beth Israel Deaconess Medical Center, Harvard Medical School.
J Clin Gastroenterol. 2022;56(5):452-456. doi: 10.1097/MCG.0000000000001575.
Tricyclic antidepressants (TCAs) are commonly used to treat disorders of gut-brain interaction (DGBI). However, these medications are often associated with side effects that lead to early treatment discontinuation. Research in other chronic medical conditions suggests that many TCA side effects may be caused by nocebo (negative placebo) effects. The current study tests a brief, verbal intervention aimed at improving tolerance of TCAs in DGBI by providing education about nocebo effects.
This pilot randomized controlled trial was performed in a tertiary care gastroenterology clinic. Participants with DGBI were randomized "standard information," describing the benefits and risks of TCAs, or "augmented information," which included an additional <30-second education about nocebo effects. Two weeks after their visit, participants were emailed a survey evaluating the number and bothersomeness of side effects, adequate relief, global improvement, and treatment satisfaction.
Thirty-one patients were randomized and 22 responded to the survey. The average age was 40% and 59% were women. Although not statistically significant, the augmented group attributed nominally fewer symptoms to TCAs than the standard group, with a medium effect size (1.5 vs. 4.2, effect size d=0.56, P=0.212) and reported being significantly less bothered by those symptoms (13.4 vs. 38.1, P=0.037). A nominally larger percentage of the augmented group reported adequate relief of symptoms after 2 weeks of treatment compared with the standard group (55% vs. 27%, respectively).
This pilot study demonstrates that a brief (≈30 s) clinical intervention addressing nocebo effects may improve tolerance of TCAs. These findings provide support for future, fully powered studies to evaluate the impact of framing on clinical outcomes, especially in chronic conditions.
三环类抗抑郁药（TCA）常用于治疗肠脑互动障碍（DGBI）。然而，这些药物常伴有副作用，导致早期停药。其他慢性疾病的研究表明，许多TCA副作用可能由反安慰剂（负面安慰剂）效应引起。本研究测试一种简短的言语干预措施，通过提供有关反安慰剂效应的教育，旨在提高DGBI患者对TCA的耐受性。
本试点随机对照试验在一家三级医疗胃肠病诊所进行。患有DGBI的参与者被随机分为“标准信息组”，即描述TCA的益处和风险，或“增强信息组”，其中包括额外的<30秒关于反安慰剂效应的教育。就诊两周后，通过电子邮件向参与者发送一份调查问卷，评估副作用的数量和困扰程度、症状缓解情况、整体改善情况以及治疗满意度。
31名患者被随机分组，22名患者回复了调查问卷。平均年龄为40岁，女性占59%。虽然无统计学意义，但增强信息组将TCA引起的症状数量名义上归因于比标准组少，效应量中等（1.5对4.2，效应量d = 0.56，P = 0.212），并报告这些症状带来的困扰明显较少（13.4对38.1，P = 0.037）。与标准组相比，增强信息组中名义上有更高比例的患者报告在治疗2周后症状得到充分缓解（分别为55%对27%）。
本试点研究表明，针对反安慰剂效应的简短（约30秒）临床干预可能提高对TCA的耐受性。这些发现为未来全面评估框架对临床结果影响（尤其是在慢性疾病中）的研究提供了支持。
