Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer E A
CURE Digestive Diseases Research Center, Department of Medicine, UCLA University of California at Los Angeles, USA.
Am J Gastroenterol. 1998 Feb;93(2):160-5. doi: 10.1111/j.1572-0241.1998.00160.x.
Tricyclic antidepressants in low doses are widely used in the therapy of patients with functional gastrointestinal disorders, yet the mechanism(s) of action of these drugs in these disorders is not known. In the current study, we sought to determine in a group of patients with functional dyspepsia and associated poor sleep how amitryptiline affects digestive symptoms, perceptual responses to gastric distension, and subjective and objective measures of sleep.
Patients were randomized to 4 wk of amitryptiline 50 mg taken at bedtime versus placebo. There was a 3-wk washout phase, followed by a cross-over to the alternate treatment. Perceptual sensitivity to gastric distention and sleep EEG were recorded at the end of each treatment period. Diaries of symptoms were maintained throughout.
Seven of seven patients reported significantly less severe gastrointestinal symptoms after 4 wk on amitryptiline compared to placebo. Five of seven patients had evidence for altered perception of gastric balloon distension during placebo. However, the subjective symptom improvement on amitryptiline was not associated with a normalization of the perceptual responses to gastric distension. Baseline sleep dysfunction in the form of reduced sleep efficiency, increased arousal, or abnormal amounts of REM sleep was found in all seven patients. Amitryptiline significantly reduced absolute and relative amounts of REM sleep, but had no effect on sleep parameters related to nonregenerative sleep.
The beneficial effect of low dose amitryptiline seen in functional dyspepsia is not related to changes in perception of gastric distension, or to measures of arousal from sleep. An increased tolerance to aversive visceral sensations may play a role in the therapeutic effect.
低剂量三环类抗抑郁药广泛用于功能性胃肠疾病患者的治疗，但这些药物在这些疾病中的作用机制尚不清楚。在本研究中，我们试图确定在一组功能性消化不良并伴有睡眠不佳的患者中，阿米替林如何影响消化症状、对胃扩张的感知反应以及睡眠的主观和客观指标。
患者被随机分为两组，一组在睡前服用50毫克阿米替林，持续4周，另一组服用安慰剂。有一个为期3周的洗脱期，然后交叉接受替代治疗。在每个治疗期结束时记录对胃扩张的感知敏感性和睡眠脑电图。全程记录症状日记。
与安慰剂相比，7名患者中有7名在服用阿米替林4周后报告胃肠道症状明显减轻。7名患者中有5名在服用安慰剂期间有胃气球扩张感知改变的证据。然而，阿米替林对主观症状的改善与对胃扩张的感知反应正常化无关。所有7名患者均存在以睡眠效率降低、觉醒增加或快速眼动睡眠量异常为形式的基线睡眠功能障碍。阿米替林显著降低了快速眼动睡眠的绝对量和相对量，但对与非再生性睡眠相关的睡眠参数没有影响。
在功能性消化不良中观察到的低剂量阿米替林的有益作用与胃扩张感知的变化或睡眠觉醒指标无关。对厌恶内脏感觉的耐受性增加可能在治疗效果中起作用。
