Siproudhis L, Dinasquet M, Sébille V, Reymann J M, Bellissant E
Service des Maladies de l'Appareil Digestif, CHU de Rennes et Université de Rennes 1, Hôpital de Pontchaillou, France.
Aliment Pharmacol Ther. 2004 Sep 15;20(6):689-95. doi: 10.1111/j.1365-2036.2004.02151.x.
Although antidepressants are used for functional gastrointestinal disorders, the mechanisms of their effects on gut are incompletely understood.
To assess the effects of two types of antidepressants (tricyclic, serotoninergic) on anorectal motility and visceral perception.
A placebo-controlled, randomized, double-blind, crossover study was performed in 12 healthy male volunteers who received a single oral dose of amitriptyline (80 mg), fluoxetine (40 mg) or placebo. Drug effects were assessed using phasic isobaric distensions of the rectum with an electronic barostat (11 levels from 1 to 51 mmHg) 4 h after drug intake. Maximal rectal volume and pressure, mean and residual pressures at upper anal canal, mean pressure at lower anal canal, defecation sensation (5-level scale) and visceral perception (visual analogue scale) were recorded at each level of distending pressure.
Ten subjects completed the study. Compared with placebo, neither amitriptyline nor fluoxetine modified rectal compliance or visceral perception. Compared with placebo, antidepressants significantly reduced mean and residual pressures at upper anal canal (-18%, P = 0.0019, and -27%, P = 0.0002, respectively, for amitriptyline; -26%, P = 0.0001, and -33%, P = 0.0001, respectively, for fluoxetine) whereas only amitriptyline significantly reduced mean pressure at lower anal canal (-16%, P = 0.0008).
Both antidepressants similarly relaxed the internal anal sphincter, probably through a non-specific mechanism, without modifying visceral perception. Only amitriptyline relaxed the external anal sphincter.
尽管抗抑郁药用于功能性胃肠疾病,但其对肠道作用的机制尚未完全明了。
评估两类抗抑郁药(三环类、5-羟色胺能类)对肛门直肠运动和内脏感觉的影响。
对12名健康男性志愿者进行一项安慰剂对照、随机、双盲、交叉研究,这些志愿者单次口服阿米替林(80毫克)、氟西汀(40毫克)或安慰剂。服药4小时后,使用电子恒压器以等压方式阶段性扩张直肠(压力范围为1至51毫米汞柱,共11个水平)来评估药物效果。在每个扩张压力水平记录最大直肠容积和压力、肛管上段的平均压力和残余压力、肛管下段的平均压力、排便感觉(5级评分)和内脏感觉(视觉模拟评分)。
10名受试者完成了研究。与安慰剂相比,阿米替林和氟西汀均未改变直肠顺应性或内脏感觉。与安慰剂相比,抗抑郁药显著降低了肛管上段的平均压力和残余压力(阿米替林分别降低18%,P = 0.0019,和27%,P = 0.0002;氟西汀分别降低26%,P = 0.0001,和33%,P = 0.0001),而只有阿米替林显著降低了肛管下段的平均压力(降低16%,P = 0.0008)。
两种抗抑郁药均通过非特异性机制类似地松弛肛门内括约肌,而不改变内脏感觉。只有阿米替林松弛了肛门外括约肌。