小剂量阿米替林对健康志愿者胃肠功能影响的随机双盲交叉对照研究

Effect of low dose amitriptyline on gastrointestinal function in healthy volunteers： a randomized, double blind, and placebo-controlled cross-over study

目的 探讨小剂量阿米替林对健康志愿者胃肠功能的影响及其不良反应.方法 采用随机、双盲、交叉、对照试验设计,将28名健康志愿者分为阿米替林＋安慰剂组（14名）和安慰剂＋阿米替林组（14名）,前者第1阶段服用阿米替林7d,中间有14 d洗脱期,第2阶段服用安慰剂7d;后者服用顺序相反.服药剂量为每次12.5 mg,每天3次.服药前,服药第1、2阶段的第7～8天对受试者分别进行饮水超声试验和乳果糖氢呼气试验.采用两阶段交叉设计资料的方差分析、符号秩和检验和卡方检验等进行统计分析.结果 饮水超声试验显示,阿米替林和安慰剂在受试者饮水200、400、600和800 mL时的近端胃横截面面积差异均无统计学意义（P均＞0.05）,在饮水800 mL后第5、10分钟的近端胃液体排空率差异均无统计学意义（P均＞0.05）；阿米替林在受试者饮水600、800 mL时的饱感度视觉模拟评分（VAS）显著低于安慰剂[（2.98±0.85）分比（3.57±0.94）分,Z=4.412,P＜0.01；（4.57±0.98）分比（5.57±0.82）分,Z=4.170,P＜0.01].乳果糖氢呼气试验显示,阿米替林的口-盲肠传输时间显著长于安慰剂[（109.29±29.68） min比（96.61±23.90） min,F=9.918,P＜0.01].常见不良反应为嗜睡、口苦、口干,程度均较轻.结论 小剂量阿米替林可显著延长口-盲肠传输时间和改善胃敏感性,但对近端胃容受性和胃液体排空无显著影响,不良反应轻,安全性好.

Objective To explore the effects of low dose amitriptyline （AMT） on gastrointestinal function and its adverse effects in healthy volunteers.Methods In this randomized,double-blind,placebo-controlled cross-over study,28 healthy volunteers were divided into AMT with placebo group （n=14） and placebo with AMT group （n=14）.The former took AMT for seven days at first stage,followed with a 14 days wash out stage and then took placebo for seven days at second stage.Patients of the latter group took medication in reverse order.The dose of medication was 12.5 mg three times per day.The subjects underwent drinking-ultrasonography test and lactulose hydrogen breath test before taking medication and between the seventh and eighth day of first and second stage.The data were analyzed by two stages cross-over analysis,Wilcoxon signed-rank test and chi-square test.Results The results of drinking-ultrasonography test showed that there were no significant differences in proximal gastric cross-sectional area between AMT and placebo after drinking 200,400,600 and 800 mL water （all P〉 0.05）.After drinking 800 mL water,there were no significant differences in gastric liquid emptying rate between AMT and placebo at the fifth and the tenth minutes （both P〉0.05）.After drinking 600 mL and 800 mL water,the visual analogue scale （VAS） of AMT was significantly lower than that of placebo （2.98±0.85 vs 3.57±0.94,Z=4.412,P〈0.01; 4.57±0.98 vs 5.57±0.82,Z=4.170,P〈0.01）.The results of lactulose hydrogen breath test revealed that orocecal transit time of AMT was obviously longer than that of placebo （（109.29±29.68） min vs （96.61±23.90） min,F=9.918,P〈0.01））.The common adverse effects were mild sleepiness,bitter taste and dry mouth.Conclusions Low dose AMT can prolong orocecal transit time and improve gastric sensitivity,but can not significantly affect proximal gastric accommodation and gastric liquid emptying.The adverse effects are mild and the safety is good.