Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial
In RCT (n=463), low-dose amitriptyline (10-30mg/day) reduced IBS severity at 6 months vs. placebo (mean IBS Severity Scoring System difference: –27.0, 95% CI –46.9 to –7.10; p=0.0079). Treatment discontinuation before 6 months occurred in 46 (20%) vs 59 (26%), respectively.
Source:
The Lancet
SPS commentary:
Adverse events were more frequent with low-dose amitriptyline, and in keeping with the known anticholinergic effects of the drug, but most were judged as mild. Withdrawals due to adverse events were slightly more frequent with low-dose amitriptyline (13% vs. 9%).
An editorial notes that there is ongoing debate about the therapeutic mechanism of antidepressants in IBS, either through central mood modulation or peripheral gut action. Together with concerns about side-effects, this may explain the hesitance that GPs and patients have regarding the use of antidepressants for IBS. It adds that the results of this trial suggest that the effectiveness of low dose tricyclic antidepressants in IBS is not related to antidepressant or anxiolytic activity, but rather to an effect on gut sensitivity and pain modulation.