Clinical Question

Does titrated, low-dose amitriptyline improve symptoms of irritable bowel syndrome (IBS) in adults for whom first-line therapies have been ineffective?

Bottom Line

The study, comprised largely of adults with IBS with diarrhea (IBS-D) or IBS with diarrhea mixed with constipation (IBS-M) of at least moderate severity despite first-line therapy, found that titrated, low-dose amitriptyline was more effective than placebo in improving symptoms. (Level of Evidence = 1b)

Synopsis

The researchers recruited adults with IBS from primary care practices in the United Kingdom. The participants could have any subtype of IBS that was at least moderate severity on the IBS Severity Scoring System (IBS-SSS), and they had to have tried first-line treatments (i.e., diet, lifestyle, antispasmodics, laxatives, or antidiarrheals) that were ineffective. The researchers randomized the patients to receive titrated, low-dose amitriptyline (n = 232) or matching placebo (n = 231). More than 80% of the participants had IBS-D or IBS-M. The initial dosage of amitriptyline was 10 mg every evening, and the dose was increased over three weeks to a maximum of 30 mg. The researchers built in many overdose safeguards, such as assessing depression and suicidality and limiting the number of pills given to participants. During the six months of the study, in addition to completing the IBS-SSS, the participants were asked, “Have you had adequate relief of your IBS symptoms?” At the end of six months, 23% discontinued their trial medication (20% of patients taking amitriptyline and 26% of patients taking placebo), usually because of adverse events. After six months, participants in both groups improved, but the participants treated with amitriptyline had a greater degree of improvement: 27 points better in the intention-to-treat analysis; the authors report, however, that 35 points is the minimum clinically important difference. More importantly, 61% of the amitriptyline group reported meaningful improvement compared with 45% of the placebo group (number needed to treat = 7; 95% CI, 4 to 16). These findings are consistent with guidelines from the American College of Gastroenterology and the British Society of Gastroenterology. The authors also provide a patient guide to self-titration of amitriptyline.