Low-dose amitriptyline superior as second-line therapy for IBS vs. placebo

Key takeaways:

• Amitriptyline was superior to placebo and increased the odds of relief from IBS symptoms.
• Researchers noted that amitriptyline should be offered to patients with IBS after first-line therapy fails.

Titrated low-dose amitriptyline demonstrated effectiveness and tolerability as a second-line therapy for irritable bowel syndrome in primary care compared with placebo, a randomized study in the United Kingdom showed.

According to Alexander C. Ford, MD, a professor of gastroenterology at the University of Leeds, and colleagues, prior studies have suggested tricyclic antidepressants may offer benefits to patients with IBS, “possibly via their pain-modifying properties and actions on gastrointestinal motility.”

“However, almost all trials have been conducted in specialist settings, where patients tend to have more severe symptoms and it is, therefore, unclear whether tricyclic antidepressants are effective in patients with IBS seen in primary care,” the researchers wrote.

In Ford and colleagues’ randomized, double-blind controlled trial, U.K. participants with Rome IV IBS and continuing symptoms in 55 general practices received either a 10 mg daily dose of amitriptyline (n = 232) or placebo (n = 231) over 6 months, with dose titration over 3 weeks.

Researchers used the IBS Severity Scoring System (IBS-SSS) to compare differences between the two study arms — the primary endpoint — while a secondary outcome was relief of IBS symptoms measured by subjective global assessment (SGA).

Participants had a mean age of 48 years, and 68% were women.

Amitriptyline showed greater effectiveness vs. placebo, with a mean difference in IBS-SSS score of:

• –23.3 (95% CI, –42 to –4.6) at 3 months; and
• –27 (95% CI, –46.9 to –7.1) at 6 months.

Amitriptyline was also superior regarding the secondary outcome, with increased odds of relief of IBS symptoms measured by SGA at 3 months (OR = 1.7; 95% CI, 1.15-2.53) and 6 months (OR = 1.78; 95% CI, 1.19-2.66).

Ford and colleagues noted that discontinuations were more common among patients taking placebo compared with those treated with amitriptyline (26% vs. 20%), although adverse events were more frequent among those who received amitriptyline, which they said were related to the drug’s anticholinergic effects. These included drowsiness and dry mouth.

“However, for most participants, these effects were judged as mild,” they said.

The researchers concluded that general practitioners “should offer low-dose amitriptyline to patients with IBS in whom first-line therapies are ineffective, with appropriate support to guide patient-led dose titration, such as the self-titration document we developed.”

“Management guidelines should be updated to reflect these findings,” they added.