Low-dose amitriptyline appears effective as second-line treatment for IBS
Patients with irritable bowel syndrome (IBS) who were randomized to titrated doses of a tricyclic antidepressant had significant improvements in their IBS symptom scores at six months compared to those receiving a placebo, a trial in primary care found.
Titrated low-dose amitriptyline is safe and effective as a second-line treatment for irritable bowel syndrome (IBS) in the primary care setting, new trial results suggest.
A total of 463 patients across 55 general practices in England were randomized to receive low-dose amitriptyline at 10 mg or a placebo once daily for six months. The oral doses were titrated over three weeks, to a maximum of 30 mg daily, based on symptom response and side effects. At baseline, all individuals recorded an IBS Severity Scoring System (IBS-SSS) score of at least 75.
Most participants were female (68%), and average participant age was 48.5 (SD, 16.1) years. Patients had IBS for a median of 10 years. The results were published by The Lancet on Oct. 16.
Patients in the intervention group had significantly improved mean IBS-SSS scores compared to the other group after six months (–27.0 [95% CI, –46.9 to –7.10]; P=0.0079). Those taking amitriptyline also had increased odds of relief of IBS symptoms according to the subjective global assessment (odds ratio, 1.78 [95% CI, 1.19 to 2.66]; P=0.0050). The proportion of patients reporting relief for at least half of the weeks within the study window was also greater in the intervention group. In general, effects were larger among men and those with higher IBS-SSS baseline scores. The treatment had no effects on anxiety or depression scores.
In the intervention arm, 46 participants discontinued use, with 30 patients attributing their discontinuation to adverse events like dry mouth and drowsiness, compared to 59 of the placebo group who discontinued use, with 20 participants citing adverse events as the reason behind their decision. Two serious adverse reactions took place in the amitriptyline group and three in the placebo group.
Tricyclic antidepressants are not often prescribed for IBS in primary care, the study authors noted. Previous trials of tricyclic antidepressants for IBS had been conducted in specialist settings, meaning patients likely had more severe symptoms. The authors recommended that primary care clinicians “offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial.”
Limitations of the study include that the majority of patients in the current trial had IBS with diarrhea or IBS with mixed bowel habits, so more research is needed on the efficacy of amitriptyline for different IBS subtypes.
An accompanying editorial noted that the effectiveness of low-dose tricyclic antidepressants in IBS is due to their effect on gut sensitivity and pain modulation. “Perhaps it is therefore more sensible to begin to refer to tricyclic antidepressants in the context of IBS as neuromodulators, rather than as antidepressants. This could help mitigate certain negative perceptions and facilitate therapeutic conversations,” it said.