Use of Amitriptyline almost doubled symptom improvement in IBS

GLASGOW, UK Amitriptyline, titrated at low doses, outperformed placebo as a second-line treatment for irritable bowel syndrome (IBS) across multiple outcomes in what researchers called a trial Largest randomized controlled trial (RCT) of tricyclic antidepressants in this condition.

According to the investigators of the Low-Dose and Titrated Amitriptyline for Irritable Bowel Syndrome as Second-Line Treatment (ATLANTIS) trial, patients receiving low-dose amitriptyline were more likely to report an overall improvement in symptoms. symptoms were nearly twice as high as those taking placebo.. They reported that low-dose amitriptyline appeared to be safe and well-tolerated.

Hazel Everitt, PhD, professor of primary care research at the University of Southampton, UK, presented these findings at the 2023 Annual Conference of the Royal College of General Practitioners (RCGP) ).

The data is also published on Finger tip and was presented at the recent Unified European Gastroenterology (UEG) Week 2023.

Clinicians “should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-directed dose titration.” multiplication,” the researchers wrote in the paper.

Despite leading treatments such as diet, fiber and antispasmodic medications, many patients with IBS continue to experience bothersome symptoms, Everitt says. Medscape Medical News. “GPs generally do not prescribe amitriptyline for IBS perhaps because of a lack of research evidence for its use in primary care.”

Everitt added that primary care physicians and patients interviewed in the study welcomed low-dose amitriptyline as a potential additional option, especially when enhancing patient-led care. “The patient-specific dose titration document for the trial gives patients more power in managing their IBS by helping them increase or decrease their dose depending on their symptoms and side effects.” .”

“Self-adjusting the dose is tantamount to empowering the patient, and if the patient can be help to manage their medications they will also be more empowered to think about lifestyle changes.”

RCT on 55 practices

The UK National Institute for Health and Care Excellence’s excellent guidance on the management of IBS in primary care says clinicians should “consider” using low-dose tricyclic antidepressants as a treatment option. second-line treatment but emphasizes the need to perform RCTs of these drugs only in the first line.

The ATLANTIS trial was conducted across 55 general practices in England and included adults with IBS Rome IV of any subtype and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score of 75) despite dietary changes and leading treatments. Participants had normal complete blood counts and C-reactive protein measurements, negative celiac serum, and no evidence of suicidal ideation. The average age was 48.5 years and 68% were female. The mean IBS-SSS score across all participants was 272.8 at baseline.

Patients were randomized 1:1 to receive low-dose oral amitriptyline (10 mg once daily; n = 232) with dose adjustments over 3 weeks (up to a maximum dose of 30 mg once daily). days) as determined by a study of participants’ symptoms and tolerability; or placebo (n = 231). Both groups participated for 6 months. The primary outcome was IBS-SSS score at 6 months.


According to the researchers, three-quarters of the participants adhered to the therapy for six months, which is especially notable because the trial was conducted during the COVID-19 pandemic.

An intention-to-treat analysis showed that at 6 months, amitriptyline was superior to placebo, with a significant mean difference in IBS-SSS score between groups of 27.0 (95% CI, 46.9 to 7.1; P =.0079; Mean IBS-SSS, 170.4 vs 200.1 with amitriptyline and placebo). Secondary outcomes showed an increased likelihood of reducing IBS symptoms by subjective global assessment (odds ratio [OR], 1.78; 95% CI. 1.19 2.66; P = 0.0050).

At 3 months, the difference in mean change in IBS-SSS scores between groups was also significant, at 23.3 (95% CI, -42.0 to -4.6; P = 0.014), the researchers reported.

People taking the drug were 70% more likely to have reduced symptoms on SGA than those taking placebo (P = 0.08), according to the researchers.

The researchers reported that low-dose amitriptyline had no effect on psychiatric symptoms, such as distressed thinking, anxiety, and depression, during a 6-month follow-up period, nor did any any impact on your ability to work or participate in social activities.

“This was a real-world trial conducted on a large number of participants with IBS, with an average duration of symptoms of 10 years and 80% had moderate to severe symptoms at baseline.” Leeds, UK and a co-investigator of the study, told Medscape. “The fact that amitriptyline showed such a strong effect compared with placebo in this patient group, with a mean reduction in IBS-SSS of nearly 100 points at both 3 and 6 months, is therefore all the more impressive.”

Mild side effects such as dry mouth and drowsiness occurred more frequently with low-dose amitriptyline than with placebo,

Everitt said ATLANTIS’s findings could change practice. Previous trials of low-dose amitriptyline for IBS have mostly been small and conducted in secondary care settings such as gastroenterology clinics with relatively short follow-up.

“This is a problem for long-term conditions that fluctuate over time and are diagnosed and managed primarily in primary care,” she said. “The ATLANTIS trial is the largest trial of low-dose amitriptyline for IBS performed worldwide and was rigorously conducted with a 6-month follow-up period, providing reliable results that can help inform General Practitioners and Patients’ Treatment Decision-Making in Routine Clinical Practice.”

On a practical level, the team has developed a dose titration document for use by patients and GPs. “Both GPs and participants found the ATLANTIS dose titration document acceptable and useful,” Everitt points out. “We have made dose titration materials freely available to assist patients and clinicians in trialing low-dose amitriptyline for IBS,” she notes.

Ford and Everitt have received funding (institution) from the National Institute for Health and Care Research.

Royal College of General Practitioners (RCGP) Annual Conference 2023: OP222 Abstracts. Presented October 19, 2023.

Lancet. Posted online October 17, 2023. Full text

Becky McCall is a freelance medical journalist based in London, UK. She has been writing for Medscape for nearly 15 years.

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