Amitriptyline for IBS: Four Checks on the ATLANTIS Trial

If IBS symptoms continue despite earlier treatment, take a list of what you have tried to the next appointment. Include how long you used each treatment, the symptom you hoped it would change and why you stopped.

Our guides to prescriptions for IBS with constipation and IBS with diarrhea cover the wider options.

Check that this was second-line IBS treatment

ATLANTIS randomized 463 adults in 55 English general practices after first-line treatment had not helped. Participants used 10–30 mg amitriptyline nightly or placebo, with supported dose adjustment. NIHR funded the trial.¹

Current NICE guidance for England says to consider tricyclic antidepressants after laxatives, loperamide or antispasmodics have not helped. It describes starting at 5–10 mg amitriptyline-equivalent nightly, reviewing regularly and increasing if needed, usually no higher than 30 mg. Ask the prescriber to write your starting dose and adjustment instructions.²

Check what the 27-point difference means

At six months, the adjusted average IBS Severity Scoring System difference favored amitriptyline by 27 points (95% confidence interval 7.1–46.9 points). It was statistically significant, but below the trial’s planned 35-point clinically important difference. An average difference between groups is not an individual response rate.¹

Ask your clinician how you will judge benefit in your own case. For example, agree whether the priority is fewer painful days, less urgency or being able to finish an activity without interruption. Keep the same measures before treatment and at review.

Check the limits of longer follow-up

Only 291 participants entered the 12-month follow-up group. They could choose whether to continue treatment after six months. The 12-month IBS symptom-score difference was not statistically significant, and the smaller, mixed-treatment follow-up cannot establish durable benefit for everyone.¹

The trial reports describe the same participants; they should not be counted as independent confirmations.¹

Check side effects and the review date

IBS is outside the indications in the current UK product information, making this an off-label use. The product information lists constipation, dry mouth and drowsiness among very common adverse effects. A lower dose still requires an individual safety review.³

Tell the prescriber about heart conditions, difficulty passing urine, glaucoma and all other medicines. The product information includes cardiac contraindications and cautions about urinary retention, narrow-angle glaucoma and interacting drugs. It also warns that sedation can affect driving and advises gradual withdrawal over several weeks when stopping.³

NICE recommends a first follow-up after 4 weeks, then every 6–12 months for people using these medicines at low doses for IBS pain or discomfort. Discuss benefit and tolerability at that first review, and agree who to contact if side effects interfere sooner.²

Bring a short record

You could ask: “What would count as enough improvement to continue? Which side effects should prompt contact? Can you write down my adjustment and stopping instructions, plus the review date?”

The Belly Clock in Bloated by Dinner records symptom times, stool form, meals, medicines and supplements. Its Gut-Side Options section places tricyclic antidepressants among prescriptions to discuss with a clinician.