Nortriptyline for Gastroparesis: NORIG Results

If nortriptyline is being considered for gastroparesis, bring your stomach-emptying report and describe the symptom you most want help with. Ask the prescriber how they will judge a response, when you will review it and what should prompt an earlier call.

What counted as improvement?

NORIG randomized 130 adults with idiopathic gastroparesis and delayed stomach emptying to nortriptyline or placebo for 15 weeks, excluding diabetic and postsurgical disease.¹

The primary target: at least 50% reduction in the Gastroparesis Cardinal Symptom Index (GCSI; total 0–45) at two consecutive assessments three weeks apart. 15 of 65 taking nortriptyline met it, versus 14 of 65 taking placebo: relative risk 1.06 (95% CI 0.56–2.00). This did not establish benefit or equivalence. Two per group without sufficient follow-up scores counted as nonresponders.¹

Who stopped treatment?

Treatment stopped in 19/65 nortriptyline versus 6/65 placebo participants. Adverse effects were the main reason in 10 versus 3, respectively, not everyone who stopped. NIDDK funded NORIG.¹

The US Pamelor label lists dry mouth, constipation and urinary retention, and warns about cardiac effects and impaired driving ability. A prescriber should review heart history, other medicines, pregnancy and breastfeeding. MAO-inhibitor combinations are contraindicated, and other serotonergic medicines can increase serotonin-syndrome risk. Do not arrange a medication washout yourself.²

What should you ask?

The 2025 AGA guidance conditionally suggests against nortriptyline as first-line gastroparesis treatment. Ask why it is being proposed at this point in your care and which outcome would justify continuing. The recommendation calls for a discussion of benefits, harms and preferences; it does not tell you to stop an existing prescription.³

US Pamelor labeling covers depression; gastroparesis use is off-label. Its boxed warning describes increased suicidal thoughts and behavior in children, adolescents and young adults, with monitoring for clinical worsening and unusual behavior at all ages. Contact your healthcare provider right away for suicidal thoughts, worsening depression or abrupt concerning mood changes. Do not stop an antidepressant suddenly without a prescriber’s plan.²

Bloated by Dinner includes “The Visit Script”: bring your symptom record, summarize the pattern, list medicines and supplements, and ask what has been ruled out and what comes next. Keep the stomach-emptying report with that record so your review starts from the tests you have had.