Ear Nerve Stimulation Fails to Beat Placebo for Chronic Constipation

Chronic constipation affects roughly 15% of adults globally and encompasses functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C). Standard treatments — fiber, lifestyle changes, and laxatives — leave more than 20% of patients unsatisfied, and up to 40% fail to respond to laxatives at all. Non-pharmacological neuromodulation approaches have therefore attracted growing interest, including transcutaneous auricular vagal nerve stimulation (taVNS), which delivers mild electrical pulses to the ear's auricular branch of the vagus nerve and is thought to modulate gut motility, sensitivity, and inflammation via the brain-gut axis.

This multicenter, randomized, sham-controlled trial enrolled 106 Rome IV-diagnosed chronic constipation patients across five Chinese tertiary hospitals. Participants were randomly assigned 1:1 to active taVNS (left tragus, 25 Hz, 0.5 ms pulse width, 0.5–1.5 mA) or sham taVNS (left earlobe, identical parameters). Both groups received twice-daily 30-minute sessions for 4 weeks, followed by 8 weeks of follow-up. Rescue laxatives were permitted if patients could not defecate for three or more consecutive days. The primary endpoint was the responder rate during weeks 1–4, defined as achieving ≥3 complete spontaneous bowel movements (CSBMs) per week without excessive rescue medication use.

The trial was halted early after a pre-planned interim analysis revealed futility. At week 4, response rates were nearly identical: 17% (9/52) in the taVNS group versus 19% (10/54) in the sham group (RR 0.92, 95% CI 0.30–2.80, p = 1.0). Both intention-to-treat and per-protocol analyses confirmed no significant benefit. Secondary outcomes — including weekly CSBM counts, PAC-SYM symptom scores, PAC-QOL quality of life scores, and anxiety/depression (SAS/SDS) scores — also showed no meaningful between-group differences. No serious adverse events were reported in either group.

These results stand in contrast to a smaller prior RCT (n=42) that showed taVNS benefit in IBS-C patients, though that study's smaller size and different patient mix may explain the discrepancy. The authors note that IBS-C and FC, while overlapping, differ in gut sensitivity profiles, and vagal modulation may be more relevant to pain-predominant IBS-C than to motility-predominant FC. It is also possible that the specific parameters used — 25 Hz frequency, 4-week duration — were suboptimal, or that the earlobe sham produced more physiological effect than expected.

The study is among the most rigorous assessments of taVNS for gastrointestinal symptoms to date, with multicenter design, blinded outcome assessment, and appropriate interim stopping rules. However, it cannot rule out that different stimulation parameters, longer treatment durations, or specific constipation subtypes might respond differently to taVNS.