What are the most effective non-acid treatments, and their risks?

The short version: for reflux that is not acid, the treatment is not more acid suppression. It is reducing the reflux events themselves, and the evidence is thin.

The retrieved studies show non-acid reflux is common and often the real culprit. In patients on acid-suppressing drugs with persistent symptoms, most reflux events were non-acid: about 4,600 of roughly 5,500 total events [1]. In children with chronic cough, weakly acidic reflux was the most frequent type and was tied to cough more often than acid reflux [3]. So the problem is real, and PPIs do not touch it.

The most direct non-acid treatment is baclofen, a drug that reduces the sphincter relaxations that let reflux happen. In a small crossover trial, baclofen cut total reflux episodes in heartburn patients from 23 to 8, and symptoms from 11 to 1 [2]. A review of eight studies found consistent reductions in reflux events and transient sphincter relaxations [5]. The catch: baclofen is a central nervous system drug with sedation, dizziness, and fatigue as real side effects, and the trials are tiny, short-term, and mostly single-dose [2][5].

Surgery is the other option. A review found antireflux surgery may help cough and throat symptoms only in highly selected patients, likely those with non-acid reflux, but the evidence quality is poor [4]. One small series of 16 patients with abnormal proximal reflux reported complete cough resolution in 13 after surgery [4]. That is promising but not proof.

My call: baclofen is the most evidence-backed non-acid treatment, but its side effects and tiny trials mean it is a trial, not a sure fix. Surgery is a last resort for severe cases. Confidence: low — the mechanism is sound, the data is not.