Motion Sickness: Current Pharmacological Treatment Strategies and the Emerging Role of Tradipitant

Abstract

Background. Motion sickness is a prevalent clinical syndrome triggered by sensory conflict, causing severe autonomic distress. While legacy treatments (anticholinergics and antihistamines) effectively manage symptoms, they cause a debilitating "pharmacological hangover" characterized by severe sedation and cognitive impairment.

Aim. This review evaluates tradipitant, a selective neurokinin-1 (NK1) receptor antagonist, investigating if targeting the Substance P pathway provides robust emetic protection without the functional decline of traditional therapies.

Material and methods. A narrative review of PubMed, Google Scholar, Embase, ClinicalTrials, and FDA databases was conducted to analyze tradipitant's pharmacology, efficacy, and safety, emphasizing Phase 2 (Motion Sifnos) and Phase 3 (Motion Syros, Serifos) trials.

Results. Tradipitant competitively inhibits Substance P in brainstem emetic centers without binding to histaminergic or cholinergic receptors. Sifnos data demonstrated a 78% relative risk reduction in vomiting during rough seas. Syros confirmed significant reductions in primary and repeated vomiting across varying sea intensities. Somnolence rates remained low (6–12%), successfully decoupling anti-emetic protection from cognitive impairment, though mild-to-moderate nausea sometimes persisted.

Conclusions. Representing the first major motion sickness advancement in 40 years, tradipitant’s targeted, non-sedating profile preserves physical comfort and cognitive clarity. It addresses a critical unmet need for travelers, though further multi-environment research is warranted.