Efficacy and Safety of Tradipitant for Motion Sickness—A GRADE Assessed Systematic Review and Meta-Analysis

Objective: To evaluate the efficacy and safety of tradipitant, a neurokinin-1 (NK1) receptor antagonist, for preventing motion sickness–induced vomiting. Data Sources: PubMed/MEDLINE, Embase, Scopus, and ClinicalTrials.gov were searched from inception through February 2026 without language or date resrictions. Study Selection and Data Extraction: Randomized controlled trials comparing tradipitant (85 or 170 mg) with placebo in adults with motion sickness were included. Two reviewers independently screened studies, extracted data, assessed risk of bias using Cochrane Risk of Bias 2, and evaluated certainty of evidence using Grading of Recommendations Assessment, Development, and Evaluation. Data Synthesis: Three randomized controlled trials (N = 808) were included. Tradipitant significantly reduced overall vomiting vs placebo (risk ratio [RR], 0.38; 95% confidence interval [CI], 0.30-0.48; I 2 = 0%) and improved the composite nausea/vomiting outcome (RR, 0.48; 95% CI, 0.35-0.65). Serious adverse events and somnolence were comparable between groups, although fatigue was more frequent with tradipitant (RR, 2.66; 95% CI, 1.02-6.93). Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs: Unlike antihistamines and anticholinergics, which are frequently limited by sedation and anticholinergic adverse effects, tradipitant significantly reduces motion-induced vomiting with minimal sedation and may benefit patients who do not respond to or cannot tolerate conventional therapies. Conclusions: Tradipitant significantly reduces motion sickness–induced vomiting while maintaining a favorable safety profile, supporting its role as an effective treatment option pending further comparative studies.