Aprepitant Use in Pediatric Cyclical Vomiting Syndrome: A Systematic Review

Abstract

Background: Cyclical vomiting syndrome (CVS) is a disorder of gut–brain interaction characterized by recurrent, stereotyped episodes of intense nausea and vomiting with return to baseline in between. Pediatric CVS often leads to frequent hospitalizations, comorbidities, and poor quality of life. Standard abortive therapies include 5-HT₃ antagonists (e.g. ondansetron) and triptans, while prophylaxis may involve cyproheptadine or amitriptyline. Aprepitant, an oral neurokinin-1 (NK1) receptor antagonist approved for chemotherapy-induced nausea, is increasingly used off-label in refractory pediatric CVS. Its efficacy and safety in this setting remain unclear.   Methods: We conducted a PRISMA-style systematic review of studies reporting on aprepitant in pediatric CVS. We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library from inception to 15 January 2025 for any study (randomized trials, cohorts, case series, reports) of aprepitant in children (<18) with CVS. Two reviewers independently screened records, extracted data, and assessed risk of bias using standard tools. Outcomes were patient-reported response (episode frequency/intensity), healthcare utilization (episodes/year, admissions), and adverse events. Due to heterogeneity, results are summarized narratively.   Results: No randomized controlled trials were identified. Evidence consisted of one retrospective controlled cohort study, one retrospective single-center case series, and one case report, with mixed findings and overall low certainty. We included three studies (total n≈1817): one large retrospective controlled cohort (Thavamani et al. 2024; n=1775, 96 received aprepitant), one single-center retrospective series (Cristofori et al. 2014; n=41), and one single-patient case report (Nivatsi et al. 2021). In the Thavamani cohort, aprepitant use as an abortive agent did not reduce 7-day readmission rates (17% vs. 16%, p=0.91), although those receiving aprepitant had more severe initial illness (longer stay: 5 vs. 3 days; higher costs: \$11,790 vs. \$6,380). Cristofori et al. reported that 81% of children on prophylactic aprepitant and 76% on abortive aprepitant had complete or partial clinical response at 12 months. Both subgroups showed significant reductions in CVS episodes per year, hospital admissions, episode duration, and improved school attendance. Side effects occurred only in the prophylactic group (31% of children) and were mild (hiccups, fatigue, appetite increase, headache, migraine). The single case (13-year-old girl) had failed standard therapy but experienced complete cessation of vomiting after starting brief oral aprepitant at prodrome.   Limitations:  All evidence is from observational or anecdotal reports with high risk of bias. The cohort used administrative data without randomized assignment, and the retrospective series lacked a control group. Adverse events were sparsely reported.   Conclusion: Preliminary evidence suggests aprepitant can reduce symptoms in refractory pediatric CVS and is well tolerated, but a large multicenter RCT is needed. Current data are insufficient to endorse routine use; aprepitant may be considered in severe, treatment-refractory cases under specialist care.