On the potential of drug repurposing in dysphagia treatment: New insights from a real-world pharmacovigilance study and a systematic review

Background: Polypharmacy is common in patients with dysphagia. Routinely used drugs may influence swallowing function either improving or worsening it. We aimed to explore the potential effects of three commonly used drug classes on dysphagia and aspiration pneumonia through a systematic review and a real-world data analysis to probe the possibility of drug repurposing for dysphagia treatment. Material and Methods: Five electronic databases were searched. Studies on adults atriskfordysphagia,treatedwithDipeptidyl-PeptidaseIVInhibitors(DPP-4i),Adrenergic Beta-Antagonists(beta-blockers),orAngiotensin-ConvertingEnzymeInhibitors(ACEi), andreportingoutcomesondysphagiaoraspirationpneumoniawereincluded.Anested case/non-case study was performed on adverse events recorded in the FDA Adverse Event Reporting System (FAERS) on patients >64 years. Cases (dysphagia or aspiration pneumonia) were compared between patients only treated with Levodopa and patients who were concomitantly treated with the drugs of interest. Results: Twenty studies were included in the review (17 on ACEi, 2 on beta- blockers, and 1 on DPP-4i). Contrasting findings on the effects of ACEi were found, with a protective effect mainly reported in Asian studies on neurological patients. Beta-blockers were associated with a reduced dysphagia rate. The study on DPP- 4i suggested no effect on dysphagia and an increased risk of aspiration pneumonia. The FAERS analysis showed a reduction of the risk for dysphagia/ aspiration pneumonia with ACEi, beta-blockers, and DPP-4i. Conclusion: Our study explores the potential drug repurposing of ACEi, beta-blockers and DPP-4i in neurological patients with dysphagia to improve swallowing function and reduce aspiration pneumonia risk. Future randomized controlled studies should confirm these results and clarify the underlying mechanisms of action.