Efficacy and safety of oral sprays used to manage dry mouth – Systematic review and network meta-analysis

Various substances have been proposed for use as sprays to alleviate dry mouth symptoms. This systematic review with network meta-analysis aimed to assess their efficacy and safety. Six publication databases were searched, along with three protocol registers and two theses and dissertations libraries. Parallel-groups randomized controlled trials involving spray-based interventions to treat dry mouth symptoms were included. Following duplicate study selection and data extraction, data of xerostomia, stimulated and unstimulated salivary flow, adverse effects, and oral health-related quality of life were analyzed. Whenever possible, paired and network meta-analysis were applied using a random-effects model. The risk of bias was assessed using RoB 2, and the certainty of evidence was assessed using GRADE. Fourteen studies (n = 761) addressed 10 spray-based interventions for dry mouth. Findings from paired and network meta-analyses suggest that 1% malic acid is the most effective over-the-counter spray-based intervention for improving xerostomia, as well as stimulated and unstimulated salivary flow. The certainty of evidence to recommend malic acid was low, due to risk of bias, imprecision, and network intransitivity. Besides, safety issues regarding 1% malic acid spray require further evidence. Low-certainty evidence suggests that 1% malic acid spray improves dry mouth better than other over-the-counter spray-based interventions. Most available interventions lack robust evidence to support clinical recommendation.