Background For decades, cough treatment has relied on centrally acting agents like codeine despite inconsistent efficacy. Advances in cough neurobiology enabled targeted therapies. Natural remedies remain widely used, though evidence for their effectiveness and safety is limited. This study aimed to compare evidence on the efficacy and safety of conventional, natural, and novel antitussives. Methods A systematic review and meta-analysis of randomized clinical trials assessed cough frequency, Visual Analogue Scale (VAS), Leicester Cough Questionnaire (LCQ) and adverse events versus placebo. Results Subgroup meta-analysis showed no significant differences between P2X3 antagonists, indicating a consistent class effect. All subgroups reduced chronic cough frequency standardized mean difference (SMD) = −0.50, 95% confidence interval (CI) (−0.67–0.34), P = 0.0001, suggesting that the observed effect is a class-related response rather than a compound-specific effect. Conclusion Conventional and natural antitussives show inconsistent efficacy. P2X3 receptor antagonists appear most promising, marking a shift beyond codeine toward targeted chronic cough therapies. Clinical Trial Registration The meta-analysis was performed according to the protocol described in PROSPERO, identifier CRD420251172660.
Marko et al. (Mon,) studied this question.