ArticleFrontiers in pharmacology2026
Beyond codeine - the evidence landscape of conventional, natural, and emerging antitussive therapies: a systematic review and meta-analysis.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
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.
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