Chronic therapeutic non-adherence: Toward a new nosological entity

Therapeutic non-adherence (TNA) significantly contributes to chronic disease burden but remains framed largely as a behavioral issue rather than a pathological process. This conceptual analysis applies the Bradford Hill criteria assessing whether chronic TNA meets the threshold for recognition as a distinct clinical syndrome. The evidence shows consistent associations between TNA and increased morbidity, mortality, and healthcare costs across multiple chronic diseases. Key features - such as temporality, specificity, dose-response relationship, and emerging biological correlates, particularly in cardiovascular disease - support its pathophysiological plausibility. Intervention studies suggest that modifying TNA alters disease trajectory, and analogies with recognized behavioral syndromes further reinforce a syndromic framing. Reclassifying TNA as a nosological entity would enable systematic identification, coding, and targeted intervention, while potentially reducing stigma and enhancing therapeutic engagement. Though care is needed to avoid overmedicalization, the current approach underestimates the complexity and clinical relevance of chronic TNA. A structured nosological reframing may therefore be conceptually and pragmatically justified. While recent reviews have comprehensively addressed the determinants, consequences, and management of non-adherence, our work offers a complementary perspective by proposing its systematic investigation within a structured nosological framework, supported by the systematic application of the Bradford Hill criteria, thereby extending the current literature from a novel conceptual angle. Further research is required to develop consensus diagnostic criteria, validate phenotypes, and assess etiology-specific interventional strategies before any formal disease classification can be established.