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Background:  Medication non-adherence has a dynamic, temporal and multifactorial nature with a significant impact on economic and clinical outcomes. Interventions to improve adherence are complex and require adaptation to patients' needs, which may include patient's medical conditions. The aim of this study was to assess the comparative effectiveness of medication adherence interventions per type of clinical condition on adult patients.   Methods:  A systematic review with network meta-analysis was performed (PROSPERO registration number of CRD42018054598). An initial Pubmed search was conducted to select meta-analyses reporting results of interventions aiming to improve medication adherence. Primary studies were selected and those reporting results with a long-term follow up (≥10 months) on adult patients were included for data extraction. Study characteristics, description of interventions and adherence outcomes were extracted. Adherence interventions were classified in four groups: educational, attitudinal, technical, and rewards. Clinical conditions were classified in four groups: circulatory system and metabolic diseases, infectious diseases, musculoskeletal diseases, and mental, behavioral or neurodevelopmental disorders. Network meta-analyses with effect sizes expressed as odds ratio (OR) with a 95% credibility interval (CrI) were built. Ranking probabilities for each measure of adherence were calculated by using surface under the cumulative ranking analysis (SUCRA).   Results:  A total of 61 meta-analysis and 149 primary studies were included in the qualitative synthesis and 80 primary studies in the quantitative analysis. The most effective interventions were: educational + technical 79.6% [OR: 0.44 (CrI: 0.26, 0.73)] and 73.3% [OR: 0.56 (0.36, 0.84)] in circulatory system and metabolic diseases and infectious diseases respectively. Attitudinal intervention had the greatest probability for musculoskeletal diseases of 92.3% in SUCRA [OR: 0.30 (0.10, 0.86)]. Finally, educational + attitudinal interventions had the greatest effect (SUCRA 73.8%) for mental, behavioral or neurodevelopmental disorders, although this was not significant according to consistency analysis.   Conclusion:  Effectiveness of interventions seems to be related to the clinical condition. Educational and technical interventions resulted in a major effect on long-term management of medication adherence in patients with infectious diseases (HIV) and circulatory system and metabolic diseases whereas attitudinal components presented a higher effect on musculoskeletal and mental, behavioral or neurodevelopmental disorders.

frontiers in pharmacology

Comparison of Interventions to Improve Long-Term Medication Adherence Across Different Clinical Conditions: A Systematic Review With Network Meta-Analysis