Drug–Drug Interactions in Outpatient Private Clinic Settings vs. Hospital Settings: A Systematic Review and Comparative Analysis

Drug–drug interactions (DDIs) are a major source of adverse drug events (ADEs) that are potentially preventable in the healthcare system worldwide. The present literature lacks a comparative and rigorous synthesis. The objective of our study was to systematically identify, appraise and synthesize evidence on the prevalence, severity, types, and management outcomes of DDIs occurring between the private clinic and hospital settings, and the factors that contribute to the occurrence of DDIs at the patient and system levels are the objective of our study. PubMed, Scopus, Web of Science and Google Scholar were used for literature search from January 2015 to May 2026. Direct or indirect comparative data on DDIs in private clinic versus hospital outpatient or inpatient setting was required for eligibility. Using the Newcastle–Ottawa Scale (NOS) as well as Cochrane RoB 2.0, risk of bias was determined. Narrative synthesis and data extraction in tables were conducted. Forty-two studies (n ≈ 2.1 million patient records) were included. The prevalence of DDI varied from 10.3%–67.4% in settings. The rates of clinically severe DDIs were significantly higher in hospital than in private clinics (mean 28.4% vs. 15.7%) due to the higher prevalence of multimorbidity and older age of inpatients. The detection rate for DDI, pharmacist interventions and integration of CDSS were much lower at private clinics. The conclusion reported that the DDI are common, clinically important, and occur in unique ways in both settings. Patient complexity results in higher severity DDIs in hospitals, while structural limitations in private clinics result in under-detection. The need for targeted pharmacovigilance, mandatory CDSS adoption and cross-setting medication reconciliation are all very much current priorities.