Acute Intoxication After Baclofen Administration: A Review of the Literature and Methodological Proposals

Baclofen intoxication, once rare, is now increasingly observed in clinical and forensic settings due to its expanding medical and off-label use. However, baclofen is not routinely included in standard postmortem toxicological panels and is usually tested only when explicitly requested. This selective approach, together with the lack of validated cut-offs and standardized interpretative protocols, complicates both clinical management and postmortem evaluation. A systematic review of the literature published between July 2005 and July 2025 was conducted according to PRISMA guidelines, including fatal and non-fatal baclofen intoxications with quantitative toxicological data. Analytical methods, biological matrices, concentration ranges, and clinical outcomes were compared to identify recurring patterns and interpretative gaps. A fatal intrathecal overdose case was also analyzed as a paradigmatic example of diagnostic and methodological challenges. In thirteen studies meeting inclusion criteria and comprising over 300 cases, reported blood concentrations ranged from 0.04 to 110 mg/L, with overlapping values between survivors and fatalities. The analysis revealed marked heterogeneity in matrices and methods, and a poor correlation between concentration and clinical severity, limiting the reliability of toxicological interpretation in both clinical and postmortem settings. Baclofen intoxication illustrates the challenges of interpreting toxicological data without harmonized analytical criteria and highlights the need for standardized procedures and shared reference databases to improve diagnostic and medico-legal accuracy.