Diagnostic pitfalls and forensic implications of hyperactive delirium with severe agitation: an Italian case series

Hyperactive Delirium with Severe Agitation (HDSA) is characterized by disorientation and aggressive behavior, constituting an acute, life-threatening medical emergency that requires prompt intervention. It is frequently associated with substance use. In prehospital settings, management often involves physical restraint, force, or pharmacological sedation; however, the diagnostic criteria and medico-legal implications of HDSA remain insufficiently defined. We retrospectively analyzed seven fatal cases exhibiting HDSA presentations, as defined by the American College of Emergency Physicians (ACEP), from the archives of two university-based forensic pathology centers. A detailed multidisciplinary review by forensic pathologists and forensic psychiatrists showed that six of seven decedents were males aged 25 to 36 years who experienced sudden cardiorespiratory arrest during episodes of severe agitation. Four deaths were preceded by law enforcement involvement, and five occurred immediately following attempts at manual restraint, implicating restraint-associated asphyxia as a potentially significant factor in mortality. Toxicological analyses detected psychostimulant exposure in five cases. This study represents, to our knowledge, one of the first to employ the updated HDSA terminology to describe fatal cases within a medico-legal forensic psychiatric context.