Clinical and toxicological epidemiology of intoxications by new psychoactive substances in Reunion Island

New psychoactive substances (NPS) represent a growing concern for emergency medicine due to their unpredictable toxicity and limited detectability in routine screening. Reunion Island, French territories in the Indian Ocean, NPS-related intoxications have been suspected for several years, but biological confirmation has remained scarce. This study aimed to characterise confirmed cases of acute NPS intoxication and describe their clinical features, toxicological profiles, and implications for emergency care and public health surveillance. A retrospective multicentre study was conducted in four public hospitals of Reunion Island between August 2022 and March 2024. Patients presenting with suspected NPS intoxication were mainly identified in emergency and intensive care units. Biological samples were analysed using untargeted high-resolution mass spectrometry (HRMS). Clinical, demographic, and toxicological data were extracted from medical records through a standardised electronic case report form. Confirmed NPS were grouped by pharmacological class, and their clinical manifestations were compared with non-NPS cases. Among 176 suspected cases, 152 (86%) had biological analyses performed. The median age was 29 years, and 77% were men. Most exposures were intentional (77.3%), but unintentional cases—more frequent among women—were also reported. Fourteen intoxications were biologically confirmed, involving synthetic cathinones (dimethylpentylone, hexedrone), cannabinoids (MDMB-4en-PINACA, HHC), a novel opioid (protonitazene), and NM-2AI. Clinical severity ranged from agitation and sedation to cardiovascular collapse, rhabdomyolysis, and respiratory failure. Inhalation was the predominant route of exposure. Alcohol co-exposure was less common in confirmed NPS cases than in conventional drug intoxications. This first series of toxicologically confirmed NPS intoxications on Reunion Island highlights the clinical diversity and potential severity of these emerging substances. For emergency departments, early recognition of unexplained toxidromes, systematic biological sampling, and close collaboration with toxicology laboratories are essential. Strengthened analytical capacity and coordinated toxicovigilance networks are urgently needed to improve detection, guide patient management, and anticipate emerging psychoactive threats.