Case Report: Atypical neuroleptic malignant syndrome induced by paliperidone palmitate—diagnostic challenges and clinical considerations

Poor treatment adherence is common in schizophrenia and constitutes a major risk factor for relapse and clinical instability. Long-acting injectable (LAI) antipsychotics are frequently prescribed to mitigate this risk; however, their use can be associated with rare but serious adverse events, including neuroleptic malignant syndrome (NMS), with certain atypical presentations posing considerable diagnostic challenges. We report the case of a 51-year-old patient with schizophrenia who, during hospitalization for a psychotic relapse following prolonged refusal of all oral medications, received an intramuscular injection of paliperidone palmitate. Within a few days, the patient experienced a rapid clinical deterioration, characterized by hyperthermia (38 °C), tachycardia (120 bpm), generalized muscular rigidity, mutism, confusion, dehydration, and refusal of oral intake. No obvious precipitating factors, including infectious or environmental triggers, were identified. Initial laboratory workup revealed marked creatine phosphokinase elevation (1700 U/L), hyperferritinemia, and evidence of a pulmonary infiltrate on chest imaging. Given this constellation of clinical and laboratory findings, a diagnosis of neuroleptic malignant syndrome (NMS) was considered. The lack of improvement with antibiotic therapy alone, the persistence of extrapyramidal symptoms, and the ongoing laboratory abnormalities supported the diagnosis of an atypical form of NMS. The patient was transferred to the intensive care unit, where symptomatic management-including intravenous rehydration, antipyretics, empirical antibiotic therapy, and diazepam-resulted in gradual clinical improvement. Complete recovery was achieved after five weeks of hospitalization. Antipsychotic therapy was cautiously reintroduced with olanzapine, which was well tolerated and not associated with any recurrence of symptoms. This case illustrates the diagnostic and therapeutic challenges of neuroleptic malignant syndrome associated with long-acting injectable antipsychotics and emphasizes the need for close and prolonged monitoring in patients receiving these formulations.