Neuroleptic malignant syndrome after risperidone therapy in a critically ill patient with mixed connective tissue disease-associated interstitial lung disease:A case report

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Background:Neuroleptic malignant syndrome (NMS) is a rare but life-threatening adverse reaction to dopamine-blocking agents. Although atypical antipsychotics are generally considered to carry a lower risk than typical agents, NMS may occur even at therapeutic doses, particularly in critically ill patients. Critically ill individuals with systemic inflammatory diseases may present with diagnostic challenges because the clinical features of NMS overlap with those of infection or disease exacerbation. Case Presentation:A 47-year-old woman with mixed connective tissue disease-associated interstitial lung disease (MCTD-ILD) developed acute respiratory failure requiring mechanical ventilation and high-dose corticosteroid therapy. During sedation weaning, risperidone was initiated at 3 mg/day to manage agitation. Within 48 hours, she developed a high-grade fever, tachypnea, and a marked creatine kinase elevation without muscle rigidity, fulfilling the diagnostic criteria for NMS. Discontinuation of risperidone and a single administration of dantrolene led to a clinical improvement. However, recurrent NMS occurred after initial stabilization, necessitating reintubation and the reinstitution of dantrolene. The patient ultimately recovered and was discharged without recurrence. Conclusion:NMS can occur and recur after therapeutic-dose atypical antipsychotic use in critically ill patients with systemic inflammatory conditions. Early recognition and close biochemical monitoring are essential when prescribing dopamine antagonists in the ICU setting. J. Med. Invest. 73 : 558-560, August, 2026