Lorazepam in Managing Atypical Neuroleptic Malignant Syndrome: A Systematic Review of Case Reports.

INTRODUCTION: Neuroleptic malignant syndrome (NMS), comprising typical and atypical presentations, is a rare but life-threatening reaction to antipsychotic medications. While typical NMS is characterized by fever, rigidity, and autonomic instability, atypical NMS often lacks these hallmark features, complicating timely diagnosis in the emergency department (ED). METHODS: We conducted a systematic review of PubMed and citation databases (1988-2024) using the keywords "Neuroleptic Malignant Syndrome" and "Lorazepam." Case reports were screened using strict inclusion criteria and appraised with the Joanna Briggs Institute Checklist. RESULTS: Lorazepam led to clinical improvement in 5 of 6 atypical and 7 of 9 typical NMS cases. Among five atypical cases, four demonstrated improvements in altered mental status (AMS), resolution of agitation, and reduction in neuromuscular symptoms within 72 hours, including two within 24 hours, compared to the usual 5-10 day recovery with supportive care alone. One atypical case presenting to the ED showed rapid improvement in AMS following early lorazepam administration, although catatonia ultimately necessitated electroconvulsive therapy. These findings highlight lorazepam's potential benefit in both timely symptom control and diagnostic clarity in atypical NMS. CONCLUSION: Lorazepam shows rapid efficacy in atypical NMS, with most cases improving within 72 hours. Yet its subtle presentation often delays diagnosis in the ED, reducing early treatment opportunities. Typical NMS cases demonstrated slower response. Emergency physicians should maintain a high index of suspicion for atypical NMS and consider empiric lorazepam therapy alongside antipsychotic discontinuation and supportive care. Prospective studies are needed to refine ED management strategies.