Article Sections

Introduction

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening neurologic disorder associated with antipsychotic medication use.  It is characterized by a distinct constellation of symptoms including severe hyperthermia, muscular rigidity, altered mental status, and autonomic instability.

Pathogenesis

Although the pathogenesis is not fully understood, NMS is considered to be an idiosyncratic drug reaction related to dopamine (D2) receptor blockade.  This is because most antipsychotics, particularly high-potency typical antipsychotics (eg, haloperidol), act as dopamine receptor antagonists in the central nervous system (CNS).  The resulting reduction in dopaminergic signaling, especially in the hypothalamus and basal ganglia, is believed to contribute to the classic symptoms of NMS.  The effects of dopamine dysregulation include:

  • Central thermoregulatory dysfunction:  dopaminergic blockade in the hypothalamus disrupts the body's ability to regulate temperature, leading to hyperthermia.

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