Neuroleptic malignant syndrome (NMS) is a life-threatening neurological disorder usually associated with antipsychotics. Clinical features include fever, muscle rigidity, autonomic instability, and mental status changes. Laboratory measures often show an elevated creatine kinase and myoglobinuria as a sign of rhabdomyolysis. Management includes discontinuation of the antipsychotic drug, supportive measures, and administration of dantrolene.
- Reaction to antipsychotic drugs (more common with high-potency first-generation antipsychotics than with second-generation antipsychotics)
- Agents that affect the CNS (e.g., carbamazepine, lithium, venlafaxine)
- Certain antiemetics (e.g., metoclopramide, promethazine)
- Genetic predisposition
- A connection between NMS and the duration of therapy or therapeutic dose has not been established.
- The underlying mechanism is not well understood. A disruption of numerous neurotransmitter pathways is suspected.
- Central D2 receptor blockade in the nigrostriatal pathway and hypothalamus, resulting in movement disorders and impaired thermoregulation
- Increased sympathetic tone disrupts autonomic regulation and increases muscle tone and metabolism.
- Increased release of calcium from the SR of striated muscle cells, resulting in increased contractility and muscle breakdown
- Onset usually occurs within 2 weeks of the first dose.
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The differential diagnoses listed here are not exhaustive.
- Discontinuation of the antipsychotic drug
- Supportive measures (e.g., ICU care)
- Electroconvulsive therapy