Neuroleptic Malignant Syndrome - Pathophysiology

Pathophysiology

The mechanism is thought to depend on decreased levels of dopamine activity due to:

• Dopamine receptor blockade
• Genetically reduced function of dopamine receptor D₂

However, the failure of D₂ dopamine receptor antagonism or dopamine receptor dysfunction does not fully explain the presenting symptoms and signs of NMS, as well as the occurrence of NMS with atypical antipsychotic drugs with lower D₂ dopamine activity. This has led to the hypothesis of sympathoadrenal hyperactivity (results from removing tonic inhibition from the sympathetic nervous system) as an etiological mechanism for NMS. Release of calcium is increased from the sarcoplasmic reticulum with antipsychotic usage. This can result in increased muscle contractility, which can play a role in breakdown of muscle, muscle rigidity, and hyperthermia. Some antipsychotic drugs, such as typical neuroleptics, are known to block dopamine receptors; other studies have shown that when drugs supplying dopamine are withdrawn, symptoms similar to NMS present themselves.

There is also thought to be considerable overlap between malignant catatonia and NMS in their pathophysiology, the former being idiopathic and the latter being the drug-induced form of the same syndrome.