Epidemiology

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Etiology

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• High-potency first-generation antipsychotics (most common association)
• Second-generation antipsychotics
• Other dopamine antagonists, e.g., metoclopramide, promethazine

Pathophysiology

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• Central D2 receptor blockade in the nigrostriatal pathway and hypothalamus, resulting in movement disorders and impaired thermoregulation

Clinical features

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• Mental status changes (encephalopathy)
  • Delirium (e.g., reduced vigilance)
  • Confusion
  • Stupor
  • Catatonia
• Parkinsonism
  • Muscle rigidity (lead-pipe rigidity)
  • Akinesia
  • Tremor
• Hyperthermia: High-grade fever is common.
  • Because muscles working overtime
• Autonomic instability
  • Tachycardia, dysrhythmias, labile blood pressure
  • Tachypnea
  • Diaphoresis

Diagnostics

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Clinical features similar to Serotonin syndrome

	Neuroleptic malignant syndrome	Serotonin syndrome
Precipitant	Dopamine antagonist	Serotonergic agent
Onset	1-3 days	<1 day
Altered mental status	Yes	Yes
Sympathetic hyperactivity	Yes	Yes
Diffuse rigidity	”Lead-pipe” rigidity	No
Clonus	No	Yes
Reflexes	Hyporeflexia	Hyperreflexia

Tip

• Neurotransmitter Specificity:
  • Dopamine Blockade in NMS: - Dopamine is crucial for inhibiting overactivity in muscle movements. Its blockade removes this inhibition, causing muscles to become rigid. - The lack of dopamine dampens reflex arcs, leading to hyporeflexia.
  • Serotonin Excess in Serotonin Syndrome: - Serotonin enhances excitatory signals in the nervous system. - Increased serotonin amplifies reflex pathways, resulting in hyperreflexia and clonus.
• Neuromuscular Impact:
  • The balance between inhibitory and excitatory neurotransmitters is essential for normal muscle function.
  • NMS tips the scale towards inhibition loss (due to dopamine blockade), causing rigidity.
  • Serotonin syndrome tips the scale towards excess excitation, leading to clonus and hyperactive reflexes.

Treatment

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• Discontinue suspected causative agent (e.g., antipsychotics).
• Pharmacotherapy
  • Skeletal muscle relaxant: Dantrolene (See Malignant hyperthermia > Treatment)
  • Dopamine agonists, e.g., bromocriptine, amantadine, or apomorphine
  • Benzodiazepines, e.g., lorazepam: can be used to treat mild symptoms of NMS and/or psychomotor agitation
  • Calcium-channel blockers: for hypertension