Neuroleptic malignant syndrome
Epidemiology
Etiology
- High-potency first-generation antipsychotics (most common association)
- Second-generation antipsychotics
- Other dopamine antagonists, e.g., metoclopramide, promethazine
Pathophysiology
- Central D2 receptor blockade in the nigrostriatal pathway and hypothalamus, resulting in movement disorders and impaired thermoregulation
Clinical features
- Mental status changes (encephalopathy)
- Delirium (e.g., reduced vigilance)
- Confusion
- Stupor
- Catatonia
- Parkinsonism
- Hyperthermia: High-grade fever is common.
- Because muscles working overtime
- Autonomic instability
- Tachycardia, dysrhythmias, labile blood pressure
- Tachypnea
- Diaphoresis
Diagnostics
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.
- Dopamine Blockade in NMS:
- 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
- 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