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Introduction
Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) can present similarly, but it is crucial to differentiate between the two to provide the correct management. They both typically present with altered mental state, autonomic instability, and hyperthermia, but there are some discerning features.
Serotonin syndrome
Serotonin syndrome is caused by increased serotonin activity in the central nervous system, which can be due to a single therapeutic agent, a combination of agents, or overdose. Common serotonergic drugs include:1
- Selective serotonin reuptake inhibitors (SSRIs), e.g. citalopram, fluoxetine, sertraline
- Serotonin and norepinephrine reuptake inhibitors (SNRIs), e.g. venlafaxine, duloxetine
- Tricyclic antidepressants (TCAs), e.g. amitriptyline, clomipramine
- Monoamine oxidase inhibitors (MAOIs) e.g. selegiline, phenelzine
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a rare, life-threatening side effect of antipsychotics and dopamine-blocking medications. The risk is high with typical antipsychotics (e.g. haloperidol)
Features
Table 1. Features between SS and NMS2
| Features | Serotonin syndrome | Neuroleptic malignant syndrome |
| Causative agent | Serotonergic agents (overdose/drug combinations) | Antipsychotic agents (idiosyncratic/normal dose) |
| Onset | Rapid (within 24 hours) | Slow (days to weeks) |
| Neuromuscular findings | Tremor, myoclonus, ocular clonus, hyperreflexia | Severe muscular rigidity (lead pipe), hyporeflexia |
| Pupils | Mydriasis (dilated) | Normal |
| Bowel sounds | Hyperactive | Normal/decreased |
| Creatine kinase | Normal/slightly raised | Raised |
| Treatment agents | Benzodiazepines, cyproheptadine | Bromocriptine, dantrolene |
| Resolution | Within 24 hours | Days to weeks |
References
- Mikkelsen N, Damkier P, Pedersen SA. Serotonin syndrome-A focused review. Basic & Clinical Pharmacology & Toxicology. 2023. Available from: [LINK].
- UpToDate. Serotonin syndrome (serotonin toxicity). 2024. Available from: [LINK].
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