From the Guidelines
Assessing for serotonin syndrome requires a systematic approach focusing on clinical presentation and history of serotonergic medication use, with the Hunter Criteria being the most commonly used for formal diagnosis, as noted in 1 and 1.
Key Considerations
- Evaluate for the classic triad of symptoms: mental status changes (agitation, confusion, delirium), autonomic instability (hyperthermia, tachycardia, diaphoresis, hypertension, dilated pupils), and neuromuscular abnormalities (hyperreflexia, clonus, muscle rigidity, tremor) 1.
- Obtain a thorough medication history, looking for recent initiation or dose increases of serotonergic agents such as SSRIs (fluoxetine, sertraline), SNRIs (venlafaxine, duloxetine), MAOIs (phenelzine, tranylcypromine), triptans, certain opioids (tramadol, meperidine), dextromethorphan, or illicit drugs like MDMA or cocaine 1.
- The presence of ocular clonus, ankle clonus, or spontaneous clonus is highly specific for serotonin syndrome, as mentioned in 1 and 1.
- Serotonin syndrome typically develops rapidly, often within hours of medication changes, which helps distinguish it from neuroleptic malignant syndrome, which has a more gradual onset over days 1.
Diagnostic Criteria
- The Hunter Criteria can be used for formal diagnosis, which requires the presence of a serotonergic agent plus one of the following: spontaneous clonus, inducible clonus with agitation/diaphoresis, ocular clonus with agitation/diaphoresis, tremor with hyperreflexia, or hypertonia with temperature >38°C and ocular/inducible clonus 1.
- The modified Dunkley criteria can also be used, which includes the presence of tremor and hyperreflexia, spontaneous clonus, muscle rigidity, temperature >38°C, and either ocular clonus or inducible clonus, among other criteria 1.
Treatment Considerations
- Treatment often involves discontinuing the precipitating agent and providing supportive care, including treatment of agitation, amelioration of hyperthermia, and management of autonomic instability, as noted in 1.
- In severe cases, emergency sedation, neuromuscular paralysis, and intubation may be considered, and physical restraints may be detrimental, as they can exacerbate isometric contractions and worsen hyperthermia and lactic acidosis 1.
From the Research
Assessment Approach
To assess for serotonin syndrome, the following steps can be taken:
- Identify patients who have been exposed to serotonergic agents, such as multiple serotonergic drugs or significant exposure to a single serotonin-augmenting drug 2
- Look for clinical features of serotonin syndrome, including:
- Mental status changes
- Autonomic instability
- Neuromuscular hyperactivity
- Use the Hunter Serotonin Toxicity Criteria to diagnose serotonin syndrome, which requires the presence of one of the following classical features or groups of features:
- Spontaneous clonus
- Inducible clonus with agitation or diaphoresis
- Ocular clonus with agitation or diaphoresis
- Tremor and hyperreflexia
- Hypertonia, temperature above 100.4 degrees F (38 degrees C), and ocular or inducible clonus 2
- Alternatively, use Sternbach's 10 clinical features to diagnose serotonin toxicity, although these features have low specificity 3
Clinical Features
The clinical features of serotonin syndrome can be categorized into three main areas:
- Neuromuscular excitation (clonus, hyperreflexia, myoclonus, rigidity)
- Autonomic stimulation (hyperthermia, tachycardia, diaphoresis, tremor, flushing)
- Changed mental state (anxiety, agitation, confusion) 3
- Other features may include:
- Fever
- Shivering
- Diaphoresis
- Ataxia
- Hyperreflexia
- Myoclonus
- Diarrhea 4
Diagnosis and Treatment
Diagnosis of serotonin syndrome is often made on the basis of the presence of at least three of Sternbach's 10 clinical features, although the Hunter Serotonin Toxicity Criteria are more specific 3 Treatment should focus on cessation of the serotonergic medication and supportive care 2, 3 Some antiserotonergic agents, such as cyproheptadine, may be used as an adjunct to supportive care, although the preferred agent, dose, and indications are not well defined 5, 4