From the Guidelines
Assessing for serotonin syndrome requires a systematic clinical evaluation focusing on the classic triad of altered mental status, autonomic hyperactivity, and neuromuscular abnormalities, as outlined in the Hunter Criteria 1. To approach this assessment, begin by obtaining a thorough medication history, particularly noting serotonergic agents such as SSRIs, SNRIs, MAOIs, triptans, certain opioids (tramadol, fentanyl), and over-the-counter medications like dextromethorphan. The physical examination should evaluate for:
- Hyperthermia
- Tachycardia
- Hypertension
- Diaphoresis
- Mydriasis
- Hyperreflexia
- Clonus (particularly ocular and inducible)
- Rigidity
- Tremor Lower extremity clonus and hyperreflexia are particularly characteristic findings. The Hunter Criteria can guide diagnosis, requiring 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
- Hypertonia with temperature >38°C and ocular/inducible clonus Laboratory tests should include complete blood count, comprehensive metabolic panel, creatine kinase, and urinalysis to rule out other conditions. Severity ranges from mild (tremor, hyperreflexia) to life-threatening (temperature >41.1°C, autonomic instability, rigidity). Prompt recognition is crucial as serotonin syndrome can rapidly progress, with treatment focusing on discontinuation of serotonergic agents, supportive care, and in severe cases, administration of serotonin antagonists like cyproheptadine 1. It's also important to consider the potential for serotonin syndrome when prescribing serotonergic medications, as the incidence and mortality from serotonin syndrome have been increasing due to the growing number and use of proserotonergic medications 1. The choice of a specific SSRI should be governed by considerations such as pharmacokinetics, pharmacodynamics, and potential for drug interactions 1. In cases where serotonin syndrome is suspected, it's essential to discontinue the precipitating agent and provide supportive care, which may include treatment of agitation, amelioration of hyperthermia, and management of autonomic instability 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