Background
A toxic drug effect characterised by mental state changes and a variety of autonomic and neuromuscular manifestations.
Causes are usually
- Intentional self-poisoning with serotonergic agents or
- When drugs that inhibit the cytochrome P450 are added to therapeutic regimens of SSRIs
Specific agents that may be implicated in serotonin syndrome include:
- amphetamines and their derivatives (ecstasy, dextroamphetamine, methamphetamine, and sibutramine)
- analgesics (cyclobenzaprine, fentanyl, meperidine, tramadol)
- antidepressants/mood stabilizers (buspirone, lithium)
- MAOIs (such as phenelzine)
- SSRIs (such as fluoxetine) & serotonin-norepinephrine reuptake inhibitors (e.g. venlafaxine)
- St. John's wort
- TCADs
- antiemetics (metoclopramide, ondansetron)
- antimigraine drugs (carbamazepine, ergot alkaloids, triptans, valproic acid)
Diagnostic criteria for serotonin syndrome
- Coincident with increase in known serotinergic agent
- Features not integral part of underlying psychiatric disorder
- A neuroleptic not started or increased prior to symptoms
- Four major or three major plus two minor signs
- Other aetiologies ruled out
Major criteria
- Impaired consciousness
- Elevated mood
- Myoclonus
- Hyperreflexia
- Diaphoresis
- Shivering
- Tremor
- Rigidity (especially legs)
- Fever
Minor criteria
- Restlessness
- Insomnia
- Incoordination
- Mydriasis
- Akathesia
- Tachycardia
- Tachypnoea
- Diarrhoea
- Changes in blood pressure
At the severe end of the spectrum there may be seizures, rhabdomyolysis and ventricular arrhythmias.
DDx of serotonin syndrome
- Neuroleptic malig synd
- Sympathomimetic overdose
- Anticholinergic toxicity
- Delerium tremens
- Sepsis
- Heat stroke
- Hepatic encephalopathy
Serotonin Syndrome
- Onset Sudden
- Within 24 hrs of intro of serotonergic agent
- Agitation, diarrhoea
- Dilated pupils, myoclonus, hyperreflexia
- Mortality Rare
NMS
- Slower onset
- Within 7 days intro of neuroleptic agent
- Dysphagia hypersalivation incontinence
- Hyperthermia (>38.5°c), akinesia
- Extrapyramidal "lead pipe" rigidity
- Rhabdomyolysis
- Mortality - 5% - 20%
Management
- Discontinue or decrease suspected medication according to the severity
- Supportive care: hydration, control physiology (esp. fever & BP)
- Basic Ix should include U&E, CK, & urine for myoglobin
- Clonazepam if myoclonus
- Diazepam if seizures
- If severe hyperpyrexia consider:
- Dantrolene (1 mg/kg over 15 minutes, repeated every 15 mins to a max of 10 mg/kg in 24 hours)
- Propanolol or cyproheptadine (after toxicological advice)
- CUH: Cyproheptidine is located in the antidotes press (DDA press) in Resus
- Paralysis/ventilation or dialysis may be required
Links/References
- The neuroleptic malignant and serotonin syndromes. Carbone J. Emergency Medicine Clinics of North America 2000; 18(2): 317-325
- An exploratory approach to the serotonin syndrome. Radomski JW, Dursun SM, Reveley MA, Kutcher SP. Medical Hypotheses 2000; 55(3): 218-224