Serotonin syndrome is a mild to potentially fatal condition caused by excess serotonin that overactivates serotonin (5-HT) receptors, especially 5-HT2A.
Drugs can raise serotonin activity through several mechanisms, including:
Another mechanism involves inhibition of certain cytochrome P450 enzymes (including CYP2D6 and CYP3A4) by SSRIs. This can cause accumulation of serotonergic drugs, including SSRIs themselves.
Symptoms usually appear within 24 hours of the inciting event. Common triggers include starting a serotonergic drug, increasing its dose, or introducing a new drug combination.
It presents with hyperthermia, hypertension, muscle rigidity, mydriasis, diaphoresis, tremors, myoclonus, hyperreflexia, agitation, pressured speech, diarrhea, flushed skin, dry mucosa, arrhythmias, dramatic swings in pulse rate and blood pressure, seizures etc.
Complications include rhabdomyolysis, myoglobinuria, metabolic acidosis, renal failure, ARDS, DIC, coma and death. Babinski sign may be positive bilaterally.
Laboratory findings include leukocytosis, elevated transaminases and creatinine levels.
Drugs and drug combinations that can precipitate serotonin syndrome
MAOIs alone or in combination with SSRIs/SNRIs/TCAs or opiates
SSRIs alone or in combination with MAOIs/SNRIs/TCAs/Triptans/opiates
Fluoxetine* with carbamazepine
Venlafaxine alone or with lithium/tramadol/MAOIs/SSRIs/TCAs/opiates
Atypical antipsychotics
Buspirone
Mirtazapine
Dextromethorphan with SSRIs/amitriptyline/chlorpheniramine
Ciprofloxacin with venlafaxine/methadone
Fluconazole with citalopram
Linezolid with SSRIs
Cocaine, MDMA (Ecstasy), LSD
St John’s wort
L tryptophan
Lithium
Metoclopramide
*Fluoxetine can cause serotonin syndrome even after being discontinued, due to its long half life.
Management includes stopping the offending drug, supportive measures, critical care, cooling measures, diazepam, cyproheptadine (5HT antagonist), esmolol/nitroprusside for hypertension and paralysis with a nondepolarizing agent with intubation and mechanical ventilation.
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