Etiology

SSRI overdose
Interaction with multiple serotonergic drugs
Predisposing factor to increase exposure to said drugs e.g. AKI
<12h onset

Clinical presentation

Bilateral ankle clonus and hyperreflexia without another explanation strongly suggests serotonin syndrome

Mental status change
Sympathetic hyperactivity
Neuromuscular hyperactivity
1. hyperreflexia
2. clonus ⚠️ rigidity
3. Akathisia
  See hunter criteria

CK (exclude rhabdo); tox screen, ECG to exclude other causes e.g. sympathomimetic toxicity

⚠ severe toxicity may initially present as moderate toxicity e.g. extended release venlafaxine
cyprohepadine (5HT2 antag) 12mg PO if ↑ temp, rhabdo, DIC, renal failure or ARDS
Dexmetomidine!
- stimulates alpha-2C in striatum → modulates serotonin
- stimulates alpha-2A in prefrontal cortex and locus ceruleus → ↓ sympathetic tone

Fever MAN: fever, mental state change, autonomic instability and neuromuscular changes

IF (spontaneous clonus = yes) THEN serotonin toxicity = YES
ELSE IF (inducible clonus = yes) AND [(agitation = yes) OR (diaphoresis = yes)] THEN serotonin toxicity = YES
ELSE IF (ocular clonus = yes) AND [(agitation = yes) or (diaphoresis = yes)] THEN serotonin toxicity = YES
ELSE IF (tremor = yes) AND (hyperreflexia = yes) THEN serotonin toxicity = YES
ELSE IF (hypertonia = yes) AND (temperature > 38ºC) AND [(ocular clonus = yes) or (inducible clonus = yes)] then serotonin toxicity = YES
ELSE serotonin toxicity = NO

SSRIs, SNRIs
TCAs
MAOIs
buspirone, buproprion
lithium?
antipsychotics acting strongly on 5-HT2A receptors- eg. olanzapine
carbamazepine, valproate
ondansetron, metoclopramide
St John's Wort
Methylene blue
Linezolid
Beware interactions with CYP inhibitors!
- ciprofloxacin, ritonavir, fluconazole