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Serotonin Syndrome & SSRI Side-Effects

Overview of serotonin syndrome:

  • Background:
    • Not an idiopathic reaction, but results from excess serotonergic agonism
    • Onset is typically rapid, within 24 hours of medication intake
    • Occurs in 15% of SSRI overdoses
  • Offending drugs: many agents can cause this, particularly if used in combination (e.g. Libby Zion case)
    • Antidepressants: SSRI, TCA, SNRI, MAOI
    • Neuroleptics: valproic acid, lithium
    • Opiates: meperidine, fentanyl, tramadol, dextromethorphan
    • Antiemetics: ondansetron, metoclopramide
    • Antimigraines: triptans
    • OTC: St. John's wort
    • Illicits: LSD, ecstasy, cocaine, amphetamines
  • Diagnosis: made on clinical grounds, as serotonin levels do not correlate with toxicity
    • Signs/symptoms: classic triad of AMS, autonomic hyperactivity, neuromuscular abnormalities - like many classic findings, not sensitive
      • Mental status: agitation, delirium, restlessness, agitation
      • Autonomic dysregulation: diaphoresis, hyperthermia, tachycardia, hypertension, diarrhea
      • Neurologic changes: tremor, rigidity, hyperreflexia/clonus (most pronounced in LEs), mydriasis
      • Rigidity can make diagnosis of hyperreflexia difficult
    • Lab findings: metabolic acidosis, leukocytosis, rhabdomyolysis, DIC, AKI
  • Differential diagnosis: When considering serotonin syndrome, should always also consider NMS, malignant hyperthermia, and anticholinergic toxicity
    • NMS: Sluggish neuro findings and reflexes (as opposed to hyperactive) and time of onset more protracted
    • Malignant hyperthermia: Rigidity is very severe, and time of onset is rapid after administration of anesthesia
    • Anticholinergic toxicity: Neuro exam normal, and characterized by hypoactive BS (as opposed to diarrhea)
  • Management:
    • Discontinue serotonergic agents
    • Supportive care for autonomic derangements in monitored setting, as decompensation can occur rapidly
      • Can sedate with benzodiazepenes to blunt neurologic hyperactivity
      • If hyperthermia is persistent, may require paralysis and intubation
    • If severe refractory symptoms, can consider serotonin antagonism with cyproheptadine (antihistamine with antiserotonergic properties)
    • Determine ultimate need for serotonergic agent, and if necessary, reintroduce slowly in monitored setting

 

 

SSRI side effects:

  • SSRIs are typically well-tolerated, but have some characteristic SEs to be aware of:
    • Decreased libido
    • SIADH
    • Bleeding from impaired platelet aggregation due to decreased intraplatelet serotonin concentrations
    • While citalopram has the fewest cytochrome p450 interactions, in overdose, it can cause seizures and arrhythmias from QT prolongation

 

(Christopher Woo MD, 12/6/10)