09. SSRI and Noncyclic Antidepressant Overdose

General Overview

  • Most SSRIs have a wide therapeutic window, so rarely cause significant toxicity in the absence of other toxic ingestions (benzodiazepines, ethanol) or massive ingestions (>150 times recommended dose).
    • Citalopram and escitalopram are most dangerous due to associated cardiac toxicity.
    • Serotonin syndrome (rare in isolated SSRI ingestion), seizure, and QTc prolongation are the most life-threatening complications.
  • SNRIs have higher risk of significant toxicity than SSRIs (venlafaxine).
  • Venlafaxine and bupropion can cause seizures and arrhythmias.

Signs and Symptoms

  • SSRIs: CNS depression, vomiting, tremor, sinus tachycardia common. QT prolongation possible (citalopram, escitalopram, venlafaxine).
    • Serotonin syndrome is rare:
      • AMS, myoclonus, rigidity, hyperreflexia (lower extremity clonus), diaphoresis, tremor, shivering, hyperthermia.
      • Generally occurs days after starting or increasing dose of SSRI but can develop minutes to hours after large ingestion.
  • SNRIs (duloxetine): CNS depression, tachycardia, HTN, vomiting, diarrhea, clonus, rarely serotonin syndrome.
  • Bupropion, venlafaxine: seizures, agitation, sinus tachycardia.
  • Alpha-blockers (trazodone, mirtazapine): hypotension, priapism.

Evaluation

  • Levels are not clinically useful in overdose. Check FSBG, Chem 10, tylenol and salicylate levels.
  • Check ECG to evaluate for QTc prolongation.

Management

  • Decontamination: 50 g activated charcoal in slurry (ensure ability to protect airway first) if within 1-2 hours. Use with caution in patients with ingestions likely to produce seizure activity such as bupropion, unless airway protected with cuffed ET tube.
  • Supportive: maintain airway, assist ventilation if needed.
  • Serotonin syndrome: aggressive external cooling, benzodiazepines for rigidity and seizures (see Drug-Induced Hyperthermia). Consider cyproheptadine or chlorpromazine for refractory cases.
  • Seizure risk: risk of delayed seizure with bupropion extended release; monitor for at least 24 hours. Treat with benzodiazepines if seizing. Monitor airway and intubate if necessary.
  • Cardiac toxicity:
    • If QRS >120ms, tall R in aVR or R/S ratio in aVR >0.7, treat with 1-3 amps (50mEq) IV push of sodium bicarbonate boluses. Monitor 12-lead ECG for resolution of QRS widening.  
    • If QTc prolonged, treat with 1-2g Mg sulfate and correct other electrolytes.

Key Points

  • Venlafaxine and bupropion are highest risk for seizures and arrhythmias.
  • Be aware of potential of noncyclic antidepressants to cause QT prolongation.

 

Goldfrank’s Toxicologic Emergencies, 9th ed 2010. 

Reilly TH, Kirk MA. Atypical antipsychotics and newer antidepressants. Emerg Med Clin North Am 2007; 25(2): 477-97.