Antidepressant Toxicity Clinical Presentation

Updated: Apr 12, 2015
  • Author: Jeena Jacob, MD, PharmD; Chief Editor: Asim Tarabar, MD  more...
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Clinical symptoms of antidepressant toxicity often progress rapidly and unpredictably, and many times, patients present asymptomatically or minimally symptomatic and progress to life-threatening cardiovascular and neurologic toxicity within an hour.



Central nervous system (CNS) findings are as follows:

  • Early manifestations include altered mental status, psychotic behavior, delirium and agitation (from anticholinergic effect), and hallucinations. These symptoms can later proceed rapidly to lethargy, stupor, and coma.
  • Seizures are usually generalized and often occur within 1-2 hours of ingestion. Seizures occurs in 4% of patients with overdose and in 13% of fatal cases. CNS depression and seizures result from mixed effects including those of neuronal fast sodium channel blockade; reuptake inhibition of monoaminergic neurotransmitters; and blockade of H1-histamine, muscarinic, GABA, and NMDA-glutamate receptors.
  • Other findings include ileus; urinary retention; hyperthermia; and dry, flushed skin from anticholinergic effect.

Cardiac findings are as follows:

  • Hypotension as a result of dysrhythmias or alpha-adrenergic blockade with a possible, lesser role played by cardiac conduction abnormalities and direct myocardial depression, autonomic neuron neurotransmitter depletion (caused by reuptake blockade), and capillary leakage
  • Dysrhythmias
  • Conduction block
  • Slowed ventricular conduction and resulting dysrhythmias from blockade of fast sodium channels
  • Tachycardia caused by muscarinic anticholinergic effects
  • Hypertension (early) caused by inhibition of norepinephrine reuptake

Pulmonary findings are as follows:

  • Acute lung injury
  • Hypoventilation
  • Aspiration pneumonitis secondary to CNS depression
  • Acute respiratory distress syndrome (ARDS)
  • Hypoxia caused by hypoventilation, aspiration, and capillary leakage

Anticholinergic findings are as follows:

  • Tachycardia
  • Hypothermia
  • Agitation (early)
  • CNS depression
  • Mydriasis
  • Dry skin and/or mucous membranes
  • Hyperthermia
  • Decreased gastric motility/ileus
  • Urinary retention


Tricyclic antidepressant toxicity can be caused by either an acute ingestion or a chronic ingestion. Toxicity secondary to chronic ingestions usually presents with symptomatology that is an exaggeration of the usual side effects of tricyclics.