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High-Yield Facts

  • The key targets of antidepressant and neuroleptic poisoning are the cardiovascular and central nervous systems.

  • Tricyclic antidepressant poisoning is potentially life threatening due to ventricular dysrhythmias and hypotension. Treatment is supportive with consideration given to sodium bicarbonate for dysrhythmia prevention and treatment, and to pressors for hypotension.

  • Children who are asymptomatic for 6 hours after the ingestion of antidepressants or neuroleptics may be discharged from the ED.

  • The serotonin syndrome (SS) is a life-threatening condition manifested by mental status changes, autonomic instability, hyperthermia, and neuromuscular abnormalities such as hyperreflexia and tremors. Its treatment is supportive with consideration given to cyproheptadine.

  • The neuroleptic malignant syndrome (NMS) is a life-threatening condition manifested by hyperthermia, skeletal muscle rigidity, and altered mental status. Its treatment is supportive with particular attention to cooling and consideration given to bromocriptine.

  • Overdose of typical neuroleptics may produce an acute dystonic reaction, which can be reversed with diphenhydramine or benztropine mesylate.


The symptoms and complications of antidepressant and neuroleptic poisoning can be difficult to distinguish. It is important to recognize the similarities and differences in patients with a potential toxic ingestion of these drugs because the initial approach has some overlap but ultimately requires different treatment. A focused approach to the specific toxic ingestion, including an accurate history and detailed physical examination, is essential to appropriately manage these patients.


Antidepressants are powerful modulators of the monoamine pathways of the CNS and are found in many households. According to the National Center for Health Statistics, antidepressants were the third most common prescription drug taken by Americans of all ages in 2005 to 2008 and the most frequently used by persons aged 18 to 44 years. From 1988–1994 to 2005–2008, the rate of antidepressant use in the United States among all ages increased nearly 400%.1 Because of their wide availability, both intentional and unintentional ingestions by children are not uncommon.

According to the 2011 report of the American Association of Poison Control Centers (AAPCC), Children younger than 6 years of age were involved in 21.7% of reported antidepressant exposures.2 There were a total of 9227 ingestions in patients younger than 6 years and 9425 in patients between 6 and 19 years of age. The vast majority of these ingestions were secondary to the 10,788 selective serotonin reuptake inhibitors (SSRIs) and 1645 due to cyclic antidepressants. However, the cyclic antidepressants resulted in more hospitalizations and serious outcomes.2 This is because of the narrow therapeutic index of TCAs compared to the SSRIs. Dosing as low as 10 to 20 mg/kg of a TCA can result in serious toxicity, whereas most adults can tolerate up to 1000 mg before encountering life-threatening consequences.


The neuroleptics or antipsychotics are prescribed to treat schizophrenia and other psychiatric disorders. The 2011 AAPCC report shows that ...

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