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

  • Tricyclic antidepressant (TCA) 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 vasopressors for hypotension.

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

  • Extended observation for up to 24 hours is recommended for ingestions of monoamine oxidase inhibitors (MAOIs), bupropion, citalopram, escitalopram, and extended-release preparations of medications such as venlafaxine or desvenlafaxine.

  • 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 primarily supportive with liberal use of benzodiazepines. In severe or refractory cases, particular attention should be paid to active cooling, and 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 primarily supportive with first-line use of benzodiazepines, active cooling as needed, and consideration of 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 Between 2005 and 2010 more than 6% of adolescents reported psychotropic medication use in the last month (3.2% antidepressants, 1% antipsychotics).2 Because of their wide availability, both intentional and unintentional ingestions by children are not uncommon.

According to the 2015 report of the American Association of Poison Control Centers (AAPCC), antidepressants accounted for 4.6% of all exposures, and children younger than 6 years of age were involved in 9.3% of reported antidepressant exposures. Antidepressant ingestion displayed the third most rapid increase in serious outcomes compared to historical data.3 There were a total of 7899 ingestions in patients younger than 6 years and 10,075 in patients between 6 and 19 years of age. The vast majority of antidepressant ingestions were due to selective ...

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