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First generation (Typical) antipsychotic medication poisoning

Eric J Lavonas, MD
Section Editor
Stephen J Traub, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM


Antipsychotic medications are primarily used to treat agitation, hallucinations, and other manifestations of psychosis arising from numerous causes, including psychiatric illnesses (schizophrenia, mania), medical illnesses (alcohol withdrawal), and neurologic disease (Alzheimer disease). When used to treat psychiatric diseases, they also aid in restructuring disordered thinking.

Antipsychotic medications are also used to treat a number of nonpsychiatric conditions, including nausea and vomiting (prochlorperazine, promethazine, droperidol), vertigo (prochlorperazine, droperidol), itching (promethazine, hydroxyzine), migraine headache (prochlorperazine, haloperidol, droperidol), Tourette's syndrome (haloperidol, pimozide), postherpetic neuralgia (fluphenazine), and hiccups (chlorpromazine).

Typical antipsychotic medications were first used clinically in 1951. Although their use in psychiatric disorders has been outpaced by that of atypical antipsychotic agents, they remain widely used to treat nausea. Poisoning and overdose from these drugs remains common. The Centers for Disease Control estimates that approximately 5800 patients are treated in US emergency departments annually for adverse effects from typical antipsychotic medication, including unintentional overdose, a rate of 26 ED visits per 10,000 outpatient prescription visits [1]. Haloperidol was responsible for a higher rate of ED visits (43.3 per 10,000 outpatient prescription visits) than any other psychiatric medication. In 2014, American poison control centers reported more than 4600 exposures to phenothiazines, resulting in one death [2,3].

Antipsychotic medications are generally categorized as "low potency," "high potency," or "atypical" agents. This topic review will discuss the management of typical, high, and low potency antipsychotic medication poisoning (table 1). A summary table to facilitate emergent management is provided (table 2). Poisoning from atypical antipsychotic agents is discussed separately. (See "Second generation (atypical) antipsychotic medication poisoning".)


The typical antipsychotic agents antagonize dopamine (D) receptors in several areas of the brain, including the cortex, basal ganglia, limbic system, hypothalamus, and chemoreceptor trigger zone. The efficacy and potency of these agents is directly related to D2 receptor binding affinity [4,5]. However, not all forms of D2 receptor blockade are desirable. D2 antagonism in the mesocortical regions impairs cognition and exacerbates the negative symptoms of schizophrenia, such as avolition, anhedonia, poverty of speech, flattened affect, and social withdrawal.

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Literature review current through: Nov 2017. | This topic last updated: Sep 19, 2016.
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