Toxicology – Antipsychotic Toxicity

Source

Antipsychotic medications are used to treat conditions such as schizophrenia, psychosis, severe agitation, and bipolar disorder. They include first-generation agents such as haloperidol and second-generation agents such as risperidone, olanzapine, quetiapine, clozapine, and aripiprazole.

Typical Presentation

A patient with excessive antipsychotic exposure may present with drowsiness, confusion, tachycardia, and hypotension. Severe toxicity can progress to respiratory depression, seizures, coma, or cardiac conduction abnormalities.

Clinical Features

Possible findings include:

• Sedation or agitation
• Ataxia
• Confusion
• Seizures
• Coma
• Respiratory depression
• Orthostatic hypotension

Some agents may also produce anticholinergic findings, including:

• Dilated pupils
• Dry skin and mucous membranes
• Tachycardia
• Urinary retention
• Reduced bowel sounds
• Agitation

ECG abnormalities may include:

• QRS widening
• QT prolongation
• Cardiac dysrhythmias in severe cases

Mechanism of Action

Most antipsychotics block dopamine D2 receptors to varying degrees. First-generation drugs generally produce stronger D2 blockade and therefore more extrapyramidal adverse effects. Many second-generation agents also affect serotonin receptors. Additional blockade of α1-adrenergic, histamine, and muscarinic receptors contributes to hypotension, sedation, and anticholinergic effects.

Management

Treatment is primarily supportive:

• Airway and respiratory support when necessary
• Continuous ECG and cardiac monitoring
• IV fluids for hypotension
• Vasopressors may be required for persistent hypotension
• Treat significant QRS widening or QT-related dysrhythmias according to toxicology and resuscitation guidance
• Benzodiazepines may be used for seizures or severe agitation

Key Points

• Antipsychotics can cause extrapyramidal symptoms, dystonia, neuroleptic malignant syndrome, anticholinergic effects, and orthostatic hypotension.
• Clozapine is associated with agranulocytosis.
• Seizures are uncommon overall but are more strongly associated with clozapine.
• Cardiac monitoring is important because some agents can prolong the QT interval or impair conduction.