Toxicology – Monoamine Oxidase Inhibitor (MAOI) Toxicity

Source

Monoamine oxidase inhibitors are antidepressants now used mainly for atypical or treatment-resistant depression. Certain MAO-inhibiting drugs are also used in Parkinson disease.

Typical Presentation

A patient taking an MAOI may present with severe agitation, hypertension, sweating, tachycardia, and altered mental status. In overdose, symptoms can be significantly delayed and may later progress from a hyperadrenergic state to profound hypotension and cardiovascular collapse.

Clinical Features

MAOI toxicity can appear in several forms:

• Hyperadrenergic crisis: Headache, flushing, diaphoresis, dilated pupils, tachycardia, severe hypertension, and agitation. This may occur after consumption of high-tyramine foods while taking an MAOI.
• Acute overdose: Similar hyperadrenergic findings plus hyperthermia, vomiting, diarrhea, psychosis, myoclonus, seizures, and marked altered mental status. Severe cases may progress to coma, hypotension, and cardiovascular collapse.
• Serotonin syndrome: May occur when MAOIs are combined with other serotonergic medications and is characterized by altered mental status, autonomic instability, and neuromuscular hyperactivity.

Symptoms after overdose may not appear for many hours and can persist for several days.

Mechanism of Action

MAOIs inhibit monoamine oxidase, the enzyme responsible for breaking down serotonin, norepinephrine, and dopamine. This causes accumulation of these neurotransmitters and excessive adrenergic and serotonergic activity.

Management

Treatment is primarily supportive:

• Airway and respiratory support when necessary
• Continuous cardiac and blood pressure monitoring
• Benzodiazepines for agitation and seizures
• Rapid cooling for significant hyperthermia
• Short-acting IV antihypertensive therapy may be required for severe hypertension
• IV fluids and vasopressors may be necessary if cardiovascular collapse develops
• Gastrointestinal decontamination may be considered in appropriate recent exposures

Because toxicity can be delayed, significant MAOI overdoses generally require prolonged monitored observation.

Key Points

• MAOI overdose can have a markedly delayed onset.
• Early toxicity often produces a hyperadrenergic state with hypertension and agitation.
• Severe poisoning may later progress to hypotension, coma, and cardiovascular collapse.
• Combining MAOIs with serotonergic drugs can precipitate serotonin syndrome.