Pediatric Monoamine Oxidase Inhibitor Toxicity

Updated: Jan 15, 2015
  • Author: Soumya Ganapathy, MD; Chief Editor: Timothy E Corden, MD  more...
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Overview

Background

The increased use of antidepressants with safer toxicologic profiles has made monoamine oxidase inhibitor (MAOI) poisoning uncommon among children. MAOIs are still used in patients with Parkinson disease and refractory and atypical depression. Some antibiotics (eg, linezolid [1] ) are MAOIs. Although MAOI ingestion is rare, MAOI overdoses can potentially cause significant morbidity and mortality. [2]

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Pathophysiology

Monoamine oxidase is a mitochondrial enzyme that functions to deaminate primary and secondary aromatic amines. The deamination of aromatic amines (eg, norepinephrine) leads to the compounds deactivation. MAOIs prevent the breakdown of aromatic amines in the neuronal cytosol, resulting in the storage of larger concentrations of active aromatic amines in neuronal vesicles and, therefore, an increased release of these neurotransmitters into the synaptic cleft with each action potential.

Two types of monoamine oxidases are recognized: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). MAO-A preferentially deaminates norepinephrine, serotonin, and dietary tyramine, whereas MAO-B mainly deaminates phenylethylamine and dopamine. MAO-B is primarily found in the basal ganglia. MAO-A is found predominantly in the liver and GI tract. MAO-A inhibitors increase the levels of norepinephrine and serotonin and are used in the treatment of clinical depression. [3, 4, 5] MAO-B inhibitors increase the dopaminergic concentrations in the brain and have been successfully used in the treatment of Parkinson disease. [6]

Many drugs and foods can potentiate the adrenergic and serotonergic effects of MAOIs. This characteristic is particularly important because many adverse affects involving MAOIs are due to drug-drug and drug-food interactions. [7]

Commonly used nonselective general MAOIs include phenelzine, isocarboxazid, and tranylcypromine. MAO-A specific inhibitors include moclobemide and clorgyline. MAO-B inhibitors include pargyline and selegiline. The selegiline transdermal system has been used to decrease the risk of a dietary tyramine-induced hypertensive crisis associated with these agents.

MAOIs are rapidly absorbed and undergo first-pass metabolism in the liver. Peak plasma concentrations are achieved within 2 hours, but maximum MAO inhibition may occur 2-3 weeks later. Therefore, a washout period of at least 2 weeks when switching from MAOIs to other antidepressants (eg, tricyclic antidepressants [TCAs] and selective serotonin reuptake inhibitors [SSRIs]) is important. A lack of a washout period can trigger serotonin syndrome.

MAOIs have a narrow therapeutic window, and a dose of 2-3 mg/kg is lethal. Most cases of toxicity are related to MAO-A inhibitors.

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Epidemiology

Frequency

United States

MAOI overdoses are rare in pediatric patients. According to the American Association of Poison Control Centers' National Poison Data System, 97 single exposures to MAOIs were reported in 2012: 15 were in children under the age of 6 years and three were in adolescents 13 to 19 years old. [8]

Mortality/Morbidity

In 2012, the American Association of Poison Control Centers reported 21 MAOI single exposures that resulted in moderate morbidity. One case of major toxicity and no deaths were reported. [8]

Age

Most unintentional ingestions occur in toddlers, and most pediatric intentional ingestions occur in adolescents.

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