Pediatric Monoamine Oxidase Inhibitor Toxicity 

  • Author: Soumya Ganapathy, MD; Chief Editor: Timothy E Corden, MD   more...
 
Updated: Mar 16, 2010
 

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. Antibiotics, such as the anti– methicillin-resistant Staphylococcus aureusdrug linezolid, are MAOIs. Although MAOI ingestion is rare, MAOI overdoses can potentially cause significant morbidity and mortality.[1]

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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.[2] MAO-B inhibitors increase the dopaminergic concentrations in the brain and have been successfully used in the treatment of disease.[3]

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.[4]

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 relatively uncommon. According to the American Association of Poison Control Centers' Toxic Exposure Surveillance System (AAPCC-TESS), 302 MAOI exposures were reported in 2007.[5] Of those exposures, 5 were in patients aged 6-19 years, and 5 were in patients younger than 6 years.

Mortality/Morbidity

In 2007, the AAPCC-TESS reported 33 exposures that resulted in moderate or major morbidity. In 2007, the AAPCC-TESS reported 0 exposures that resulted in death.

Age

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

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Contributor Information and Disclosures
Author

Soumya Ganapathy, MD  Department of Emergency Medicine, Beverly Hospital

Soumya Ganapathy, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Frank Anthony Maffei, MD, FAAP  Associate Professor of Pediatrics, Temple University School of Medicine; Medical Director, Pediatric Intensive Care Unit, Janet Weis Children's Hospital at Geisinger Health System

Frank Anthony Maffei, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael E Mullins, MD  Assistant Professor, Division of Emergency Medicine, Washington University in St Louis School of Medicine; Attending Physician, Emergency Department, Barnes-Jewish Hospital

Michael E Mullins, MD is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Emergency Physicians

Disclosure: Johnson & Johnson stock ownership None; Savient Pharmaceuticals stock ownership None

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD  Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center

Disclosure: Merck Salary Employment

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Timothy E Corden, MD  Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

References

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  18. Siberry GK, Iannone R, eds. The Harriet Lane Handbook. In: A Manual for Pediatric House Officers. 15th ed. Mosby-Year Book; 2000.

  19. Siderowf A, Kurlan R. Monoamine oxidase and catechol-O-methyltransferase inhibitors. Med Clin North Am. Mar 1999;83(2):445-67. [Medline].

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  22. Wax P, Hoffman J, Keyes CD. Neuroleptics, lithium, and monoamine oxidase inhibitors. In: Rosen P, Barkin R, eds. Emergency Medicine. 3rd ed. 1992:2624-2628.

 
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