eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Toxicology

Toxicity, Monoamine Oxidase Inhibitor

Author: Soumya Ganapathy, MD, Consulting Staff, Department of Emergency Medicine, Union Memorial Hospital
Coauthor(s): Frank A Maffei, MD, FAAP, Associate Professor of Pediatrics, Temple University School of Medicine; Director of Medical Student Affairs, Geisinger Health System; Pediatric Critical Care Attending Physician, Janet Weis Children's Hospital at Geisinger Medical Center
Contributor Information and Disclosures

Updated: Jan 23, 2008

Introduction

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 aureus drug linezolid, are MAOIs. Although MAOI ingestion is rare, MAOI overdoses can potentially cause significant morbidity and mortality.1

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 and serotonin, whereas MAO-B mainly deaminates phenylethylamine and dopamine. MAO-A inhibitors increase the levels of norepinephrine and serotonin and are used in the treatment of clinical depression. MAO-B inhibitors increase the dopaminergic concentrations in the brain and have been successfully used in the treatment of Parkinson disease.2

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.3  

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 hypertensive crisis.

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. 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.

Frequency

United States

MAOIs overdoses are relatively uncommon. According to the American Association of Poison Control Centers' Toxic Exposures Surveillance System (AAPCC-TESS), 285 MAOI exposures were reported in 2003. Of those exposures, 35 were in patients aged 19 years or younger, and 32 were in patients younger than 6 years.

Mortality/Morbidity

  • In 2005, the AAPCC-TESS reported 107 exposures that resulted in moderate or major morbidity
  • In 2005, the AAPCC-TESS reported 2 exposures that resulted in death.

Age

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

Clinical

History

Monoamine oxidase inhibitors (MAOIs) are not typically prescribed to children; they are prescribed to adults in a household. Therefore, as in all suspected pediatric ingestions, inquiring about all drugs in the home and evaluating each as a possible cause of the child’s presentation is essential.

MAOIs may not produce symptoms for as long as 24 hours after an acute overdose. Symptoms can be attributed to various physiologic derangements, as follows:

  • Symptoms related to a hyperadrenergic state
    • Dizziness
    • Headache
    • Agitation
    • Blurry vision
    • Shortness of breath
    • Chest pain
  • Symptoms related to serotonin excess
    • Altered mentation (confusion, anxiety, agitation)
    • Fever
    • Muscle cramps or rigidity
    • Hallucinations
    • Anxiety
    • Agitation
    • Diaphoresis
    • Diarrhea
  • Symptoms related to cardiovascular compromise (usually delayed)
    • Pallor
    • Syncope or presyncope
  • Weakness

Physical

Signs of MAOI overdoses depend on the quantity ingested, the time elapsed since the ingestion, and the presence of co-ingestions.

  • Cardiac system
    • Hypertension due to a hyperadrenergic state may be observed early. It may be transient and should not be aggressively treated unless the patient is symptomatic.
    • Orthostatic hypotension and frank hypotension can occur later.
    • Tachycardia is usually present. Arrhythmias are relatively uncommon unless a co-ingestion is involved.
  • Pulmonary system - Pulmonary edema (late finding)
  • Autonomic findings
    • Hyperpyrexia
    • Mydriasis
    • Diaphoresis
    • Flushing
  • CNS
    • Agitation
    • Hyperreflexia
    • Muscular rigidity
    • Tremors/muscle spasms
    • Seizures
    • Coma

Causes

Signs and symptoms depend on the time of presentation and whether a co-ingestion occurred. The mechanisms for MAOI-related toxicity can be divided into those related to MAOI overdose alone and those related to MAOI interactions with other substances.

  • The adverse effects related to an MAOI overdose alone can be divided into 4 phases.
    • Phase 1 is a period of latency that lasts approximately 6-12 hours. The delayed appearance of signs and symptoms is thought to be related to the gradual accumulation of norepinephrine and serotonin.
    • Phase 2 is characterized by a catecholamine surge that causes sympathetic and CNS excitation.
    • In phase 3, hypotension and CNS depression occur.
    • Phase 4 involves secondary complications such as rhabdomyolysis, renal failure, pulmonary edema, myocardial infarction, and disseminated intravascular coagulopathy.
  • Reactions caused by the interactions of MAOIs with other drugs and foods can also cause toxicity.
    • Drug and food interactions related to MAOIs can occur at therapeutic or toxic doses.
    • The effects of indirect-acting adrenergic drugs are markedly potentiated when combined with MAOIs. These agents include methylphenidate (Ritalin), phenylephrine, ephedrine, cocaine, and amphetamines.
    • Direct-acting sympathomimetics such as epinephrine, norepinephrine, isoproterenol, carbidopa, and L-methyldopa directly act on the postsynaptic receptors rather than the releasing presynaptic vesicles, and they do not cause such a marked adrenergic response.
    • Tricyclic antidepressants (TCAs) block the inactivation of norepinephrine and serotonin;4 TCAs taken in combination with MAOIs can lead to excessive catecholamine and serotonin activity, a potentially life-threatening situation. Because of the prolonged action of MAOIs, a 2-4 week washout period must be observed before treatment with TCAs is started.
    • In conjunction with selective serotonin reuptake inhibitors (SSRIs), MAOIs can produce a hyperserotoninergic state known as serotonin syndrome. An altered mental status, autonomic instability, and neuromuscular dysfunction characterize the syndrome.
    • Similar toxicity can occur when MAOIs are combined with drugs that have serotonin reuptake inhibitory properties, such as tramadol, linezolid, meperidine, or dextromethorphan.
    • Foods containing tyramine, such as aged cheese, red wine, overripe foods, aged meat, fava beans, beer, avocado, and yeast extracts, can cause a similar hyperadrenergic state, leading to hypertension or stroke, in individuals taking MAOIs.

More on Toxicity, Monoamine Oxidase Inhibitor

Overview: Toxicity, Monoamine Oxidase Inhibitor
Differential Diagnoses & Workup: Toxicity, Monoamine Oxidase Inhibitor
Treatment & Medication: Toxicity, Monoamine Oxidase Inhibitor
Follow-up: Toxicity, Monoamine Oxidase Inhibitor
References
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References

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Further Reading

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Keywords

monoamine oxidase inhibitor, antidepressant overdose, antidepressant poisoning, antidepressant overdoses, antidepressant poisonings, antidepressant-induced hepatotoxicity, childhood ingestions, MAO antidepressant, MAO antidepressant overdose, MAO antidepressant toxicity, MAO antidepressant poisoning, MAOI, MAOIs, MAOI overdose, MAOI toxicity, MAOI poisoning, monoamine oxidase A, MAO-A, monoamine oxidase B, MAO-B, phenelzine, tranylcypromine, isocarboxazid, Parkinson disease, methicillin-resistant Staphylococcus aureus, hypertension, tachycardia, hyperpexia, mydriasis, diaphoresis, rhabdomyolysis, renal failure, pulmonary edema, myocardial infarction, disseminated intravascular coagulopathy, serotonin syndrome

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Contributor Information and Disclosures

Author

Soumya Ganapathy, MD, Consulting Staff, Department of Emergency Medicine, Union Memorial Hospital
Soumya Ganapathy, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Frank A Maffei, MD, FAAP, Associate Professor of Pediatrics, Temple University School of Medicine; Director of Medical Student Affairs, Geisinger Health System; Pediatric Critical Care Attending Physician, Janet Weis Children's Hospital at Geisinger Medical Center
Frank A Maffei, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Michael E Mullins, MD, Assistant Professor, Department of Emergency Medicine, Washington University School of Medicine
Michael E Mullins, MD is a member of the following medical societies: American Academy of Clinical Toxicology and American College of Emergency Physicians
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Jeffrey R Tucker, MD, Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut and Connecticut Children's Medical Center
Jeffrey R Tucker, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Pediatrics, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Clinical Assistant Professor of Pediatrics, University of North Dakota, School of Medicine and Health Sciences; Consulting Staff, Altru 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.

 
 
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