AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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 

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Ethanol withdrawal
Malignant hyperthermia
Sedative/hypnotic withdrawal
Serotonin syndrome
Heat stroke/heat exhaustion

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Rapid bedside glucose determination
• ABG determination - Indicated if a compromise in oxygenation or ventilation is suspected
• Lactate level - May be useful in phases 2 and 3 of an acute overdose to help determine end-organ perfusion
• Determination of serum electrolyte, calcium, and magnesium levels - Calculation of the anion gap possibly helpful in screening for co-ingestions
• Evaluation of serum acetaminophen and salicylate levels - Indicated in intentional overdoses
• Screening for serum levels of alcohol (ethanol, methanol, isopropyl alcohol) - Indicated if alcohol ingestion is clinically suspected
• Urine pregnancy test - Indicated in all women of childbearing age
• Urinalysis and urine pH determination - May be useful in the setting of rhabdomyolysis
• Urine drug screening - Comprehensive drug screening and screening for commonly abused drugs possibly helpful in assessing co-ingestions
• Evaluation of levels of specific monoamine oxidase inhibitor (MAOI) drugs - Not readily available and, therefore, not clinically useful

Imaging Studies

• Chest radiography is indicated if aspiration is a concern.
• Perform postintubation chest radiography to evaluate the position of the endotracheal tube in relation to the carina if respiratory support is needed.

Other Tests

• Sinus tachycardia is the most common ECG abnormality.
• Nonspecific T-wave changes are also reported.

Procedures

• Endotracheal intubation may be required.
• • Maintaining a stable airway is the most important step in the management of any toxic ingestion.
  • Intubation is required in any patient with a decreasing level of consciousness or signs of impending respiratory failure.
  • Secure the airway before administering activated charcoal or performing gastric lavage in patients with compromised mental status.
• Venous access should be obtained.
• • Two large-bore peripheral intravenous lines should be placed in symptomatic patients.
  • Central access may be necessary for the infusion of vasoactive agents.
• Gastric lavage is reserved for patients with life-threatening overdoses (2-3 mg/kg) who present within 1 hour of the ingestion.
• • A large-bore orogastric tube should be used.
  • Isotonic sodium chloride solution is preferred to water in young children because of the risk of an electrolyte imbalance and water intoxication.
  • Before proceeding with any decontamination, secure the patient's airway.
• Foley catheterization of the bladder is indicated to assess urine output, especially in the setting of hemodynamic compromise or rhabdomyolysis.
• Arterial line placement is indicated for continuous blood pressure monitoring and frequent blood sampling in patients with a severe ingestion and cardiovascular instability.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

As with most toxic ingestions, the cornerstone of management is continuous monitoring, decontamination when clinically indicated, and meticulous supportive care.

• Give careful attention to airway management.
• Maintain euvolemia because patients with monoamine oxidase inhibitor (MAOI) poisoning can become dehydrated secondary to their hypermetabolic state.
• Maintain euthermia, especially in patients with suspected serotonin syndrome. Water mist sprays with fanning are effective. The removal of clothing and the use of cooling blankets may also be effective.
• Treat seizures and agitation with intravenous benzodiazepines.
• Decontamination with activated charcoal should be performed with caution and with attention to the possibility of airway compromise.
• Treat hypertension only if it is sustained and clinically significant.

Consultations

• Close consultation with a medical toxicologist or personnel from a regional poison center is recommended.
• Consult a pediatric intensivist.
• Consult a psychiatrist in cases of suspected intentional ingestion.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug Category: Decontamination agents

Consider activated charcoal decontamination in any patient who presents within one hour of the ingestion. Activated charcoal is used for drug adsorption and may be sufficient in mild-to-moderate toxicity. It is not absorbed and is excreted entirely through the GI tract.

Drug Category: Vasopressors

Sympathomimetics produce direct or indirect stimulation of adrenergic receptors and have various actions depending on the specific receptors involved. Stimulation of alpha1-receptors produces smooth muscle contraction. In the cardiovascular system, this effect leads to vasoconstriction and increased blood pressure; in the eye, this effect leads to mydriasis. Other affected organs include the urinary sphincter and uterus. Stimulation of beta1-receptors has an inotropic effect and also increases the heart rate. Stimulation of beta2-receptors leads to smooth muscle relaxation and produces vasodilatation.

Hypotension is initially treated with isotonic fluids. Vasoactive agents are used if hypotension remains refractory despite the administration of intravenous fluids. Norepinephrine is preferred to dopamine because dopamine is an indirect sympathomimetic and can cause an uncontrollable and erratic release of norepinephrine.

Drug Category: Antihypertensives

Do not use these drugs routinely. Often, the hypertension is transient and clinically insignificant. Avoid administering pure beta-blockers because they can produce an unopposed alpha effect.

Drug Category: Anticonvulsants

These agents are used to prevent seizures and terminate clinical and electrical seizure activity.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Patients with monoamine oxidase inhibitor (MAOI) overdoses should be admitted to the hospital primarily because of the prolonged latent stage.
• All patients with suspected MAOI ingestion require 24 hours of ICU care or frequent monitoring in an inpatient facility.

In/Out Patient Meds

• Avoid indirect sympathomimetics and foods that contain tyramine.
• Avoid drugs such as meperidine, dextromethorphan, and SSRIs (eg, fluoxetine, sertraline) because they can lead to a hyperserotonergic state.
• Avoid ketamine.

Transfer

• Any child with evidence of MAOI toxicity should be stabilized and transferred to a tertiary pediatric center.

Deterrence/Prevention

• Keep medications and other ingestible substances locked or safely stored where children cannot reach them.

Complications

• Pulmonary edema
• Coma
• Myocardial ischemia
• Intracerebral hemorrhage
• Rhabdomyolysis
• Acute renal failure
• Disseminated intravascular coagulation
• Hemolysis
• Subarachnoid hemorrhage
• Serotonin syndrome

Prognosis

• Mortality and morbidity are dependent on the time of presentation, the occurrence of co-ingestions, and the status of the patient upon his or her arrival in the emergency department.
• Most patients recover without sequelae when given careful supportive care.

Patient Education

• Families must be made aware of the dangers of prescription drugs, over-the-counter medications, and other potential toxins in the home.
• Patients who are taking MAOIs should be educated about the potential for drug and food interactions.
• For excellent patient education resources, visit eMedicine's Poisoning - First Aid and Emergency Center, Substance Abuse Center, and Mental Health and Behavior Center. Also, see eMedicine's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to properly manage the airway during decontamination is a pitfall.
• Failure to monitor patients is a pitfall, even if they are initially asymptomatic. Signs of MAOI toxicity may be delayed as long as 24 hours after the ingestion.⁵
• Failure to avoid the use of indirect sympathomimetics and serotonergic drugs is a pitfall.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. Dawson JK, Earnshaw SM, Graham CS. Dangerous monoamine oxidase inhibitor interactions are still occurring in the 1990s. J Accid Emerg Med. Mar 1995;12(1):49-51. [Medline].
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14. Sarko J. Antidepressants, old and new. A review of their adverse effects and toxicity in overdose. Emerg Med Clin North Am. Nov 2000;18(4):637-54. [Medline].
15. Siberry GK, Iannone R, eds. The Harriet Lane Handbook. In: A Manual for Pediatric House Officers. 15^th ed. Mosby-Year Book: 2000.
16. Siderowf A, Kurlan R. Monoamine oxidase and catechol-O-methyltransferase inhibitors. Med Clin North Am. Mar 1999;83(2):445-67. [Medline].
17. Tollefson GD. Monoamine oxidase inhibitors: a review. J Clin Psychiatry. Aug 1983;44(8):280-8. [Medline].
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Article Last Updated: Jan 23, 2008