Monoamine Oxidase Inhibitors
GENERAL PRINCIPLES
• Monoamine oxidase inhibitors (MAOIs) were the first class of effective antidepressants. They have fallen out of widespread use due to their numerous drug and food interactions and extreme toxicity in overdose.
• MAOIs may still be prescribed for treatment-resistant depression; one MAOI, selegiline, is used in the treatment of Parkinson disease.
Pathophysiology
• Monoamine oxidase is an enzyme responsible for the inactivation of biogenic amines such as epinephrine, norepinephrine, tyramine, dopamine, and serotonin. Inhibition of this enzyme results in an increase of synaptic concentrations of biogenic amines.
• As MAOIs affect an enzymatic pathway, there may be a significant delay in the development of toxicity after overdose.
• The duration of action of the MAOIs (especially the older irreversible inhibitors) significantly exceeds their half-life. A long washout period is necessary before other antidepressants can be safely administered.
DIAGNOSIS
Clinical Presentation
• Acute overdose of an MAOI initially produces a sympathomimetic toxidrome, with tachycardia, hypertension, diaphoresis, mydriasis, and agitation.
î Onset of toxicity may be delayed for 24 hours or more after overdose. 18
î Hyperthermia, seizures, and intracranial hemorrhage may occur in severe cases.
î The excitatory phase may be followed by coma and refractory cardiovascular collapse if complete monoamine depletion occurs.
• Coadministration of any serotonergic, dopaminergic, or adrenergic xenobiotic with an MAOI (including after discontinuation of the MAOI) may precipitate a sympathomimetic crisis or serotonin syndrome.
• Consumption of foods rich in tyramine (aged cheeses, red wine, cured meats) while taking a MAOI may precipitate a hypertensive crisis.
Diagnostic Testing
LABORATORIES
• Obtain a BMP to evaluate for acidosis, hyperkalemia, and renal failure.
• Obtain a creatinine kinase to evaluate for rhabdomyolysis.
• Obtain serial troponins to evaluate for myocardial infarction.
• Obtain coagulation studies to evaluate for disseminated intravascular coagulation in severe cases.
ELECTROCARDIOGRAPHY
Electrocardiography may demonstrate sinus tachycardia, evidence of myocardial ischemia, or ventricular dysrhythmias.
IMAGING
Computed tomography of the brain should be obtained on any patient with MAOI poisoning who has an altered mental status or complains of a headache to evaluate for intracranial hemorrhage.
TREATMENT
• Strongly consider aggressive GI decontamination.
• Treat hypertension with short-acting, titratable parenteral agents (e.g., nicardipine, clevidipine, or nitroglycerin) given the risk of rapid fluctuations in blood pressure.
• Avoid beta blockers (BBs) due to the theoretical risk of unopposed alpha-adrenergic stimulation.
Treat agitation and seizures with benzodiazepines or other directly GABAergic sedatives.