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Chapter 179: Monoamine Oxidase Inhibitors

Frank LoVecchio

INTRODUCTION

Monoamine oxidase inhibitors (MAOIs) were the first class of antidepressants, but current use of these agents is primarily limited to treating atypical and refractory cases of depression (Table 179-1).1 Newer antidepressants have a more favorable side effect profile, less overdose toxicity, and no dietary restrictions. The declining popularity of oral MAOIs for the treatment of depression is partially offset by increasing use of agents in this class for the treatment of Parkinson's disease.2 In addition, a transdermal method of selegiline administration is approved for use in major depression and appears to avoid some of the worrisome aspects associated with traditional oral therapy.3,4,5

TABLE 179-1U.S. Food and Drug Administration Approved Monoamine Oxidase Inhibitors
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TABLE 179-1 U.S. Food and Drug Administration Approved Monoamine Oxidase Inhibitors
Agent Indication Formulation Average Daily Therapeutic Dose Maximum Daily Therapeutic Dose Selectivity
Isocarboxazid Major depression 10-milligram tablet 10–40 milligrams 60 milligrams Nonselective
Phenelzine Major depression 15-milligram tablet 45–75 milligrams 90 milligrams Nonselective
Tranylcypromine Major depression 10-milligram tablet 20–40 milligrams 60 milligrams Nonselective
Selegiline Major depression 6 milligrams, 9 milligrams, and 12 milligrams per 24-h patch 6 milligrams per 24-h patch 12 milligrams per 24-h patch Nonselective (as a skin-patch formulation)
Rasagiline Parkinson's disease 0.5- and 1.0-milligram tablets 0.5–1.0 milligram 1 milligram MAO-B
Selegiline Parkinson's disease 5-milligram tablet 10 milligrams 10 milligrams MAO-B (as an oral formulation)
1.25-milligram oral disintegrating tablet 1.25 milligrams 2.5 milligrams MAO-B (as an oral formulation)
Moclobemide* Major depression, social anxiety 150- and 300-milligram tablets 300 milligrams 600 milligrams MAO-A

Abbreviations: MAO-A = monoamine oxidase isoenzyme A; MAO-B = monoamine oxidase isoenzyme B.

*Not available in the United States.

Safety and effectiveness of MAOIs in children have not been established, and the four agents used for treatment of depression have the identical U.S. Food and Drug Administration–mandated black box warning stating that patients <24 years old may have increased suicidal thinking and behavior while taking any type of antidepressant medication.

MAOIs are associated with tyramine reactions, serotonin syndrome, and medication incompatibilities that are unique to this class of antidepressants. Overdoses of MAOIs are considered life-threatening emergencies, and even one pill could potentially kill a toddler. The onset of clinical toxicity is often delayed to between 6 and 24 hours after ingestion, which can lead to misdiagnosis and mismanagement.

MAOI antidepressants with improved safety and tolerability, such as moclobemide, are available in Canada, Australia, and Europe, but not the United States. St. John's wort (Hypericum perforatum) contains many active ingredients, some of which have the ability to inhibit monoamine oxidase and block serotonin reuptake.6 St. John's wort is considered generally safe when taken at recommended dosages, but even modest monoamine oxidase inhibition may become clinically significant in overdose, may contribute to serotonin syndrome, or may participate in a drug–drug ...

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