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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 their increasing use for the treatment of Parkinson’s disease.2 In addition, a transdermal method of selegiline administration, approved for use in major depression, appears to avoid some of the worrisome aspects associated with traditional oral therapy.3-5

TABLE 179-1U.S. Food and Drug Administration Approved Monoamine Oxidase Inhibitors

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 (MAO) and block serotonin reuptake.6 St. John’s wort is considered generally safe when taken at recommended dosages, but even modest MAO inhibition may become clinically significant in overdose, contribute to serotonin syndrome, or participate in a drug–drug interaction.

Medications with MAO inhibition as a pharmacologic action unrelated to their clinical indication (e.g., linezolid, procarbazine, furazolidone, and methylene blue) can precipitate serotonin syndrome ...

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