Which medications in the drug class Antidepressants, MAO Inhibitors are used in the treatment of Depression?

Updated: Aug 06, 2020
  • Author: Jerry L Halverson, MD; Chief Editor: David Bienenfeld, MD  more...
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Antidepressants, MAO Inhibitors

Monoamine oxidase inhibitors were the first antidepressants discovered, in the early 1950s. They are widely effective in a broad range of affective and anxiety disorders. MAOIs irreversibly block monamine oxidase, which has 2 forms, including MOAa and MOAb. MAOa breaks down serotonin and norepinephrine. MOAb metabolizes phenylethylamine. Both forms break down dopamine.

MOAIs are not considered first-line treatment for depression because of the side effects, drug-drug interactions, and dietary restrictions. Common side effects include hypotension, dizziness, dry mouth, gastrointestinal upset, urinary hesitancy, headache and myoclonic jerks. Because of the risk of hypertensive crisis with drugs that specifically inhibit MAOa in the gastrointestinal tract, patients on these medications must follow a low-tyramine diet.

Selegiline transdermal patch (Emsam)

Selegiline inhibits MAOb at lower doses and both forms at higher doses. Because it does not inhibit MAOa, it does not require dietary restrictions at lower doses. Lower doses of oral selegiline (Eldepryl) appear to lack antidepressant properties and are usually prescribed to treat Parkinson disease. Higher doses are used to treat major depressive disorder, and the selegiline transdermal patch is FDA approved for this indication. Selegiline is sometimes used off-label to treat attention-deficit/hyperactivity disorder.

Dietary restrictions are not required for the 6 mg/24 hour patch because there is no risk of hypertensive crisis with this dose, given the lack of MAOa inhibition. Higher doses require dietary restrictions. The patch may be beneficial to those that cannot take oral medications. To avoid serotonin syndrome, initiating and stopping selegiline must be handled carefully.

Tranylcypromine (Parnate)

Tranylcypromine is used to treat major depression. It binds irreversibly to MAOa and to a lesser extent to MAOb, thereby reducing monoamine breakdown and enhancing synaptic availability. Clinical effects are not normally seen for 2-4 weeks. It has similar side effects as other MAOIs, but it is more likely to cause insomnia.

Phenelzine (Nardil)

Phenelzine is used to treat depression. It irreversibly inhibits both MOAa and MOAb. Side effects are similar to those of other MAOIs, but anticholinergic side effects are more common. Phenelzine causes less insomnia than tranylcypromine but is more likely to cause sedation, weight gain, and sexual dysfunction.

Isocarboxazid (Marplan)

Isocarboxazid is a nonselective hydrazine MAOI that is indicated for the treatment of depression. The mechanism by which MAOIs act as an antidepressant is not fully understood, but it is thought to be that these drugs increase the CNS concentrations of norepinephrine, dopamine, and serotonin.

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