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Monoamine Oxidase Inhibitors (MAOIs)

Monoamine Oxidase Inhibitors (MAOIs) are among the oldest antidepressants, available since 1959.  The first MAOI (isocarboxazid) entered the market two years after the oldest TCA (imipramine, 1957). MAOIs are highly effective for treatment of depression, including cases resistant to modern antidepressants. MAOIs are particularly effective for “atypical depression”, characterized by increased appetite, excessive sleep, fatigue, sensitivity to rejection, and moods that are highly reactive to circumstances. 

Monoamine Oxidase Inhibitors (MAOIs) mnemonics by Dr Jason Cafer MD psychiatry

“TIPS” – the MAOIs approved for depression:

  ► Tranylcypromine  (PARNATE) 

  ► Isocarboxazid  (MARPLAN)

  ► Phenelzine (NARDIL) 

  ► Selegiline transdermal (EMSAM)

Monoamine Oxidase Inhibitors (MAOIs) mnemonics by Dr Jason Cafer MD tranylcypromine PARNATE isocarboxazid MARPLAN phenelzine NARDIL selegiline EMSAM ELDEPRYL rasagiline AZILECT safinamide XADAGO

The three oral MAOIs approved for treatment of depression in the U.S. are irreversible inhibitors of both MAO-A and MAO-B. Strict dietary restrictions are necessary to avoid the “cheese effect” of hypertensive crisis described in the isocarboxazid monograph, which is also applicable to phenelzine and tranylcypromine. Half-life for these MAOIs is irrelevant because inhibition of MAO is irreversible, with effect continuing for up to two weeks after the medication is discontinued. 

Monamine Oxidase Inhibitor MAOI mnemonic pharmacodynamic interactions by Dr Jason Cafer MD

In a simplified sense, MAO-A is more responsible for breaking down 5-HT and NE, while MAO-B is more specific for DA. For treatment of Parkinson's disease, MAO-B needs to be blocked. For treatment of depression, MAO-A needs to be blocked (to enhance 5-HT and NE), and blocking MAO-B may also be helpful (to enhance DA). In some countries, safer reversible inhibitors of monoamine oxidase A (RIMAs) are available for treatment of depression. Selective MAOIs available in the US block MAO-B for treatment of Parkinson’s disease, and only one of these is reversible—safinamide (Xadago).


Due to risk of serotonin syndrome, all serotonergic medications are contraindicated with MAOIs. A washout period is necessary when switching to an MAOI, dependent on the half-life of the serotonergic agent (SSRI, SNRI, etc). As a rule of thumb, a drug clears the body after 5 half-lives. Wait at least 5 weeks after stopping fluoxetine (Prozac), which has a long half-life of 1 week. For the other SSRIs, wait two weeks after stopping the SSRI to start the MAOI. 


A few antidepressants are safe to pair with MAOIs, including bupropion, trazodone, and those TCAs with minimal serotonergic activity such as nortriptyline, desipramine, maprotiline and trimipramine (Thomas and Shin, 2015)— “Non-Disparaged MOAI Tagalongs”.


It is recommended that MAOIs be discontinued at least 10 days prior to elective surgery to avoid potentially fatal interactions with anesthetic agents.

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