• Depression is highly prevalent and is a leading cause of disability worldwide.
• Bipolar disorder is often misdiagnosed as major depression due to patients’ underreporting of manic/hypomanic symptoms.
• Several medications are effective in treating major depression, including TCAs, MAOIs, SSRIs, and SNRIs.

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• Consider prescribing an MAOI for patients with depression who have had 2 or more unsuccessful trials of SSRIs or other newer antidepressants.
• Guidelines generally reserve MAOIs as third- or fourth-line treatments due to concerns over safety and tolerability, but newer formulations can lessen the risks.
• When prescribing MAOIs, educate patients about necessary dietary restrictions and the potential for hypertensive crisis and serotonin syndrome due to drug interactions.

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• Dietary restrictions are required with older, irreversible MAOIs and are lessened with low dosages of selective MAO-B inhibitors and with transdermal formulations.
• Drug interactions can occur with all MAOIs.
• Washout periods should be carefully observed when switching between an MAOI and a serotonergic agent.
• Counsel patients to inform other physicians that they are taking an MAOI and to carefully select over-the-counter drugs.

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• MAO is an enzyme that metabolizes serotonin, norepinephrine, and dopamine; inhibiting MAO allows these neurotransmitters to accumulate in the synaptic cleft.
• MAOIs have potentially serious side effects, such as hypertensive crisis and serotonin syndrome, due to diet and drug interactions.
• To avoid these adverse effects, patients should be educated regarding dietary restrictions and drug interactions.
• A transdermal MAOI formulation with a greater tolerability and safety profile than oral MAOIs is available, which, at the minimum effective dosage, avoids the need for dietary restrictions.

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• Adherence to an antidepressant affects treatment response and remission rates for patients.
• Patients who appear to be treatment-resistant may be experiencing treatment failure due to nonadherence.
• Multifaceted strategies employing educational, behavioral, affective, and provider-targeted strategies enhance treatment adherence.
• A transdermal MAOI formulation may help to address adherence barriers for patients with treatment-resistant or atypical depression.

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• Consider using MAOIs for patients with atypical depression or patients with depression who have not experienced adequate symptomatic improvement with traditional first-line treatments.
• Consider MAOIs for other patient populations that may benefit from MAOI treatment, such as those with anxiety or panic disorders or anergic bipolar depression.
• When prescribing MAOIs, be mindful of drug interactions with the patient’s current medications, follow the required washout period, and advise the patient of dietary restrictions, if necessary.
• When prescribing MAOIs, consider the transdermal formulation, which mitigates some concerns about adverse events and dietary restrictions that accompany oral MAOIs.

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