Welcome to the chapter on Monoamine Oxidase Inhibitors (MAOIs), a class of antidepressants with a unique mechanism of action and a distinctive profile when it comes to treating depression. This chapter is crafted to guide you through the complex pharmacology of MAOIs, their clinical applications, and the critical considerations for their use. By mastering the content of this chapter, you’ll gain the knowledge and confidence needed for Pharmacy Examining Board of Canada (PEBC) evaluation exam to navigate questions on MAOIs and to make informed decisions in clinical practice. Equipped with this knowledge, you'll be well on your way to success in the PEBC evaluation exam and to becoming an adept pharmacist who can contribute meaningfully to the field of mental health in Canada.

Monoamine Oxidase Inhibitors

Function of Monoamine Oxidase (MAO): MAO is an enzyme in nerves and other tissues like the gut and liver deactivates excess neurotransmitters like norepinephrine, dopamine, and serotonin in the neuron that leads a decrease in their amount and might cause depression or other disorders

Mechanism of Action of MAOIs:

MAOIs, or Monoamine Oxidase Inhibitors, work by blocking an enzyme in the body called monoamine oxidase. This enzyme usually breaks down excess chemicals in the brain like serotonin, norepinephrine, and dopamine—substances that help regulate mood.

When MAO is inhibited by these medications, it can’t break down these neurotransmitters as it normally would. As a result, the levels of these mood-related chemicals increase in the brain, this buildup can help improve communication between nerve cells, potentially lifting a person's mood and helping with depressive symptoms. It's important to note that because of the way MAOIs work, they can interact with certain foods and other medications, so they require careful management.

Drugs: 

• Phenelzine, 

• Tranylcypromine, 

• Isocarboxazid, 

• Selegiline (also used for Parkinson’s and available as a patch).

Delay in Antidepressant Action: Full inhibition of MAO occurs within days, but antidepressant effects are delayed, similar to SSRIs, SNRIs, and TCAs.

Adverse Effects:

Most common → orthostatic hypotension.

Irreversible: Edema, Orthostatic hypotension, Sexual dysfunction

Reversible: Insomnia, Nausea, dizziness

Example:

If a patient has not responded well to typical antidepressants like SSRIs, a doctor may consider prescribing an MAOI. However, the patient would need to follow a strict diet to avoid foods high in tyramine, such as aged cheese, and be aware of the potential for a hypertensive crisis. Additionally, the patient would need to wait two weeks after stopping an SSRI before they could safely start an MAOI to prevent serotonin syndrome.

Exam Points:

• Note 1: Foods high in tyramine can trigger a dangerous spike in blood pressure when eaten with irreversible MAOIs, leading to a hypertensive crisis.

• Note 2: When switching from MAOIs to SSRIs, a two-week washout period is necessary to clear the MAOI from the body.

• Note 3: Combining MAOIs with stimulant drugs like amphetamines or ephedrine can lead to severe increases in blood pressure, seizures, or hallucinations.

• Note 4: Moclobemide, a reversible MAOI, does not come with the same strict food restrictions as the irreversible MAOIs.

• Note 5: SSRIs and MAOIs must not be combined due to serotonin syndrome risk.

• A washout period of 2 weeks (6 weeks for fluoxetine) is needed before switching between SSRIs and MAOIs.

• Note 6: MAOIs are typically reserved for patients not responding to other antidepressants due to their complex dietary restrictions.

• Note 7: Some MAOIs may cause agitation or insomnia due to stimulant effects.