MAOIs or monoamine oxidase inhibitors are among the earliest drugs developed for use in the treatment of depression, particularly atypical depression. They rolled out of the laboratory soon after the tricyclic antidepressants.

MAOIs came to be used widely as antidepressants in the early 1950s. They were the drugs of choice for depression between the years 1957 and 1970.

Their popularity began to wane when it was found that they caused serious interactions with sympathomimetic drugs and tyramine-containing foods. Tyramine is associated with the amino acid tyrosine. It is typically found in fermented and aged foods.

Such interactions could lead to dangerous hypertensive emergencies such as hemorrhagic stroke.

Do read the drug interactions and foods to avoid when on MAOIs.

The MAO inhibitors are quite effective but their use is reserved as a last resort because of their potential side effects. They have been replaced now by safer drugs such as SSRIs.

A monoamine is an amine compound, which contains one amine group that functions as a  neurotransmitter. Monoamines are naturally occurring brain chemicals called neurotransmitters such as serotonin, dopamine, epinephrine, and norepinephrine and are responsible for the transmission of brain signals.

Monoamine oxidase is a protein enzyme of the brain and liver, which brings about the oxidation of the monoamine and deaminates it.

MAOI – Monoamine Oxidase Inhibitor 

An MAOI drug or monoamine oxidase inhibitor is a substance that inhibits the activity of monoamine oxidase thereby increasing the levels of monoamines in the brain. An increase in levels of monoamines like serotonin, dopamine, and epinephrine helps to maintain the good mood effect.

MAOIs can cause negative interactions (a sudden rise in blood pressure) with other medications and certain types of food, especially those rich in tyramine. Such foods include cheese, chocolates, bananas, wine, and chicken liver.

Such a reaction between such foods and MAOIs is called the “cheese effect”. Tyramine is a naturally occurring monoamine, which acts as a dopamine, epinephrine, and norepinephrine-releasing agent.

The positive side of MAOIs is that they can show positive results in certain forms of depression where other medications have been ineffective.

Uses of MAOIs

Monoamine oxidase inhibitors are used in the treatment of the following mental disorders.

  • Atypical depression
  • Bipolar depression
  • Panic disorder with agoraphobia
  • Social anxiety
  • Post-traumatic stress disorder
  • Parkinson’s disease
  • Bulimia
  • As an alternative to migraine prophylaxis

How do MAOIs Work? Mechanism of action

MAOIs also act like other antidepressants but their action is on a wider range of neurotransmitters. Neurotransmitters are naturally occurring brain chemicals, which are also called monoamines.

They include serotonin, norepinephrine, and dopamine. They act as messengers of the brain and are responsible for maintaining the mood of the person. Lower levels of these substances lead to depression.

Once they have played their function of transmitting nerve signals, they are burnt up causing their levels to fall. This is brought on by a protein called monoamine oxidase (MAO), which is a liver and brain enzyme.

Monoamine oxidase inhibitors (MAOIs), as the name suggests, block this action of monoamine oxidase leading to the retention of these neurotransmitters and maintaining adequate levels of the neurotransmitters in the brain. This gives a “good mood” to the depressed person.

The monoamine oxidase enzyme not only reduces the levels of the neurotransmitters but also of tyramine. Therefore, the rise in levels of neurotransmitters is also associated with rising levels of tyramine. This can be dangerous.

Though high levels of neurotransmitters are beneficial, the simultaneous increase in tyramine can be disastrous as this can cause high spikes in blood pressure, which can even lead to a stroke due to brain hemorrhage (bursting of an artery) due to the interaction between MAOIs and tyramine.

List of MAOI drugs

Below is the list of MAOIs examples, which are used in the treatment of certain mental conditions.

Generic names and brand names

  • Phenezil – Nardil
  • Tranylcypromine – Parnate
  • Isocarboxazid – Marplan
  • MAOI patch:  Selegiline – Emsam. This is a newer MAOI, which is stuck to the skin as a patch and not swallowed. It causes fewer side effects than oral MAOIs.

Side Effects of MAOIs

Common side effects of MAOIs or monoamine oxidase inhibitors include

  • A headache
  • Nausea
  • Restlessness
  • Dizziness
  • Insomnia
  • Increased appetite leading to weight gain
  • Drowsiness but difficulty falling asleep
  • Blurred vision
  • Sexual problems
  • As explained above, a sudden increase in blood pressure with certain foods.
  • Orthostatic hypotension is common in older patients on MAOI.
  • Though not addictive, there may be withdrawal symptoms on stopping the drug abruptly, and therefore, this drug is to be withdrawn in tapering doses.

Precautions with MAOIs

If you are taking MAOIs, take the following precautions.

  • Do not eat foods containing tyramine. If you are on MAOI, make sure you note the list of foods to avoid when on MAOI.
  • MAOI and alcohol. Do not drink alcohol or any non-alcoholic fermented drinks. Drinking alcohol when on MAOIs can make you feel drowsy. Even moderate drinking of alcohol can delay the therapeutic effect of antidepressants.
  • Do not smoke cannabis. The effect of cannabis when on MAOIs is unpredictable.
  • MAOI and Smoking. Do not smoke tobacco when on MAOI as it worsens the addictive potential of smoking.
  • MAOI interaction with other antidepressants. Combining MAOIs with certain other antidepressants can be dangerous. A combination of SSRIs and MAOIs can lead to a life-threatening condition called serotonin syndrome. A period of at least five weeks has to elapse if you are switching from SSRIs to MAOIs.
  • MAOI interaction with other drugs. When on MAOIs, do not take other medicines such as painkillers, medicines for colds, weight loss pills, and stimulants.
  • MAOIs and insulin. MAOIs can augment the response to insulin and other hypoglycemic drugs. This can increase the risk of hypoglycemia.
  • MAOI during pregnancy and breastfeeding. The US FDA has classified MAOI as Category C in pregnancy, which means that there is no evidence of its safety for use during pregnancy and lactation. Per se, the overall view is that you should avoid MAOIs during pregnancy and lactation.
  • Stick to your MAOI dose. Overdose can cause death.

When to call the doctor if you are on MAOIs?

Call for medical help, if you develop any of the following when on therapy with MAOI:

  • An allergic reaction such as a hive or a swollen face or lips
  • Stiff or sore neck
  • Chest pain
  • Rapid or slow heartbeat
  • A severe headache radiating to the front of the head
  • Nausea and vomiting
  • Breathing difficulty
  • Sensitivity to light

Besides the allergic reaction, the other signs and symptoms indicate a severe rise in blood pressure due to the interaction between MAOIs and tyramine.