A class of antidepressants called MAOIs can help people manage treatment-resistant depression, but there are possible side effects.

Depression is one of the most common mental health disorders in the United States.

According to the National Institute of Mental Health (NIMH), over 8% of adults in the United States have experienced at least one major depressive episode. That’s a total of 21 million adults.

Antidepressants are an effective treatment for many, but they aren’t always as effective as some might hope. Between 10% and 30% of people prescribed antidepressants see no improvement, or only partial improvement, in their depression symptoms.

If you have taken at least two different antidepressants and haven’t seen enough improvement, you may have what’s called treatment-resistant depression. In this case, your doctor may suggest using a less-common antidepressant called monoamine oxidase inhibitor (MAOI).

MAOI is not the first choice for an antidepressant due to its potential side effects and required dietary restrictions, but it may be an effective option for those experiencing treatment-resistant depression.

MAOIs are a class of drugs that mental health professionals use to treat depression when other antidepressants haven’t had the desired effect.

This medication can treat the symptoms of depression, which include a low mood, anhedonia (an inability to feel pleasure), and a loss of motivation.

The Food and Drug Administration (FDA) has approved the following types of MAOI medication:

  • isocarboxazid (Marplan)
  • phenelzine (Nardil)
  • selegiline (Emsam)
  • tranylcypromine (Parnate)

A 2005 study reported that MAOIs were effective in 56% of people with treatment-resistant depression. They were far more effective in people with early-stage treatment-resistant depression as opposed to late-stage treatment-resistant depression.

“Early-stage” in this study was when a person had tried three or fewer antidepressants before trying an MAOI. Though less effective, 12% of late-stage treatment-resistant depression participants still reported feeling considerably better after taking MAOIs.

How do MAOIs work?

MAOIs improve your mood by blocking an enzyme called monoamine oxidase. This enzyme naturally helps to remove mood-enhancing neurotransmitters from the brain, which include:

When monoamine oxidase removes too many of these neurotransmitters from your brain, you may begin to experience depressive symptoms. By blocking their action, MAOIs can sometimes alleviate these feelings of depression.

The cause of depression isn’t always related to low levels of neurotransmitters, but it’s a common source. Taking MAOIs can increase norepinephrine, serotonin, and dopamine, therefore potentially increasing feelings of happiness and improving overall mood.

How do MAOIs and SSRIs compare?

According to a 2021 study, mental health professionals most commonly prescribe selective serotonin reuptake inhibitors (SSRIs) for depression because there are fewer side effects compared to other types of drugs, particularly MAOIs.

However, MAOIs are considered a stronger antidepressant because they target more neurotransmitters compared to SSRIs, which only target serotonin levels.

For this reason, mental health professionals tend not to prescribe MAOIs during the first round of treatment. Instead, they are considered a more favorable option for the second, third, or even fourth round, when other antidepressants, such as SSRIs, are not improving symptoms.

How do MAOIs and tricyclic antidepressants compare?

A 2019 study compared the effectiveness of MAOI with another drug class called tricyclic antidepressants. The researchers found that MAOI was more effective than tricyclic antidepressants for countering treatment-resistant depression.

However, the difference was far less significant in those who hadn’t noticed improved symptoms with more than one other antidepressant.

Mental health professionals tend not to prescribe MAOIs when a person first presents with depression due to the potential side effects they may cause and the food restrictions they require.

A 2021 study stated, “MAOIs are only a treatment option when all other medications are unsuccessful.”

According to the FDA, potential side effects for MAOIs include:

  • nausea
  • restlessness
  • trouble sleeping
  • dizziness
  • drowsiness
  • headache

Potential safety concerns include:

  • stroke
  • fainting
  • heart palpitations
  • blood pressure changes

Additionally, the FDA recommends avoiding the following foods when taking MAOIs:

  • cheese
  • wine
  • protein foods that have been aged, such as cured meats
  • any food containing tyramine (e.g.,sauerkraut, kimchi, pickled cucumbers, tofu, miso, soy sauce, oranges, grapefruits, lemons, limes, and tangerines)

If you are experiencing resistant-treatment depression, meaning you have not seen an improvement in your depression symptoms after trying at least two forms of antidepressants, you may want to speak with your doctor about the antidepressant MAOI.

Research has shown that MAOIs tend to be effective for managing resistant-treatment depression, especially in the early stages of treatment resistance.

However, there are some potential side effects, dietary restrictions, and safety concerns to prepare for before taking MAOIs. Your doctor can help you manage these side effects and ensure you remain safe while taking MAOIs.

It can be frustrating when you aren’t seeing the results you hoped for from an antidepressant, but there are many options available. Everyone is unique, and sometimes it takes time to find the right treatment plan for you.