Monoamine Oxidase Inhibitors (MAOIs)

This article provides a comprehensive overview of monoamine oxidase inhibitors, including their mechanisms, specific types, side effects, and their role in professional mental health treatment plans.

Key Takeaways:

• MAOIs are a group of antidepressant drugs. They work by inhibiting an enzyme in the brain that leads to an increase in various mood-supportive neurotransmitters, such as dopamine, serotonin, and norepinephrine.

• MAOIs are typically used only after other antidepressants have been tried, due to their higher level of side effects, risks, and interactions with many drugs and foods.

• While not used as often, they can still be effective, particularly for atypical depression and in some cases of treatment-resistant depression.

Understanding MAOIs

Monoamine oxidase inhibitors (MAOIs) are a specific group of prescription antidepressant drugs. They were one of the first antidepressant drug types introduced, initially appearing in the 1950s. Today, they are not considered first-line treatments for depression or other mental health issues, mainly due to their increased risk of side effects, safety concerns, and potential interaction with several medications and foods. They are typically only prescribed after other antidepressants have failed to provide benefits. ^{[1] [2]}

How Do MAOIs Work?

MAOIs work by inhibiting the activity of an enzyme called monoamine oxidase (MAO). This enzyme is used to break down various neurotransmitters in the brain, including dopamine, serotonin, norepinephrine, and epinephrine, as well as tryptamine, histamine, and tyramine. ^{[1] [2]}

Therefore, inhibiting the MAO enzyme leads to increased levels of these neurotransmitters. In particular, increased levels of serotonin, dopamine, and norepinephrine are thought to primarily result in MAOIs’ antidepressant effects. ^[2]

Serotonin is involved in mood, sleep, appetite, and general well-being. Dopamine and norepinephrine play key roles in alertness, motivation, and arousal, among other areas. Thus, all of these neurotransmitters are essential for mental well-being. ^[3]

Are MAOIs Still Widely Used?

MAOIs are not widely used anymore. Compared to newer types of antidepressants, MAOIs have more safety concerns, increased risk of side effects, and significant potential to interact with other medications and foods. With that said, they still have benefits for some individuals, such as in cases of depression with atypical features, and for individuals who do not respond to other forms of antidepressants. ^{[1] [4]}

MAOIs to Treat Depression

Several specific types of MAOIs are approved to treat depression. They are typically grouped into first-generation, second-generation, and third-generation MAOIs. Before looking at these specific types, it’s helpful to understand the different ways MAOIs can work.

Firstly, MAOIs can either have reversible or irreversible effects. Irreversible means that the drug permanently deactivates the MAO enzyme, while a drug with a reversible profile temporarily deactivates enzyme activity, but normal activity can resume more quickly after the drug is stopped. ^{[1] [2]}

In addition to this, MAOIs can either act on one or both of the forms of MAO, which are MAO-A and MAO-B. Selective inhibitors are more specific and only inhibit one of these forms, whereas non-selective inhibitors inhibit both. ^{[1] [2]}

First-generation MAOIs are irreversible and non-selective. They include:

• Isocarboxazid (Marplan®)

• Phenelzine (Nardil®)

• Tranylcypromine (Parnate®)

Second-generation MAOIs are irreversible but have selective effects. They include:

• Selegiline (Emsam®) (selective effects mainly on MAO-B, but can be MAO-A at higher doses)

• Rasagiline (selective for MAO-B only)

Third-generation MAOIs are reversible and have selective effects. They include:

• Moclobemide (Manerex®) - MAO-A selective (not available in the US)

• Safinamide - MAO-B selective

Overall, these medications are not considered first or second-line treatments for MDD. They are primarily used for treatment-resistant depression or depression with atypical features. The latter includes specific symptoms, such as oversleeping, eating too much, sensitivity to rejection, and mood reactivity. ^{[1] [2]}

Other Conditions Treated by MAOIs

Some MAOIs are also approved for other conditions, such as: ^{[1] [3]}

• Panic disorder

• Social anxiety disorder (SAD)

• Parkinson’s disease

MAOIs may also sometimes be used off-label for various conditions, including: ^[3]

• Attention-deficit/hyperactivity disorder (ADHD)

• Multiple system atrophy

Common Side Effects of MAOIs

There are many possible side effects of MAOIs, which is one of the reasons why alternative medications are recommended first. Common side effects include: ^{[1] [2] [3] [5]}

• Daytime sleepiness

• Insomnia

• Nausea

• Hypotension (low blood pressure)

• Weight gain

• Dry mouth

• Diarrhea

• Constipation

• Dizziness and/or lightheadedness

• Sexual dysfunction

• Headache

Rare and Severe Side Effects

One rare but potentially serious side effect is a hypertensive crisis. This sometimes occurs when people take MAOIs alongside foods high in tyramine, such as aged cheeses, beer, and dry sausage. This can result in a significant and dangerous increase in blood pressure that, in some cases, can be fatal. ^{[1] [2]}

(For a full list of possible foods that may interact with MAOIs, make sure to consult with your doctor. This provides the most appropriate and individualized recommendations.

MAOIs also have the potential to cause serotonin syndrome, particularly when used in combination with other medications or substances that increase serotonin as well. Serotonin syndrome leads to abnormally elevated levels of serotonin in the body, which can lead to several symptoms, including delirium, sweating, confusion, rapid heart rate, high blood pressure, spasms, and tremors. In severe cases, it may lead to coma or death. ^{[1] [2]}

Potential drug-drug interactions with an increased risk of serotonin syndrome include: ^{[1] [3] [5]}

• Selective-serotonin reuptake inhibitors (SSRIs)

• Serotonin-norepinephrine reuptake inhibitors (SNRIs)

• Tricyclic antidepressants

• Bupropion

• Mirtazapine

• St. John’s Wort

• Opioids

• Certain “street drugs” (e.g. cocaine, amphetamines)

Suicide Risk

MAOIs may increase the risk of suicidal thoughts or behaviors, especially in children and young adults under age 25. This risk is highest when you initially start taking an MAOI or when you change doses. ^[2]

Overall, it’s essential to watch out for any warning signs. If you or your child is taking an MAOI and notice any suicidal thoughts or behaviors, these should be addressed immediately. Call your healthcare provider who prescribed the medication or dial 988 for the suicide hotline. ^[3]

Getting a Prescription for MAOIs

MAOIs are typically only prescribed after other classes of antidepressants are tried, such as SSRIs and SNRIs. The most common situations where you may be prescribed an MAOI are treatment-resistant depression and depression with atypical features. They may also be used for treatment-resistant SAD and panic disorder.

In these cases, MAOIs can potentially be very valuable medications to help relieve depressive symptoms. In fact, some research has shown that MAOIs may be more effective than traditional antidepressants for some cases of atypical depression. ^[6]

Furthermore, you may want to ask your doctor about MAOIs if you have Parkinson’s disease or multiple systems atrophy; MAOIs may be an appropriate adjunct treatment in these cases. ^[1]

When to Seek a Diagnosis for Depression

Sometimes, depressive symptoms are due to normal fluctuations in life and go away on their own. However, it’s important to seek a diagnosis for depression if you’re experiencing symptoms that significantly interfere with your well-being and ability to function in daily life. Common symptoms that warrant seeking a diagnosis include:

• Mood swings

• Agitation

• Trouble sleeping (either too much or too little)

• Lack of appetite or overeating

• Low libido

• Decreased interest in activities and hobbies

• Suicidal thoughts

• Intense feelings of guilt or shame

• Hopelessness

MAOI Treatment Plan

If you are prescribed an MAOI, your doctor will determine the most appropriate treatment plan for you. Typically, the effects of MAOIs start to become noticeable after 2 to 3 weeks, but you will most likely take an MAOI for at least 6 months to achieve maximum benefits. Taking your medication for at least 6 months also reduces the risk of relapse. ^[1]

Importantly, MAOIs are often started after other antidepressants have been tried. Therefore, your doctor will instruct you to gradually taper off your current antidepressant medication before starting an MAOI. Typically, there is a period of at least 2 weeks between stopping your previous antidepressant and starting MAOI treatment to minimize side effects and interactions. ^[2]

How Long Does it Last?

Treatment with MAOIs usually lasts at least 6 months in order to achieve the maximum reduction in depressive symptoms and to reduce the likelihood of returning symptoms. Some individuals with chronic depression may take MAOIs indefinitely, while others may only need MAOIs for a shorter period of time, such as 6 months to a year. Always consult regularly with your doctor to see what treatment approach is best for you.

Safely Stopping MAOI Medication Treatment

Suddenly stopping MAOIs can cause antidepressant discontinuation syndrome. This leads to withdrawal-like effects, including insomnia, nausea, dizziness, agitation, anxiety, and flu-like symptoms. Therefore, it’s important to only stop MAOI treatment under the guidance of your doctor. ^{[2] [3]}

Your doctor will gradually reduce the dose of the MAOI medication you’re taking over a period of several weeks. This is the safest approach and helps to minimize withdrawal effects.

Expect the full process to take a minimum of 4 weeks. Notably, the exact time that it takes for the full process depends on many factors, such as your current dose, how long you’ve been taking it, and your individual tolerance to dosage reductions. ^[3]

Final Thoughts

MAOIs aren’t the first medications of choice when treating depression, since other antidepressants typically have fewer side effects and interactions. However, MAOIs can still be highly beneficial in many instances, such as for individuals with treatment-resistant depression and atypical depression. Always talk with your doctor to determine which medication and treatment plan is best for you. While it may take time, many individuals eventually find treatments that work for them.

Commonly Asked Questions About MAOIs

What substances react badly with MAOIs?

MAOIs may interact significantly with various medications and certain foods. Regarding medications, MAOIs may react badly with other antidepressants (such as SSRIs and SNRIs), leading to excessive levels of serotonin.

MAOIs may also cause hypertension when they are used while consuming foods high in tyramine. This includes aged cheeses, soy sauce, fermented sausages, cured fish, overripe fruits, sourdough bread, and other items. Make sure to tell all healthcare providers that you take MAOIs, so they can tell you a full list of foods and medications to avoid.

Do MAOIs cause weight gain?

MAOIs can cause weight gain in some individuals. This does not happen for everyone.

Are there any effective alternatives to MAOIs?

Yes. In fact, MAOIs are not considered first or second-line treatments for depression. SSRIs and other antidepressants are typically used first and may be more effective for depression, particularly the typical forms.