MAOIs: Uses, Types, Side Effects, & More

How MAOIs Work

MAOIs work by limiting the activity of specific enzymes in the body that break down or metabolize different neurotransmitters. The neurotransmitters include chemicals like serotonin, epinephrine, and dopamine, all of which are thought to be linked to depression. MAOIs work to keep levels of these chemicals elevated which is thought to help relieve symptoms of depression.¹

Monoamine oxidase enzymes are found throughout the body, especially in the brain, gut, liver, and nerves. It is this wide distribution of enzyme locations that causes such extensive food and drug interactions. MAOI drugs act not just on the nervous system, but also in the gut, changing the way we digest amine-rich foods.¹

Types of MAOI Drugs

While many MAOI medications have been developed in past years, currently there are 4 drugs FDA-approved for use. Three medications are approved to treat depression in some form, while Selegiline is only approved as an add-on treatment for Parkinson’s patients also taking carbidopa/levodopa.

MAOIs can be divided into selective and non-selective groups. Selegiline is the only selective MAOI and since it only acts on certain MAO enzymes in the body it does not show any antidepressant action.¹

Here are the available types of MAOI medications:

• Isocarboxazid (Marplan): This medication is approved for the treatment of depression but it is not usually considered the first option, and it can be used if first-line treatments are intolerable, ineffective, or contraindicated for any reason. The dose usually starts at 10 mg twice daily and up to a maximum of 30 mg twice daily.²
• Phenelzine (Nardil): This medication is approved for the treatment of depression, specifically atypical or neurotic depression. Again this medication is rarely used as the first treatment.³
• Selegiline (Emsam): Emsam is not used to treat depression. It is used as an additional treatment for carbidopa/levodopa in Parkinson’s patients. It has been shown to reduce tremors, increase speech ability and improve overall disability in Parkinson’s patients.⁴
• Tranylcypromine (Parnate): Parnate is used to treat depression in adults but it is not usually considered the first option, and it can be used if first-line treatments are intolerable, ineffective, or contraindicated for any reason.⁵

What Are MAOIs Used to Treat?

MAOIs are mostly used to treat depression in patients that do not respond to other forms of treatment. They can also be used to treat patients with less common forms of depression.¹ Examples include atypical depression, depression with symptoms of anxiety, and depression with phobias.³ Selegiline is the unique MAOI not used for depression but instead to improve movement symptoms in Parkinson’s patients.⁴ Many times MAOIs are used as off-label treatments. This kind of use is not approved by the FDA but happens when a prescriber decides to use a medication based on their professional judgment.

MAOIs may be used as an FDA-approved medication to treat:

• Major depressive disorder (MDD) in adults
• Adjunct therapy to carbidopa/levodopa in Parkinson’s patients

MAOIs can also be used off-label (non-FDA-approved) for treating:

• Bipolar depression
• Depression with anxiety
• Phobias
• Treatment-resistant depression
• Panic disorder

Who Should Not Take MAOIs?

Many patients should not take MAOIs to avoid unnecessary risks. You may fall into this category based on your previous health history or current medications you are taking. The list of those who should not take MAOIs is long and you should review your full medical history with your doctor to ensure taking an MAOI is safe for you.

People who may need to avoid taking MAOIs include:

• Pregnant and breastfeeding women
• People with cardiovascular disease or hypertension
• People with liver disease
• People with a history of seizures
• People with severe renal impairment
• People with pheochromocytoma
• People taking any other antidepressant

MAOI Dosages for FDA-Approved Treatment

MAOIs have been studied extensively and are FDA-approved for the treatment of depression in certain situations. Each medication has specific strengths, but the way each medication is dosed to treat depression is similar. It is important to follow your doctor’s directions exactly to ensure a safe and effective treatment.

MAOI tablets are taken 2 to 4 times daily at the lowest effective dose. This means you will start at the lowest dose and increase slowly over weeks to months until the target dose or response is safely achieved. If you are using patches they will be applied once every 24 hours rotating sites. It is important to clearly understand directions and not to miss doses or double up on doses. This can lead to irregular medication concentration and increase the likelihood of side effects.

Formulations for MAOIs

MAOIs are currently available in two forms, tablets and patches. All current MAOIs are available as tablets are taken 2 to 4 times daily. Taking so many tablets each day can sometimes be hard to remember. The patches are a more recent formulation and are only available as selegiline. The patch is applied just once daily and aims to simplify medication administration.

What Happens If I Miss a Dose of MAOIs?

If you miss a dose of your MAOI it is important to take the missed dose as soon as you remember. If it is almost time for your next dose, you should skip the missed dose and continue on with the next scheduled dose. It is important not to double up on doses. Taking too much medication at once is dangerous.

If you would like to stop taking your MAOI it is important not to stop taking it abruptly. You should alert your doctor and together come up with a discontinuation plan. Your doctor will direct you to slowly decrease your dose over time to reduce unwanted side effects.

Side Effects of MAOI Drugs

There are many potential side effects when taking MAOIs because the medication works in many different places in the body. Many side effects include changes in blood pressure as a hypertensive crisis or orthostatic hypotension (low blood pressure when standing after sitting or lying down). Other effects can be insomnia, drowsiness, or nausea. Communicating with your doctor regularly about side effects can allow your doctor to make changes in drug therapy as needed to combat different side effects.¹

Common Side Effects of MAOIs

Common side effects when taking MAOIs usually occur when starting treatment or when changing doses. Your doctor should provide you with recommendations should any of these occur. The side effects usually go away with time as your body adjusts to the medication.¹

Common side effects of MAOIs include:*

• Decreased appetite
• Drowsiness
• Orthostatic hypotension
• Sedation
• Weight gain
• Edema
• Muscle pain
• Insomnia
• Nausea
• Sexual dysfunction

*All medications, including MAOIs, can cause side effects that can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and understand the potential side effects and benefits of any medication.

Serious Side Effects of MAOIs

Serious side effects from taking MAOIs are dangerous and it is important to recognize these side effects and get help immediately. Serious side effects can happen at any time during treatment, so never let your guard down against recognizing these symptoms. Talking with your doctor before starting treatment can help you reduce the risk of experiencing serious side effects.^1,3,5

Serious side effects of MAOIs may include:*

• Hypertensive crisis: This can occur after taking MAOIs with certain food or drugs and symptoms include palpitations, headache, neck stiffness, and changes in heart rate. Getting help immediately is crucial.
• Serotonin syndrome: This is a life-threatening reaction that occurs from taking too many medications that increase serotonin in the body. Symptoms include sweating, increased heart rate, and agitation, and it is necessary to get help immediately.
• Antidepressant withdrawal: This can happen when MAOIs are stopped too quickly causing severe symptoms including worsening depression. Alert your doctor right away and additional medication may be prescribed.
• Worsened anxiety symptoms: Taking MAOIs can cause worsening anxiety symptoms that should be addressed immediately. This can be dangerous if untreated.
• Seizures: MAOIs can reduce the normal threshold for seizures. Anyone with a previous history of seizures should not take MAOIs and if you have a seizure, someone should contact 911 immediately.
• Hepatotoxicity: MAOIs can cause changes in liver function. It is important to have regular liver tests during treatment and look for signs of jaundice (yellowing of the skin).
• Suicidality: Taking MAOIs can increase the risk of self-harm. It is important to understand this risk and get help right away if you have any suicidal thoughts.

*All medications, including MAOIs, can cause side effects that can be mild or serious. This is not a comprehensive list of all possible side effects. You should talk with your doctor about any questions you have and understand the potential side effects and benefits of any medication.

MAOI Withdrawal

Stopping MAOIs needs to be done carefully to avoid symptoms of antidepressant withdrawal. This can happen when an MAOI drug is stopped abruptly. This can cause symptoms like rebound anxiety and depression, sweating, changes in heart rate and blood pressure, and flu-like symptoms. When you would like to stop taking an MAOI, your doctor should direct you to slowly reduce your dose gradually.²

Allergic Reactions to MAOIs

Allergic reactions to MAOIs are serious and can be life-threatening. It is important that if you experience any itching, swelling of the throat or face, or trouble breathing you contact 911 immediately. If you have had any serious allergic reactions to medications including MAOIs in the past you should let your doctor know.

Allergic reactions to MAOIs may include:

• Trouble breathing
• Swelling
• Rash/hives
• Itching

If you experience any of these symptoms contact 911 immediately. Once your reaction has been treated do not continue taking the MAOI. Contact your doctor immediately to determine what the next step is for treatment.

MAOIs Warnings & Precautions

There are many precautions to be aware of when taking an MAOI. Thoroughly understanding these warnings and heeding them can reduce the risk you undertake. If any of these apply to you, bring them up with your doctor. Some risks may warrant additional tests or changes in doses, while others may prevent you from taking MAOIs altogether.^1,2,3

Warnings and precautions for taking MAOIs include:

• Increased risk of suicidal thoughts: Taking MAOIs can cause an increased risk of suicidal ideation or self-harm. If you have a history of suicidal ideation, MAIOs may not be right for you.
• Hypertension crisis: Taking MAOIs can cause dangerously high blood pressure that can be fatal. If you have high blood pressure or a history of cardiovascular disease you should avoid taking MAOIs.
• Risk of Seizures: MAOIs can cause the threshold for seizures to be lowered. If you have a history of seizures you should discuss with your doctor if taking an MAOI is safe.
• Risk of manic episodes: All patients taking MAOIs should be screened for bipolar disorder. Taking an MAOI can trigger a manic episode of untreated or undiagnosed bipolar disorder as a manic episode.
• Use in liver or kidney impairment: MOAIs should not be used in individuals with liver disease or kidney disease. This can cause unnecessary risk of adverse reactions.
• Taking MAOIs while pregnant: MAOIs have not been studied in pregnancy and are not considered safe for use in pregnancy or while breastfeeding. Speak with your doctor if you are planning to become pregnant or if you become pregnant while taking antidepressants or an MAOI.
• Taking MAOIs and consuming alcohol: This should be avoided especially beer and wine, which contains fermented alcohol.
• Avoid taking specific tyramine-rich foods: Avoiding all foods that contain tyramine-rich foods is crucial while taking MAOIs to avoid severe side effects. These include aged cheeses, aged meats, pickled vegetables, and chocolate and caffeine.

Interactions With MAOIs

There are numerous drugs that negatively interact with MAOIs. It is important to be vigilant and avoid all of these medications while taking an MAOI. You should alert all of your doctors, pharmacists, and therapists that you are taking an MAOI. Interactions can happen with prescribed medications, over-the-counter medications, and vitamins and supplements too. Interactions can cause symptoms including severe headache and hypertension as well as drowsiness.^5,1

Four substances you should avoid while taking MAOIs include:

• Other antidepressants: It is important to avoid other serotonergic medications, which include most antidepressants. They should be avoided for the duration of MAOI treatment and 2 weeks before and after to ensure harmful interactions do not occur.
• Oral migraine medication: Triptans taken orally to stop treating migraines should not be used with MAOIs.
• Amphetamines: These can include ADHD medications and weight loss drugs. They can exacerbate the risk of severe hypertension when taken with MAOIs.
• Cold and flu remedies: Specifically, those that contain decongestants like phenylephrine, pseudoephedrine, and ephedrine. They cause severe hypertension.

MAOI Diet Precautions

Adhering to the MAOI diet is an important part of MAOI treatment. Its purpose is to prevent dangerous side effects that come about from eating tyramine-rich foods. Eating foods with high tyramine levels while taking MAOI medications can cause a life-threatening hypertensive crisis.

While many foods have been said to be avoided, some cheeses and meats are okay for consumption. It is important to be thorough and truthful with your physician about your current diet and ability to change diets for a prolonged amount of time. Studies have shown that foods with a small amount of tyramine will not put patients at risk.¹

Here are foods to avoid while taking MAOI medications:

• Soy sauce and other fermented soy products
• Aged or cured meats
• Aged cheeses
• Broad bean (fava) pods
• Spoiled meats
• Marmite
• Sauerkraut
• Soybean products
• Draft beers
• Kimchi
• Wine
• Yogurt

Can You Overdose on MAOIs?

Overdosing on MAOIs is a real risk that should be taken seriously. It is important not to take more medication than prescribed or increase your dose without direction from your prescriber. Symptoms of an overdose usually occur within 12 hours of ingestion of a large dose of an MAOI. Symptoms can include severe headache, agitation, changes in pulse, and fainting. Calling 911 is crucial and immediate medical attention is necessary.²

What Should You Do If You Take Too Much MAOI Medication?

If you take too much MAOI medication you should call 911 right away. Let someone you know right away as well so they can stay with you. Keep your medication with you or tell someone you trust which medication you took and if possible how much you took. This can help with treatment. The most important thing is to get to a hospital right away for proper treatment and support.²

Questions to Ask Your Healthcare Provider About MAOIs

Taking an MAOI can be an important and impactful part of depression treatment. However, there are many potential risks that come along with taking an MAOI. Taking time to discuss these risks with your doctor before starting treatment with an MAOI is very important. Staying vigilant about what other foods and drugs you consume while on an MAOI can help to ensure a successful treatment. In addition, finding the right therapist can be a beneficial part of depression treatment while taking an MAOI.

Questions to ask your care team about MAOIs include:

• Can I use an MAOI along with therapy to treat depression?
• How soon might I notice side effects from taking an MAOI?
• Am I at risk for more severe symptoms if I am already taking other anxiety /depression medications?
• What is the best dosage to ensure fewer side effects?
• Are there drugs I am taking that could have negative interactions?
• When should I reach out to you if I am experiencing side effects?
• Is there anything I should tell my therapist about this new medication?
• What foods should I not eat while taking an MAOI?
• If I am switching medications, how long should I wait before I start the MAOI?
• What if I want to stop taking the MAOI?
• Am I a good candidate for the patch instead of a tablet?

How to Get an MAOI Prescription

All MAOIs require a prescription from a licensed healthcare professional. Since MAOIs are rarely used as the first drug for treatment, you should discuss therapy with an MAOI with your current mental health care provider. They can help determine if using an MAOI is right for you. Always remember that utilizing an online psychiatry service is a great option. You should plan to see the same provider for the duration of treatment with an MAOI since you will need to check in with them frequently over the entire time you take the MAOI.

In My Experience

In my experience, MAOIs are not commonly used, but they can be beneficial for some patients struggling to find an effective treatment for depression. It is important to fully understand all the risks involved with taking an MAOI and all the food and drugs to avoid while taking an MAOI. This information, along with consistent communication with your healthcare team, can help you safely take an MAOI.

For Further Reading

• MAOIs, an overview from the Mayo Clinic
• Mental Health Medications
• MAOIs and Diet
• How Long Does It Take For Antidepressants to Work?
• How to Treat Depression: Therapy, Medication, Procedures, & Self Help