How SSRIs Compare to MAOIs

A guide to MAOIs

How SSRIs Compare to MAOIs

Monoamine oxidase inhibitors (MAOIs) were the first class of antidepressants, but they're not prescribed as often as newer depression medications

MAOIs list | What are MAOIs? | How they work | Uses | Who can take MAOIs? | Safety | Side effects | Costs

With the discovery in the 1950s of iproniazid, the first monoamine oxidase inhibitor (MAOI), the era of drug treatment for depression had begun. As is often the case, chance played a part in its discovery as iproniazid was originally studied as a treatment for tuberculosis.

Side effects seen in tuberculosis patients given iproniazid, such as feelings of euphoria, increased appetite, and improved sleep, led researchers to experiment with the drug in patients with depression.

The success in relieving patients of depressive symptoms led to iproniazid becoming the first pharmacological treatment of depression.

Unfortunately, iproniazid was found to be “non-selective,” or not specific, in its activity in the body, which led to safety concerns and ultimately its removal from the U.S. market.

One important safety concern was termed the “cheese reaction,” so-called because many aged cheeses contain high levels of an amino acid called tyramine that, when combined with iproniazid, led to dangerous increases in heart rate, high blood pressure, and sweating.   

Advances in medical research led to a renewed interest in MAOIs because of the discovery of more selective types that had fewer side effects yet maintained their antidepressant action.

Today, even though MAOIs continue to be effective in treating depression, their use has declined because of newer antidepressant medications that have fewer side effects and do not have strict dietary restrictions. MAOIs are, however, still a good option for some people when other treatments have failed.

The table below lists available MAOIs followed by information on how they work, what conditions they treat, safety, and cost.

What are MAOIs?

MAOIs are a class of drugs different from other antidepressants. They’re used for treating depression and other neurologic conditions such as Parkinson’s disease and Alzheimer’s disease.

Even though MAOIs were the first drugs discovered for treating depression, they are no longer considered first-line due to safety issues and the introduction of newer, safer classes of drugs such as serotonin antagonist and reuptake inhibitors (SARIs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). MAOIs are typically prescribed for depression only when other classes of antidepressants are not effective.

How do MAOIs work?

The monoamine oxidase enzyme is naturally present in the body. It breaks down—or inactivates—certain neurotransmitters (including serotonin, dopamine, epinephrine, and norepinephrine) known collectively as monoamines.

It is believed that patients with depression have decreased amounts of these neurotransmitters in the brain.

MAOIs work by inhibiting monoamine oxidase, which, in turn, prevents the breakdown of monoamines and increases the levels of the neurotransmitters in the brain.

What are MAOIs used for?

MAOIs are primarily used to treat depression but may also used be used to treat the following conditions:

Who can take MAOIs?

Despite their potentially serious side effects, MAOIs have been proven effective in treating depression in adults. They’re used less frequently than other antidepressants because of dietary precautions and risks of adverse reactions when combined with certain drugs.

Use caution when prescribing MAOIs to seniors

Older patients may be at greater risk of adverse reactions when taking MAOIs. In general, dose selection for an older patient should start at the low end of the dosing range, particularly if they have decreased liver, kidney, or cardiac function. Seniors are also more ly to have a secondary disease or be on drug therapy that may impact the effectiveness or safety of an MAOI.

Warnings for MOAIs in children and adolescents

Antidepressants, including MAOIs, have a mandated “boxed warning,” also called a black box warning, from the U.S.

Food and Drug Administration (FDA) due to increased risk of suicidality in children, adolescents, and young adults (up to 24 years of age). For most MAOIs, safety and effectiveness have not been established for pediatric use.

When considering the use of an MAOI in a child or adolescent, the prescriber must balance the potential risks with the clinical benefit.

MAOIs carry a boxed warning regarding the risk of increased suicidal thinking and behavior in some younger patients.

Patients of all ages who are started on antidepressants should be monitored for signs of suicidal thoughts and behaviors.

MAOIs have a second boxed warning regarding a sudden, severe increase in blood pressure that can occur when certain foods or beverages are consumed during treatment.  

Before starting an MAOI, patients should be aware of the serious drug-food drug-drug interactions that could cause serotonin syndrome or hypertensive crisis.

Serotonin syndrome

Serotonin syndrome is a serious and potentially life-threatening condition in which there is too much serotonin in the body. Symptoms of serotonin syndrome may include high fever, seizures, uneven heartbeat, or passing out.

Emergency medical care may be needed if any of these symptoms occur. MAOIs should not be taken in combination with other drugs that can increase serotonin levels.

Following is a list of drug classes and medicines that should not be taken with MAOIs due to concerns of serotonin syndrome:

  • Selective serotonin reuptake inhibitors (SSRIs) such as Prozac (fluoxetine), Zoloft (sertraline), or Paxil (paroxetine)
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as Effexor (venlafaxine) or Cymbalta (duloxetine)
  • Tricyclic antidepressants (TCAs) such as Elavil (amitriptyline), Pamelor (nortriptyline), or Tofranil (imipramine)
  • Atypical antidepressants such as Wellbutrin (bupropion), Ludiomil (maprotiline), Serzone (nefazodone), or Desyrel (trazodone)
  • Opioids and other pain medicines such as MS Contin (morphine sulfate), OxyContin (oxycodone), Demerol (meperidine), Duragesic (fentanyl), Dilaudid (hydromorphone), Dolophine (methadone), or Ultram (tramadol)
  • Sympathomimetic drugs, such as amphetamines, as well as some cold, hay fever or weight-reducing products that contain dextromethorphan, pseudoephedrine, phenylephrine, or ephedrine
  • Triptans such as Imitrex (sumatriptan), Maxalt (rizatriptan), or Zomig (zolmitriptan)
  • Miscellaneous drugs such as Flexeril (cyclobenzaprine), Tegretol (carbamazepine), Buspar (buspirone), lithium, dopamine, reserpine, or St. John’s wort

Hypertensive crisis

A severe increase in blood pressure may occur when there are excess levels of tyramine in the body. Tyramine is a naturally occurring amino acid that helps regulate blood pressure and is also commonly found in certain foods. The enzyme monoamine oxidase breaks down excess tyramine.

Because MAOIs reduce the action of monoamine oxidase, tyramine levels can build up to dangerous levels in the body. This increase in tyramine can lead to a serious spike in blood pressure that may require emergency treatment.

All patients should be warned that the following foods and beverages must be avoided while taking MAOIs and for two weeks after discontinuing their use:

  • Meat and fish
    • Pickled herring
    • Liver
    • Dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna)
    • Any spoiled or improperly stored meat, poultry, and fish
  • Vegetables
    • Broad bean pods (fava bean pods)
    • Sauerkraut
  • Fruits
    • Overripe avocados, bananas, raisins, or figs
  • Dairy products
  • Beverages
    • Beer and wine
    • Alcohol-free and reduced-alcohol beer and wine products
  • Miscellaneous
    • Yeast extract (including brewer’s yeast in large quantities)
    • Meat extract
    • Most soybean products (including soy sauce and tofu)
    • Excessive amounts of chocolate and caffeine
    • Over-the-counter supplements containing tyramine


There are no current MAOI recalls as of April 2021.


MAOIs should be used with caution, or not at all, for those with the following conditions:

  • A history of mania associated with bipolar disorder
  • Epilepsy (unless the epilepsy is well controlled)
  • Pheochromocytoma (a tumor of the adrenal glands)
  • Serious kidney, liver, or heart problems

Can you take MAOIs while pregnant or breastfeeding?

There are no adequate and well-controlled studies regarding the use of MAOIs in pregnant women. A decision to use MAOIs during pregnancy is the balance between risk and benefit.

wise, it is unknown if MAOI drugs are present in human milk or what the effect may be on the nursing infant.

A woman’s healthcare provider is the best source of information when managing antidepressant treatment when pregnant or breastfeeding.

Stopping MAOIs

Never stop an antidepressant medicine without first talking to a healthcare provider. Missing several doses of an MAOI in a row or stopping treatment abruptly may cause withdrawal- symptoms, including the following:

  • A general feeling of uneasiness
  • Restlessness
  • Anxiety
  • Depression
  • Confusion
  • Hallucinations
  • Headache
  • Weakness
  • Diarrhea
  • Nausea
  • Dizziness
  • Lethargy

Whenever possible, gradually reduce the dose rather than abruptly stopping the medication. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. The healthcare provider may continue decreasing the dose but at a more gradual rate.

Are MAOIs controlled substances?

No, MAOIs are not controlled substances.

The following are potential common side effects of MAOIs. This is not an exhaustive list and you should always consult a healthcare professional for professional medical advice before taking MAOIs.

  • Orthostatic hypotension (temporary lowering of blood pressure, usually related to suddenly standing up) 
  • Dizziness
  • Headache
  • Insomnia
  • Restlessness
  • CNS stimulation
  • Muscle spasms
  • Tremor
  • Myoclonic jerks (sudden muscle contraction)
  • Anxiety
  • Agitation
  • Weakness
  • Blurred vision
  • Nausea
  • Vomiting
  • Drowsiness
  • Loss of appetite
  • Palpitations
  • Tachycardia
  • Ejaculatory dysfunction
  • Impotence
  • Dry mouth
  • Swelling of lower legs or hands
  • Diarrhea
  • Constipation
  • Paresthesia (tingling or prickly sensation in hands or feet)
  • Tinnitus (ringing or buzzing in the ears)
  • Urinary retention
  • Rash

RELATED: Going on antidepressants: A beginner’s guide to side effects

How much do MAOIs cost?

MAOIs have a wide price range depending on the specific drug, quantity, and dosage. Since several MAOIs are available in generic form, they are much less than the brand-name counterpart. For example, generic tranylcypromine costs about $661 for 120, 10 mg tablets.

The brand-name version, Parnate, could cost more than $1,000 for the same strength and quantity. You can compare costs of generic vs. brand-name drugs on, and use a free SingleCare card to reduce certain prescription costs up to 80% at participating pharmacies.


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