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How MAOIs Work

It is believed that the brain contains several hundred different types of chemical messengers called neurotransmitters that act as communication agents between different brain cells. These chemical messengers are molecular substances that can affect mood, appetite, anxiety, sleep, heart rate, temperature, aggression, fear, and many other psychological and physical functions.

Monoamine oxidase (MAO) is an enzyme that degrades or breaks down three neurotransmitters associated with mood and anxiety: serotonin,norepinephrine, anddopamine. MAOIs reduce the activity of the MAO enzyme, leading to higher levels of norepinephrine, serotonin, and dopamine in the brain. The benefits of these increases are improved mood and an anti-panic effect.

Some common MAOIs include:

What Are MAOIs?

How SSRIs Work

Serotonin is a neurotransmitter that is important in modulating a variety of body functions and feelings, including our mood. According to research, low levels of serotonin transmission have been linked to depression.As the name implies, SSRIs inhibit the reuptake of serotonin in the brain. This causes an increase of serotonin in an area of the brain called the synaptic cleft, the small space between brain cells.

Examples of SSRIs include:

Another medication called Viibryd (vilazodone) is not just an SSRI. It is both an SSRI and a serotonin 1α (5HT-1α) partial agonist (like the anti-anxiety medication buspirone), so it is classified as a multimodal serotonergic agent. Of note is that while fluvoxamine is an SSRI, it is also the most potent of the SSRI’s at the σ-1 receptor, which may make it more effective in reducing severe anxiety and depression as well as aiding cognitive functioning.

What Are SSRIs?

Why SSRIs Prescribed More Often Than MAOIs

SSRIs are generally the first choice for treatment of depression because beyond their effectiveness, they generally cause fewer problems with side effects. Because ofdietary restrictionsand concerns over hypertensive reactions, as well as serotonergic crises from drug interactions (serotonin syndrome), MAOIs are often used only after other agents have failed.

People should try to avoid foods high in tyramine, which can be elevated due to MAOI use and may lead to critically high blood pressure. Foods to avoid include beef liver, hot dogs, bacon, sour cream, aged cheese, red wine, and brewer’s yeast. The lowest dose of Emsam (6 mg), however, carries no dietary precautions.

Other common side effects of MAOIs include:

One of the attractions of SSRIs is that they are believed to be safer and produce fewer unwanted side effects than otherclasses of antidepressants. But any medication can cause side effects, especially at the beginning of treatment. Some common side effects of SSRIs include:

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In general, primary care providers should not prescribe MAOIs unless they have experience with these medications.

MAOIsAffects serotonin, norepinephrine, and dopamine levelsLess commonly prescribedMore side effectsRequires dietary restrictionsSSRIsAffects serotonin levelsMore commonly prescribedFewer side effects

MAOIsAffects serotonin, norepinephrine, and dopamine levelsLess commonly prescribedMore side effectsRequires dietary restrictions

Affects serotonin, norepinephrine, and dopamine levels

Less commonly prescribed

More side effects

Requires dietary restrictions

SSRIsAffects serotonin levelsMore commonly prescribedFewer side effects

Affects serotonin levels

More commonly prescribed

Fewer side effects

Other Types of Antidepressants

In addition to MAOIs and SSRIs, there are other classes of antidepressant medications available, including serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and multimodal medications.

How SNRIs Work

Venlafaxine (Effexor) was approved in 1993 and was the first FDA-approved SNRI. SNRIs are often used to treat the chronic pain linked to depression as well as generalized anxiety, post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), panic disorder, and nerve pain associated with fibromyalgia. They work similarly to SSRIs, but they inhibit the reuptake of both norepinephrine and serotonin.

SNRI use can trigger amanicorhypomanicepisode.

How Reuptake Inhibitor Drugs Work

Examples of SNRIs include:

Common side effects of SNRIs include:

How TCAs Work

Tricyclic antidepressants (TCAs), which are primarily used to treat depression, bipolar disorder, and other conditions such as chronic pain and insomnia, were first introduced in the 1950s. TCAs work similarly to reuptake inhibitors in that they block the absorption of serotonin and norepinephrine into nerve cells, however, these drugs are known to have more side effects than newer classes of antidepressants like SSRIs.

In a meta-analytic review,researchers found that patients with major depressive disorder (MDD) who took TCAs discontinued treatment 27% of the time due to side effects compared with 19% on SSRIs. The percentage was even greater in elderly patients—33% and 16%, respectively.

When compared with MAOIs, TCAs have also been found less effective fortreatment-resistant depression(TRD). However, TCAs still have their place in depression treatment.

Examples of TCAs include:

Some side effects of TCAs include:

Overview of Tricyclic Antidepressants

How Multimodal Medications Work

There are also multimodal medications such as Viibryd, Trintelix, bupropion (Wellbutrin), and mirtazapine (Remeron). These drugs work in unique ways so that they do not fit in the same classes as other antidepressants so they are often called atypical antidepressants or multimodal antidepressants.

Some different types of atypical antidepressants include:

Possible side effects of atypical antidepressants include:

A Word From Verywell

There’s no one-size-fits-all treatment for depression and what works for someone else might not work for you. Since all antidepressants can help with symptoms of depression, deciding which one to take may come down to which side effects you can and can’t tolerate. Other factors include your symptoms, treatment history, and current medications (including prescription drugs, over-the-counter medications, vitamins, and supplements).

When starting a new drug, do your best to have patience (it can take up to eight weeks tofeel substantial improvement) and monitor any drug side effects to discuss with your doctor.

If your side effects are intolerable and begin to interfere with your quality of life, call your doctor right away but don’t stop treatment on your own. Stopping abruptly can cause withdrawal symptoms, including chills, dizziness, fever, headache, lethargy, nausea, and vomiting.

How to Know Which Antidepressant Is Best for You

4 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Ramachandraih CT, Subramanyam N, Bar KJ, Baker G, Yeragani VK.Antidepressants: From MAOIs to SSRIs and more.Indian J Psychiatry. 2011;53(2):180-2. doi:10.4103/0019-5545.82567Harvard Health Publishing.What causes depression?Harvard Medical School.Santarsieri D, Schwartz TL.Antidepressant efficacy and side-effect burden: A quick guide for clinicians.Drugs Context. 2015;4:212290. doi:10.7573/dic.212290Cleveland Clinic.What are the side effects of antidepressant medications?Additional ReadingKima T, Xua C, Amsterdam J.Relative effectiveness of tricyclic antidepressant versus monoamine oxidase inhibitor monotherapy for treatment-resistant depression.Journal of Affective Disorders.2019;250:199-203.doi:10.1016/j.jad.2019.03.028

4 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Ramachandraih CT, Subramanyam N, Bar KJ, Baker G, Yeragani VK.Antidepressants: From MAOIs to SSRIs and more.Indian J Psychiatry. 2011;53(2):180-2. doi:10.4103/0019-5545.82567Harvard Health Publishing.What causes depression?Harvard Medical School.Santarsieri D, Schwartz TL.Antidepressant efficacy and side-effect burden: A quick guide for clinicians.Drugs Context. 2015;4:212290. doi:10.7573/dic.212290Cleveland Clinic.What are the side effects of antidepressant medications?Additional ReadingKima T, Xua C, Amsterdam J.Relative effectiveness of tricyclic antidepressant versus monoamine oxidase inhibitor monotherapy for treatment-resistant depression.Journal of Affective Disorders.2019;250:199-203.doi:10.1016/j.jad.2019.03.028

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Ramachandraih CT, Subramanyam N, Bar KJ, Baker G, Yeragani VK.Antidepressants: From MAOIs to SSRIs and more.Indian J Psychiatry. 2011;53(2):180-2. doi:10.4103/0019-5545.82567Harvard Health Publishing.What causes depression?Harvard Medical School.Santarsieri D, Schwartz TL.Antidepressant efficacy and side-effect burden: A quick guide for clinicians.Drugs Context. 2015;4:212290. doi:10.7573/dic.212290Cleveland Clinic.What are the side effects of antidepressant medications?

Ramachandraih CT, Subramanyam N, Bar KJ, Baker G, Yeragani VK.Antidepressants: From MAOIs to SSRIs and more.Indian J Psychiatry. 2011;53(2):180-2. doi:10.4103/0019-5545.82567

Harvard Health Publishing.What causes depression?Harvard Medical School.

Santarsieri D, Schwartz TL.Antidepressant efficacy and side-effect burden: A quick guide for clinicians.Drugs Context. 2015;4:212290. doi:10.7573/dic.212290

Cleveland Clinic.What are the side effects of antidepressant medications?

Kima T, Xua C, Amsterdam J.Relative effectiveness of tricyclic antidepressant versus monoamine oxidase inhibitor monotherapy for treatment-resistant depression.Journal of Affective Disorders.2019;250:199-203.doi:10.1016/j.jad.2019.03.028

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