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  • MAOI Vs. SSRI | Differences, Similarities, & How They Work

    Woman Looking At SSRI Pill-MAOI Vs. SSRI | Differences, Similarities, & How They Work

    Monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitors (SSRIs) are both medications used to treat depression but they have quite a few differences, including how they work, how often they are prescribed, and what drugs they interact with.

    Differences Between MAOIs & SSRIs

    MAOIs and SSRIs are different in a variety of ways. While they may treat similar disorders and are both antidepressant medications, they are very different drugs.

    Mechanism Of Action

    MAOIs work by reducing the activity of the MAO enzyme that normally degrades and breaks down the neurotransmitters serotonin, norepinephrine, and dopamine. 

    MAOIs reduce that breakdown and lead to a higher level of those neurotransmitters in the brain. This can increase mood and decrease symptoms of depression, anxiety, and panic.

    Some of the most common MAOIs include:

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

    SSRIs work by stopping the reuptake of serotonin in the brain. This allows for the increase of serotonin and improves mood which can help ease the symptoms of major depressive disorder and anxiety disorder.

    Some examples of SSRIs include:


    MAOIs and SSRIs also differ in how often they are prescribed. SSRIs are prescribed more often than MAOIs. This is mainly because MAOIs have more negative reactions to drugs and certain foods and that can be an issue for many people.

    Drug Interactions

    The drugs (and foods) that interact with MAOIs and SSRIs also differ quite a bit. MAOIs negatively interact with quite a few more drugs than SSRIs do.

    MAOIs should not be taken with the following substances:

    • other antidepressants including trazodone, paroxetine, fluoxetine, amitriptyline, nortriptyline, and bupropion
    • serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine (Cymbalta) and venlafaxine (Effexor)
    • pain medications such as methadone, tramadol, and meperidine
    • dextromethorphan
    • St. John’s Wort
    • mirtazapine
    • seizure medications like carbamazepine (Tegretol) and oxcarbazepine (Trileptal)
    • pseudoephedrine
    • phenylephrine
    • ephedrine
    • phenylpropanolamine

    MAOIs also require quite a few dietary restrictions because of how the drug reacts to the following foods:

    • aged cheese
    • wine
    • cured meat
    • sauerkraut
    • fermented soy products, including miso, soy sauce, or tofu
    • raisins, dates, or other dried fruits
    • nuts
    • other foods or drinks with tyramine

    SSRIs should not be taken with the following substances:

    • MAO inhibitors
    • tricyclic antidepressants (TCAs) like amitriptyline (Elavil), clomipramine (Anafranil), and imipramine (Tofranil)
    • sumatriptan (Imitrex)
    • linezolid (Zyvox)
    • St John’s Wort
    • tramadol (Ultram)
    • meperidine (Demerol)
    • nonsteroidal anti-inflammatory drugs (NSAIDs)
    • warfarin (Coumadin and Jantoven)

    Onset Of Effects For Depression

    SSRIs become fully effective at a slower rate than MAOIs. SSRIs can become effective in 1-4 weeks with a positive mood change fully setting in after 4-6 weeks.

    MAOIs usually take between 1 and 6 weeks to work but the average timeframe for them to be fully effective is only 2-4 weeks.

    Average Dosage

    The common dosage of each drug also differs. The most common dose for MAOIs is between 0.5 mg and 1 mg daily. 

    For SSRIs, the common dosage is between 10 mg and 20 mg daily but for some SSRIs, the average dose can be from 20-80 mg.

    Similarities Between MAOIs & SSRIs

    While these two types of antidepressants are quite different, they do have a few similarities.

    Approved Uses

    One of the biggest similarities between MAOIs and SSRIs is what they treat. They are both approved to treat depression. 

    But that’s not to say that’s the only thing they treat. SSRIs also treat anxiety and panic disorder while MAOIs can improve some of the symptoms of Parkinson’s disease.

    Side Effects

    The side effects of the two drugs are also quite similar. There are a few differences, but the most common side effects are the same.

    The side effects these two antidepressant medications share can include:

    • diarrhea
    • drowsiness
    • nausea
    • vomiting
    • dry mouth
    • headache
    • agitation
    • sexual dysfunction
    • weight gain

    MAOIs can also lead to confusion, dizziness, high or low blood pressure, and weakness. SSRIs can also bring on insomnia and upset stomach.

    Coming Off SSRIs & MAOIs

    MAOIs and SSRIs are not addictive and are often used in addiction treatment as a way to treat co-occurring depression or anxiety disorder.

    But while they aren’t addictive and are not classified as controlled substances by the FDA, people can become physically dependent on these antidepressant drugs, which may require tapering (taking a lower and lower dose over time) or a detox program

    If you or a loved one are struggling with any kind of addiction, please call our helpline today.

    Written by Ark Behavioral Health Editorial Team
    ©2022 Ark National Holdings, LLC. | All Rights Reserved.
    This page does not provide medical advice.
    Article Sources

    Indian Journal of Psychiatry - Antidepressants: From MAOIs to SSRIs and more
    National Library of Medicine: MedlinePlus - MedlinePlus — Antidepressants
    National Library of Medicine: StatPearls - Monoamine Oxidase Inhibitors (MAOI)
    National Library of Medicine: StatPearls - Selective Serotonin Reuptake Inhibitor

    Medically Reviewed by
    Kimberly Langdon M.D.
    on November 29, 2022
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