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SSRIs vs. MAOIs for Treating Depression

Depression is a common mood disorder. Without appropriate treatment, depression can have significant negative effects on a person’s life or prompt the person to consume intoxicating substances to self-medicate depressive symptoms. Fortunately, there are many antidepressants available to treat people with all types of depression. When combined with therapy or counseling, antidepressants are an effective way to regulate mood and improve symptoms.

All antidepressants interact with neurotransmitters, but they work with different ones and in different ways. SSRIs and MAOIs are two prominent types of antidepressant medications; they work differently and can lead to different effects.

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Selective Serotonin Reuptake Inhibitor Antidepressants

SSRIs (selective serotonin reuptake inhibitors) are currently the most type of popular antidepressant. These medications are prescribed primarily to treat forms of depression, but they can be prescribed for some forms of anxiety and other mood disorders, although this usually involves off-label use. They are considered safe and very effective, with little likelihood of abuse.

What Are They?

An SSRI seems to affect only serotonin, which is one of the most important neurotransmitters involved in regulating mood. Other antidepressants typically affect more neurotransmitters, but because SSRIs focus on just one neurotransmitter, they are more predictable, with fewer side effects. These medications prevent the rapid reuptake of serotonin by neurons, so the neurotransmitter stays in synapses for longer, allowing neurons to communicate more effectively. This helps to elevate mood.

Monoamine Oxidase Inhibitor Antidepressants

Although SSRIs are the current frontline treatment for depression, MAOIs (monoamine oxidase inhibitors) were the first antidepressants developed. They are typically more potent than SSRIs because they affect more neurotransmitters, and they can cause more side effects. However, they are still prescribed to people who do not experience benefits from other antidepressants.

What Are They?

Woman looking through a foggy window An MAOI inhibits the effectiveness of monoamine oxidase, a chemical in the brain that removes neurotransmitters from the brain. People who suffer from depression, and sometimes anxiety, do not have enough neurotransmitters present to keep neurons in contact, which can cause low mood. When monoamine oxidase does not remove neurotransmitters, mood can be lifted because neurons are better able to communicate.

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How Long Do They Take to Be Effective

Wooden blocks that spell out wellnessSSRIsSSRIs become fully effective in 1-4 weeks, when the medication has reached a saturation level in the body, and the brain has a consistent amount accessible. Positive changes to mood fully set in after 4-6 weeks.


Similar to SSRIs, MAOIs can take 1-6 weeks to work. The average timeframe is 2-4 weeks for the medication to become fully effective.

Side Effects

Happy family walking on grassSSRIsAlthough SSRIs cause fewer side effects than other antidepressants, there are still some side effects that can develop. They include:

  • Nausea
  • Diarrhea
  • Drowsiness
  • Sleepiness
  • Insomnia
  • Dry mouth
  • Restless or agitation
  • Headache
  • Blurry vision
  • Joint pain or aches


MAOIs cause more side effects than SSRIs. Side effects include:

  • Nausea, diarrhea, or constipation
  • Dry mouth
  • Drowsiness
  • Headache
  • Dizziness or lightheadedness
  • Insomnia
  • Muscle twitches or twinges, which are involuntary
  • Low blood pressure
  • Weight gain
  • Muscle cramps
  • Tingling or pricking sensations on the skin


SSRIsSSRIs are less effective when alcohol is present in the body. They may also interact with other antidepressants, especially MAOIs or tricyclic antidepressants, if these drugs have not fully left the body when a person is changing medications. Other medications, like benzodiazepines or sleep aids, may also interact with the drug, and some herbal supplements, like St. John’s wort, can reduce the effectiveness of SSRIs.

MAOIsLike all prescription medications, SSRIs should not be combined with other medications, and they should not be mixed with alcohol or illicit substances. Other than that, SSRIs have few limitations; MAOIs, on the other hand, require dietary restrictions to be effective and safe. Some of these restrictions include:

  • Aged cheese
  • 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