How Do SSRIs Compare to MAOIs?

A Comparison Between Two Types of Antidepressants

Assorted pills falling into man's head
Getty Images/Gary Waters

Monoamine oxidase inhibitors (MAOIs) are considered to be perhaps the most effective antidepressant agents in the psychiatrist's medical arsenal. They work by inhibiting the enzyme monoamine oxidase in the brain. 

Selective serotonin reuptake inhibitors (SSRIs), on the other hand, are used to treat depression in addition to many anxiety-related illnesses, including panic disorder (PD).  They work by inhibiting the reuptake of serotonin in the brain, causing an increase of serotonin.

How Do MAOIs Work?

It is believed that the brain contains several hundred different types of chemical messengers (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 occurrences.

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

The benefits of these increases are improved mood and an anti-panic effect.

How Do SSRIs Work?

Serotonin is a neurotransmitter that is important in modulating a variety of body functions and feelings, including our mood.

 Low serotonin levels have been linked to depression and anxiety. 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, which is a small space between brain cells.

If MAOIs Are More Effective, Why Are SSRIs More Often Prescribed?

SSRIs are generally the first choice for treatment of depression because, beyond just being effective, they have fewer problems with side effects.

Because of dietary restrictions and concerns over hypertensive reactions, MAOIs are often used only after other agents have failed. 

Other common side effects of MAOIs include:

  • decreased sleep/insomnia
  • nausea
  • diarrhea
  • dry mouth
  • hypertension (high blood pressure)
  • hypotension (low blood pressure)
  • dizziness
  • weight gain
  • edema (water retention)
  • sexual dysfunction
  • muscle spasms
  • weakness
  • confusion

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

  • nausea
  • sexual dysfunction, including reduced desire or orgasm difficulties
  • headache
  • stomach upset
  • nervousness
  • weight gain
  • drowsiness
  • insomnia

Some of these side effects will be eliminated after your body adjusts to the medication. If they don’t and are bothersome, your doctor may try another SSRI. Although SSRIs function by a similar mode of action, they are different.

Certain side effects with one SSRI may not be a problem with another.

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

More About Antidepressants

Monoamine Oxidase Inhibitors (MAOIs). MAOIs are a class of antidepressants that were developed in the 1950s. They are effective in treating depression, panic disorder, and other anxiety disorders. Although they are generally as effective as SSRIs and tricyclic antidepressants (TCAs), they are used less frequently because of necessary dietary precautions and risks of adverse reactions when mixed with certain drugs.

Monoamine Oxidase Inhibitors (MAOIs). Further information on dietary restrictions, drug interactions, and other side effects.

Selective Serotonin Reuptake Inhibitors (SSRIs). Further information on the antidepressant / anti-anxiety medication.

Continue Reading