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Antidepressants are the most prescribed therapy for depression. The exact mechanism of action of antidepressants is unknown. The prevailing theory is that antidepressants increase the concentration of one or more brain chemicals (neurotransmitters) that nerves in the brain use to communicate with one another. The neurotransmitters affected by antidepressants are norepinephrine, serotonin, and dopamine. The different classes of antidepressants differ in the neurotransmitters they affect. This determines some of their side effects and potential drug interactions. All available antidepressants are effective, and for most cases of depression there is no good evidence that any antidepressant is more effective than another. Side effects and potential drug interactions are major factors that influence selection of antidepressants and compliance with therapy. This article discusses side effects and potential drug interactions of the major antidepressant classes.

What are monoamine oxidase inhibitors (MAOIs)?

MAOIs were the first class of antidepressants to be developed. They fell out of favor because of concerns about interactions with certain foods and numerous drug interactions. MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine oxidase. Monoamine oxidase breaks down norepinephrine, serotonin, and dopamine. When monoamine oxidase is inhibited, norepinephrine, serotonin, and dopamine are not broken down, increasing the concentration of all three neurotransmitters in the brain.
Monoamine oxidase also breaks down tyramine, a chemical present in aged cheese, wines, and other aged foods. Since MAOIs inhibit monoamine oxidase they decrease the break down of tyramine from ingested food, increasing the level of tyramine in the body. Excessive tyramine can elevate blood pressure and cause a hypertensive crisis. Patients treated with MAOIs should adhere to recommended dietary modifications that reduce the intake of tyramine. Interestingly, the 6 mg/24 hour dose of selegiline transdermal system (EMSAM) does not require dietary restrictions because at this dose EMSAM does not substantially inhibit tyramine. Higher selegiline transdermal system (EMSAM) doses require dietary restrictions.
MAOIs are associated with several significant drug interactions; limiting their usefulness in patients who are treated with multiple drugs. MAOIs interact with drugs that increase serotonin activity in the brain, increase norepinephrine, constrict blood vessels, or inhibit monoamine oxidase. Drugs that increase serotonin in the brain include:

  • selective serotonin reuptake inhibitors, for example, fluoxetine (Prozac) and sertraline (Zoloft),
  • serotonin norepinephrine reuptake inhibitors, for example, venlafaxine (Effexor) and desvenlafaxine (Pristiq),
  • tricyclic antidepressants, for example, imipramine (Tofranil),
  • St. John’s Wort,
  • meperidine,
  • tramadol (Ultram),
  • methadone,
  • propoxyphene (Darvon), and
  • other MAOIs, for example, tranylcypromine (Parnate), phenelzine (Nardil).

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