Antidepressants (Depression Medications)

  • Pharmacy Author:
    Omudhome Ogbru, PharmD

    Dr. Ogbru received his Doctorate in Pharmacy from the University of the Pacific School of Pharmacy in 1995. He completed a Pharmacy Practice Residency at the University of Arizona/University Medical Center in 1996. He was a Professor of Pharmacy Practice and a Regional Clerkship Coordinator for the University of the Pacific School of Pharmacy from 1996-99.

  • Medical and Pharmacy Editor: Jay W. Marks, MD
    Jay W. Marks, MD

    Jay W. Marks, MD

    Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.

What are examples and side effects of monoamine oxidase inhibitor (MAOI) medications?

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 breakdown 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, and MAO inhibitor) does not require dietary restrictions because at this dose EMSAM does not substantially inhibit tyramine. Higher selegiline transdermal system (EMSAM) doses require dietary restrictions.

What are the side effects of MAOIs?

  • MAOIs are associated with headache and insomnia which may decrease with continued use. Headaches may require treatment with nonsteroidal anti-inflammatory drugs (for example, ibuprofen), and insomnia may require treatment with benzodiazepines (for example, diazepam [Valium]) or other drugs for insomnia.
  • Because MAOIs stimulate the nervous system, they may be beneficial for depressed patients who over sleep or are fatigued.
  • Hypertension may occur during therapy with MAOIs. Therefore, blood pressure should be monitored periodically during MAOI treatment. Hypertensive crisis may occur when MAOIs are combined with tyramine containing foods or drugs that constrict blood vessels.

Symptoms of hypertensive crises include

Other side effects and adverse events of MAOIs include:

  • Bleeding in the brain also may occur. Patients should be aware of signs and symptoms of hypertensive crisis and should seek immediate medical treatment if these signs or symptoms are present. Hypertensive crisis may be managed with nitroprusside (Nitropress), labetalol (Normodyne, Trandate), or phentolamine.
  • Orthostatic hypotension (feeling faint upon standing due to decreased blood flow to the brain) also occurs. Patients should rise slowly from a sitting position to reduce the effect of orthostatic hypotension. Orthostatic hypotension may be treated with steroids.
  • Some patients may experience peripheral edema (swelling of the lower legs and ankles) which can be improved by wearing support stockings.
  • MAOIs also are associated with sexual side effects such as decreased sexual drive, erectile dysfunction, difficulty ejaculating or reaching orgasm. Sexual side effects may diminish with time or a reduction in dose.

What drug interactions may occur with MAOIs?

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), paroxetine (Paxil, Paxil CR, Pexeva), fluvoxamine (Luvox), and sertraline (Zoloft)
  • serotonin norepinephrine reuptake inhibitors, for example, venlafaxine (Effexor) and desvenlafaxine (Pristiq)
  • tricyclic antidepressants, for example, imipramine (Tofranil), desipramine (Norpramin), amitriptyline
  • St. John's Wort
  • meperidine
  • tramadol (Ultram)
  • methadone
  • fentanyl (Sublimaze, Duragesic)
  • propoxyphene (Darvon)
  • other MAOIs, for example, tranylcypromine (Parnate), phenelzine (Nardil), isocarboxazid (Marplan)

Combining MAOIs with drugs that increase serotonin may cause

  • confusion,
  • tremor,
  • hyperactivity,
  • coma, and
  • death.

Combining MAOIs with norepinephrine or drugs that constrict blood vessels (epinephrine, amphetamines, pseudoephedrine, ephedrine, phenylpropanolamine, and phenylephrine) may increase blood pressure to dangerous levels.

The antibiotic linezolid (Zyvox) and intravenous methylene blue should not be combined with MAOIs because they also inhibit monoamine oxidase.

MAOIs should be discontinued at least two weeks before administration of drugs that interact with MAOIs. Drugs that interact with MAOIs should be discontinued at least 1-2 weeks before administration of MAOIs. Because the effect of fluoxetine lasts for several weeks after discontinuation, MAOIs should not be initiated for at least five weeks after stopping fluoxetine.

What are examples of MAOIs?

  • phenelzine (Nardil)
  • tranylcypromine (Parnate)
  • isocarboxazid (Marplan)
  • selegiline transdermal system (EMSAM)

What other antidepressants are available?

Reference: FDA Prescribing Information

Medically Reviewed by a Doctor on 10/14/2016

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