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Are Old Antidepressants (MAO Inhibitors) Still Helpful?

Depression is common and disabling. Modern antidepressants are not as effective as many think. Are older MAO inhibitors worth consideration?

It is estimated that depression affects as many as 1 out of 10 Americans. Teenagers and young adults are even more vulnerable, with as many as 17% impacted. There are ongoing questions about the effectiveness of modern antidepressants. These are drugs like fluoxetine (Prozac) and sertraline (Zoloft). Should we reconsider older medications such as MAO inhibitors? What are the pros and cons of such drugs?

Discovering MAO Inhibitors in a TB Ward:

The first antidepressant medications were discovered completely by accident. In the 1950s, doctors discovered that drugs designed to treat tuberculosis had unexpected benefits.

Patients being treated at Sea View Hospital on Staten Island were quite ill. When they received the experimental TB medicine iproniazid, some became surprisingly energized. In their JAMA report (Nov. 8, 1952), the investigators mentioned “mild euphoria” and “sexual stimulation” as side effects.

These observations piqued the interest of other scientists. It was discovered that the TB drug iproniazid was helpful for people who were depressed even if they did not have tuberculosis. At the same time, researchers were unraveling the mechanism of action of MAO inhibitors.

How Do MAO Inhibitors work?

The TB medication blocked an enzyme called MAO (monoamine oxidase). This in turn boosted levels of brain neurotransmitters such as dopamine, serotonin and norepinephrine. Iproniazid raised liver enzyme levels, however, and was ultimately replaced by other MAO inhibitors. These included isocarboxazid (Marplan), phenelzine (Nardil) and tranylcypromine (Parnate).

Doctors prescribed MAOI antidepressants enthusiastically until the late 1980s. That’s when Prozac (fluoxetine) entered the market. This selective serotonin reuptake inhibitor (SSRI) and its chemical cousins preempted the MAO inhibitors.

MAO Inhibitors and Food Interactions:

MAOIs lost favor partly because of the enthusiasm surrounding new antidepressants. It was also because drugs like Marplan, Nardil and Parnate were dangerous when combined with some foods. These antidepressants can interact with cheddar cheese, pepperoni, salami, soy sauce and avocados, to name just a few foods with tyramine.

One classic MAOI story involves involves the cheese effect (Lancet, May 16, 1964):

“On September 3, 1963, a 40-year-old man was put on Parnate (tranylcypromine) for serious depression. A month later, he complained of a slight headache, but ate supper with his family. He consumed beef casserole, cheese, and crackers. The cheese was cheddar, Caerphilly (a Welsh cheese similar to cheddar) and some Danish blue. During the night, he felt much worse. He was dizzy, nauseated, and his headache was unbearable. By morning, he felt well enough to eat breakfast with his family and consumed two or three large slices of cheese. Shortly thereafter he became distressed and incoherent. He started bleeding from his nose, and was agitated, aggressive, and confused. By the time he got to the hospital, he was incoherent, his temperature was 104.5° F, and his pulse and blood pressure were elevated. He died at 8:30 P.M. On autopsy, his brain was found to be swollen with intense vascular congestion. The physicians concluded that it was the combination of the cheese and his medicine that killed him.”

Caerphilly and other aged cheeses contain tyramine. In the presence of MAO inhibitors, tyramine can push blood pressure to life-threatening levels. There are also other medications that can interact with these antidepressants.

Should MAO Inhibitors Be Prescribed?

It’s not surprising that this class of antidepressants fell into disfavor. Some psychiatrists are now reporting, however, that these drugs can be helpful when newer antidepressants are ineffective or stop working. We have heard from readers who report that MAO inhibitors can be surprisingly beneficial.

Here are two examples:

“I have tried many different medications for anxiety and depression, and Nardil is by far the most effective. However, the side effects were unbearable. I gained 40 pounds in just six weeks. Instead, my doctor switched me to Parnate. It works nearly as well for me without the unpleasant side effects.

“These are both old drugs but no psychiatrist would prescribe either one until I was referred to a university program for treatment-resistant depression. I am disappointed that psychiatrists are so reluctant to prescribe these MAO inhibitor medicines. I do need to be careful not to overdo on tyramine-containing foods. However, I worry more about interactions with other drugs. My doctor had to lower my doses of blood pressure medicines. Perhaps you could help spread the word about how valuable these MAOI medicines can be for severe depression.”

Another reader wrote:

“When I was 37, my psychiatrist prescribed Nardil, a MAO inhibitor. I’ve been on it for 40 years. It’s an old drug that is rarely used these days. This antidepressant transformed my life.”

The Pros and Cons of MAO Inhibitor Antidepressants:

For some people, a MAO inhibitor may be extremely helpful against depression. They work differently from tricyclic antidepressants such as amitriptyline (Elavil), desipramine (Norpramin) or imipramine (Tofranil). They are also quite different from more modern antidepressants such as citalopram (Celexa), desvenlafaxine (Pristiq), duloxetine (Cymbalta), escitalopram (Lexapro), sertraline (Zoloft) and venlafaxine (Effexor).

MAO inhibitor drugs require extra caution because of interactions and side effects. If physicians and pharmacists are vigilant, though, they can help protect patients against such dangers. That means providing a list of all foods and other medications that might interact. It also requires thoughtful counseling about adverse reactions. All antidepressants carry risks. But so does major depression. You may find our eGuide to Dealing with Depression of value. It can be found under the Health eGuides tab.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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