MAO inhibitors: the forgotten antidepressant that saved my life

A science writer recounts his longtime struggle with panic disorder, which led to an unusual solution

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I had my first panic attack in 1972 when I was 20 years old and a student at the University of London. It took me 10 years to be diagnosed and another 15 years to find a medication that would help me. The medication is Nardil (phenelzine) and it is a monoamine oxidase inhibitor or MAOI, the oldest antidepressant.

The drug is rarely used anymore and most people, including young doctors and medical students, don't know much about it. If you've heard the term MAOI, it is probably in conjunction with an ad for a drug such as Prozac (fluoxetine) and the warning "don't take this drug if you are on an MAO inhibitor."

Nardil has saved me from a life of fear, shame, loneliness and isolation. It allows me to write, have relationships, play tennis and travel – things I could not do when my panic attacks were at their worst.

Hardly anyone takes MAO inhibitors anymore because they have dietary restrictions and interactions with other drugs and because of the popularity of selective serotonin reuptake inhibitors, or SSRIs, antidepressants which can also be effective treatments for panic disorder. This class of drugs includes Prozac (fluoxetine) Zoloft (sertraline) Lexapro (escitalopram) and Paxil (paroxetine). However, Prozac, the first SSRI, was not approved for use until 1987 by the US Food and Drug Administration (FDA). So even if I had been diagnosed properly in 1972, these drugs were not an option.

I also had the misfortune of developing panic attacks before panic disorder was recognized as a distinct illness. In the late 1970s, researchers had seen enough cases like mine to realize they were dealing with an illness that did not fit the pattern of traditional anxiety. People had attacks "out of the blue," unrelated to stresses in their lives, to the effects of a drug, or to another medical condition. And the attacks could not be treated through traditional medicines for anxiety or talk therapy. Panic disorder was first included in the American Psychatric Association's Diagnostic and Statistical Manual in 1980. But it took several years for the medical establishment to catch up with this new illness.

“Help me, I’m dying!”

My first panic attack occurred on a beautiful Sunday morning in the spring. I woke up with an impending sense of doom. The feeling was very powerful, yet I was in no pain and was not disoriented. At first I thought I was dreaming, but the feeling that I was going to die did not go away. My heart was racing. I felt as If I couldn't breathe.

I shouted out to my roommate, “Help me, help me, I am dying!”

He thought I was kidding. “Really? What are you dying of?”

I had no answer. “I don’t know what’s happening to me.”

I still have no explanation of why it happened that particular day. Except for worrying about getting good grades in high school and college, I was not a particularly anxious person. And I was never depressed. In fact, I had just come back from traveling in France, Italy and Switzerland during a break between semesters and had a wonderful time.

What is panic disorder?

There is a lot known about panic disorder know. The Anxiety and Depression Association of America estimates that about 6 million Americans experience panic disorder annually, and women are twice as likely as men to have it. Unlike phobias, they are not linked to a specific fear, such as flying or being in an elevator, but occur without warning, often when one is feeling relaxed and even during sleep.

According to the National Institute of Mental Health, the symptoms include:

  • Sudden and repeated attacks of fear
  • A feeling of being out of control during a panic attack
  • An intense worry about when the next attack will happen
  • A fear or avoidance of places where panic attacks have occurred in the past
  • Physical symptoms during an attack, such as a pounding or racing heart, sweating, breathing problems, weakness or dizziness, feeling hot or a cold chill, tingly or numb hands, chest pain, or stomach pain.

My roommate suggested we go for a walk, and over the course of the day, I felt better. But the next day I woke up again in a panic again. I went to the university clinic and told a doctor what was going on. The doctor examined me but found nothing wrong. I told her, "I'm scared I'm going to die," but she assured me that there was nothing wrong and referred me to the school's psychiatrist. He prescribed Valium (diazepam) to ease my nerves. He advised returning home to the United States as soon as school was over, ascribing my anxiety to being homesick.

Unfortunately going home was not a cure. I went to an internist who told me that he couldn't find anything wrong either and referred me to a neurologist because sudden changes in behavior were often due to a brain tumor. Well, luckily, I didn't have a brain tumor or epilepsy, nor did I have hypoglycemia (low blood sugar), which was a popular diagnosis in the 1970s.

What I did have was an increasingly thick medical file but no diagnosis. Valium helped a bit, but not much. I had attacks daily, up to five in one day, and even less confidence than before.

The attacks often came during those rare moments when I felt relaxed – when I was daydreaming, for instance, or taking a walk. The worst attacks struck at the end of dreamless naps. I woke up completely drenched, disoriented, my heart pounding. Often I felt detached from myself, as if it was happening to someone else, not me. Objects looked strange, even unreal. I felt no sense of the past or future. I was totally in the moment, except instead of feeling one with the universe, I felt terribly alone and afraid.

Although panic attacks feel like they are lasting forever, they don't. They last about 10 minutes, although one is shaken up a lot longer. So I was able to return to Johns Hopkins University and finish my senior year there, and then I went on to complete a Master of Arts degree in the university’s Writing Seminars program. It was during this time that I started to write plays. I wrote comedies which were well received. But my life during this time was not fun. I attended classes, saw a shrink and went to the school clinic when I had an attack. I didn't date and I didn't have many friends. I stayed in my apartment because I didn't want anyone to see me having a panic attack because those who did were frightened by them and ran.

After finishing my master's, I went back home to Long Island to live with my parents. I stumbled into a career in public relations, working for the county's Department of Drug and Alcohol Addiction. Many of the people I worked with were ex-addicts, ex-alcoholics. I felt right at home, another impaired person. And although I did have occasional attacks on the job, people were generally accepting.

In 1977, five years after my first attack, a strange thing happened. The severity of my attacks dramatically declined. I was able to go into New York City to begin dating again, to start enjoying life a little more. I rediscovered a sense of play. When your every thought is of dying, you lose your sense of humor and enjoyment over little things — the pleasures of having an ice cream cone, enjoying a sunny day or reading a book. Though my severe attacks disappeared, I continued to have minor attacks, especially when I took a nap. Although I dated during this time and enjoyed life, I was ever vigilant waiting for the first signs of anxiety that would signal the return of my illness.

In June 1982, the attacks returned with a vengeance. This was a real problem as I was getting married that September. Over the years, I had learned to hide the effects of my attacks quite well, so for a long time my former wife did not know how bad they were. By coincidence, her brother was a psychiatrist studying panic disorder. I spoke to him about what was happening to me.

My now ex-brother-in-law was the first medical specialist to give a name to my illness – panic disorder – and he showed me a book listing all its symptoms: the very same symptoms I'd been experiencing all these years: fear of dying, shortness of breath, dizziness, etc. Best yet, he told me there were ways to treat panic disorder. He referred me to a colleague, Dr. Roger Brunswick, who confirmed the diagnosis and began treating me.

Dr. Brunswick offered me a choice; antidepressant medication or coming twice a week for therapy. I took the latter. I did not like the choices of drugs and I wanted to give therapy a chance. For many people, psychotherapy, especially cognitive behavioral therapy, helps with depression and panic disorder. Unfortunately it didn't help me. My panic attacks were severe and biologically based.

In 1982, the drug of choice to treat panic attacks was Tofranil (imipramine), a tricyclic antidepressant that was first used by scientists in 1955 in Switzerland as a treatment for schizophrenia. It didn't help them, but it did lift their mood. A Swiss psychiatrist, Ronald Kuhn, gave imipramine to several hundred severely depressed patients and reported his results in 1958. His findings were confirmed by other researchers, and Tofranil became available in the United States in 1960.

The symptoms of depression are very different from the symptoms of panic disorder. So they were not prescribed for people with anxiety disorders. Donald F. Klein, a Research Psychiatrist at the Nathan S Kline Institute at Columbia University, was told by his patients who had depression that their anxiety symptoms disappeared when given Tofranil. Dr. Klein saw that Tofranil could block panic attacks and that antidepressant drugs were a better treatment for people with panic disorder than anti-anxiety agents such as Valium.

Unfortunately, Tofranil didn't work for me. I found it difficult to tolerate its side effects, which include dry mouth, blurry vision, constipation and urinary retention. There was only one other class of drugs left to try: the MAO inhibitors — the drugs of last resort for treating depression or panic disorder.

A “happy accident”

MAOIs have an interesting history. They were discovered by physicians at Sea View Hospital on Staten Island, who were testing drugs for tuberculosis in the 1950s. Besides fresh air and rest, there was little doctors could do at the time to treat tuberculosis. The two drugs they tested were isoniazid and iproniazid. At the time, no one would have dreamed that they would be the basis for the first antidepressant medication.

Monoamine oxidase is an enzyme involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain. MAOIs work by inhibiting this enzyme and thus maintaining these brain chemicals, which are thought to improve mood by boosting communication among brain cells. This is in contrast to SSRIs, such as Prozac and Zoloft, which only work on serotonin. (Source: <a target="_blank" href="">Mayo Clinic</a>. Image: Public Domain via Wikiemedia Commons)

Of the two, isoniazid proved the most effective for tuberculosis. It is still used today. Although iproniazid had some positive results for tuberculosis, it was not as good as isoniazid. But it had an unusual effect; it made people happy. One of the doctors noted that patients who took iproniazid had greater vitality, participated more in social activities and expressed a desire to leave the hospital and go home despite the fact they were dying. A photograph in the Associated Press from 1953 showed patients at Sea View Hospital dancing. The caption read "A few months ago, the only sound here was the sound of victims of tuberculosis, coughing up their lives.”

"Based on the observations of one clever doctor, the use of medication to treat depression began," said Dr. Patrick J. McGrath, Co-Director of the Depression Evaluation Service at New York State Psychiatric Institute and Professor of Clinical Psychiatry in the College of Physicians and Surgeons of Columbia University. "It was a serendipitous discovery."

In fact, many of the drugs used today are "happy accidents." Viagra was first studied as a drug to treat angina. It didn't work for that, but one of the investigators noted it had an unusual side effect: it gave the males in the study erections. The rest is history.

The downside of MAOIs

Hardly anyone prescribes MAOIs anymore. Your general internist won't offer it to you. It’s only prescribed by specialists in psychiatric drugs to patients who have failed on every treatment. MAOIs fell out of favor because of the "cheese effect," which caused life-threatening headaches in people on MAOIs who ate products that contained cheese. The connection was discovered by a British pharmacist who noticed that his wife, who was taking an MAOI, had a severe headache whenever she had a meal with cheese.

Cheese contains tyramine, a compound found in many foods that has been linked to headaches in migraine sufferers. For people on an MAOI, eating products with tyramine can cause a rapid and dangerous rise in high blood pressure that can result in a fatal stroke. Aged cheeses, such as cheddar, are especially high in tyramine. People who take MAOIs are advised not to eat aged cheese (cottage, cream cheese and farmer's cheese are allowed), fava or broad beans, sauerkraut, pickles, olives, soy sauce, teriyaki sauce, tap beer, vermouth or red wine and to limit their intake of chocolate, caffeinated beverages, yogurt, sour cream, avocados and raspberries.

MAOIs also interact with both prescription and over-the-counter medications. You can't take an antihistamine such as Sudafed and have to remind your dentist not to use Novocain to avoid an interaction that could cause a hypertensive crisis.

The MAOIs available today include Nardil (phenlzine) and Parnate (tranylcypromine). "They have been around for decades. They are just as effective as Tofranil or Prozac," Dr. McGrath notes. "In terms of treating depression and panic disorder, we have made no progress in efficacy since the 1960s."

In 2006, a MAOI patch called Emsam TD (selegiline transdermal) was approved. Patient wear a patch that administers selegiline, a drug used to treat Parkinson's disease, through the skin and into the bloodstream. Patients on low doses of Emsam do not have to follow any dietary restrictions. However, at higher doses, the FDA recommends patients follow the MAOI dietary restrictions.

Despite its favorable side effect profile and efficacy, Emsam is rarely used. "Most patients and psychiatrists are not used to patches. Emsam is also expensive ($450 a month), and most insurance companies do not cover it," Dr. McGrath said. "It's a shame because they are effective and well-tolerated by patients, with few side effects."

Giving SSRIs a try

Today SSRIs are still the first line of treatment for patients with depression and panic disorder. Although they have side effects, including delayed ejaculation in men and difficulty achieving orgasms in women, they only need to be taken once a day and can be prescribed by internists.

A few years Prozac was approved in 1987, I decided to give it a try. I missed eating pizza. In order to go on Prozac, I had to stop taking Nardil and be off it for two weeks. But Prozac was too stimulating for me. I could not go above 2 mg, and the standard dose was 20 mg. When Zoloft was approved, I tried that. But it gave me panic attacks and I couldn't sleep. This was a huge disappointment to me as I was working at Pfizer at the time, which marketed Zoloft, and knew that it was effective as Prozac but had a low agitation rate of only 2 percent. Unfortunately I was among the 2 percent and advised never to take an SSRI again. So I went back on Nardil, and that's what I take today along with low doses of Xanax (alprazolam), an anti-anxiety medication.

Dr. Brunswick said I am his only patient on an MAOI. Although he has offered it to patients who failed on other medications he told me they are reluctant to try it because of the dietary restrictions and the drug interactions that can occur.

A case for MAOIs

Despite the downsides of MAO inhibitors, I have made my peace with it. I would rather take Nardil then have panic attacks. I wear a MedicAlert tag that says I take MAO inhibitors and I carry around a blood pressure medication in case I accidentally eat a food or take a medication that interacts with Nardil. Since I started to take Nardil, I have never had a problem or had to raise my dose. In fact, I have lowered my dose substantially over the years. I believe for people who don't respond to other medications for depression and panic attacks, it's a good alternative.

Both Drs. McGrath and Brunswick say MAOIs should be used more.

"I have had patients with depression who have been given electroconvulsive therapy (ECT) and it did not make them better,” Dr. McGrath said. "But they responded well to MAOIs. I wish more doctors considered trying an MAOI first before going to ECT."

Dr. Brunswick notes that with patients whose symptoms are not totally relieved by Prozac or Zoloft, psychiatrists often add antipsyhotic drugs such as Seroquel (quetiapine) to their medication regimen, but these can cause extreme weight gain and metabolic disorders such as diabetes. "Everyone is looking at alternative treatments for depression and other mental illnesses, including transcranial magnetic stimulation and ketamine,” he said. “No one knows how well these new treatments will work, but we do know that MAOIs work, and they are as effective as any existing treatment for both depression and panic disorder."

Elsevier Connect Contributor

David LevineDavid Levine (@Dlloydlevine) is co-chairman of Science Writers in New York (SWINY) and a member the National Association of Science Writers (NASW). He served as director of media relations at the American Cancer Society and as senior director of communications at the NYC Health and Hospitals Corp. He has written for Scientific American, the Los Angeles Times, The New York Times, More magazine, and Good Housekeeping, and was a contributing editor at Physician's Weekly for 10 years. He has a BA and MA from The Johns Hopkins University.

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