One morning in the fall of 2010, my husband got out of bed and crashed to the floor, unconscious. As Eddie came to, he complained of a painful pressure in his chest. In the hospital, his condition worsened. Every test confirmed what I as a nurse already knew, that his heart was shutting down. A day later he died.

As I mourned Eddie’s death, I worried that it would plunge me deeper into an episode of depression that had begun earlier that spring after a succession of harrowing family crises.

My mother had sporadically suffered from debilitating depression, and the Black Dog hounded me as well. As a longtime health care provider, I had developed a toolbox of remedies to manage my symptoms and turn around my dark moods. I took Wellbutrin, an antidepressant, which helped for several years. I applied myself diligently to exercise, meditation, and dance. I soaked up extra sun and sleep.

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As my mood darkened during the summer before Eddie’s death, I pulled out all the well-sharpened tools. They didn’t work. “The lights are going out,” I told him, by which I meant my emotional vitality was fading.

I wondered whether the shock of my husband’s sudden death would reset the wiring of my mangled, 66-year-old brain. It did not. Within a couple of months, the depression emerged from my grief in full force, and from then on indisputably ruled the roost. I experienced an incapacitating weariness, sleeping as many as 18 hours a day. While I never crafted a suicide plan, a longing for death intruded itself into every corner of my waking mind. I wandered the streets, hoping to be hit by a truck. No person, no activity, no event penetrated the darkness. This episode of major depression, by far my worst, lasted for three years.

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During that time, I was treated by a succession of psychiatrists and prescribed 10 or more different medicines in the various combinations and augmentations that the guidelines advise. I was hospitalized twice. I underwent a 12-session course of electroconvulsive therapy (ECT), which made a small difference, as if parking lights were dimly shining through the fog. I stopped thinking about death all the time, but instead worried about memory loss and the likelihood of relapse. The logistics of keeping up the ECT treatments — the transportation and the necessary caregiving of friends — became impossible to maintain.

I eventually bonded with an older Austrian psychiatrist. While under her care, I secretly tapered myself off my medicines to see what of my original self remained. Little changed, except that I experienced anxiety in addition to my other symptoms.

When I admitted to my psychiatrist that I had made myself drug free, another option emerged. At the proverbial end of the road, where every other class of antidepressant and several other types of psychotropic medication had failed, she started me on tranylcypromine (Parnate). It belongs to the first family of antidepressants, called monoamine oxidase inhibitors (MAOIs), which were discovered in the late 1950s. Parnate was approved in the U.S. for treating depression in 1961.

Though long acknowledged to be highly effective in the management of treatment-resistant depression, MAOIs have been linked to two potentially serious risks: serotonin syndrome and hypertensive crisis. Later generations of allegedly better antidepressants replaced MAOIs. They are now seen as “drugs of last resort,” and have all but disappeared from the list of drugs that doctors prescribe for depression.

I accepted the Parnate prescription with the same hopelessness with which I had accepted the others. I abided by the complex food restriction lists, though I immediately noticed major discrepancies in them.

About 10 days later, sitting in my parked car, I heard on the radio the legendary jazz saxophonist Ben Webster. A shiver of pleasure invigorated me. Later in the day, I bought bags of fresh food at the market, smiled at a chubby baby, and became overwhelmed by the devotion of a friend. The lights were blinking brightly, and then miraculously they were staying on.

I’ve been well now for four years, in my right mind because of an old, inexpensive, and uncommonly prescribed drug.

I’ve been well now for four years, in my right mind because of an old, inexpensive, and uncommonly prescribed drug. I’ve grown increasingly appalled at how long it took for a clinician to prescribe it and that ECT, a costly and invasive procedure, was prescribed before I was finally offered this single oral medication that gave me such rapid and unequivocal relief.

I have sorted through the notorious risks of MAOIs and determined that they were greatly exaggerated and outdated. An editorial entitled “Much Ado About Nothing” by Dr. Ken Gillman, an Australian neuropharmacologist who is a world expert on MAOIs and serotonin toxicity, provides a succinct and comprehensive overview that supports my own conclusions.

According to recent evidence summarized by Gillman, while many drugs were once thought to pose serious risks if taken with MAOIs, only the combination of MAOIs with drugs that affect the uptake of serotonin cause serotonin toxicity and are of significant concern. These include Prozac and other antidepressants in the family of serotonin reuptake inhibitors; the antihistamine chlorpheniramine; and the opioid-based pain medications Demerol and tramadol.

Tyramine, an amino acid found largely in aged, fermented, cured, and spoiled foods, when combined with an MAOI can cause the rapid increase in blood pressure known as a hypertensive crisis. Aged cheeses were once the most problematic food. Fortunately, modern food processing techniques have greatly lowered dietary tyramine levels, and many foods once implicated in causing hypertensive crisis, such as coffee, most types of alcohol, and chocolate, have been found to have no significant amounts of tyramine. The risk of hypertensive crisis is dose related, so consuming only small portions of tyramine-containing foods is an obvious precaution. While vigilance is important when taking any drug, the risk of hypertensive crisis with MAOIs has been overblown, and a strict no-tyramine diet is unnecessary.

A doctor friend once told me that if a medicine does not have any side effects, it probably doesn’t work. The common side effects of MAOIs, insomnia and lightheadedness, were for me temporary and manageable. My few months of insomnia were difficult, but also oddly joyful because I was no longer depressed. I laid in bed at night giggling with relief, reminiscing about old times when I had been kind, brilliant, full of fun. It was like being reunited with an adored identical twin who the disease had convinced me was dead.

No drug is right for everyone, and I am sure I responded to Parnate in a particular neurochemical way that others with similar symptoms might not. Yet given the effectiveness and relative safety of MAOIs, how can withholding them in favor of newer drugs that patients report to be ineffective, and that come with their own worrisome risk profiles, be justified?

More than 40 percent of people with depression do not experience a meaningful response to any of the second- and third-generation antidepressants. Among those who do, the response is often ephemeral, and relapse is common.

Since the patent on most MAOIs expired decades ago, it is not in the financial interest of drug companies to market these older, inexpensive medicines. Generations of doctors have been warned against MAOIs, have no experience using them, and are reluctant to prescribe them. This shameful blindness has been unfortunate for the countless people with major depression who might have benefited from their use. It will take strong advocacy by patients to undermine psychiatry’s entrenched prejudice against them.

Waking up in one’s right mind is at least half of what an individual needs to navigate the joy and suffering that is the human condition. Thanks to an almost-forgotten and long-discredited medicine, I am vibrantly engaged. Life is full.

Sue Trupin worked as a staff nurse in the adult medical clinics of San Francisco General Hospital for more than 30 years.

  • I first used Parnate in 1985 before SSRI’S. It worked great compared to
    anything since but the insomnia was awful and not treated so I had to discontinue it. Fast forward to January 2019. Doctor and I decided
    to try Parnate. In less then two weeks my depression was gone along with social phobia. I felt great
    for the first time in many years. Unfortunately, it started wearing off and depression was returning. About that time I was approved for TMS treatment which was starting to work but my insurance pulled the rug out, and would not pay for it.

    Will be trying Parnate at a higher dose or switch to Parnate. SSRI’S do nothing for me but dull me out with many side effects I will never use one again. Can’t wait to feel human
    again as I did with Parnate. The loss of that absence of depression with Parnate was a real blow to me, knowing that I could feel REAL emotions again and having no
    social phobia.

  • I am considering requesting a script for Parnate. I have suffered from MDD since my early 20s. I was prescribed Prozac in my 40s and it was such a wonderful feeling to be in the land of the living again. This episode of depression has been unremitting for close to 3 years and I was hospitalized last December, starting on nortriptyline which initially provided short term release. My psychiatrist suggested etc and never mentioned this class of medications. I am almost afraid to hope. I left my job in 2018 and feel like I’m not living my life; I tried TMS and meditate daily when I can. I’m grateful for everyone who shared their stories.

    • Find a psychiatrist willing to prescribe tranylcypromine(Parnate). Print out one or two of the links I’ve provided in my article for the doctor to review. If he refuses find someone else. Good luck.

  • I was diagnosed with depression that has turned out to be chronic fatigue for which high does parnate helps (120g). I have no side affects apart from insomnia if I take them after4.00pm. I have a suspicion that many of those with refractory depression who resort to high dose parnate in fact have chronic fatigue that is rarely looked for, while the level of competency amongst psychiatrists where I live in Melbourne Australia is absolutely criminal it is so bad

  • My Mother takes Parnate – not as an Anti-depressant, but due to its side effect of stopping her chronic tremours. However, there is currently a major shortage in Australia, one that came with no warning, and we are running low – My Mom halved her dose to buy her more time, but even then, we have little over 2 weeks of stock. My Mom’s tremours are REALLY bad, and this sudden decrease in dosage is really dangerous for her since she doesn’t have enough to taper off usage slowly. We have desperately called all the pharmacies and hospitals in our area, but no one has any. Do you have any advice on what to do? We are rather desperate.

    • If you give me your address, I have some I can send you. I’ve never heard of Parnate working for tremors.

  • Well, I *do* keep stuff stashed away in the refrigerator, so my expiry date gets prolonged.

    I have an interesting hypothesis on Parnate’s mode of action, if you care to email me privately.

    • I would be curious to know your hypothesis of action! I constantly research meds. Parnate was the best med I’ve ever taken. Unfortunately, it stopped working. I have my own hypothesis on why it stopped working and I will post my updates on this website in a few weeks when I have time. I am starting Parnate again soon.. would be very interested about your hypothesis

  • “I had half a bottle stashed away from a decade ago and started up again”. Well Ophelia, So much for use by dates!
    My group’s statement about MAOIs has just been published and waving a copy at a doctor may be of some use! It’s available free from the ‘CNS Spectrums’ Journal website
    Revitalizing monoamine oxidase inhibitors: A call for action
    http://dx.doi.org/10.1017/S1092852919001196

  • I’d forgotten just how efficacious Parnate was until I found myself, once again, in that bottomless pit. I had half a bottle stashed away from a decade ago and started up again. Jeez! What a relief. Quick onset, too: maybe 10 days? Maintenance for me is only 20 mg/day, load at 30 for a couple weeks.

    More doctors need to learn that their “received wisdom” re MAOIs is for the birds.

  • Parnate is a life changer. However it’s very difficult finding consultants who are willing to prescribe it. It’s certainly not a first line choice but for people with long term, treatment resistant presentations it should, at the very least, be explored as an option.

  • Reading about how you giggled in relief in your re-found happiness made me cry, tears of happiness for you and tears of desperation for myself. How I long to feel those feelings again. Thank you for sharing your story.

  • I’m a nurse too, for 32 years, and have found parnate to be the most effective of all the meds I’ve taken over 40 years. I agree with everything in your article and feel it is criminal to not teach new providers about the efficacy of MAOI’s. I am curious as to the dose of parnate that is best for you.

    • 30 mg a day was the best dose for me. After 3.5 years I tapered myself off Parnate very very slowly. I’ve been off it for almost a year and am doing fine. Thank you for your comment. Sue

    • Thank you, Sue, for sharing this wonderful article about your experience and the underuse of MAOIs in modern Psychiatry. I am so glad that you found relief and continue to do well. Your persistence in fighting a very dark demon paid off. All the best to you. Mark

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