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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.

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.


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.

  • Thank you for writing this–but there is more to be said. I take Parnate with 75mg of dextroamphetamine per day and obey virtually no dietary restrictions. Most doctors think I should be dead. On the contrary, I am very much alive. Moreover, Parnate is even more effective at ~1.5mg/kg/day (maximum dose of ~200mg/day). At this dose, its amphetamine-like metabolites reach concentrations where they become effective in their own right. Their pressor effect ameliorates the orthostatic hypotension common at lower doses.

    Search pubmed for articles on high-dose tranylcypromine. One is by Amsterdam, another by Berwish. The dose-limiting factor is increasing risk of thrombocytopenia, which tends to manifest if a patient raises their dose well beyond 200mg/day.

    Unfortunately, it can be difficult to find a doctor willing to prescribe an MAOI at any dose, let alone off-label ones.

    As you suggested, people should read P.K. Gilman. By comparison, all of the new “modern” antidepressants don’t work at all. This is similar to how people who have taken a benzodiazepine for anxiety at some point in the past do not respond to buspirone. One I tried an MAOI, I found SSRIs wholly intolerable.

    My guiding principle in medication choice is to choose the drug that is most effective and had been in use the longest. Many people tell me, “But there are so many newer drugs!”. So? I have no use for expensive active placebos.



    Some refs:

  • Sue, I am SO grateful to a psychiatrist at Kaiser SF (Dr. Hamilton) for suggesting Parnate to me, and for sending me your most articulate and inspiring Stat article (thereby turning me on also to Dr. Ken Gilman’s work.
    I am insisting that my current Psych. doc. at Kaiser let me try it. He (alas) is highly skeptical & out-of-date as to his MAOI information, even though he’s Head of the SF Kaiser Psych Dept. However, he said he will (reluctantly) let me try it. We have to be informed and be our own advocates. Like you, I have suffered for decades from severe depression. Nothing has really worked, including multiple SSRIs and oral ketamine which I just tried. Parnate may not help me, but I want to give it a chance. Wish me luck! 😁

    Disgusting how big Pharma single-mindedly pursues big profit over the suffering of patients, and also how complicit (whether knowingly or cluelessly) the psychiatric establishment is.
    Thanks, Kathleen

    • Kathleen hello again. I’m rereading comments on my article and saw yours again. I’m wondering how it went, if you ever did a trial of Parnate or another MAOI. I’m curious if your psychiatrist, the head of his department, ever came around.
      Wishing you my best, Sue

    • My story is very similar to yours. Have tried everything, meds, psychotherapy, exercise, naturopathic, ketamine infusions ( oh my worst experience ever and I paid a crazy amount of $3,000). 9 Years of suffering. Just finished rTMS with a bit of improvement. I want to live, I have two children even though I’m not feeling them. Tomorrow I’ll start Parnate… if there is God, and this med will help me, I don’t care at all about the dietary restrictions. I’m wishing with all my heart which I don’t feel a heart bit of it, that Parnate will work. How r u doing?

    • Dayne, thank you for this article. I love this site ( which I only recently discovered. The original title of my essay was “The Demoralization of Psychiatry- a Castle Built on Sand”.

    • Dyane, have you ever suffered from clinical stubborn depression? If not, I’m sorry but you have no opinion to give or article to recommend. Ask me, a mother of two young children suffering for 9 years and I can explain every detail! You won’t like my story! Simply because you have never experienced it.

    • I read that article and made me more hopeless than ever. I have tried without drugs, therapy, exercise, meditation, naturopathic and nth has helped me.. and rTMS, and ketamine and and . And, now I have a 1% hope that Parnate might help and people dare to take that hope away from me and push me to think about death. It’s not right! I don’t believe in meds cause they haven’t bring me back to life, but I know that so many people friends on mine live on them and enjoy life so yes I’m going to try Parnate… if it doesn’t help, I don’t know what else I can do. 9 years of suffering… I have lost 9 years of my children’s life. I have treatment resistant depression caused by anxiety attacks.. I’m in tears cause it’s easy to suggest or judge when you are not going through it

  • What a beautifully written and poignant story! My 16 year old niece had a similar situation with lithium. This first generation medication was not prescribed for 1.5 years as my niece got worse and worse and was not able to continue in her high school. Her behavior was frightening to all of us. A very social person before her illness, she lost all her friends. My sister, a nurse practitioner, did extensive research on her own, leading to lithium eventually being prescribed. My niece now lives a full life, free from the debilitating symptoms of bipolar. Newer is not necessarily better; just more profitable for Big Pharma.

  • When treating depression use a tailored approach to the management of drugs if one wants to get a good result. Tailors cut and fit the dress many times to get the best fit and customer satisfaction. Similarly, try different drugs that give the best results finally. Many old drugs are also ones that can give very good results in a particular individual. Protocols sometimes make one to stick to certain patterns of management like the readymade garments.

  • Regardless of new drugs or old drugs – the assumptions that go with giving medicines for mental issues is highly problematic. A recent article states that current psychiatric trainees and junior psychiatrists blindly accept the methods used in psychiatry because they simply (wrongly) assume that much smarter people before them have somehow sorted out all the details relating to the theories underlying psychiatry – here’s the reference: McLaren, N. (2016). Psychiatry as Bullsh*t. Ethical Human Psychology and Psychiatry, 18(1), 48-57.

    We must remember that science does not understand the mind (consciousness). Just because brain activity is correlated with mental activity, the field of psychiatry makes the incorrect assumption that the brain needs to be treated in order to address mental problems. Also, these medicines (that pharmaceutical companies come up with on a ‘hit or miss’ basis) interfere with the normal brain chemistry making matters worse for the patients in the long-term.

    Numerous studies have shown that it is HUMAN EXPERIENCE that results in changes in the structure of neurons and neurochemicals. For example, being subjected to various psychological stresses results in changes in brain chemicals and these chemicals fall back to normal if these psychological stresses are addressed. I can provide references if anyone wants to see.

    • I agree with you and Niall McLaren here:

      and many others with similar concerns. Yes, physchiatry is full of bullshit. What is worse is that not many people feel something is wrong with its present state. However, psychology has its own share and it probably is even bigger.

      Al least some physchiatrists and neuropharmacologists do real science i.e. their findings are based on experiments that eventually get replicated. I will just quote Richard P. Feynman here:

      “Incidentally, psychoanalysis is not a science: it is at best a medical process, and perhaps even more like witch-doctoring. It has a theory as to what causes disease—lots of different “spirits,” etc. The witch doctor has a theory that a disease like malaria is caused by a spirit which comes into the air; it is not cured by shaking a snake over it, but quinine does help malaria. So, if you are sick, I would advise that you go to the witch doctor because he is the man in the tribe who knows the most about the disease; on the other hand, his knowledge is not science. Psychoanalysis has not been checked carefully by experiment. ”

      This can be woefully extended to most of the psychology. It does not mean it is not useful. Placebo effect is extremely useful/powerful for instance, that is why pharmaceutics have so many problems getting new drugs to beat it. So they have to cheat to keep profits coming.

    • I agree that psychoanalysis is not a science. However, the ‘mind’ can be understood in a very systematic manner. You may wish to take a careful look at the academic article titled “Theoretical Foundations to Guide Mindfulness Meditation: A Path to Wisdom,” published in the journal ‘Current Psychology’ (2017).

    • Well, that is the problem with that article and so many others (I wouldn´t dare to say all). They have a “theoretical framework” and explain something (hopefully within logical discourse). Ok, that cannot be taken as anything more than a working hypothesis.

      Seems like another quote by R. P. Feynman is customary:

      “It doesn’t matter how beautiful your theory is, it doesn’t matter how smart you are. If it doesn’t agree with experiment, it’s wrong.”

      But I like this one better:

      “In theory, there is no difference between theory and practice. But, in practice, there is.”

      Or this shorter one:


      Will anybody take the time to test that “theoretical framework”?

      Will ever be an experiment of some class?

      I guess not. It could be proven wrong and that would be a disaster for publishing more. But this is just not fair as the authors do not seem engaged in frenzied publishing.

      However, the first reference is “Quantum Mechanics: Theory and Applications”. I cannot comprehend how a reference to quantum mechanics could surface in this type of article except for bullshitting the reader, just because it is a shocking (too?) popular (verified) physics theoretical framework.

      Quantum mechanics, that mysterious, confusing discipline, which none of us really understands but which we know how to use. No, not my words…is another quote. Changed physicist this time 😀

      Now we understand (although it is really just one of my sociological working hypothesis) why quantum mechanics is so popular between bullshiters all around the globe! String theory is a distant second once reserved to those with pedigree that can spell “vielbein”.

      Bullshiting behaviour is not precisely confidence building in my book.

      And it is not that I have any problems with anything theoretical. Indeed I like it. I even have a Ph. D. in theoretical physics if that means anything.

    • Hi Juan: That article makes perfect sense to me. When reading the article, you need to understand that there are TWO ‘levels of analyses.’ All your arguments are just on one level only. Please check out the following article in order to understand these two levels clearly:
      Karunamuni, N.D. (2015). The Five-Aggregate Model of the Mind. SAGE Open, 5 (2).

      Also, I just checked the quantum physics reference you mention. It is cited in the article for stating that atoms and subatomic particles are continuously changing and I don’t see anything wrong with using that reference to back that statement.

      Additionally, if you read the article carefully, it is possible to clearly understand what it presents – for example, one can understand within oneself that the present moment is experienced either through the five senses or as thoughts, whereas the past and the future are experienced only as thoughts in the present moment. One does not have to carry out elaborate research studies to verify things like that.

    • Hi, there was no need to reference a book in quantum mechanics for that… with one Deepak Chopra is more than enough.

      I have just gotten those references thanks to a nice repository. Given the latest developments of Researchgate and the greedy scientific publishing industry probably authors will be less willing to use it to exchange its own work.

      I will share a “gem” of psychological research (I will not qualify it yet):

      done by academics as well. Hope you can finish it, I couldn´t.

      BTW, from a physics standpoint Mindfulness has sense. The present is the only lapse of time where you can actuate. You can travel in time to the future or the past (not by much now) however past, present and future are causally connected (causality cannot be violated). So the easiest way to affect the future is acting now, the present, and cheaper than time travel. So “being mindful” of what happens now makes perfect sense. Well, my teachers just said “pay attention!” but I guess they meant something else 🙂

      Although a reminder of the past can be useful to avoid repeating the same mistakes…which happens too often.

      Regarding the future, Séneca summed it up quite well in my opinion:

      “A man who suffers before it is necessary, suffers more than is necessary.”

      Anyway, when people are depressed all this does not work as well. I can tell you.

    • Hi – Regarding the “gem of psychological research”– I am not talking about whether depression is useful for people or not, but how the mind can be understood in a very systematic manner (this is clearly explained in the articles I mentioned).

      Anyway, it looks like you don’t understand what I am trying to say (in terms of two distinct levels of analyses, etc.), and I don’t know how to explain it more clearly either. Perhaps you can read the following article written by a physicist – he describes the whole world and the universe as being entirely mental and spiritual:

      Henry, R. C. (2005). The Mental Universe, Nature, 436, 29.

      It is this ‘mental world’ that can be understood using mindfulness theory (such as the articles I mentioned). It is very important not to mix the two separate levels of analyses. When you state that quantum physics explains mindfulness, etc., you are doing the same mistake as what you are accusing Deepak Chopra of doing.

      By the way, if one wants to be critical, one has to criticize components of a theory itself, rather than merely quoting general statements condemning theories that have been put forth by other people, or by referring to different articles. This is how we can progress in science.

    • I’m sorry I have to ask you. Have you ever been clinically depressed? If not, you don’t know how it is and you can’t share content just without experiencing the black dog. I’m a mother of two children and never never thought would happen to me. I have tried everything out there, modern meds, old meds, therapy, no meds at all, exercise, naturopathic, CBT therapy, DBT therapy, and all this for 9 years. Yes, 9 years of suffering and not feeling my own children. But, I’m not giving up! I tried rTMS treatments, didn’t work. Tomorrow I’ll try Parnate. I hope to be my miracle to my 9 years of suffering. Only a person going through clinical depression knows how it is. Everybody else just has no idea how it is and only give advise based on what they read. It’s a horrible, horrible illness. I can’t believe I’m still alive and I don’t know what I’m going to do if Parnate doesn’t work as well. Therapy is good but doesn’t work for everyone especially for severe treatment resistant depression! Thank you and wish me and other people suffering luck.

    • Genta: If everything fails, I would suggest that you try mindfulness meditation. However, I would strongly suggest learning it from a teacher, instead of learning on your own. If possible try to do an 8-week MBSR course (if not, I could perhaps suggest guided meditations by Mingyur Rinpoche). Set aside about 20mins daily for meditation – results will take time, but you will see a difference. You would also change your outlook in life (it did for me in unimaginable ways).

  • There are a number of molecular drug entities which are simple and easy to synthesise and should cost next to nothing, as indeed was the case for many of them, such as tranylcypromine and clomipramine, around the 1990s.

    However, various predatory pricing practices and regulations have all conspired to artificially inflate the price of many of these drugs, and I have written about various aspects of this my website, for those interested. Sadly, it is one of the ‘unacceptable faces of capitalism’ that allows various financial interests to artificially tilt the playing field. The factors involved go all the way from naked greed to criminal behaviour, such as that engaged in by one or two individuals, who recently became widely known in North America, and at least one of whom finished up in jail. I will not mention any names in order to avoid any kind of retribution (bullying & threatening behaviour of various sorts has been widely engaged in by those who wish to profit excessively). Then there are various technically legal but commercially dubious practices. A simple example is buying up small companies that produce generic drugs, and then hiking the price, or simply ceasing production.

    I could, theoretically, start a small company and produce tranylcypromine and clomipramine at a modest profit by selling bottles of 100 tablets for $20. Needless to say, unnecessary regulations effectively prevent me from doing that, or make jumping through those regulatory hoops prohibitively expensive, for no good reason.

    Then we have another crazy situation where citizens of one country are prohibited by their government from importing a therapeutic drug from another country where it is available and less pricey. There is a strong argument that is an infringement of individual human rights: how can a government rightfully prevent a citizen obtaining a legal therapeutic substance, just because it is not on ‘their list’. There are aspects of a ‘police state’ in countries that would not think of themselves like that.

    The whole situation seems to me to be both immoral, scandalous, and irrational, but that just reflects the current zeitgeist of Western leadership.

  • Bravo — an old medication vindicated. I am so glad it brought relief. Far too often we are taught to fear older medications not because they are so terrible but because they are low cost competition for new meds still under patent. Lithium is a case in point. When Depakote came to market Abbot launched a storm of studies magnifying the dangers of using lithium. Lithium prescriptions collapsed and many docs are afraid to write it. Ironically lithium is the only mood stabilizer proven to reduce the risk of suicide. But we don’t use it because of drug company marketing disguised as scientific studies.

  • Wonderful article. Dr Gillman’s work is eye opening. Many older, tried-and-true inexpensive drugs seem to be avoided by doctors who will happily write script for the newest heavily advertised drugs. It makes a patient wonder if this is defensive (lawyers always go after the deepest pockets), profitable (the drug reps in the waiting room aren’t spreading just information) or are people really following the commercials’ command to “…ask your doctor about…” the drug of the week.

    It’s no wonder so many turn to new age snake oil. Sadly too many MDs are neglecting scientific rigor as well.

    • Certainly it is not the latter. In Spain there are not commercials on this type of drugs. Let´s stop the blaming to the patients, something too frecuent regarding this illness.

      The only thing I have asked my doctor about are MAOIs and she refused that line of treatment and even assured they were no longer commercialised here (utterly false).

      All in all she was quite helpful as made me steer away from incompetent, negligent psychiatrists and look up for myself the way out.

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