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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.

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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 disagree with the author in just one item. Tranylcipromine or TCP for short (brand name Parnate) is no longer inexpensive. It just used to be.

    Seems like links are not allowed here but you can google the price. Make sure it is updated.

    Certainly it is inexpensive to manufacture but, probably as a testament to its effectiveness, price has increased enormously in the recent years.

    Dr. Ken Gillman makes an impeccable rationale comparing prices of TCP and another (supposed) antidepressant, Mirtazapine.

    I have found (low dose) Mirtazapine useful as a sleep inducing drug though.

    I began the treatment by myself after reading (in its entirety) Dr. Gillman´s website. Probably the only reliable source of information on MAOIs and other psychotropical drugs accesible to the public on the whole internet.

    I am indebted to him not only for setting up this site but his support and counseling on the treatment as well. I would probably still be stranded without his help. A big thank you Ken.

    I have found research papers by Dr. Jay D. Amsterdam and (very) few others very revealing as well.

    Devastating side effects of SSRIs, now prescribed as if they were sugar pills, can be summarised in a Ted Talk by Elizabeth Kenny “On a scale of 1-10, how crazy are you?”.

    Emotive and funny (if you are not the patient that is).

    I have been lucky and now I find my moral duty to spread the word so others can benefit as well.

    • Regarding the expense, I am a senior on Medicare and Kaiser, so it is cheap. $10 per month. I’m sorry if I misrepresented the expense; something to take up with ones insurance.

    • About $10 a month is what it would cost me IF (big if) any psychiatrist would dare to treat me with MAOIs in Spain.

      Now it costs me almost $300 a month and that is with a canadian supplier whose price is a third of the price in Europe.

      So for people without insurance or resident in countries with a dysfunctional National Health Care service that is the cost. Hefty.

      Maybe it is useful to find out how much Medicare really pays for your treatment and enlighten them about the price gouging practices so that it becomes more affordable (for them) in the future. A drug that has been available for almost 60 years and has been out of patent for decades should be cheaper. And it was until not so long!

      That could open the way to a more widespread use of this kind of drugs.

    • BTW, I don´t want to sound hypercritical with your article that I found excellent AND helpful.

      Cheers.

    • Dear Juan,

      I have been corresponding with Ken Gillman about TCP availability in Spain and would very much like to get in touch with you. I have also reached out to an MAOI expert in Madrid on Ken Gillmans expert list. I can be reached at admin ( AT ) mascupon ( DOT ) com.

  • There is just one point I disagree with the author. Tranylcipromine or TCP for short (brand name Parnate) is no longer inexpensive. It just used to be:

    https://www.drugs.com/price-guide/tranylcypromine

    Certainly it is inexpensive to manufacture but, probably as a testament to its effectiveness, price has increased enormously in the recent years.

    Dr. Ken Gillman makes an impeccable rationale comparing prices of TCP and another (supposed) antidepressant, Mirtazapine:

    http://psychotropical.info/anti-depressants/maois/2-uncategorised/130-mirtazapine-tranylcypromine

    I have found (low dose) Mirtazapine useful as a sleep inducing drug though.

    I began the treatment by myself after reading (in its entirety) Dr. Gillman´s website. Probably the only reliable source of information on MAOIs and other psychotropical drugs accesible to the public on the whole internet.

    I am indebted to him not only for setting up this site but his support and counseling on the treatment as well. I would probably still be stranded without his help. A big thank you Ken.

    I have found research papers by Dr. Jay D. Amsterdam and (very) few others very revealing as well.

    Devastating side effects of SSRIs, now prescribed as if they were sugar pills, can be summarised in this Ted talk:

    http://www.tedmed.com/talks/show?id=299419

    Emotive and funny (if you are not the patient that is).

    I have been lucky and now I find my moral duty to spread the word so others can benefit as well.

    • Dear Juan,

      I have been corresponding with Ken Gillman about TCP availability in Spain and would very much like to get in touch with you. I have also reached out to an MAOI expert in Madrid on Ken Gillmans expert list. I can be reached at admin ( AT ) mascupon ( DOT ) com.

      Many thanks and I look forward to hearing from you.

  • Great article. I just started Parnate after being treated unsuccessfully with a variety of antidepressants as well as TMS. Am going to be sure my psychiatrist has a copy.

  • A fascinating article offering both hope and clarity. I will send it to my therapist and internist in the morning.

  • Antidepressants work for some people (those who can tolerate them), only because of the placebo effect. Lots of studies have shown this. I also suggest reading the article “Outcome Reporting Bias in Antipsychotic Medication,” by Dr. Peter Simons.

    • Is this a sarcastic comment swfoutsida? Pharmaceutical companies come up with various medicines (using a hit-or-miss approach), and they work for a few patients only due to their placebo effects – these medicines also lead to devastating long-term problems.
      Pharmaceutical companies also provide authentic sounding complicated neuro-jargon to justify how these pills work. We need to remember that despite decades of research, scientists have not been able to find any structural or other brain differences between patients with ‘mental conditions’ and healthy individuals (this is why there are no objective tests to detect them). Innocent patients are deceived into thinking that they have some ‘problem in their brains,’ needing medicines.

    • About as sarcastic as saying heart surgery only helps people because of the placebo affect. Or that people get high on x,y,z drugs because of the placebo affect.

    • swfoutsida: Mental problems cannot be compared AT ALL to heart disease (that require surgery), etc., because a clear physical reason can be observed for those problems. On the other hand, the pharmaceutical companies come up with various psychiatric medicines using a ‘hit or miss’ approach although decades of research have failed to find any structural or other brain differences between patients with ‘mental conditions’ and healthy individuals (this is why there are no objective tests to detect them). Additionally, because pharmaceutical companies mostly have profits in mind, the trials they conduct (to demonstrate the effectiveness of these pills) are known to have a great deal of selective reporting, data mischaracterization, etc.

      So, as I stated, for a few people, these pills may work only due to the placebo effect but many endure terrible life-long side effects. When you disturb a natural system by adding an agent (molecular substance) that someone interprets as the solution for an issue at hand, one creates many additional problems – many of these chemicals that are introduced (in the name of “therapeutic agents”) interfere with normal biochemical functioning of the brain and adversely affect the brain in the long term.

    • Haha! Somehow they don’t have long term data, but yet that isn’t a problem to make up long term side affects.

      But maybe you’re right. Anti-venom, vitamins, blood pressure meds, aspirin, antibiotics, etc. and etc. obviously only work as placebos.

    • swfoutsida: You still don’t get this. Things like anti-venom, antibiotics, etc., have clear mechanisms of action. This is not the case at all for psychiatric drugs – the ‘chemical imbalance theory’ is a myth.

      The brain is very complex organ with billions of neurons and trillions of synapses that connect and interact in complex ways – there is so much we do not know about this organ. So, introducing chemicals to it following a hit-or-miss fashion (with someone’s idea of “treating” mental illnesses), simply messes up the natural biochemical pathways. It is also very important to note that many studies have convincingly shown that it is HUMAN EXPERIENCE that brings about structural changes in the brain (i.e., neuroplasticity and epigenetics pathways) – so the causal pathways actually go the other way around! For example, if an animal is subjected to psychological stresses (such as being restrained in a cage), their brain chemicals gradually change, and structural changes in the brain can also observed. When these animals are released however, their brains come back to normal. So, introducing chemicals to the brain (thinking that it will somehow heal the condition) is a very dangerous way of treating mental issues.

      Regarding long-term studies of adverse effects, please check out the following references:

      Harrow, Martin, and Thomas H. Jobe. “Does Long-Term Treatment of Schizophrenia With Antipsychotic Medications Facilitate Recovery?” (2017). Schizophrenia Bulletin 39.5 (2013): 962–965.

      Vittengl, J. R. (2017). Poorer long-term outcomes among persons with major depressive disorder treated with medication. Psychotherapy and Psychosomatics, 86, 302-304.

      Currie, J., Stabile, M., & Jones, L. (2014). Do stimulant medications improve educational and behavioral outcomes for children with ADHD?. Journal of health economics, 37, 58-69.

      Goff, D. C., et al. (2017). The Long-Term Effects of Antipsychotic Medication on Clinical Course in Schizophrenia. American Journal of Psychiatry, 174 (9).

      Kinderman, P. (2014). Why We Need to Abandon the Disease-Model of Mental Health Care, Scientific American, Mind Guest Blog.

      Also, since you mentioned, I should also add that many medicines in use today are merely placebos. Meta analyses have shown that active drugs and placebos have similar effect sizes for many drugs [see the reference: Howick J, et al. (2013) Are Treatments More Effective than Placebos? A Systematic Review and Meta-Analysis. PLoS ONE 8(5): e62599].
      This appears to be especially true for psychiatric drugs.

  • Note that the referenced editorial by Dr Gillman “Much Ado About Nothing” was published in the February 2017 issue of CNS Spectrums, a neuroscience journal of Cambridge University Press.

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