Next is Sue’s account (she had a letter about this published in ‘CNS Spectrums’ (1) after my editorial (2). It illustrates that a little inventiveness and persistence gets most people through the side effects that can occur. However, most patients who have had a lot of previous treatment find they have less side-effects than almost any of the other treatments. It also illustrates, and she comments on this, how many doctors do not understand pharmacology and drug interactions and are discouraged from starting Parnate because they suppose all sorts of dire problems are going to occur (see here re this Q). Such misconceptions have profound negative effects on the way patients’ drug treatment is managed, which are unnecessary, and emanate solely from the incomplete knowledge and lack of experience in using MAOIs. Her doctor (as she recalls) said: ‘You know, you’ve been so ill, I didn’t dare take you completely off the medicines (referring to the washout period). The other drugs weren’t really helping you, it’s true, but I couldn’t take the risk of what would happen to you without them, what you might do.’
I hope I am not the only one who sees an inherent perverseness of logic in that way of thinking.
My first episode of major depression occurred in the mid 1970s when I was 34. A prolonged and horrendous divorce lead to six moves in two years. A single mom with two little boys, I managed to complete a demanding nursing program. I passed my boards but immediately succumbed to an extreme exhaustion. I was treated for hyperthyroidism but nonetheless suffered what was aptly called a nervous breakdown. Six months later, unable to tolerate the side effects of the tricyclic antidepressant to which I was minimally responding, I started twice weekly sessions of acupuncture with an old Chinese doctor in Berkeley. I remember walking out of the fourth session and feeling the hot sun on my face, the return of warmth to my bones. I smiled at a chubby baby, at a handsome older man who passed me by. In the next week or two the depression lifted as if it were a toxic vapor that had evaporated and blown away.
In the years after my first episode I remarried happily and enjoyed a fulfilling career in the clinics of a large public teaching hospital. If occasionally I had difficulty managing my mood, I kept a daily log, noting one to ten the presence of a distinct emotional dullness when my interest in life became murky. “The doldrums” I called it. “There’s no wind in my sails,” I told my husband to describe how enthusiasm now existed in some distant realm. One difficult summer I tried Prozac which propelled me into a panicky and morbid state. I tried a then newer class of antidepressants, Wellbutrin (bupropion) which seemed to help and I stayed on it for years. If my mood descended, I reapplied myself diligently to favorite activities from which I’d recently pulled away- hiking, dancing, more sleep, sex and sunshine.
A particularly persistent descent of mood began in my mid-60s. Moving towards retirement, still loving my husband of thirty years, all that amused and engaged me appeared increasingly flat. Ours was a combined family of five sons. My younger boy had died of AIDS fifteen years earlier. A recent cluster of crises and drama relating to our now almost middle age sons accumulated, bringing us to already bruised and scabby knees. Parenting as a life sentence, those were the glasses I wore that summer. Exuberance and passion became utterly foreign, as if they had just picked up and left me for some distant shore. This was not grief or sadness, not the blues which though dark is more a vital, rolling force. I tried my usual bag of remedies but failed to turn the mood around. “The lights are going out,” I exclaimed to my frightened husband.
A devoted and optimistic guy, my husband stood closely by. I saw on his face however growing bewilderment and despair. One morning in September he stood up from the bed and fainted, crashing to the tile floor. He complained of a heavy pain in his chest. For the next twenty-four hours in the hospital, they did what they could but the gruesome reality unfolded clearly. Our sons and closest friends arrived, family was called. I made difficult decisions, signed papers, comforted him as best I could. On the afternoon of the second day, he died.
That very evening the temporary disbelief that comes mercifully with sudden loss set in. At the same time, I understood that it would always be the case that the last months of my husband’s rich and noble life had been heavily burdened by my illness. It would always be possible that had I not been so strangely ill, he might have lived to eighty rather than to seventy-three.
Oddly perhaps, I hoped that the shock of his sudden death would reset the mangled wiring of my brain, that I would somehow grieve normally but be well. After the tributes were done, however, when I was told one’s grief really takes hold, the depression returned in full force as well. As difficult as it can be to sort one from the other, it was from then on depression that ruled the roost. I was unable to work. While I never harbored a distinct suicide plan, a longing for death occupied every parcel of real estate in my waking brain. I sat idly in my car for hours, napped in my car, got in and out of my car frequently with the hope of being hit by a passing truck.
I slept eighteen of twenty-four hours in the day. I was so profoundly weary every mundane task necessitated a period of sleep. My longing and preoccupation with death continued. I put myself in riskier situations on the road, wandering on foot by the side of highways, made more than a few visits to the Golden Gate Bridge. I ate mindlessly in erratic bursts of hunger. I could not find simple words or solve easy problems. I could not concentrate enough to read or hold my own in any conversation. I had absolutely nothing to say.
I changed doctors and medicines multiple times but no regimen of drugs, no activity or event, happy or sad, penetrated the remoteness and detachment of my mind. I was hospitalized twice. Around eighteen months in, I finally bonded with an older Austrian psychiatrist. She was kind and never betrayed the boredom and impatience to which other doctors understandably succumb in the face of such dedicated despair. A treatment resistant depressive can suck all light and energy from the room.
In desperation, I agreed to a course of electroconvulsive therapy (ECT) which did help somewhat, but the routine was impossible to maintain. After a few weeks there were not the people needed to pick me up and watch me in the evening, a requirement of the treatment. The lights in my brain which had been off switched on to parking lights dim, but I worried about my memory, the likelihood of relapse. Without telling my doctor, I tapered myself off of all my medicines. I was curious by then to see what of my authentic, original self remained. Unfortunately, the depression and grief persisted and there was an additional level of anxiety that had been absent before. After about a month without medicines, I revealed to my doctor what I had done. Without missing a beat, she said “Well, now is a perfect time to start an MAOI.”
I accepted a prescription for tranylcypromine (Parnate), an MAOI, with the same hopelessness and passivity I had taken all the other many medicines I had been given. I remembered from nursing school how these medicines were also associated with certain tyramine related dietary restrictions and I abided seriously by the antiquated, mandatory food restriction list my doctor handed me. About eight days later sitting in my car, I heard a tune by legendary jazz saxophonist Ben Webster on the radio. The beauty of it made me shudder and passed through me like an invigorating wave. Later that same day I went to the market and filled my basket with a dozen fresh foods. There followed a succession of small pleasures, the sun on my face, a giggle here and there, a flush of genuine gratitude towards a helpful friend. The lights were blinking brightly and then they were staying on.
I came into my next appointment highly animated. I described the change, the emergence of curiosity and even joy. I was cautiously hopeful, not yet fully believing in what was taking place. I thanked her once again for her dedication but asked, almost accusatorially, why she had not given me an MAOI earlier. I suspect she was taken aback by the dramatic change, the clarity of my thinking, the directness with which I addressed her. She said quietly, “You know, you’ve been so ill, I didn’t dare take you completely off the medicines (referring to the washout period). The other drugs weren’t really helping you, it’s true, but I couldn’t take the risk of what would happen to you without them, what you might do.”
Suicide is any responsible clinicians worst fear. One argument against the MAOIs suggests that the washout period, when a patient is on no antidepressants, puts him or her at increased risk. My major depression had by then lasted well over three years. It was indeed remarkable that I had survived. And yet, had not the months and then years of minimally effective medicines not increased my sense of hopelessness and therefore, also, my risk of suicide? Given that I had no history of psychosis or suicide attempts, would temporarily discontinuing my antidepressants as part of a monitored strategy really constitute any greater risk?
It took some time to understand how my unrelenting longing for death had not in fact led me to suicide. Even in my state of deep emotional detachment, I was acutely aware of the lifelong pain my suicide would cause my son. I also saw suicide as a crime not against God but against nature, more odious and perverse than the suffering to which I had become listlessly accustomed. It was not the defining legacy for which I wished to be remembered.
I came to realize also that my symptoms of major depression did not include acute feelings of self hatred. It was numbness and a longing for death that most defined my state of mind. Maybe because I had been sick in this way before and was a knowledgeable medical provider, I understood clearly that I was seriously ill. I was so entirely not myself, I could infer a distinct neurochemical etiology. The devotion of my closest friends during this time also confirmed my sense of myself as a worthy person. This broader understanding did not lessen my symptoms but did, I believe, keep me from killing myself.
Over time, I experimented with small amounts of allegedly restricted foods. I also unintentionally transgressed, neither of which caused an increase in blood pressure. As an old hippy, I had long maintained a healthy diet, meaning fresh and unprocessed foods, whole grains, nuts, many fruits and vegetables, a minimum of refined sugar. It was not a great sacrifice to do without foods such as prosciutto, salami, tofu, fava beans or many aged cheeses. Real sacrifices like forgoing chocolate, wine and coffee were fairly easy to tolerate given given how well I felt; it seemed a small price to pay. I did fall in love with a Bulgarian sheep feta (not on any list) from a nearby Arab grocery, convincing myself it was not an aged cheese. I gathered after a while that the feta either wasn’t aged enough to cause any problems or the one or two ounces I consumed in a day were below the threshold for risk. Any temporary, small increases in blood pressure, I attributed to salt or a failure to exercise daily; also to stress. For the homeless patient without refrigeration or the food bingeing patient, MAOIs are perhaps not a good fit.
Regarding the side effects of the older MAO inhibitors, they are surely no worse than many of the other second or third generation antidepressants. The side effects of the tricyclic antidepressants are notoriously disabling and yet they are still widely prescribed. Patients on some popular modern antidepressants and antipsychotics are experiencing alarming weight gain and developing metabolic syndrome. One wonders how well these medicines fare in any decent cost-benefit analysis.
The most reported side effect of MAOIs is postural hypotension causing a lightheadedness and dizziness, ironically from low blood pressure. While concerning in the elderly at risk for falls and fractures, one learns to stay hydrated and to stand up slowly. Any exercise routine that improves balance decreases risk. I experienced postural hypotension for about six months especially on very hot days.
I also experienced an extreme insomnia with the MAOIs. I took zolpidem (Ambien) and Melatonin a few nights a week, which helped during this time. I cut back on coffee to one weak cup in the morning and increased my exercise routine. I took short naps. The strangest aspect of the insomnia was that because I was no longer depressed, those hours in the middle of the night were almost ecstatic. To be awake and in my right mind brought me extraordinary joy. I remembered funny stories and giggled, I reminisced about loved ones, recalled almost forgotten times when I had been kind, brilliant, proud. I laid there in the darkness, sometimes dozing, but mostly just swimming through waves of heart pounding relief, deep oceans of gratitude. I embraced my much missed sanest self as if I were being reunited with my beloved identical twin whom I had been made by the disease to believe was dead.
In the three years since I have been well, it has become increasingly appalling to me that the MAOIs (a single oral agent) have been relegated to the lowest level of last resort. It is dumbfounding to me that ECT, while vastly more humanely practiced than in its darker days, is, at exorbitant cost, almost always considered as a treatment option before an MAOI. The bias against these medicines is so entrenched in psychiatry, it seems only patients and their loved ones could turn this prejudice around. One can only surmise the role of the pharmaceutical industry in perpetuating the decades long discrediting of these [what should be] inexpensive and efficacious medicines.
1. Trupin, S, A perspective on the editorial by Ken Gillman:‘“Much ado about nothing’: monoamine oxidase inhibitors, drug interactions, and dietary tyramine’’. CNS Spectr, 2017: p. 1-1.
2. Gillman, K, “Much ado about nothing”: monoamine oxidase inhibitors, drug interactions, and dietary tyramine. CNS Spectr, 2017: p. 1-3.
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