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Introduction [KG]
Failure to deploy MAOIs for the treatment of chronic serious depression is a (depressingly) recurrent theme: but the outright refusal to even try MAOIs in one’s own professional colleagues demonstrates the depth and strength of anti-MAOI prejudice and ignorance amongst psychiatrists. During years and years of illness Bev was given many treatments, even including several off-label medications, and ‘experimental’ ones, before, eventually, her doctors were persuaded, reluctantly, to trial an MAOI — surely a demonstration of poor risk-benefit assessment, and certainly not evidence of a rational logical treatment algorithm.
SSRIs frequently lead to modest improvement that falls (far) short of remission; that has inured practitioners to accept partial improvement, not full remission. It is astonishing to me that her psychiatrist treated her for 20 years or so and yet she says, ‘I lived mostly depressed with the occasional short respite that was unrelated to any trial of medication’.
This is what we must continue to challenge. Her long period of complete remission following treatment with Marplan (isocarboxazid) is a reminder of how useful this less-used MAOI can be. Her description of a transformative response, starting within a few days, and reaching remission after two to three weeks, is one we hear often, ‘One morning I woke up with an unmistakable feeling of genuine happiness’. When one sees treatment responses like this one does not need a second-rate depression rating scale to know that someone is better. Nor indeed, should one need to be persuaded by an RCT: real world decisive treatment responses like this remove the need for RCTs (see section on evidence in science). This is also a reminder that, contrary to commonly accepted teaching, improvements with effective antidepressant are frequently evident within a few days — it has been forgotten that this was the observation of the early pioneers way back in the late 1950s (Cf. Arvid Carlsson, et al.).
One hopes that our efforts through the expert group will ensure the continued availability of Marplan.
Bev’s story
In 2021 I retired as an Associate Professor Emeritus at a top-ranked medical center in the United States, after a 25-year career in the Department of Psychiatry. One of my research areas was, ironically, depression. I had everything I desired: a wonderful husband, marriage, and career; many friends; a dog and a horse that I was deeply attached to; and hobbies I thoroughly enjoyed. My professional and personal experiences did not remotely prepare me for the severity of depression I would experience over a period of decades, beginning when I was around 41 years old. Considering my background, however, perhaps depression was inevitable. I had a traumatic, anxiety-ridden childhood from the age of 4 to my early teens. My mother was severely mentally ill, with diagnoses ranging from borderline personality disorder to severe sociopathy. She left my father when I was 4, and I was sent to live with my grandparents for several years. On the other side of the family, my paternal grandfather committed suicide. So, red flags aplenty were there.
The depression emerged one winter when my work life suddenly became excessively challenging. Our lab was a “grant shop,” so we were typically under significant funding stress. But this was a different kind of stress. It began when my mentor, with whom I was close, became severely depressed and began drinking heavily at work. His dysfunction not only threatened my employment and financial security, it also created significant daily distress, as he behaved inappropriately with me both at work and during out-of-hours phone calls.
I was extremely torn about how to handle this. It eventually became apparent that I had to let others in our lab know what was going on. Ultimately this led to my beloved mentor being forced into early retirement. I felt horrible about this. It also put my career in turmoil.
Around this time I began having some distressing unusual physical and psychological experiences such as urticaria, extreme flushing, nausea, and increasingly intense levels of anxiety. I became convinced I had a condition known as mastocytosis. I was no longer rational. I developed significant depressive symptoms, including morbid fear and obsession with death and a near-delusional fixation on my physical symptoms. I lost my appetite and lost a good deal of weight, which I attributed to my imagined illness. I developed an obsession with my weight, stepping on scales frequently throughout the day.
A physician I saw could not account for my odd pattern of symptoms but did try to assure me that I did not have mastocytosis. He prescribed Zoloft to treat my anxiety. The drug did mildly improve my anxiety and mood, but also created intolerable GI symptoms. My husband, a clinical psychologist, had a frank talk with me about the fact I was obviously seriously depressed and I needed more specialized psychiatric care. The first psychiatrist I saw was an elderly woman who was extremely hostile, dismissive, and demeaning. I suggested to her the possibility that some of my symptoms might be related to my possible menopausal status. She countered that this was impossible because I was currently taking birth control pills. She recommended Lamictal. I balked at this and switched psychiatrists.
I then found a psychiatrist I was comfortable with, and remained under his care for over 20 years. I first started Lexapro and I went into remission after about a month. I remained on Lexapro for over a year and since I was no longer depressed I decided to stop taking the drug. In about a year’s time I fell into another depression that did not respond to Lexapro. At this point I began the very typical medication roulette, trying everything available. During the next 20 years or so I lived mostly depressed with the occasional short respite that was unrelated to any trial of medication. By the end of this long painful period I had tried virtually every antidepressant medication available, as well as combinations of up to 3 medications at once.
With each failure I became more despondent. I tried ketamine and every flavor of TMS (transcranial stimulation), neither of which helped my depression. Because my psychiatrist was involved in research I also got to try several off-label medications, as well as things that were yet to be approved. I consulted with the ECT group but opted not to go that route, as the psychiatrist indicated that my profile suggested a limited chance of success. I’d venture to say I tried over 50 various treatments. During the last few years of this period, I became despondent and voiced suicidal ideation a number of times.
Around then I happened upon the writings, and scientific publications, of Dr. Ken Gillman, a recognized expert on the use of MAOIs. Until that time I had been reluctant to try MAOIs because I was concerned about having to washout from the medications I was taking (despite their limited effectiveness). After a few Skype visits with Dr. Gillman I was convinced I should try an MAOI. My psychiatrist was reluctant to prescribe a drug in this class, but ultimately he consented to do so. Thanks to the encouragement provided by Dr. Gillman and his website Psychotropical Research I became determined that I should give this one last thing a shot before I gave up entirely on my life.
Dr. Gillman suggested Parnate. After 12 days on Parnate I felt that the side effects of increased anxiety and significant orthostatic hypotension were unmanageable. Dr. Gillman suggested I switch to Marplan (isocarboxazid) as it might have a better side effect profile for me. [Bev did a direct swop, ceasing TCP and starting 40 mg of Marplan the next day]. Several weeks after starting I had a remarkable, sudden response. One morning I woke up with an unmistakable feeling of genuine happiness rather than the terrifying morning dread I had felt over the years! In fact, for a few days I was probably a bit too happy, experiencing a mild hypomanic state. This quickly resolved and I miraculously had my life back in every respect. I felt like myself for the first time in many long years. I also had only mild side effects, primarily difficulty sleeping, which was manageable.
As I write this I have remained depression-free for over 3 years.1 There was one exception: last year I stopped Marplan for a few weeks for a surgical procedure and I became severely depressed. After the operation I quickly resumed Marplan, desperately hoping that it would work again. Once I was on my full dose of 60 milligrams, my depression was almost resolved within days, and within another week or two I was completely back to normal. All of this seems ample demonstration that Marplan is remarkably effective for me [K.G. and many others!].
I would like to conclude by again thanking Dr. Ken Gillman for his tireless and enthusiastic advocacy for MAOIs. I would also like to thank the International MAOI Expert Group (https://www.imaoi.org/). I cannot express enough gratitude for this work, as without it I’m not sure I would be here today.
1 One might also add that this improvement has been maintained with virtually no psychiatric care or consultations. The economic saving compared to her previous intensive and expensive treatment is enormous.