These accounts are from people with whom I have recently interacted via my web site. This first gentleman’s account illustrates vividly how rapidly Parnate can be effective, despite treatment failure of, among many things:
- The usual ‘guideline recommended’ regimes with various additions and combinations
- ‘38 ECT treatments
- six weeks of daily transcranial magnetic stimulation treatments
- multiple (and very expensive) IV ketamine doses’.
Understanding, or justifying, the pathological avoidance of Parnate by psychiatrists is quite beyond my understanding — as illustrated by the above prolonged and extraordinary measures, before Parnate was tried. [see my AD algorithm]
This account may be found a little upsetting by some people, so to ease the suspense for readers, I will quote his comment about the ‘result’, from near the end of this long story, right now: “The change seemed to occur overnight, almost exactly 3 weeks in; one morning I woke up and knew — with some certainty — that something was different and that, for want of a better phrase, the nightmare was over; really, actually, over”.
In my ‘Guidelines’ commentary I discuss why RCTs and statistics bamboozle researchers and doctors. These RCTs are all about a few rating-scale-points improvement — not complete remission of a prolonged illness in 3 or 4 weeks. When you have seen a number of examples of responses such as these below (I have seen a great many) you may be inclined to re-assess your evaluation of RCT data and use Parnate more often, and sooner, in the course of the illness.
Just think about the suffering this man endured, never mind the wasted time and money. I hope that will pain you as much as it pains me, and may make you wish you could ‘turn-down’ your capacity for empathy. And, ‘lest we forget’, for every story like this, there are the ones we will never know of, because those people did commit suicide. Remind yourself of that, Doctors, next time you are blathering like a blithering idiot about some trivial SE, like low or elevated blood pressure, or whatever***.
I should also repeat that this story is not exceptional: I am contacted by large numbers of patients with not dissimilar stories, many of whom respond dramatically and quickly to tranylcypromine.
*** One can ‘blather’, or ‘blither’, but only properly be a ‘blithering idiot’: the vagaries of English are so delightfully quixotic. That may be because the vowel order is jarring; one says ‘tic, tac, toc, or tick-tock (sound of a clock). To say ‘toc, tic’ just sounds wrong — native English speakers follow this ‘rule’ without even being conscious of it. Perhaps that is why ‘blathering idiot’ never came into use?
Not everybody either wants to, or finds it easy to, revisit such traumatic experiences and write an account of them. Indeed, this gentleman took some months to do it because it was a process that aroused powerful memories and emotions.
In so far as this story is not exceptional, and one cannot say that without thinking of Dr Osheroff, recently deceased, and his legal case against the infamous ‘Chestnut Lodge’ hospital around 1980. Osheroffhas an uncanny number of parallels to this first story. I will not go into the case in detail, comment is plastered all over the Internet, and it is often a part of the teaching of doctors in training. For those who are interested, I suggest using the search terms: Osheroff, Chestnut Lodge, Bernard Carroll, Gerald Klerman, and Mickey Nardo (also recently deceased).
The first story
One of the clinics where he was an inpatient, having psychological treatment, as well as medication, was a famous institution the name of which would be known to every psychiatrist in America. Incredibly — he obtained his own clinical notes subsequently — when they failed to improve him with their medication treatment, they blamed him for being uncooperative, and ‘sabotaging his own therapy’, and invoked the same kinds of judgemental comments concerning his personality, as Chestnut Lodge had done with Dr Osheroff. In this day and age, I find that almost unbelievable, but that is the extraordinary psychological attitude that is commonly invoked by doctors, who deny their own therapeutic incompetence, and project their failure on the patient (Freud’s egregious legacy dies hard).
NB. I advised this gentleman to increase the Parnate unusually rapidly because I could tell, from the other side of the world, that he was quite likely to succeed in killing himself if he did not improve ‘PDQ’ [pretty damned quickly].
His own story
‘I am a working professional in my forties, and completed several years of postgraduate education. I experienced my first episode of incapacitating clinical depression in my 20s which resulted in about 3 weeks of inpatient treatment, followed about 10 years later with another episode lasting almost a year, for which I took 6 months off work. This second episode rather miraculously (at the time) responded to a short course of ECT.
Now, another decade after that, I had relapsed into yet another agitated clinical depression, and after a year or so of various intense and wholly unsuccessful treatments I felt I’d reached the end of the line. Agoraphobic and practically housebound, I’d spend all of each waking day in frenzied pacing back and forth between my dining room and kitchen, my mind clouded in a nonfunctioning fog of regret, indecision, and self-deprecation. I was unable to read, listen to music, watch TV, or even sit still for that matter; I was consumed with how productive and functional I once was, and how it seemed things would never be that way again.
It seemed like I’d tried everything the psychiatric establishment had to offer for the treatment of depression. During the year, I’d had 3 separate rounds of ECT, which had been curative in an agitated depression 10 years prior, but failed to have any positive effect this time around despite 38 sessions total of mostly bilateral ECT, which seemed to have wreaked havoc on my memory and cognition. I’d also undergone 40+ sessions of repetitive Transcranial Magnetic Stimulation (rTMS), 5 sessions of IV ketamine, and dozens of medication trials. I’d taken, for various lengths of time, duloxetine, venlafaxine, aripiprazole, olanzapine, clonazepam, escitalopram, quetiapine, Lyrica, lamotrigine, triazolam, risperidone, Pristiq, Brintellix, methylphenidate ER, mirtazapine, citalopram, diazepam, alprazolam, loxapine, lurasidone, EMSAM patch, clonidine, chlorpromazine, clomipramine, hydroxyzine, tizanidine, nefazodone, buprenorphine, bupropion, temazapam, Phenibut, and cannabis in various forms.
Each medication in turn brought worse anxiety, agitation, or mental clouding, or simply didn’t work. I did take small doses of benzodiazepines (clonazepam, lorazepam, etc.) once or twice a day, which might help the anxiety somewhat for 2-4 hours; higher doses would merely leave me dazed and drowsy and I was terrified of dependence; it only added to my discouragement that I was probably already dependent anyway after all the months of taking it.
Between January and April of 2016 I’d also been hospitalized at 4 different facilities, once for a high-end 6-week program where each day was filled with group therapy, dialectical behavioral therapy, various other group activities, meditation, yoga, and individualized psychiatry and psychotherapy visits, none of which resulted in much improvement, culminating in fact in a transfer to an actual hospital where 2 weeks of ECT were performed. There was actually some improvement after these sessions, but I quickly and fully relapsed within 7-10 days afterwards.
By April I’d had several months of self-destructive impulses to go along with the increasing agitation and despondency; I’d made many attempts with a noose I’d fashioned out of an electrical cord but found I was just unable to let go completely … and my final thoughts just before losing consciousness seemed to always be of my parents, whereupon I would release the pressure and inhale deeply. Sometimes I’d spend 30-45 minutes repeating this process, each time with the same result. Finally, I drove to the local firearms store and even in my completely flat, depressed, suicidal state, discovered that obtaining a gun was shockingly easy. In a daze, I bought a pistol and later returned to pick it up after the waiting period, and early one morning at home prior to a scheduled ECT (it was ~5AM) I loaded it and played around with it and aimed it at myself from various angles and then, without thinking, cocked it; as soon as I did that I decided I wasn’t going to go through with it then and there but that I had no idea how to un-cock the gun … I stood up and placed it on the bed and suddenly it fired loudly in a cloud of black smoke and light, fortunately in a direction away from me and toward the sliding glass door, leaving a clean round bullet hole in a vertical blind. I heard my friend, who had arrived to bring me to ECT, frantically running up the stairs toward my room, calling out my name, and I quickly put the gun in the nightstand drawer. When she reached me, she later said, what she saw was entirely not what she expected to see: me standing at the side of the bed, looking distraught, but alive.
In a trembling voice she asked what happened, to which I could only reply that I didn’t know. Pushing aside the vertical blind with the bullet hole revealed a large spider’s web of cracked glass with pieces randomly falling off; suddenly the entire section crumbled to the ground, followed by an inflow of crisp early morning air. She asked me where the gun was, and said I needed to give it to her; I told her I wasn’t sure, and that I wanted to keep it. I pleaded with her not to tell anyone about it; she said she wasn’t sure what she was going to do, as she was still in a state of shock. Needless to say, we did not make it to ECT that day, and it’s hard to believe but I did do two more outpatient ECT sessions later that week before finally ending the ECT as it obviously was not helping.
I struggled along, barely hanging on for the next two weeks with my only social interaction being my friend who would come often to see me and keep me company for limited periods of time, as she had throughout my illness. We decided that I really ought to tell my outpatient psychiatrist about the recent incident, and so at my next visit with him, in my deeply despondent state I told him about accidentally shooting the gun off in my room, whereupon he said I needed to give the gun to somebody immediately or he would call the police, citing legal obligations and saying I was mentally unstable and a danger. I told him I would give the gun to my friend and she would call him to confirm; after I got home I was deciding how to proceed when my cellphone rang - it was the police and they were outside my place.
As soon as I went outside they handcuffed me and explained that my psychiatrist had called them and told them I had a gun and was potentially suicidal, but reassured me that I was not under arrest. I was brought back upstairs to my room where I showed them where the gun and ammunition were; these were both confiscated. They then looked through my drawers and shelves and while there was nothing else to find, I was told that I would be brought to a yet another psychiatric facility as a 5150-involuntary patient, to which I expressed my sincere belief that this would only probably make things worse, to no avail.
So, that night I was driven in handcuffs in the back of police car to a locked ward at a mental health facility about 3-4 miles away; my experience there, while better than at the previous facility in March, was mostly unpleasant and filled with anxiety and despondency; the psychiatrists there were no less baffled than anyone else as to what I could try next and at some point there I was even on a trial of Saphris (asenapine), an atypical antipsychotic, as monotherapy for my suicidal agitated depression, which, looking back, would never, ever have worked. But regardless I stopped after two days due to severe worsened anxiety and insomnia, after which they tried giving me Vyvanse, paroxetine, and finally Brintellix (vortioxetine), on which I was discharged after two weeks in the hospital, on May 6, 2016.
I tried my best to tolerate the Brintellix and took it for almost two weeks, with questionable change in depression, but constant and increasing nausea, belching, brain fog; my body felt like it was on fire when I tried to lie down, and my body kept twitching furiously. I just couldn’t continue it, and stopped around May 20. The next week consisted of me desperately trying to self-medicate with 2 other antidepressants, literally spending 2-4 hours each morning deciding between taking venlafaxine again or a small dose of escitalopram, but with increased anxiety either way; I also tried taking some Concerta, a long-acting form of Ritalin, which I had been prescribed earlier in the year but had never taken. This did help the mood one day but the next day the despondency seemed even worse. Then, I saw on an internet message board that some people had anecdotal improvement in their depressions with Suboxone, and went to see my psychiatrist, who said he would be willing for me to try a tiny dose of buprenorphine, which is the opiate portion of suboxone, with the knowledge that opiate addiction was a possible outcome, if I were to stay on it for more than a couple of weeks or so.
So, he gave me a prescription for buprenorphine buccal formulation, which was one patch to the inner cheek twice a day; not only was it not covered by my insurance, it was not carried in stock by any of the pharmacies in the area so it had to be ordered; i picked it up several days later at $300 for 50 doses and started with the first cheek dose before I got home from the pharmacy. No effect whatsoever. The next 2-3 doses had no effect either, other than giving me the feeling that I was heading down the road to opiate addiction. My psychiatrist suggested I increase the dose up from 1 dose twice a day to 2 doses twice a day, and I took that once I believe.
It was at this time that my friend told me she had scheduled a consultation for me with a psychiatrist in Beverly Hills, one she had been referred to because “he’s not afraid of treatment-resistant depression.” I was sure there was no point in going to this since 1) it was unlikely there was anything left to try, 2) this was at least an hour away with traffic and it seemed absurd that I would be able to follow up with a psychiatrist so far away, and 3) the initial consultation was a week away and it was doubtful I would make it that long anyway. But I did and when the morning of the appointment arrived my friend gave me a final chance to decline going, and finally with great reluctance I agreed to at least to go see what he had to say. So she drove us there through the sludge of traffic (with a terrible head cold she’d had for several days, I might add) and as we waited in the psychiatrist’s waiting room I stood, sat, got up, paced, sat, paced, in my usual agitated fashion. Finally, he called us into his room and invited me to tell my story; after I had spoken for about 10 minutes he suddenly stated that what I would need to do would be to stop the buprenorphine immediately, and begin a dopaminergic antidepressant like Wellbutrin or nortryptiline. I explained I’d taken the Wellbutrin before, with severe anxiety as a result, but he said he thought that instead of Wellbutrin (bupropion hydrochloride) I should take a newer form called Aplenzin (bupropion hydrobromide), as it had less associated anxiety due to the bromide group. Finally, if this didn’t help, the next step, he said, would be another MAO inhibitor. I had used the EMSAM patch in the past, but he felt strongly that I would benefit from one I had never heard of, called Parnate.
Aplenzin turned out to be impossible to find at any pharmacy anywhere, and no pharmacy was interested in ordering it unless I committed to paying for it - a reasonable request except it wasn’t covered by insurance and would cost $1200 for a 2-week supply! And the likelihood it would be tolerable for more than a few doses seemed low given my previous reaction to Wellbutrin. Plus I had just spent $300 on the buprenorphine, of which I only took 3 days-worth of before stopping. So, after speaking to the psychiatrist I started another trial of regular Wellbutrin instead of the Aplenzin. This lasted one day as I was overcome by severe nausea and headache in addition to the increased agitation and anxiety I’d previously had with it.
I called the psychiatrist again and he said it was time for an MAO inhibitor, “a real one, not EMSAM,” and again recommended Parnate, saying it would probably work faster than the other option, Nardil. “Two or three weeks,” he said.
So, I set upon the internet to research Parnate and what little information was available suggested it was rarely used anymore due to the typical MAO-I concerns (food and drug interactions), and was felt to likely increase agitation and anxiety due to its amphetamine-like structure; furthermore I discovered that it is currently FDA approved only for “Depression Without Melancholic Features,” characterized by things like sleeping too much, weight gain, and ability to be ‘cheered up’ by positive events - none of which I had. In fact, for my “subtype” of depression - “melancholic” depression, characterized by complete inability to find pleasure in things, lack of mood reactivity to positive events, agitation, guilt, etc. — Parnate appeared to be contraindicated.
Other than this, there appeared to be practically no useful or encouraging information available. While researching, however, I happened upon an intriguing website called psychotropical.com, where an entire section was devoted to dispelling many of the prevailing notions regarding MAO-I usage; the author, an Australian psychiatrist named Dr. Ken Gillman, felt strongly that not only are MAOIs quite safe and effective for all kinds of depression - whether “atypical” or “melancholic” or “psychotic” etc. — but also that they are vastly underused for reasons borne out neither by the available research nor by his clinical experience, which included many hundreds of patients he had treated through the years. Also, there were several essays providing evidence that the “modern” pharmacologic framework for depression treatment is extremely flawed, especially in its reliance on medications such as the SSRIs and Remeron (mirtazapine).
Finally, there was a portion of the website where he described depression as a sort of “mental anemia,” akin to, say, an iron-deficiency anemia, where tactics such as increasing one’s physical activity, going running, thinking more positively, etc, were likely to be counterproductive if not impossible as they did not address the underlying biochemical issues at root - a description I could definitely relate to.
Along with the website’s informational resources, Dr. Gillman also included his contact information, including how to reach him via Skype if requested. Soon enough I was videoconferencing with him, from my location in USA to his in Australia; he listened patiently to my tale of woe and my numerous questions and hesitations about MAO-I’s, and stated that he did feel that Parnate would likely be helpful, although the dosage would need to be increased as quickly as tolerated to a level that would produce the desired biochemical effect (inhibition of monoamine oxidase) - and he related that the majority of psychiatrists nowadays, whether in the U.S., Australia, or elsewhere, likely did not have enough experience with the MAOI’s to properly escalate the dosage as a result of the focus on “newer” therapies such as SSRI’s, SNRI’s, etc. during their training. But he encouraged me nonetheless to obtain a prescription from my psychiatrist and if needed he could help titrate the dosage, which he felt would need to be at least 40-50mg a day to be effective.
He also agreed to speak separately with my friend and with my family, and offered them encouragement that there was a good chance the Parnate would be beneficial, probably within two or three weeks if I could hang on a while longer.
So, I returned to my psychiatrist and discussed the possibility of trying Parnate, of which he was willing (as we had tried just about everything else), though he did think it would merely worsen the agitation and thereby be intolerable; with this in mind he prescribed 5mg twice a day, to be increased every 2 weeks as tolerated.
Dr. Gillman checked in with me via Skype nearly every day at first, and reiterated that the dosage needed to be higher and also increased faster, and to this end suggested fairly rapidly titrating the dosage to 40mg a day over the course of about a week — in fact, he had found in his experience that when the correct dosage was reached, a particular pattern of blood pressure readings would occur, and at 40mg a day my blood pressure readings, as he predicted, were indicative of having reached this point.
At that time, after the first week, I would say that I felt something positive and different, and though the anxiety and agitation were not necessarily that much improved, they were definitely not any worse; in addition, the suicidal ideations seemed to be decreased. However, my blood pressure readings were quite labile, with systolic readings in the 180-200 range followed by 80-90 range readings; in addition, there was a distinct sensation of feeling quite cold, which was odd as this was in June and during fairly hot weather. Splitting the 40 mg into two or three doses during the day helped to some extent, though there remained a very noticeable “chest agitation” that had been present for several months and remained severely limiting.
After several days of feeling somewhat better, it suddenly seemed to wear off; as a result, Dr. Gillman suggested going up to 50 mg a day, which I did in 3 split doses as the blood pressure readings continued to be quite labile. On this dose, the previous positive trend returned, and the sensation of chest agitation even seemed blunted until later in the day; and though I was still fairly incapacitated especially having been sick for so long, I did manage to go out to dinner with some friends one evening, something I hadn’t done in many months - it didn’t feel quite normal, and the chest sensation returned with a vengeance halfway through, but it was tolerable and something of an encouraging sign for what it was worth.
Still, I repeatedly voiced my doubts and ambivalence about the Parnate to Dr. Gillman during those initial 2-3 weeks, and each time he reiterated that I just needed to hold on a bit longer, and that probably after 3 weeks I would notice a significant difference. He had also connected me with another person he had been talking with over Skype who was in a similar situation as mine and who had also just started Parnate; that individual also offered support and encouragement and persuaded me to hold on a bit longer.
The change seemed to occur overnight, almost exactly 3 weeks in; one morning I woke up and knew — with some certainty — that something was different and that, for want of a better phrase, the nightmare was over; really, actually, over.
That day I went to Target, which, while seemingly a simple task, had been something I had avoided for at least 8 months due to unrelenting and unexplainable anxiety - and yet there I was, walking around, surrounded by people, completely unfazed. I called my family, who were shocked at how different I sounded - in fact, almost everyone who had spent any time with me during the months prior conveyed the same sense of amazement, often using the same words - shocking, miracle, amazing, unbelievable. The next day I went to Costco, always a chaotic mess of people of all ages, carts and tempers colliding, and cacophonous noise - and yet I felt confident I’d be able to handle it just fine and I did - and as with Target, it had been at least 8-9 months since I’d last even felt close to being able to go there.
My friend noticed with relief and gratification that I’d begun referring to the depression in the past tense; she had unconditionally helped me through months and months of a dark, suicidal illness and was ultimately the person that had set me on the path to try Parnate - for which I will always be beyond grateful.
Gone was the chest anxiety and agitation and constant panic and envy; gone, too, of course, were the suicidal thoughts. My blood pressure was still labile but within reasonable limits, and the sensation of coldness, while still present, would slowly resolve. There have been various side effects of varying duration - mid-afternoon drowsiness seems to be a particularly persistent one - but they are far better than the incapacitation and desolation of severe clinical depression.
My diet has generally been fairly liberal, though I’ve never been a fan of aged cheeses and there are usually alternatives to things like draught beer and fermented foods like kimchi. The need to avoid cold medications with dextromethorphan and pseudoephedrine was probably my biggest concern but has turned out to be not as difficult as imagined, as cold symptoms go away on their own anyway. There has been only one episode that I’d attribute to an MAO-I interaction - Costco sells frozen yakisoba noodles that have edamame mixed in, to which I developed a very severe headache starting in the occipital region about 45 min after consuming, with blood pressures over 210 systolic and nausea, and which resolved within about 60-90 min. There may have been an issue with the freshness of that batch of noodles as well.
But all in all, after an ordeal which included the failure of 38 ECT treatments, six weeks of daily transcranial magnetic stimulation treatments, multiple (and very expensive) IV ketamine doses, dozens of medications, 4 hospitalizations, and several very serious suicide attempts, it took three weeks of Parnate (with Dr. Gillman’s dosing recommendations) to completely eradicate a very severe, agitated clinical depression. I am very lucky of course, to have had unwavering support in general (and in particular the dedication of my friend who never gave up despite how bleak it was for a long time), as well as the good fortune to happen upon Dr. Gillman's website, without which, at best, I would have been on 5-10 mg of Parnate for two weeks before possibly increasing it - and would have stopped it by then for sure, with literally no hope of recovery. A sobering thought, indeed!