Consider the source. Goodbye.

I am shocked and dismayed by what I *perceive* to be a negative reaction of the entire Psycho-Babble community. I hope my suspicions are unfounded, but I dont like the way the board looks. For the few posting members who have remained as regular participants in Psycho-Babbles waning years, I have seen a single post in days. I think this is a reaction to what I have posted over the last few weeks.

1. My writing voice must have seemed overly enthusiastic, pedantic, pontificating, and assertive. I used too many exclamation marks. I was perhaps too optimistic for some people, which is perfectly understandable. Hope is sometimes a curse.

2. In my opinion, the majority of the people who continue to post on Psycho-Babble have evolved over time to have the absolute worst treatment behaviors. These people have been sabotaging their treatment for years and years. If they continue down the paths that they have chosen, they will likely die depressed and without respite.

I hope that it is only my tone / writing voice that people reject or are otherwise offended by. Is my ego too strong for some of you folks? Nevertheless, I know that the content of my words is invaluable, and likely not to be seen again by any of you. I didnt get well by changing my treatment every few days. I never used Effexor as a PRN. I reject the type of self-medication that evolved on Psycho-Babble over the years. In my estimation, it has wasted years of peoples lives.

Remission is not found in knowing how histones are affected by lithium so as to effect neuroprotection, especially in neurodegenerative diseases. Remission is not found by studying the modulatory effect of lithium on second-messenger cascades facilitated by the activity of transmembrane G-proteins, which in turn control the rate of adenyl-cyclase phosphorylation to form cyclic AMP (cAMP) from ATP.

Knowing the neurophysiology of low-dosage lithium administration had nothing to do with my decision to try it. Lithium worked for me, despite my ignorance of lithium pharmacology. I just opened my mouth and swallowed lithium pills.

I swallowed my first pill in the Spring of 1982. It was a course of imipramine monotherapy that reached a dosage of 450 mg/day. Over the top?

I got lucky in finding remission, but only while following the clinical guidelines and using the insights of notable doctors that I spoke to along the way. Over the course of decades, I picked the brains of some of the best. Up until I found remission, I followed a treatment course / philosophy that took into consideration the clinical wisdom that I was exposed to over the course of 4 decades. I did not follow amateur armchair neuroscientists with nothing to offer you *clinically*.

1. In a way that relates to the observation and treatment of actual patients rather than theoretical or laboratory studies.

2. Of, relating to, or conducted in or as if in a clinic such as: involving direct observation of the patient. clinical diagnosis: based on or characterized by observable and diagnosable symptoms.

My advice to you is to study pure neuroscience less and clinical application more find out how to actually get well. Clinicians spend their time testing treatments on real people. They are much more concerned with discovering treatments that work than being concerned with knowing how they work. In 2022, does anyone really know?

Who here knows what the accepted next step was to a failed course of Parnate by the research team at Columbia Presbyterian in 1982? Does this clinical protocol have any value today, or is it too old even though it worked?

I saw a Psycho-Babble member exclaim that there are no new drugs. First of all, thats not true. Even if it were, of what consequence is that to me, who attained remission using drugs that were available in 1996? In fact, all but one of them were available in the 1970s. Too old?

Lucky for me that I remained unconcerned with the approval date of psychotropic medications.

1.Baron Shopsin
2.Frederick Quitkin
3.Robert Post
4.Patrick McGrath
5.Andrew Nierenberg
6.William Z. Potter

* Dr. Baron Shopsin was the protégé of Nathan Klein the father of psychopharmacology - while they were both performing their ground-breaking research at NYU. Shopsin wrote a ton of literature about lithium before it was approved. Actually, he helped R. R. Fieve get lithium approved by the FDA. The FDA was very resistant to this at first. These two men and their colleagues in the fledgling field of psychopharmacology brought lithium to America. Shopsin, among other things, helped describe a new diagnosis schizoaffective disorder. He proudly showed me his published book about this illness. Im sure that I would not have understood it.

Shopsin was way ahead of curve with the study of investigational serotonergic drugs from France. None of the pro-serotonergic agents that he used on me were ever submitted to the FDA for approval. Trazodone was actually the first (non-selective) serotonin reuptake inhibitor. I was treated with it in 1982, a year after it was approved. This was while I was at Columbia Presbyterian as a subject in their clinical research program. At dosages used to treat depression, I found trazodone to be a very dirty drug. It has been reported to both agonize (stimulate) and antagonize (block) various 5-HT receptors along with its serotonin reuptake properties. Trazodone acts at both postsynaptic and presynaptic 5-HT receptors. Its effects as a ligand at receptor binding sites are varied.

What I don't like about trazodone is that it is metabolized in the body into mCPP. Trazodone is a very dirty drug. Among its properties are the blockade of acetylcholine receptors ubiquitous in the hippocampus (memory center). THEORETICALLY, it can be argued that the anticholinergic properties of trazodone would actually enhance its therapeutic potential. Sadly, trazodone is a poor antidepressant as demonstrated *clinically*. It has some use in insomnia and anxiety, but thats about it as far as positive therapeutic psychiatric effects are concerned.

I miss Baron Shopsin, although our relationship ended up being strained later on. He had a mind that was particularly well-suited to operate in a frontier that had very little scientific guidance to develop treatment principles. I ate it up. I was one of the first people in the US to take a selective serotonin reuptake inhibitor. I was probably the only one to take a pure serotonin releaser (much like fenfluramine). These drugs were available to me 3-4 years before fluoxetine (Prozac) was approved. I took 3 serotonergic investigational compounds that I doubt more than a handful of psychiatrists had access to. The 3 investigational 5-HT drugs I tried (in order) were:

1. Mixed 5-HT reuptake inhibitor and releaser Indalpine.
2. Selective 5-HT reuptake (transporter) inhibitor - SSRI.
3. Pure 5-HT releaser (presynaptic)

Only indalpine made it to market, and that was exclusively in France. I dont know why it was discontinued, but my guess is lack of efficacy in treating depression. It did have some anxiolytic effects, though. I found it to be a crappy antidepressant. It just made me yawn. Im not sure, but yawning might be a startup side-effect that emerges only during the first exposure to a SSRI.

One of the last things Dr. Shopsin said to me before moving to Indianapolis was to ask me to perform research intended to expose the unethical relationship between pharmaceutical companies and the FDA. I doubt he would have listed me as co-author, though. His ego was too big. Shopsin said that I do better work than his medical school students at NYU who were blessed with 170 IQ. My mistake was to tell him mine. At the time, I really didnt think 170 was stratospheric. I was genuinely naïve. Things between us deteriorated after that. He went on to tell me that he wasnt sure why I was so refractory to treatment. However, he said that my receptors were f*ck*d-up. When he left for Indianapolis, I was forced to find another doctor. On his last day, I chased him as he was pulling out of the parking lot with is Maserati. This was in 1986. He rolled down his window, and said but one word to me Periactin. Then he drove off. Periactin is cyproheptadine a drug primarily used as an antihistamine. However, its serotonergic actions were ignored. I never tried cyproheptadine, but my guess is that Shopsin thought its underappreciated serotonergic properties would help me.

I miss Baron Shopsin. He had a mind that was particularly well-suited to operate in a frontier of medicine that had very little scientific guidance to develop treatment principles. My access to him proved to be an invaluable resource to my future treatment decisions.

For some reason, Shopsin told me that lithium successfully treats neuroblastoma. That was in 1984. I didnt understand the significance of this at the time, but I never forgot what he said. I never looked into it until recently. I snickered and shook my head after performing a search on PubMed.

I found Malcolm Kaswan of Beth Israel. He was never a big name in the field. He did have a private practice, though. He actually brought me very close to full remission by combining tranylcypromine (Parnate) 60 mg/day + desipramine (Pamelor) 150 mg/day. It took about 2 months to get there once I began to see the first signs of improvement. Unfortunately, a delusional mania emerged in me after 6 months of a stable remission. The mania was predominantly dysphoric. It was not much fun. Kaswan had me discontinue treatment entirely. After almost exactly 2 months, I relapsed. Unfortunately, Prozac was approved by the time I saw him again. A new toy. After Prozac proved worthless to me, Kaswan refused to put me back on the drugs that got me well the first time. It made clinical sense at the time, though. So, I was forced to:

1. Suffer an anergic depression with psychomotor retardation and cognitive impairments - just like before. It was a severe depression that I would suffer with and battle against for the next 33 years. I NEVER allowed myself to make a plan or perform Google searches to find out the most effective formulas to successfully commit suicide *.

* I would like to introduce here the term I came up with that I find to be more accurate when describing many but not the majority of suicides. I would certainly exclude acts of impulse:

Lesson for TRD: Never discontinue or otherwise f*ck around with a treatment that works for you. You might not respond to it a second time.

* The bottom line is that I learned from the first two generations of psychopharmacologists. I doubt there are too many people here on Psycho-Babble who were a part of the advent of biological psychiatry. If so, I hope they weigh in.

Jeffrey Apter treated me between 1990 and 2000. He was an assistant professor at Princeton. I was his patient between 1990 and 2000. He was perhaps the most aggressive psychopharmacologists that I encountered. He was very comfortable putting me on a combination of:

1.Parnate (tranylcypromine) - MAOI
2.Pamelor (desipramine) - TCA
3.Ritalin (methylphenidate -or- Dexedrine (amphetamine)
4.Parlodel (bromocriptine)
5.T4 thyroid supratherapeutic dosages.

Good luck finding a doctor who would be willing to replicate this treatment regime for you.

One day, I came in to see Dr. Apter in a hypomanic state that was precipitated by a change made in my treatment. I'm guessing it was 1997. I told him that "we" had figured out depression, and that the next frontier would be Alzheimer's Disease. Later, Dr. Apter asked me to help him write a paper on buspirone. However, he had not taken into consideration that the severity of my depression made that impossible. I had to remind him that I was no better that day than I was when first I walked through his door. After so many years, I think it might have been a sort of desensitization process for him. Thats perfectly understandable. Maybe switching doctors occasionally would obviate this.

I once asked Dr. Apter what he thought of physostigmine well before it was approved to treat Alzheimers Disease. Physostigmine (Antilirium) is an acetylcholine acetylcholinesterase inhibitor, which is analogous to a MAOI, but spares acetylcholine rather a monoamine. I had been keeping up with Alzheimer's Disease and the advent of drugs to treat it since the early 1980s while I was researching my own illness at the Rutgers medical school library. Back then, Alzheimer's was a disease that not many people knew about. I remember thinking that it was a weird and hideous disease, but not at all common. I was fascinated and horrified at the same time, but I didnt feel people in general had anything to worry about. That was the consensus of experts at the time. Then, modern medicine helped people live into their 90s. This was a different situation entirely. I think that Aricept (donepezil) is the most often prescribed of these drugs. There are less than a handful of cholinesterase inhibitors. Namenda (memantine) plays the role the go-to adjunct if Aricept monotherapy fails to work well enough. I really dont know why scientists thought a drug that blocks NMDA glutamatergic would be clinically useful. However, memantine might possess an as of yet undiscovered pharmacological property. Unfortunately, the consensus among neurologists today is that these drugs really dont work. Sad. My mother contracted Alzheimers. The combination of Aricept (donepezil) and Namenda (memantine) was inert. However, Aricept caused her to lose her sense of taste, or made food taste different and unpalatable taste perversion. I had her doctor take her off both drugs. Perhaps her greatest pleasure was the taste of food. I refused to take this away from her when the drug that caused the taste perversion was useless.

I began taking lithium over 10 years ago. I experienced a very real, but mild improvement within 6 hours. After several months of taking an inadequate regime, I decided to keep it onboard for only one reason. I wanted to reduce my risk of getting Alzheimers Disease. People with a history of unipolar or bipolar depression are *much* more likely to develop Alzheimers. There is a plethora of papers to be found on PubMed describing lithium as having the property of reducing the risk of getting Alzheimers. I first encountered this literature 20 years ago.

By the way, this prophylactic effect of lithium occurs at dosages far lower than the lowest dose available. I stuck with 300 mg/day because that is the dosage that produced the mild improvement. At low dosages, 300-450 mg/day, lithium usually does not produce any long-lasting side effects. There will likely be some mild psychiatric side effects, including sedation, brain fog, and passivity (not to be confused with apathy). These are the things that will probably disappear by 2 weeks.

Why do I need 300 mg/day of lithium to produce an improvement in my bipolar depression when I relapse at 450 mg/day? (Lithium also works for unipolar depression, most often as an adjunct). Okay, time for a pharmacology lesson. Lithium has a bimodal response curve. People who present with depression only, including bipolar depression, improve at low dosages. However, high dosages (up to 1500 mg/day) are necessary to treat bipolar mania and as prophylaxis of bipolar mania - and possibly a necessary component when treating ultra-rapid cyclicity. This is a *clinical* observation. A pharmacological observation shows that lithium also has a bimodal distribution curve when looking at glutamatergic activity.

Low dosages = Successful treatment of depression.
Low dosages = Increased glutamate release.
Low dosages = Increased brain activity.

High dosages = Successful treatment of depression.
Low dosages = Increased glutamate release.
High dosages = Increased brain activity.

20 years after I moved on from Dr. Apter to Matthew Smith at NYU, Apter found a way to make a fortune. I was surprised that he had had such entrepreneurial savvy. He shifting his career from clinical psychiatry to founding a company that performed clinical trials that were paid for by pharmaceutical companies (by the head). He owes me money. He opened his clinical trial operation by focusing exclusively on Alzheimer's Disease. Im reluctant to bust his chops, though. I still have a good relationship with him.

I felt a sense of urgency to convey to Psycho-Babble what I had learned from true experts along my journey. Once I responded to treatment, I had access to the memories of my treatment history and the insights of the first two generations of psychopharmacologists. I listed many of them by name here. I was finally able to put together the knowledge, experience, and clinical gems that I was taught by these people. In 1992, when I was a research inpatient at the National Institutes of Health (NIH), I began to witness in the newest generation of biological psychiatrists the loss of the insights of the doctors who treated me outright or with whom I had consultations.

Too many people on Psycho-Babble appear to not allow medical doctors manage their treatment. *No* doctor would ever contemplate prescribing Effexor for intermittent use as a palliative PRN. The first important piece of expert advice that I received came from Columbia Presbyterian. They advised me to avoid pulsing antidepressants. Of course, this is something seen commonly on Psycho-Babble. *No* doctor would keep giving their patient the same drugs over and over again and expect different results. I know that the efforts of every single member of Psycho-Babble are brave and noble. They demonstrate great compassion and altruism. However, they also demonstrate a woeful lack of education and insight regarding the *clinical* applications of the information they find on PubMed. Remission is not found in knowing how histones are affected by lithium so as to effect neuroprotection, especially in neurodegenerative diseases.

My advice is that you spend more time researching clinical methods of treatment that result in remission rather than researching the role of adenyl cyclase in producing second-messenger cascades. Pay attention to the old along with the new. With the exception of lamotrigine, the rest of the drugs used in my treatment regime were available in the 1970s. Lamotrigine came out in 1996. I tried it as soon as it was approved. Why? Because the seizure disorder unit at the NIH told the clinical pharmacology department that a whole bunch of their patients taking lamotrigine reported that their depression improved dramatically. Their improvement was probably short-lived, though. They didnt tell my unit that, though, probably because their patients hadnt been treated with lamotrigine for very long when they reported the phenomenon Dr. Potter.

So, all of the drugs that I am currently responding to were available in 1996. I was 36 at the time. Isnt that a kick in the *ss? Instead, I struggled for another 24 years until finally, at age 60, I was freed from the bondage of bipolar depression. I doubt very much I would have found remission by using Effexor periodically for a few days as a palliative PRN, and never taking an antidepressant for more than 2 weeks. To do this is absolutely insane. This would be immediately clear to you were you to have had the privilege to be treated by some of the best minds in the field.

SMART: To achieve remission, I used a strategy that I have already described on Psycho-Babble numerous times.

LUCK: Over ten years ago, I decided to continue taking lithium in order to reduce my risk of getting Alzheimers Disease. I used 300 mg/day for prophylaxis. Dosages of lithium far lower than this have been reported as being effective. So, it turns out that had I not been taking lithium in the background, I would not have achieved remission two years ago. It was surely inadvertent.

Sometimes quite often, actually - serendipity plays a role that is just as important as the decisions of your physician.

For those of you who want to enhance your chances of finding a successful treatment for their treatment-resistant depression, you might find some value in what I have written over the last few weeks. If you are not receptive now, perhaps you will be a year from now. You might as well go back over the last few weeks and copy my posts to your computer.

I havent decided whether or not to post on the board anymore. If anyone wants to converse with me, you can use Babblemail. No one else will know.

I will not be writing anything so comprehensive and post it on Psycho-Babble again. This must include those posts of mine that are scattered around the board.