Homeostasis and Patience. Easy to say, hard to do.

This is a long post. However, since it is my last one (again), I encourage you to read it in its entirety.

Psycho-Babble might very well have saved my life. I hoped to return the favor. I must have done everything wrong because I certainly didnt accomplish that. Most people who are treated successfully on Psycho-Babble have historically disappeared, never to be heard from again. I didnt want to be one of them.

Frankly, I can see how my words have been off-putting. Maybe my ego is inflated. If so, I like it that way. I think assertive or aggressive is a more apt characterization. I was too frustrated to continue watching business as usual. Bad habits. Regardless, it would be to your benefit to ignore my attitude and read the content. Theres a lot to benefit from. At least, thats my current opinion. That could change.

Here are the two most important words in the English language for treating Major Depressive Disorder and Bipolar Depression:

For some people, continuing to neglect these two words might be a tragic oversight.

Every day, people with depression kill themselves because they failed to respond to a handful of treatments. What about trying Effexor? If a doctor told a patient with severe Major Depressive Disorder or Bipolar Depression to take Effexor for only three consecutive days and see him in a month, what might be the clinical results of such patient instructions? Yet, this is precisely how one person on Psycho-Babble uses Effexor today, as he described in one of his more recent posts. This person is perhaps the most intelligent and knowledgeable layman I know regarding the facts reported by neuroscientists. He has a remarkable memory for detail. He synthesizes ideas that are considerably more insightful than mine. However, he is also the absolute worst role model for any of you to follow if you want to feel and function better.

I imagine this person has constructed a website for everyone to migrate to as he did once before. I genuinely opened my heart to this person numerous times over the last 20 years, despite our history of arguments. I invite you to review his posts beginning in 2001, in which he insisted to the Psycho-Babble community that antidepressants dont work. I challenged him by insisting that they do. It was a rather tumultuous intercourse. What happened? This person now fills his gut with all sorts of drugs, nutraceuticals, and anything else he can get his hands on. The list of substances that he takes, as he recently provided us with, is insanely long. What substance does what? I have never seen him go more than a 2-3 weeks without changing something.

From what I remember, this is the first time in 25 years that this person reported experiencing remission. After my use of quotation marks around the word remission, he all of a sudden has his first remission. His explanation of being absent for two weeks is that he wanted to enjoy his "remission". Thats one hell of a case of serendipity. God works in mysterious ways, I suppose.

It would be instructive to ask this person what persuaded him that antidepressants do work after all. He has been using antidepressants regularly ever since - but THE WRONG WAY. For those who have had a terrible time finding an effective treatment, thinking outside-the-box is often necessary to find one. However, inside the box are tools that have been proven to work for well over half a century, but only if they are used the way that the field of medicine has established to be effective. Using a screwdriver to pound a ring-nail into 3/4 inch plywood is usually futile. The tools inside the box thus become useless. Worst of all, no course of treatment is ever carried out long enough to arrive at conclusions about that treatment. No information is gleaned - just circles.

I recently offered this person a treatment idea that I had thought up for him. Perhaps I was motivated to do this just to prove that I was smarter than he is?

For all I know, this treatment could make this person monumentally worse. However, taking Effexor for only 3 consecutive days is not very likely to produce remission.

How can anyone with this persons history of treatment failures take nortriptyline, respond to it with a 75% improvement (as reported by him), and then stop taking it altogether in order to play with more toys? Recently, he reported to the community that he was going to take Effexor for a few days. Whenever he does take Effexor (multiple times), he limits the dosage to 37.5 mg/day. The dosages of Effexor that doctors find effective range between 150-300 mg/day. This is the person that you give enough credibility to and look towards for advice? How about remaining on nortriptyline as the core treatment, and building a regime of adjuncts around it? To do this is a no-brainer. I think this person offers great information. It is probably good advice to listen to what he says, but stay far away from what he does.

Most of the established drug treatments for depression require 6 weeks as a minimum to evaluate their utility. If, after 6 weeks, there is no significant improvement, dosages must be pushed higher to tolerance. What does that mean? I guess that threshold is different for each one of us and for each drug tried. It takes an enormous amount of patience and self-discipline not to make any changes along the way. For me, I gladly made the decision to trade significant side effects in order to experience the world without being suffocated by the warping of my psyche by depression. I wanted to return to society. I wanted to be with the rest of the people of the world who I watched for decades laughing and frolicking on the beach while I remained chained to the bottom of a murky ocean from which there was no escape. Well, I guess suicide is a form of escape. I was sick and tired of being alone in the world, even while being surrounded by family and friends. So, I put up with sitting on the toilet for between 30-45 minutes until I was able to urinate. Because of a Nardil side effect, I was petrified that I would have to go to the hospital to be catheterized. I suppose thats worse than fainting from dizziness that was the result of taking Nardil. How about trading the ability to orgasm for a cure? Of course, orgasm is not much of a problem when an SSRI like Paxil robs you of your desire to have one.

Often, a drug will produce start-up side effects that either mitigate over time or disappear altogether. They can also reemerge with subsequent dosage increases. How do you know whether or not side effects will dissipate unless you remain on a treatment regime for 2 weeks or longer?

Statistically, there are very few people who fail to respond at all to 6 weeks of antidepressant treatment who later go on to respond by 12 weeks.

I see a resurrection of the antidepressant pipeline. Novel chemicals and treatment protocols are emerging. One drug that I have been following for years is zuranolone (formerly SAGE-217). Zuranolone is the second in a series of compounds that act as positive allosteric modulators of GABA-A receptors. The first of this series to be approved by the FDA was brexanolone (Zullresso). It was granted the indication for postpartum depression. Unfortunately, it can only be administered by I.V. infusion. Zuranolone is, by contrast, administered orally. It is reported to produce a robust antidepressant response in both Major Depressive Disorder and Bipolar Depression within the first week. It even seems to work well when taken intermittently.

What we do to are brains with a procession of drug trials is to assault it over and over again, making some of us less likely to respond to anything. Im sure my prior drug exposures were no help. I just got lucky.

How can anyone with this persons history of treatment failures take nortriptyline, respond to it with a 75% improvement (as reported by him), and then stop taking it altogether in order to play with more toys? Recently, he reported to the community that he was going to take Effexor for only a few days for the temporary relief that it might provide him with. Whenever he does take Effexor, he limits the dosage to 37.5 mg/day. The dosages of Effexor that doctors find effective range between 150-300 mg/day. This is the person that you give enough credibility to so as to follow him in order to escape me? What about remaining on nortriptyline as the core treatment with its 75% improvement, and building a regime of adjuncts around it? This is truly a no-brainer.

Question: How do you expect the brain to travel a long journey towards remission (which can take a year or more) when you are constantly changing the rules of the game on it?

The brain's journey towards establishing a new and functional homeostasis requires a new set of equilibriums to be established. It is not necessary for that equilibrium to arrive at the same values that it functioned at before the emergence of depression. In fact, this is almost impossible. The therapeutic effect of currently available traditional antidepressants is not what the drug does at the synapse. If it were, you would feel much better within 30 minutes of swallowing your very first pill. Rather, it is what the brain does in response to the actions of a drug at the synapse that is the therapeutic effect.

The therapeutic effect of a traditional antidepressant is the product of the brain making adjustments to its innumerable thermostats as a reaction to its exposure to a drug. The brain does all the work, not the drug. The brain is *forced* to adjust synaptic receptor sensitivities, gene expression, negative feedback loops, modulation of neural excitability by heteroreceptors, postsynaptic second messenger cascades that direct the cell nucleus, peptide neurohormone release, co-receptors function, plus a whole bunch of other stuff that I am clueless about. Again, the brain does all the work, not the Prozac.

The following analogy occurred to me. Forcing the brain to establish new set points of its innumerable "thermostats in response to drug exposure can establish a functional dynamic that approximates that of an otherwise healthy brain. It is like transposing a song into another key. The song remains the same because the ratios of the differences in frequencies between the notes remain the same.

Someone recently replied to me regarding Psycho-Babble. He said that it had the most expertise on the Internet. So I asked him, "Expertise in what?". He never replied. How would you answer that question?

Desperation can sabotage the best of treatments. If your doctor is wholly inadequate, I recommend that you spend more of your research time devoted to researching the clinical pearls of wisdom offered by expert clinicians rather than the pure research of neuroscientists. If you need to fix yourself because no one else seems capable of doing that, read more about what works rather than spending all of your time focusing on how things *might* work. Studying both is rational. Theorizing is stimulating and fun. You might even synthesize your own clinical pearls of wisdom that have gone unrecognized by the entire medical field. In 1983, Wilma Harrisonm M.D. of the Columbia depression research department laughed in my face when I told her that I thought dopamine was involved in the genesis of depression. I first asked for bupropion (Wellbutrin) which was not marketed at the time. Her boss, Frederick Quitkin, M.D. said no. When I then requested bromocriptine (similar to pramipexole / Mirapex) as an alternative, she laughed again, remarking that it would be fine if I wanted to throw up all day long. I left.

Newly identified treatments such as psilocybin and ketamine have the potential to elicit an antidepressant response within hours. Patience will no longer be a requirement to achieve remission. However, establishing homeostasis will be.

Good luck to all of you. Im certain that everyone I came to know here will remain good people.

P.S. Roslynn no longer communicates with me via Babblemail. If this is the result of any of your actions, then it is on you to make sure she is still around a year from now. Had I not reached out to her one evening, she said that she would have carried out her plan to kill herself the next morning.

Some see things as they are and ask why.
I dream of things that never were and ask why not.

The only thing necessary for the triumph of evil is that good men do nothing.

Homeostasis and Patience. Easy to say, hard to do.

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