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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by linkadge on November 29, 2022, at 15:58:04
We decided to go on the past combination that seemed to work best.
- venlafaxine 37.5
- mirtazapine 7.5mg
- lithium 300mg
- ritalin 10mgWellbutin was doing something, but it wasn't nearly as grounding as ritalin.
Linkadge
Posted by rjlockhart37 on November 30, 2022, at 3:30:53
In reply to Saw doctor today, posted by linkadge on November 29, 2022, at 15:58:04
wellbutrin from my limited knowledge is less worked on dopamine, and more norepinephrine. It always gave me jitters and anxiety, edgy. I tolerated it for a while, but then edgy side effect happened. Hope ritilin works good
Posted by SLS on November 30, 2022, at 8:05:38
In reply to Saw doctor today, posted by linkadge on November 29, 2022, at 15:58:04
> We decided to go on the past combination that seemed to work best.
>
> - venlafaxine 37.5
> - mirtazapine 7.5mg
> - lithium 300mg
> - ritalin 10mg
>
> Wellbutin was doing something, but it wasn't nearly as grounding as ritalin.
>
> Linkadge
Most of my angry words towards and about you were actually an expression of great frustration - frustrations about seeing you continue down a path of accepting merely palliative relief.I renew my suggestion for your staying away from SRIs for 3 months. I *think* the dynamics of your serotoninergic system(s) have become overly sensitive due to an unending course of on/off/on exposure to SRIs. This includes non-response and acute side-effects.
From what you have written recently, I suggest that at a point in the not-too-distant future, you begin attacking your illness with things that you have NOT tried yet. In my opinion, my limited knowledge of your treatment behavior has you running around in circles.
To me, the most obvious selection of drugs at this point are a combination of:
1. Nortriptyline
- respect the existence of two distinct effective dosage ranges - each forming a therapeutic window.
- low dosage range: 25-75 mg/day
- high dosage range: 100-150 mg/day
- use blood tests of nortriptyline blood levels in order to determine which range to remain at.
- if you respond to nortriptyline as robustly now as you did before (75% improvement), leave it in place indefinitely and build a regime around it. Just keep on taking it unless contraindicated with a new treatment choice, or side effects become intolerable. Give the side effects that emerge with each dosage increase time to recede before increasing the dosage again. You might want to wait until 2-3 weeks have passed after the side effects mitigate. Perhaps you can gage your titration rate according to a2. Lithium - Continue low dosaage at 300 mg/day.
3. Wellbutrin SR or XL - 300 mg/day
4. Palliative treatments that are not contraindicated and that you know gives you enough relief that it will allow you to continue trialing different treatment regimes. (Ritalin, etc.)
5. Anything else you can think of that targets *remission* rather than a palliative dead-end. The key might be to *design* treatments around drugs that helped you in the past that might work synergistically rather than additively. Which other treatments have helped, regardless of magnitude or brevity? Make a list of treatments you have tried to give you some framework around which to choose drugs that help and avoid drugs that hurt.
Perhaps this approach will be of little value to you in your pursuit of a truly robust improvement. However, I do not think it a waste of time to try a very different and logical strategy to attack your illness. At the very least, use logic to determine which treatment regimes to avoid for lack of efficacy or for producing intolerable side effects.
I do not envy your situation, including your *current* denial of access to putatively effective treatments. It is *paramount*, therefore, that you use your formidable critical thinking to troubleshoot the problem of access. You would be surprised by what you can accomplish for free using a the phone or email. You have an obstacle. Figure out ways to surmount it. I think is a better use of your time right now to do the legwork and figure out how to get drugs that are novel to your brain (Nardil, for example) rather than cycling endlessly between failed treatments. Look for a university research program that will treat you *inpatient*. Allow the clinical researchers navigate your treatment and observe the results. This includes different treatment regimes - including new ways to use old drugs, including those you had "failed" on. You might also have access to novel compounds in the approval process. If you respond, the research program will likely supply you with a drug until it is approved and becomes available.
Experts will determine what is to be defined as treatment "failure" and treatment "success" - not you. Give research doctors the opportunity treat your challenging case. That's what they do for a living.
The cool part of doing this is that it's FREE. It will cost you only the funds necessary for transportation.
- Scott
Posted by SLS on November 30, 2022, at 14:33:09
In reply to My frustration in watching you. I apologize. » linkadge, posted by SLS on November 30, 2022, at 8:05:38
Linkage
I read that you have had problems with nightmares. If any kind of PTSD or complex trauma disorder is hinted at in your history, I would avoid SRIs for now and try taking prazosin as 10 mg t.i.d. with or without buspirone or clonidine. I would choose buspirone as an adjunct before clonidine. Clonidine has a liability to exacerbate a preexisting depression or precipitate depression in someone who has no history of depession.Guanfacine might work for PTSD, but the results of investigations are equivocal.
- Scott
Posted by SLS on November 30, 2022, at 14:34:02
In reply to My frustration in watching you. I apologize. » linkadge, posted by SLS on November 30, 2022, at 8:05:38
Linkage
I read that you have had problems with nightmares. If any kind of PTSD or complex trauma disorder is hinted at in your history, I would avoid SRIs for now and try taking prazosin as 10 mg t.i.d. with or without buspirone or clonidine. I would choose buspirone as an adjunct before clonidine. Clonidine has a liability to exacerbate a preexisting depression or precipitate a de novo depession.Guanfacine might work for PTSD, but the results of investigations are equivocal.
- Scott
Posted by linkadge on November 30, 2022, at 15:33:28
In reply to My frustration in watching you. I apologize. » linkadge, posted by SLS on November 30, 2022, at 8:05:38
SLS. I would encourage you to be a bit more concise in your responses as I don't have the emotional drive to read through everything (in full respect of your intentions).
>I do not envy your situation, including your >*current* denial of access to putatively effective >treatments.
Again. You're just not getting it. I don't control the prescription pad. Your notion of "access" is flawed. Perhaps you have doctors that give you whatever you ask for, but this is not my experience.
Also, I'm not even 100% convinced I am suffering from depression (in the sense that other people here may be experiencing). Lithium helps, but antidepressants are not (or to a very limited extent). Ritalin helps. I may be dealing with bipolar II (in denial) and ADHD. I don't know.
So please don't assume that my situation is as simple as popping an antidepressant that worked at one point. Everything fluctuates and sometimes I feel better coming off the antidepressant (not just a rebound effect).
Last year, I did well for 6 months on just lithium, ritalin and a punch of mirtazapine for sleep (at an antihistamine dose) plus omega-3 and methylfolate. Things went off the rails in the spring (as they often do). But again, its' complicated. It's not just a matter of taking the same thing every day and feeling fine. It has NEVER worked that way for me, and I do (and will continue) to make ongoing adjustments.
Linkadge
Posted by SLS on December 1, 2022, at 11:59:47
In reply to Re: My frustration in watching you. I apologize. » SLS, posted by linkadge on November 30, 2022, at 15:33:28
Linkadge,
Cc: Psycho-Babble,
Please read this entire post giving it your full attention. The decisions are yours, not mine. They are not even your doctors.
Which of the following drugs do you not have access to?1. Nortriptyliine
2. Wellbutrin / bupropion
3. Lithium
4. Lamictal / lamotrigine (?)
This is the regime that I thought was better than running back to Effexor - a drug that you can't tolerate at dosages that most people respond to (150-300 mg/day). NO NARDIL is necessary. I never said that it would be. Are you exquisitely sensitive to side-effects of Effexor? Right now, it seems that you are. Did you experience these same side effects to the same degree the very first time you took Effexor? What dosage of Effexor were you able to tolerate the first time you took it?You have never tried combining the drugs that I listed above, right? (Different is different). I should think that it is worth trying at this juncture. At the very least, it would require you to abstain from taking SRIs for a few months. (3 seems to be the magic number).
Is it a genius treatment?
Not even close. It is simple and logical. Why did you stop taking nortriptyline if it gave you a 75% improvement? That's a HUGE number. Is it logical that you did this? Keeping nortriptyline on board indefinitely while you build a regime around it is a no-brainer.
Wellbutrin helped you to an unsatisfactory degree. But it did help you. Adding it is another no-brainer.
Lithium continues to improve your condition at 300 mg/day. Dont change it. Keep it exactly at 300 mg/day. Doing this is another no-brainer.
Lamotrigine? Unless you had intolerable side effects in the past, taking lamotrigine at a dosage between 200-300 mg/day might be a necessary component of your treatment regime. You reported in the past that you had suspicions that there was a bipolar component of your depressive illness. Isn't there a first-degree relative that is bipolar or schizoid? If so, then adding lamotrigine is another no-brainer.
If you can tolerate lamotrigine at 200 mg/day, It makes little sense to discontinue it as you go through subsequent drug trials. Adding lamotrigine as an adjunct to treat TRD unipolar depression is pretty close to being a no-brainer. If you are experiencing side effect that are of great magnitude and persistent, just discontinue it. Be aware that side effects often disappear over the course of weeks or months. Responding well to *any one dosage* often takes 3-4 weeks, so wait before increasing the dosage. For me, this was true of cognitive and memory impairments. I found them to be more of a startup side effect than a persistent one. START LOW and GO SLOW. Don't allow a rapid titration to *trigger* side effects.
One of the first tidbits of wisdom bestowed upon me as a patient at Columbia Presbyterian was that "pulsing" antidepressants is perhaps the worst thing you can do (Frederick Quitkin). It makes people less responsive to antidepressants and often produces a sensitivity to side effects. Use Quitkin's advice - not mine. Stay away from SRIs for 3 months. This is another no-brainer.
Pulsing is just one of the things that you *seem* to be unaware of. You can't talk to Quitkin or any of the other research clinicians I saw. They are all dead.
Do you think for one second that I would settle for a merely palliative treatment? I decided to leave Columbia when, after much research into the dopamine system, I decided that Wellbutrin was a logical next step. It was still investigational at the time. Quitkin refused my request. This was on top of telling me that I was likely to be in the 85% who were not treatable (Michael Liebowitz). I made a phone call to Donald Sweeney. I forgot how I found him. He had been using Wellbutrin in a clinical trial. When I spoke to him, I described my rationale for using pro-dopaminergic drugs. He told me that Wellbutrin didn't work the way I thought it did, even though it was listed as a dopamine reuptake inhibitor. However, he said that the drug looked good. Sweeney's clinical trial of Wellbutrin had been completed. So, he recommended that I try Baron Shopsin.
-----
Donald Sweeney - Obituary.
----
Baron Shopsin memorium in "Nature":
https://www.nature.com/articles/s41386-018-0060-6
----
Baron Shopsin was one of the first investigators of lithium in America, and a protege of Nathan Klein when they were both at NYU.
https://pubmed.ncbi.nlm.nih.gov/?term=shopsin%5BAuthor%5D+lithium&sort=pubdate&size=200
---
Shopsin also went on to help describe schizoaffective disorder as a single illness. His books are still out there somewhere.
----
One of Shopsin's last papers:
https://pubmed.ncbi.nlm.nih.gov/25287313/
Shopsin was one of the psychopharmacologists who asked me to help him write a paper for publication. Interestingly, it was to be about amoxapine and the unethical practices of the FDA in approving it. After poking around the medical school library at Rutgers, I discovered evidence to corroborate Shopsin's thesis. Unfortunately, Shopsin relocated from NYU in Manhattan to Indianapolis, so the project remained incomplete. That was in 1986.
----
This is a more recent treatise regarding the same thesis:
"From FDA to GSK: The Dangerous Partnership between Government and Big Pharma"
https://www.huffpost.com/entry/from-fda-to-gsk-the-dange_b_115117
----
The only drug that Shopsin saw me very much improved on was nomifensine. It was an investigational drug that was a potent dopamine reuptake inhibitor. It was used as the "gold standard" biological probe to investigate dopamine function.
Shopsin insisted that nomifensine (later to be approved as Merital) was "a piece of sh*t", but he eventually relented. It was the only drug that he ever saw me significantly improved on. However, the antidepressant response to nomifensine didn't last for more than a week. Shopsin was an investigator of Wellbutrin, and treated me with it using a dosage of 900 mg/day. It exacerbated my depression to a moderate, but very perceptible degree. When I discontinued it, I experienced a discontinuation rebound-improvement. This was a common reaction for me with tricyclics and MAOIs. However, this never occurred when discontinuing SSRIs. I can't remember it happening with SNRIs either.
----------------------------------
An extremely important example of how the same drug can affect the same person in very different ways is represented by my experience with Effexor. I have been on Effexor at least a handful of times with some success at a dosage of 300 mg/day. 225 mg/day was ineffective. The last time I tried Effexor, things were very different. I had just switched to Effexor immediately after a trial of Trintellix. Trintellix effectively played the role of an experimental pretreatment to Effexor. Upon starting Effexor, I reacted to it in a very different way. It exacerbated my condition and gave me some pretty severe zombie brain-fog effects. It felt very strange and resembled dissociation.Effexor, then, is one drug that produces different clinical effects, depending upon which drug(s) preceded it. Stay away from SRIs during these drug trials (experiments). Use all of your tricks to ameliorate your depression as you move from drug trial to drug trial. Keep your head above water. These are palliative measures only, since that seems to be the limit to what they are capable of helping you.
* And for God's sake, restart nortriptyline and leave it there indefinitely (if you did indeed experience a 75% improvement on it).
Once your trial of above drugs is complete, you will probably be at the 3 month mark. Then you can reintroduce a SRIs. I would add either Effexor or Pristiq before going with any other SRIs. KEEP IN PLACE the above drugs if you reach dosages that are normally therapeutic.
If you reach another dead end, then make phone calls to doctors and ask them (through their secretaries) if they use Nardil to treat depression. If you turn up empty after calling as many doctors you can find locally (1-2 hours by car), then contact university psychiatric departments. Either they will place you into a research study or treat you outright. I would expect them to provide you with Nardil if they feel its warranted.
I am absolutely sure that you will think of alternative strategies to find treatments outside the sphere you have been stuck in for decades.
Searching for expert clinicians who will treat you with a MAOI if necessary should take up *all* of your time - not studying neuropsychopharmacology. Let the medical community do that.
This the best that I can contribute right now. Oh yeah. Moclobemide is a sh*tty drug for *most* people. I've described why in the past. Descriptions of my experience with moclobemide was clinical and observational rather than being biological guesses. Psychiatrists in clinical practice often give greater weight to their observations and those of their colleagues.
Let the doctors determine if you are an odd-ball that responds only to sub-therapeutic dosages of standard antidepressants. Personally, I am dubious of this. You may have developed an alteration in the dynamics of your serotonin system(s). Although this might be your current reactivity to SRIs, this could be the result of pulsing these drugs repeatedly.
Let the doctor be your doctor as long as he or she is a good one and has your confidence. Whether or not a doctor uses MAOIs is a good index of experience and competence.
That's it. The rest is up to you.
Bye...
- Scott
Posted by linkadge on December 1, 2022, at 14:33:33
In reply to Re: My frustration in watching you. I apologize. » linkadge, posted by SLS on December 1, 2022, at 11:59:47
SLS,
As I just said. I do not have the capacity right now to read a response (including links) of that length. I am (as always) open to new ideas, but please present them to me in a manageable way. Again, I respect your intentions. Pick your top idea an put it into a paragraph (or not).
Linkadge
Posted by SLS on December 1, 2022, at 21:42:42
In reply to Re: My frustration in watching you. I apologize., posted by linkadge on December 1, 2022, at 14:33:33
> SLS,
>
> As I just said. I do not have the capacity right now to read a response (including links) of that length. I am (as always) open to new ideas, but please present them to me in a manageable way. Again, I respect your intentions. Pick your top idea an put it into a paragraph (or not).
>
> LinkadgeFirst of all, my memory and cognitive impairments appeared in the autumn of 1980. I struggled decades being unable to read more than two sentences word-for-word. I learned how to skim in the medical school library at Rutgers after I was told that I was untreatable. It is only over the last two years that I have been able to read beyond a paragraph.
Strangely enough, over the course of the last 3 decades, I could write 10-20 paragraphs for every one I could read.
My point is this - You are no different than a great many others. There is no rush for you to read anything. My crap will be here forever(?)
Also, there is no debate to be had. I would be happy if anything that I wrote to you is ultimately helpful.
I've been trying to help you for years, Linkadge. Right now, I need some time to get over my indigence.
- Scott
Posted by SLS on December 2, 2022, at 7:26:07
In reply to Re: Saw doctor today, posted by rjlockhart37 on November 30, 2022, at 3:30:53
> wellbutrin from my limited knowledge is less worked on dopamine, and more norepinephrine. It always gave me jitters and anxiety, edgy. I tolerated it for a while, but then edgy side effect happened. Hope ritilin works good
Your characterization of Wellbutrin falls in line with those of some experts. However, I think most the research community will tell you that they still have no idea how Wellbutrin works - this after 56 years of study.
With Wellbutrin, I didn't experience anything close to the strange stimulation / anxiety that the tricyclics produced in me as a startup side effect. These drugs act to great degree as norepinephrine (NE) reuptake inhibitors. These phenomena doesnt occur with me and TCAs anymore. Something is different, now that I have been exposed to TCA multiple times. The drugs that you trial and fail to respond to therapeutically nevertheless produce lasting alterations in brain function. Ask yourself if there are any drugs that affect you differently now compared to the first time you tried it. Baron Shopsin gave me the advice to remain as "clean" as possible during the time between trying new compounds or newly discovered combinations of old drugs.
Frederic Quitkin and Wilma Harrison of Columbia Presbyterian / New York State Psychiatric Institute told me that it was never a good idea to "pulse" antidepressants - on/off/on/off... It often leads to treatment-resistance and side effects that are either new or of greater magnitude. This is perhaps most true of Paxil (paroxetine) among the SSRIs. After the first exposure to a psychotropic drug, the brain is left altered in some way, probably indefinitely or persistently. Treatment choices should take this into consideration.
Paxil is the SSRI most likely to work, the SSRI most likely to stop working, and the most likely to become ineffective once stopped and restarted. Paxil is also the SSRI likely to produce the most robust side effects. Weight gain, sedation, anticholinergic effects, and perhaps anorgasmia. They tend not to mitigate over time. However, Paxil is the go-to SSRI for anxiety disorders.
When I first took a MAOI for the first time, I experienced a complete cessation of dreaming or at least had no memories of dreaming. This was most likely due to a ubiquitous side effect related to the inhibition of REM sleep. So much was it inhibited in me, that upon a rather abrupt discontinuation, I was dreaming while my eyes were wide open. I could see my bedroom, but could not get myself to move, despite my efforts to get out of bed and stand up. This is called sleep paralysis. It is a manifestation of the REM-rebound effect caused by the discontinuation of a potent REM sleep inhibitor like the MAOIs.
Interestingly, many people with depression feel less depressed the day after one nights total sleep deprivation. I found that the improvement I experienced didnt last much beyond late morning. After that, I deteriorated again. Scientists have remarked on this phenomenon as early as the 1970s. Some people incorporate a sleep deprivation schedule to augment drug therapy.
For a healthy person, REM sleep begins no sooner than 90 minutes after falling asleep (REM latency). For depressives, it is 45-60 minutes. The more severe the depression, the shorter is the period of REM latency. The sleep rhythm is somehow altered by the exposure to an antidepressant particularly TCAs and MAOIs. I now dream on both Parnate and Nardil regardless of dosage. I also no longer experience drug-discontinuation REM rebound. Its been like this for over 20 years.
I think we might be better off not f*ck*ng around with drugs so cavalierly
- Scott
This is the end of the thread.
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