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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 6 of 6. This is the beginning of the thread.
Posted by undopaminergic on December 8, 2023, at 9:20:14
With reference (for background and context) to my last thread about vortioxetine (Brintellix; Trintellix), at:
https://www.dr-bob.org/babble/20230117/msgs/1122171.htmlAfter a few months on 15 mg of vortioxetine [VTX], on 05 December 2023, I took the 20 mg dose for the first time. Therefore, it is still early to come to any conclusions. The half-life of this drug is around 66 hours, and it takes more than a week to reach steady-state:
https://en.wikipedia.org/wiki/VortioxetineAt first, I was a little disappointed as I didn't notice much improvement, but today I've had a more promising experience.
Regarding how I'm feeling at different times, I've long used the terminology that it is "pretty good", "good", etc., but now I'm finding myself using the terminology "pleasant", and occasionally "comfortable". Another thing I've noticed is that my armswing when walking is better -- this is an anti-Parkinsonian effect.
I'm speculating that I may be experiencing more of the 5-HT1A agonism, because I haven't felt much change in the symptoms I associate with serotonin transporter blockade, eg. my anorgasmia did not worsen, and my apathy also did not worsen, but even on the contrary. For example, today I had no problems staying out of bed after getting up.
Feelings of reward in response to positive experiences, such as completing a task, have returned. Moreover, I've noticed myself looking forward to certain activities such as writing in my diary.
This (20 mg) is the highest recommended dose of VTX, and I doubt the doctors are going to increase it more. Assuming that is correct, I have a couple of other things to suggest we try next:
(I) add lithium, up to 300 mg, and
(II) replace trimipramine with nortriptyline.-undopaminergic
Posted by SLS on December 8, 2023, at 9:43:46
In reply to Vortioxetine revisited at 20 mg, posted by undopaminergic on December 8, 2023, at 9:20:14
Hi, U_D.
You make a perfect example of the patience that I explained was necessary to achieve success.It can take between 2 weeks to 3 months to allow the drug/brain interaction do their work. I hope you now understand why the words I shouted at people were, nevertheless valuable. For those people who continue to avoid me, perhaps you can do *them* a favor. Please have them consider the source - again. It's not a statement regarding I.Q. It is a statement regarding the decades of my exposure to the minds of world-renowned psychopharmacologists in Manhattan, Boston, Bethesda, Princeton, and Red Bank.
Man, I hope you scored a touchdown.
Even if no one else has the motivation to post on Psycho-Babble anymore, please keep me informed of your progress. You have suffered so much and WORKED so hard to arrive at today alive. I told you. I have a special interest in your finding a life worth living.
- Scott> With reference (for background and context) to my last thread about vortioxetine (Brintellix; Trintellix), at:
> https://www.dr-bob.org/babble/20230117/msgs/1122171.html
>
> After a few months on 15 mg of vortioxetine [VTX], on 05 December 2023, I took the 20 mg dose for the first time. Therefore, it is still early to come to any conclusions. The half-life of this drug is around 66 hours, and it takes more than a week to reach steady-state:
> https://en.wikipedia.org/wiki/Vortioxetine
>
> At first, I was a little disappointed as I didn't notice much improvement, but today I've had a more promising experience.
>
> Regarding how I'm feeling at different times, I've long used the terminology that it is "pretty good", "good", etc., but now I'm finding myself using the terminology "pleasant", and occasionally "comfortable". Another thing I've noticed is that my armswing when walking is better -- this is an anti-Parkinsonian effect.
>
> I'm speculating that I may be experiencing more of the 5-HT1A agonism, because I haven't felt much change in the symptoms I associate with serotonin transporter blockade, eg. my anorgasmia did not worsen, and my apathy also did not worsen, but even on the contrary. For example, today I had no problems staying out of bed after getting up.
>
> Feelings of reward in response to positive experiences, such as completing a task, have returned. Moreover, I've noticed myself looking forward to certain activities such as writing in my diary.
>
> This (20 mg) is the highest recommended dose of VTX, and I doubt the doctors are going to increase it more. Assuming that is correct, I have a couple of other things to suggest we try next:
> (I) add lithium, up to 300 mg, and
> (II) replace trimipramine with nortriptyline.
>
> -undopaminergic
>
Posted by undopaminergic on January 7, 2024, at 10:13:06
In reply to Re: Vortioxetine revisited at 20 mg » undopaminergic, posted by SLS on December 8, 2023, at 9:43:46
Hi SLS, and thank you for your reply and well-wishes. I hope you get to continue to enjoy remission.
Unfortunately, the increase of vorioxetine from 15 mg to 20 mg has not helped much, if any.
Now, I'm thinking of gradually replacing the trimipramine with nortriptyline. An alternative is keeping the trimipramine and adding lithium, up to 300 mg or so.
I would not normally have this kind of patience, it's just the situation I'm in. You are lucky to have had access to these world-class psychopharmacologists. Meanwhile, I am the best psychopharmacologist I'm acquainted with, and I don't have powers of prescription. If it were up to me, I'd go back on buprenorphine and methylphenidate, which is the combination that yielded my best (stable) results so far. To that, I'd experiment with adding tranylcypromine and/or lithium, or substituting amphetamine for methylphenidate. Memantine was great at its best, but I feel it is too dangerous (risk of manic impulsiveness) to play with on my own.
-undopaminergic
> Hi, U_D.
>
> You make a perfect example of the patience that I explained was necessary to achieve success.It can take between 2 weeks to 3 months to allow the drug/brain interaction do their work. I hope you now understand why the words I shouted at people were, nevertheless valuable. For those people who continue to avoid me, perhaps you can do *them* a favor. Please have them consider the source - again. It's not a statement regarding I.Q. It is a statement regarding the decades of my exposure to the minds of world-renowned psychopharmacologists in Manhattan, Boston, Bethesda, Princeton, and Red Bank.
>
> Man, I hope you scored a touchdown.
>
> Even if no one else has the motivation to post on Psycho-Babble anymore, please keep me informed of your progress. You have suffered so much and WORKED so hard to arrive at today alive. I told you. I have a special interest in your finding a life worth living.
>
>
> - Scott
>
>
>
> > With reference (for background and context) to my last thread about vortioxetine (Brintellix; Trintellix), at:
> > https://www.dr-bob.org/babble/20230117/msgs/1122171.html
> >
> > After a few months on 15 mg of vortioxetine [VTX], on 05 December 2023, I took the 20 mg dose for the first time. Therefore, it is still early to come to any conclusions. The half-life of this drug is around 66 hours, and it takes more than a week to reach steady-state:
> > https://en.wikipedia.org/wiki/Vortioxetine
> >
> > At first, I was a little disappointed as I didn't notice much improvement, but today I've had a more promising experience.
> >
> > Regarding how I'm feeling at different times, I've long used the terminology that it is "pretty good", "good", etc., but now I'm finding myself using the terminology "pleasant", and occasionally "comfortable". Another thing I've noticed is that my armswing when walking is better -- this is an anti-Parkinsonian effect.
> >
> > I'm speculating that I may be experiencing more of the 5-HT1A agonism, because I haven't felt much change in the symptoms I associate with serotonin transporter blockade, eg. my anorgasmia did not worsen, and my apathy also did not worsen, but even on the contrary. For example, today I had no problems staying out of bed after getting up.
> >
> > Feelings of reward in response to positive experiences, such as completing a task, have returned. Moreover, I've noticed myself looking forward to certain activities such as writing in my diary.
> >
> > This (20 mg) is the highest recommended dose of VTX, and I doubt the doctors are going to increase it more. Assuming that is correct, I have a couple of other things to suggest we try next:
> > (I) add lithium, up to 300 mg, and
> > (II) replace trimipramine with nortriptyline.
> >
> > -undopaminergic
> >
>
>
Posted by SLS on January 8, 2024, at 12:15:36
In reply to Re: Vortioxetine revisited at 20 mg » SLS, posted by undopaminergic on January 7, 2024, at 10:13:06
Hi.
> I am the best psychopharmacologist I'm acquainted with...
I don't doubt that for a second - which is both fortunate and unfortunate.
I like lithium 300-600 mg/day based upon my personal experience. My therapeutic window (actually, therapeutic index) lies at exactly 300 mg/day. Changing the dosage by 150 mg/day up or down ruins the antidepressant response to my regime. The other reason to take lithium is to significantly reduce the risk of developing Alzheimer's Disease. 150 mg/day is way more than enough from what I've read.
Memantine produced no noticeable improvement for me. I'm pretty sure I used the maximum recommended dosage. My illness leaves me vulnerable to manic reactions to Nardil and Parnate when combined with a TCA. However, this has happened no more than a handful of times. In the 1990s, I was pounded with a Parnate-desipramine combination combined with amphetamine. At the moment, I don't recall adding methylphenidate to a MAOI-TCA combination, but I do recall taking it. I remember that it felt "harsher" than amphetamine. I also chose to add bromocriptine and pergolide (separately) to this combination, as both are DA receptor agonists. Both are available in the U.S. to treat Parkinson's Disease. I experienced a few days of relief before I relapsed. Did any of the DA receptor partial agonist antipsychotics have any positive effects on you at all?
I commend you on your current approach towards treatment. It will greatly increase the odds of your finding an effective treatment.
To reiterate the most fundamental principle in the treatment of depressive mood illnesses with a standard antidepressant, one must allow enough time to see a therapeutic improvement. It takes at least two weeks for the action of a drug to prompt a sufficient compensatory response by the brain to alter the dynamics of brain function. This can take between 2-12 weeks. That very much sucks.
A depiction explaining the latency between the beginning of treatment and the emergence of a therapeutic improvement might help to explain this. By the end of day one of treatment with a TCA or SRI, the drug is already blocking the presynaptic uptake transporter. Yet, there is no significant improvement seen on day 2. Why is that? In the 1980s, I encountered a great many medical journal articles suggesting that it took two weeks to see an appreciable compensatory reduction in NE beta receptor binding. It was also suggested that NE beta receptors had a turnover of two weeks. This suggests an explanation for the latency in treatment response.How can one justify allowing every new treatment three months to work? The experience of even one day of depression can be tormenting. What about suffering for 84 consecutive days (12 weeks) without relief, and then having to start all over again with a new treatment regime? Repeated observations demonstrate that if there is absolutely no improvement by the end of 6 weeks of antidepressant treatment, it is unlikely that waiting another 6 weeks will help.
This is what is currently working for me:
Phenelzine (Nardil) - 90 mg/day
Nortriptyline - 100 mg/day
Lamotrigine (Lamictal) - 300 mg/day
Lithium - 300 mg/day1. Removing any one drug produces a relapse.
2. Changing the dosage of any one drug produces a deterioration or a relapse.
Suggestion:1. Make a list of drugs that produced any improvement - regardless of how robust or how short-lived.
2. Make a list of drugs that produced a worsening of the condition being treated, regardless of side effects.
3. Make a list of drugs that had no effect at all on the condition being treated.
4. Make a list of drug combinations that had a positive effect, especially wherein monotherapy with either drug failed to produce an improvement.
All of the drugs that I am using in combination were chosen from list #1. This was my approach to choosing drugs to combine. As monotherapy, each drug from list #1 produced some improvement.I guess that's all for now.
- Scott
Posted by undopaminergic on January 23, 2024, at 10:38:14
In reply to Re: Vortioxetine revisited at 20 mg, posted by SLS on January 8, 2024, at 12:15:36
> Hi.
>Hi SLS!
> Memantine produced no noticeable improvement for me. I'm pretty sure I used the maximum recommended dosage.
>It is my experience and understanding from what I've read, that the initial dose, if sufficient, should make you feel "weird".
My first dose was 10 mg, and I did feel weird, so I did not take more, until weeks or months later, and then it produced a nice antidepressant response, without any "weirdness". I don't recall whether my second dose was 10 or 20 mg.
At a (months) later point, I needed 60 mg, so the maximum recommended dose may not be sufficient. I survived an overdose of several grams (a gram is 1000 mg), so I would not personally worry about taking a couple of 100 mg or so on a regular basis.
> I also chose to add bromocriptine and pergolide (separately) to this combination, as both are DA receptor agonists. Both are available in the U.S. to treat Parkinson's Disease. I experienced a few days of relief before I relapsed.
>Unfortunately, it may not be a good idea to take ergoline-based dopamine agonists in the longer term, as they can produce fibrosis and valvulopathy. Lilly was sued over this.
> Did any of the DA receptor partial agonist antipsychotics have any positive effects on you at all?
>No, they didn't, but I never tried 2.5 mg of aripiprazole (Abilify), only higher doses.
-undopaminergic
Posted by SLS on January 23, 2024, at 11:15:56
In reply to Re: Vortioxetine revisited at 20 mg, posted by undopaminergic on January 23, 2024, at 10:38:14
> > Hi.
> >
>
> Hi SLS!
>
> > Memantine produced no noticeable improvement for me. I'm pretty sure I used the maximum recommended dosage.
> >
>
> It is my experience and understanding from what I've read, that the initial dose, if sufficient, should make you feel "weird".
>
> My first dose was 10 mg, and I did feel weird, so I did not take more, until weeks or months later, and then it produced a nice antidepressant response, without any "weirdness". I don't recall whether my second dose was 10 or 20 mg.This might not apply to your experience with memantine, but...
Feeling "weird" is sometimes exactly what you should experience as the brain begins to change its functional dynamics as it reacts to its exposure to an antidepressant substance. With my multiple experiences with Nardil, if I begin to feel weird in the second week, I know that I will ultimately experience some sort of robust antidepressant response.Another example is the treatment with psilocybin, a psychedelic hallucinogen. Clinics have emerged whose treatment protocol involves a single hallucinogenic dose along with the support and guidance of facilitators. The psilocybin "trip" is truly an altered state of consciousness. Perhaps of critical importance is that while in this state, the brain becomes extremely plastic. This allows for brain function to be more easily altered by medication. However, unless this threshold of dissociation is reached, nothing happens.
Being in the midst of a psychedelic reaction to psilocybin must surely feel weird, but is necessaqry. It is nothing short of an altered state of consciousness that is a surely a very weird experience. No trip, No improvement. With me, no brain fog early in treatment = no response.
As you know, there is growing interest in using psilocybin in microdose amounts daily. It works, and one need not reach the dosage that elicits dissocciation go on have to go on trips.
Ketamine shows a similar behavior. If the dosage used fails to produce a dissociative state, it will likely fail to produce a therapeutic response. -John Krystal, MD - Yale.
- Scott
>
> At a (months) later point, I needed 60 mg, so the maximum recommended dose may not be sufficient. I survived an overdose of several grams (a gram is 1000 mg), so I would not personally worry about taking a couple of 100 mg or so on a regular basis.
>
> > I also chose to add bromocriptine and pergolide (separately) to this combination, as both are DA receptor agonists. Both are available in the U.S. to treat Parkinson's Disease. I experienced a few days of relief before I relapsed.
> >
>
> Unfortunately, it may not be a good idea to take ergoline-based dopamine agonists in the longer term, as they can produce fibrosis and valvulopathy. Lilly was sued over this.
>
> > Did any of the DA receptor partial agonist antipsychotics have any positive effects on you at all?
> >
>
> No, they didn't, but I never tried 2.5 mg of aripiprazole (Abilify), only higher doses.
>
> -undopaminergic
>
This is the end of the thread.
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