Psycho-Babble Medication Thread 1121240

Shown: posts 1 to 25 of 27. This is the beginning of the thread.

 

Finally trying vortioxetine -- initial impressions

Posted by undopaminergic on December 9, 2022, at 8:14:21

I finally initiated vortioxetine today at 5 mg/day.

I've noticed a definite, but still modest, effect. I feel a slight improvement in mood, cognition, and attention. I am less certain about a stimulant-like effect with regard to amelioration of apathy.

I've tried to find research on the effects of vortioxetine on dopamine. I did not find anything intriguing, only comments in passing about an increase in the release of dopamine and several other neurotransmitters (at least serotonin, noradrenaline, acetylcholine, and histamine).

I found this interesting citation:
https://pubmed.ncbi.nlm.nih.gov/26209859/
--quote--
... Antidepressants had a positive effect on psychomotor speed ...
Of note, after removal of vortioxetine from the analysis, statistical
significance was lost for psychomotor speed.
--end-quote--

All in all the trial is off to a good start.

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by SLS on December 9, 2022, at 13:10:40

In reply to Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 9, 2022, at 8:14:21

Hi UD.

One of my many examples of unsolicited advice:

> All in all the trial is off to a good start.

I'm happy to hear that. I'll say a prayer or two for you. Even if there's no God, I don't see how it could hurt.

I hope this stuff helps. I think it is a healthy posture to take. It might bring you closer to discovering a successful, and possibly unique treatment. It should help to optimize your treatment trials in order to search for remission.


1. Just take the pill for a minimum of 4 weeks. If you feel even a mild, but discernible improvement at 4 weeks, go at least 2 more. If not, consider adding adjunctive medications.

2. Stop looking microscopically at how vortioxetine is affecting you day by day - or even hour by hour. You will only obsess - and perhaps abort the trial prematurely. Just take the pill and forget about it. Spend your time doing normal stuff that has nothing to do with your mental illness. Reduce your visits to Psycho-Babble. Doing normal stuff is the only way you can truly evaluate your degree of improvement in mood and function.

3. Increase your brain stimulation frequently by changing your environment and performing varied - and especially novel tasks.

4. Go for walks.

5. Perform 20 minutes of aerobic exercise at least a few days per week. Anaerobic exercise helps too, but only minimally.

6. Don't worry about the pharmacology of vortioxetine. You will only obsess - and perhaps abort the trial prematurely.

7. Take the pills and live your life.

* The only reason to stop taking vortioxetine that I can think of, other than for lack of efficacy, is if significant treatment-emergent adverse events (side-effects) appear that do not show a trend towards dissipating. Don't do *anything* without talking to your doctor first unless there is urgency.

* If you are going to perform any research at all to improve your chances of getting well, change your focus. Spend less time researching pure neuroscience and more time researching the clinical application of psychiatry. Research various treatment modalities, including medication. Study observed phenomena and statistics when treating real people.

* Just take the pills and don't give it another thought unless side effects become problematic.

Good luck!!!


- Scott


 

Any thoughts? (nm) » undopaminergic

Posted by SLS on December 10, 2022, at 7:25:31

In reply to Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 9, 2022, at 8:14:21

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by SLS on December 10, 2022, at 8:11:59

In reply to Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 9, 2022, at 8:14:21

Hi again, UD .


> I finally initiated vortioxetine today at 5 mg/day.

> I've noticed a definite, but still modest, effect. I feel a slight improvement in mood, cognition, and attention. I am less certain about a stimulant-like effect with regard to amelioration of apathy.

I've tried to find research on the effects of vortioxetine on dopamine. I did not find anything intriguing, only comments in passing about an increase in the release of dopamine and several other neurotransmitters (at least serotonin, noradrenaline, acetylcholine, and histamine).
>
> I found this interesting citation:

> https://pubmed.ncbi.nlm.nih.gov/26209859/

> --quote--
... Antidepressants had a positive effect on psychomotor speed ...
Of note, after removal of vortioxetine from the analysis, statistical
significance was lost for psychomotor speed.
--end-quote--

-------

That is an EXCELLENT article, and it absolutely describes what happens to me as I approach remission. However, I might relapse by the time I finish typing this sentence. Nothing is guaranteed to work forever. Nardil often stops working after 10 years of remission. It appears as being spontaneous. However, this might actually be a result of stressing the brain too much. It is CRITICAL that one remove as much psychosocial stress and anxiety as much as possible. This often requires psychotherapy. Otherwise, one may experience a "medication breakthrough" relapse.

I told my main research doctor at the NIH that I wanted to go to medical school. He was quite emphatic in recommending that I don't. He said that it would be too much stress on the brain. This is particularly true of not having a regular circadian rhythm as one does their internship in a hospital. The hours shift all the time. All of this combined would almost guarantee that I suffer a medication-breakthrough relapse. Remember, if you achieve remission, it will be under the conditions that you achieved it.

-------

> All in all the trial is off to a good start.

-------

I am glad that your initial reaction was an almost instant improvement in depression. This is what the National Institutes of Health (NIH) called a "blip". They considered a TEMPORARY blip early during the course of a drug trial to be predictive of eventual treatment success - although not necessarily remission.

Keep taking your antidepressants if this blip at the beginning comes and goes. You might have to wait 4-6 weeks to see the beginnings of a true clinical response.


- Scott

 

Re: Finally trying vortioxetine -- initial impressions

Posted by undopaminergic on December 11, 2022, at 4:26:15

In reply to Re: Finally trying vortioxetine -- initial impressions » undopaminergic, posted by SLS on December 10, 2022, at 8:11:59

Thank you for your comments, SLS. I will reply in more detail later.

The effects I described are less noticeable now, probably because the improvement is becoming a new baseline. It may sound silly, but I've also noticed that I'm better at whistling. I regard that as a possible drug effect on psychomotor function.

-undopaminergic

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by SLS on December 11, 2022, at 9:40:01

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 11, 2022, at 4:26:15

Hi, UD.


-------------------------


> Thank you for your comments, SLS. I will reply in more detail later.


-------------------------


Okay. I look forward to it.


-------------------------


> The effects I described are less noticeable now, probably because the improvement is becoming a new baseline. It may sound silly, but I've also noticed that I'm better at whistling. I regard that as a possible drug effect on psychomotor function.


-------------------------


No!

It is not a side effect at all!

It is a step towards remission - or at least a robust response! You are responding!!!

Way to go!

Keep doing what you are doing! Don't change a single thing (for now)!

Be patient!

A full remission can take as long as a YEAR for Treatment-Resistant Depression!

Wait at least 6 more weeks at the same dosages of everything you are currently taking before making changes or declaring the trial a failure!

If you are continuing to see an improvement - but not remission - seriously consider finding augmenters / adjuncts. If you are not currently taking low-dosage lithium, you might consider adding this first or reducing the dosage to 300 mg/day if you are already taking it. Prescription lithium carbonate only!

If it is obvious that you are significantly improved, don't give your treatment another thought!

Engage in activities without thinking about your illness or its treatment. A truly therapeutic response can be either gradual or rapid. In my experience, a gradual improvement results in a more robust response and is more likely to persist long-term.!

Have fun!

Stay away from the computer and find other things to do. Get out of the house!


-------------------------


For ME, my symptoms of depression include:


1. Psychomotor retardation.

2. Affects my gait while walking: Ataxia.

3. Prevents me from singing on key - even the timbre of my voice.

4. Generally clumsy.

5. Unable to track fast-moving objects. e.g. I am unable to track a baseball in the outfield. The ball jumps all over the place while in the air. Once I began to respond well to treatment, I was able to track the ball normally. It was really cool!

6. Dry mouth. My guess is that this is a symptom of the illness. It exists in the absence of drug side-effects, and completely resolves upon remission - normal salivation. The dry mouth is probably the result of "dysautonomia" (a generic term) resulting from an imbalance of the in the autonomic nervous system - too much sympathetic and too little parasympathetic. I had guessed this as a strong possibility in 1982 while I was waiting to be treated for the very first time at Columbia. In 1990, I was treated by a doctor who agreed with me. In fact, he was the one who taught me that the name for this condition was dysautonomia. It is not "familial dysautonomia", which most often affects people of Jewish descent.


_________________________________________________________________

* I know this sounds pretentious (very), but I had been about 10 years ahead of the curve since the 1980s. I would say that psychiatry has now caught up with us at Psycho-Babble due to the establishment of translational medicine research. This was another idea that I came up with in the early 1990s - before there was such a thing. I had recognized that there was very little communication between pure neuroscience research and the clinical application of neuroscience discoveries. I called the remedy for this the "clinical application of neuroscience". I was close to writing an essay about it, but what would I do with it? It ends up that my research clinician at the NIH went on to join the fledgling department of translational medicine for Johnson & Johnson in Belgium. He started out in their brain imaging department. He learned how to perform PET scans of the brain and poking people's spinal canal (lumbar puncture) for CSF fluid by practicing on me. He missed the first 2 punctures. Not fun. My brain was one of the first to be scanned. They actually built their own cyclotron. None existed at the time to synthesize FDG (fluorodeoxyglucose). This substance is utilized by the body in place of glucose in the brain and the body. The more active a tissue, the more glucose is consumed (broken-down / metabolized). However, when cells split the FDG-labelled glucose molecule for energy, matter (electrons) and antimatter are released and quickly collide, thereby producing an annihilation event. Gamma-rays are released and detected on the inner surface of the imaging tube - much like a MRI. The release of gamma-rays is a direct measure of tissue activity. The PET scan is an invaluable tool for locating cancerous tissue throughout the entire body. Cancerous tissue is much more active than normal body cells. More gamma-rays are released as glucose (FDG) is consumed at a higher rate.

The following is a typical PET scan comparison brain activity between people with depression and people without depression. My scans at the NIH looked very similar. The scans were rendered just like a weather map.

Orange = Very Active
Yellow = Active
Blue = Inactive

https://www.mayoclinic.org/-/media/kcms/gbs/patient-consumer/images/2017/05/15/20/19/c7_pet_depression-8col.jpg

Scary, right?


- Scott

 

An oversight on my part... Correction.

Posted by SLS on December 13, 2022, at 15:24:10

In reply to Re: Finally trying vortioxetine -- initial impressions » undopaminergic, posted by SLS on December 11, 2022, at 9:40:01

This is an extremely important correction:

I wrote,

"If you are not currently taking low-dosage lithium, you might consider adding this first or reducing the dosage to 300 mg/day if you are already taking it."

---------------------------------------------

People who are using lithium to treat bipolar mania, or to act as a prophylactic against future manic episodes, should NOT reduce their dosage of lithium.

---------------------------------------------


- Scott

 

Re: Finally trying vortioxetine -- initial impressions

Posted by undopaminergic on December 16, 2022, at 4:37:54

In reply to Re: Finally trying vortioxetine -- initial impressions » undopaminergic, posted by SLS on December 9, 2022, at 13:10:40

> Hi UD.

Hi SLS!

> > All in all the trial is off to a good start.
>
> I'm happy to hear that. I'll say a prayer or two for you. Even if there's no God, I don't see how it could hurt.
>

Thank you.

> I hope this stuff helps. I think it is a healthy posture to take.
>

What posture?

> 1. Just take the pill for a minimum of 4 weeks. If you feel even a mild, but discernible improvement at 4 weeks, go at least 2 more. If not, consider adding adjunctive medications.
>

There are dosage increases to be done before initiating adjunct medications. I'm only taking 5 mg/day, and 10 mg is the recommended starting dose.

I intend to remain on the 5 mg dose for at least 2 weeks, because the drug's half-life is 66 hours and it takes 10 days or more to reach steady-state.

Interestingly, it takes 7 to 11 hours after a dose to reach peak concentrations of the drug.

It is also worth noting that we did not cease the trimipramine (150 mg/day), but we added vortioxetine on top of it. I'm also on clozapine, sulpiride, and lamotrigine (200 mg/day).

> 2. Stop looking microscopically at how vortioxetine is affecting you day by day - or even hour by hour. You will only obsess - and perhaps abort the trial prematurely. Just take the pill and forget about it. Spend your time doing normal stuff that has nothing to do with your mental illness.
>
And:
>
> Reduce your visits to Psycho-Babble. Doing normal stuff is the only way you can truly evaluate your degree of improvement in mood and function.
>

I cannot go back to living my life as it was before my burnout (which slowly took on the characteristics of a more typical depression). If I could, I would be in remission, which has actually happened once in the form of a (hypo)manic episode.

My normal routine nowadays includes keeping track of how I'm feeling. When I notice something is different, I note it in my diary. In connection with that, after initiating a new medication, it is difficult not to think about the possible involvement of the drug. At that point, I may be somewhat biassed insofar I attribute changes to the drug. However, I don't obsess.

For the time being, I haven't been very active on Psychobabble, in large part because I'm following the football (soccer) World Cup.

I agree that the best test to determine whether I'm doing better in terms of feeling and functioning, is to live life as normally as possible. Perhaps the most valuable observations one can make are objective measures, such as the level of success and time taken in completing different tasks.

> 3. Increase your brain stimulation frequently by changing your environment and performing varied - and especially novel tasks.
>

I'm confident that variety and moderation are good and healthy things, and I have long been striving to do different things that at best complement each other, and I seek tasks that are as stimulating as possible.

That said, there are a number of things I cannot do due to the illness. For example, due to the anhedonia, I'm not able to play computer games. Also, due to apathy and emotional numbing, it takes more (than it used to) to arouse me.

> 4. Go for walks.
>

I'm very big on walks, and I usually walk for more than 2 hours a day, except sometimes when I'm busy with something more urgent.

> 5. Perform 20 minutes of aerobic exercise at least a few days per week. Anaerobic exercise helps too, but only minimally.
>

I run, or more typically jog, intermittently during my walks. Sometimes I feel better afterwards, and I'm wondering if it's the endorphins, but I've never experienced "runner's high".

From what I keep hearing/reading, exercise is a panacea for all sorts of different ailments, including mental. It's not in question that it's beneficial in moderation (too much of it can lead to "sports" injuries, which I have experienced a few times).

> * The only reason to stop taking vortioxetine that I can think of, other than for lack of efficacy, is if significant treatment-emergent adverse events (side-effects) appear that do not show a trend towards dissipating.
>

Nausea is probably the most common adverse effect associated with vortioxetine, and I seem to get a touch of it, but it feels more like a positive case of butterflies in the stomach (as if I were excited) than aversive nausea.

> Don't do *anything* without talking to your doctor first unless there is urgency.
>

The doctors involved here are very slow and conservative, so I don't think there is any risk that I'll make premature changes.

> * If you are going to perform any research at all to improve your chances of getting well, change your focus. Spend less time researching pure neuroscience and more time researching the clinical application of psychiatry. Research various treatment modalities, including medication. Study observed phenomena and statistics when treating real people.
>

I enjoy both pure neuroscience and clinical psychiatry. A few days ago I read an article about the pro-cognitive effects of vortioxetine, and found it a bit inspiring. I've also read reviews from other users of this drug, and perhaps the most promising experience, although not frequent, is the lifting of "brain fog".

> * Just take the pills and don't give it another thought unless side effects become problematic.
>

That is much the same thing I commented on above. It would not be easy for me to ignore the fact that I'm trying a new treatment, and it would not be normal for me to do so.

> Good luck!!!

Thank you!

-undopaminergic

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by SLS on December 16, 2022, at 7:26:52

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 16, 2022, at 4:37:54

Hi UD.

I won't be posting on Psycho-Babble much anymore. I made an exception for you because I think you might be getting close.

I feel that the advice given by me and the doctors whose brains I picked along the journey I began in 1982 is being ignored and squandered. When someone habitually starts and stops antidepressants in less than a week, often as a sort of palliative PRN, they are likely to die depressed. They will never know a normal human state of consciousness. My first lesson in research psychiatry was to NEVER "pulse" medications on and off and on and off... It most often leads to a condition of persistent *refractoriness* to pharmacological treatment, a worsening of the depressive state, and an increaseed sensitivity to side-effects.

You know who you are.

Tragic. I had been trying to change this scenario.

As for you, keep expanding your role as a nurturing and compliant a higher probability of success. Go back and read everything I have written and posted over the last week. Really. My presentation offers an true hope to anyone who follows my advice - the advice of the first two generations of psychopharmacologists. This is not a guarantee of instant success, but it sure enhances one's chances of ultimately finding it when compared to the current state of affairs of most of the current posters on Psycho-Babble.

I am not pretentious. I am cured.

Semantics aside, that is exactly what it feels like to achieve remission.

UD, I have more to write to you, but I have an appointment that I have to keep.

Take advantage of your new hope. You have no logical reason to be completely demoralized today. Do not give in to desperation. It usually doesn't help.

See you later...


- Scott

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by SLS on December 16, 2022, at 7:32:22

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 16, 2022, at 4:37:54

UD.

I forgot to mention something that I consider important.

I try to use words with precision.

I said, "Take the pills and live your life."

I did not say, "go back to living your life.".

I cannot go back to living my life as it was before my burnout (which slowly took on the characteristics of a more typical depression). If I could, I would be in remission, which has actually happened once in the form of a (hypo)manic episode.

This is a great example of self-care. You have come to know how to mitigate your pain and frustration. This is part of your current life. Use all of what little God gave you to work with. You will get there.


- Scott

 

Re: Finally trying vortioxetine -- initial impressions

Posted by undopaminergic on December 16, 2022, at 10:19:41

In reply to Re: Finally trying vortioxetine -- initial impressions » undopaminergic, posted by SLS on December 10, 2022, at 8:11:59

> Hi again, UD .

Hi again SLS!

>
> I told my main research doctor at the NIH that I wanted to go to medical school. He was quite emphatic in recommending that I don't. He said that it would be too much stress on the brain. This is particularly true of not having a regular circadian rhythm as one does their internship in a hospital. The hours shift all the time. All of this combined would almost guarantee that I suffer a medication-breakthrough relapse. Remember, if you achieve remission, it will be under the conditions that you achieved it.
>

I have no regular circadian rhythm when I'm left to my own devices and let my sleep-wake cycle be decided by how sleepy or how wakeful I'm feeling. When I'm using stimulants heavily, I'm up for days on end -- I pretty much make it a lifestyle. I think this may be regarded as a stereotypy.

>
> I am glad that your initial reaction was an almost instant improvement in depression. This is what the National Institutes of Health (NIH) called a "blip". They considered a TEMPORARY blip early during the course of a drug trial to be predictive of eventual treatment success - although not necessarily remission.
>
> Keep taking your antidepressants if this blip at the beginning comes and goes. You might have to wait 4-6 weeks to see the beginnings of a true clinical response.
>

It's been blipping several times a day so far.

-undopaminergic

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by Jay2112 on December 16, 2022, at 16:54:52

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 16, 2022, at 4:37:54

Hi UD:

I too take vortioxetine, and find the nausea is very least when I take it later in the day/evening, with food. Ginger also helps. I have read the nausea may be from the cholinergic effects, which are a positive aspect of this drug. Ginger is an excellent anti-nauseant.

Jay

 

Re: Finally trying vortioxetine -- initial impressions » Jay2112

Posted by SLS on December 16, 2022, at 18:53:35

In reply to Re: Finally trying vortioxetine -- initial impressions » undopaminergic, posted by Jay2112 on December 16, 2022, at 16:54:52

> Hi UD:
>
> I too take vortioxetine, and find the nausea is very least when I take it later in the day/evening, with food. Ginger also helps. I have read the nausea may be from the cholinergic effects, which are a positive aspect of this drug. Ginger is an excellent anti-nauseant.
>

Hi, Jay.

Is that PRO-cholinergic? How does that work?

Thanks.


- Scott

 

Re: Finally trying vortioxetine -- initial impressions

Posted by NKP on December 17, 2022, at 6:54:48

In reply to Re: Finally trying vortioxetine -- initial impressions » Jay2112, posted by SLS on December 16, 2022, at 18:53:35

> > Hi UD:
> >
> > I too take vortioxetine, and find the nausea is very least when I take it later in the day/evening, with food. Ginger also helps. I have read the nausea may be from the cholinergic effects, which are a positive aspect of this drug. Ginger is an excellent anti-nauseant.
> >
>
> Hi, Jay.
>
> Is that PRO-cholinergic? How does that work?
>
> Thanks.
>
>
> - Scott
>
>

Are there other antidepressants that are pro-cholinergic too? Might this account for the side-effect of excessive sweating that many antidepressants have?

 

Re: Finally trying vortioxetine -- initial impressions » NKP

Posted by SLS on December 17, 2022, at 15:40:49

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by NKP on December 17, 2022, at 6:54:48

> > > Hi UD:
> > >
> > > I too take vortioxetine, and find the nausea is very least when I take it later in the day/evening, with food. Ginger also helps. I have read the nausea may be from the cholinergic effects, which are a positive aspect of this drug. Ginger is an excellent anti-nauseant.
> > >
> >
> > Hi, Jay.
> >
> > Is that PRO-cholinergic? How does that work?
> >
> > Thanks.
> >
> >
> > - Scott
> >
> >
>
> Are there other antidepressants that are pro-cholinergic too? Might this account for the side-effect of excessive sweating that many antidepressants have?

That's a great question. I never looked into it. The first antidepressant I ever tried

No. It is anticholinergic drugs (muscarinic receptor antagonists) that produce increased sweating.


- Pro-cholinergic drugs are depressogengic (pilocarpine).

- Anti-cholinergic drugs are antidepressant (scopolamine).

Scopolamine has been studied as a rapid-acting antidepressant. I don't see much about it anymore. However. I haven't been following it.


- Scott


 

Re: Finally trying vortioxetine -- initial impressions

Posted by Jay2112 on December 17, 2022, at 17:25:46

In reply to Re: Finally trying vortioxetine -- initial impressions » Jay2112, posted by SLS on December 16, 2022, at 18:53:35

> > Hi UD:
> >
> > I too take vortioxetine, and find the nausea is very least when I take it later in the day/evening, with food. Ginger also helps. I have read the nausea may be from the cholinergic effects, which are a positive aspect of this drug. Ginger is an excellent anti-nauseant.
> >
>
> Hi, Jay.
>
> Is that PRO-cholinergic? How does that work?
>
> Thanks.
>
>
> - Scott
>
>

Hi Scott:

That should be, "..it acts as a cholinesterase inhibitor". My apologies,

Jay

 

Cholinergic agents - Man, was I wrong... Sorry.

Posted by SLS on December 17, 2022, at 17:40:35

In reply to Re: Finally trying vortioxetine -- initial impressions » NKP, posted by SLS on December 17, 2022, at 15:40:49


> No. It is anticholinergic drugs (muscarinic receptor antagonists) that produce increased sweating.


-----

Ouch.

Anticholinergic agents *reduce* sweating, and are used to treat hyperhidrosis.

-----


> - Pro-cholinergic drugs are depressogengic (pilocarpine).
>
> - Anti-cholinergic drugs are antidepressant (scopolamine).
>
> Scopolamine has been studied as a rapid-acting antidepressant. I don't see much about it anymore. However. I haven't been following it.
>
>
> - Scott

 

Re: Finally trying vortioxetine -- initial impressions

Posted by Jay2112 on December 17, 2022, at 17:52:29

In reply to Re: Finally trying vortioxetine -- initial impressions » NKP, posted by SLS on December 17, 2022, at 15:40:49

> > > > Hi UD:
> > > >
> > > > I too take vortioxetine, and find the nausea is very least when I take it later in the day/evening, with food. Ginger also helps. I have read the nausea may be from the cholinergic effects, which are a positive aspect of this drug. Ginger is an excellent anti-nauseant.
> > > >
> > >
> > > Hi, Jay.
> > >
> > > Is that PRO-cholinergic? How does that work?
> > >
> > > Thanks.
> > >
> > >
> > > - Scott
> > >
> > >
> >
> > Are there other antidepressants that are pro-cholinergic too? Might this account for the side-effect of excessive sweating that many antidepressants have?
>
> That's a great question. I never looked into it. The first antidepressant I ever tried
>
>
>
> No. It is anticholinergic drugs (muscarinic receptor antagonists) that produce increased sweating.
>
>
> - Pro-cholinergic drugs are depressogengic (pilocarpine).
>
> - Anti-cholinergic drugs are antidepressant (scopolamine).
>
> Scopolamine has been studied as a rapid-acting antidepressant. I don't see much about it anymore. However. I haven't been following it.
>
>
> - Scott
>
>
>
>
>

I have found amitriptyline, at very high doses, to seem to be similar to scopolamine. Both are strong anti-cholinergic's. I found 200mg's of amitriptyline to be a)powerful sleep inducer b)powerful anti-anxiety. Amitriptyline doesn't seem to have the overpowering, akathisia-inducing effects of SSRI's.

Jay

 

Re: Finally trying vortioxetine -- initial impressions

Posted by undopaminergic on December 23, 2022, at 13:03:13

In reply to Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 9, 2022, at 8:14:21

I found this article (free full text available) to be a good summary review of vortioxetine, including pre-clinical and clinical aspects:

https://pubmed.ncbi.nlm.nih.gov/25016186/
"Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data".

-undopaminergic

 

Re: Finally trying vortioxetine -- initial impressions

Posted by SLS on December 27, 2022, at 22:25:07

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 23, 2022, at 13:03:13

> I found this article (free full text available) to be a good summary review of vortioxetine, including pre-clinical and clinical aspects:
>
> https://pubmed.ncbi.nlm.nih.gov/25016186/
> "Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data".
>
> -undopaminergic
>


Around the same time vortioxetine was approved, there was an increased interest in the properties of the 5-HT7 receptor as a site to exploit to treat depression as an antagonist. To my knowledge, vortioxetine is the only antidepressant possessing this property. Another drug with this property is lurasidone, an antipsychotic. Lurasidone has been advertised as a treatment of bipolar II depression. However, I have not seen any great successes with lurasidone for this indication. I dont know how well it has proven to treat schizophrenia. People with depression often report being able to think more clearly (improved cognition) with vortioxetine before an improvement in depression occurs. I dont know why.

Has anyone spoken about lumateperone (Caplyta) for depression here? It is rather unique as an antipsychotic. It is a modulator of glutamate neurotransmission as well as for dopamine and serotonin. As secondary effects, it increases both dopamine and glutamate activity in the medial prefrontal cortex. Lumateperone is supposed to effect an antidepressant effect for both Bipolar I depression and Bipolar II depression. I think it might be worth taking a look at. I have not researched clinical trials for depression, so I dont know how effective it is statistically. It is currently used for bipolar depression as monotherapy or combined with lithium or valproate.

Im beginning to think that low-dosage lithium should be tried routinely in people for whom treatment-resistance has been demonstrated - and leave it there in the background. The stresses that lithium places on the kidneys and thyroid gland are dosage-dependent. At 300 mg/day, the risks are virtually 0%. I was on lithium 300 mg/day by accident, but it turned out to be crucial for my attaining remission. At the very least, it will promote neurogenesis in the hippocampus, which is almost universally shrunken in depression. The hippocampus, in addition to being the primary site for memory, also regulates emotion. Lithium also slows or prevents neurodegeneration and acts as and prevents oxidative. The list of things that lithium does in the brain is very long. Lithium is like aspirin for the brain. Unbelievably, lithium *lengthens* telomeres. Telomeres form a cap at the end of each arm of a chromosome, and serves to contain the DNA strand from unwinding. As one ages, the length of telomeres shortens, and is an index of apoptosis (programmed cell death). Lithium reduces the risk of getting Alzheimers Disease, and is being looked at for Parkinsons and other neurodegenerative diseases. It was the reduction in my risk of contracting Alzheimers Disease that was precisely the reason why I had been taking it. That it turned out to be a critical component of my successful treatment of bipolar depression was serendipitous and an unexpected gift.


- Scott

 

Re: Finally trying vortioxetine -- initial impressions

Posted by undopaminergic on December 28, 2022, at 10:52:39

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by SLS on December 27, 2022, at 22:25:07

>
> Around the same time vortioxetine was approved, there was an increased interest in the properties of the 5-HT7 receptor as a site to exploit to treat depression as an antagonist. To my knowledge, vortioxetine is the only antidepressant possessing this property. Another drug with this property is lurasidone, an antipsychotic. Lurasidone has been advertised as a treatment of bipolar II depression. However, I have not seen any great successes with lurasidone for this indication. I dont know how well it has proven to treat schizophrenia.
>

I tried lurasidone, and it was a disappointment. It didn't have any notable adverse effects though.

> People with depression often report being able to think more clearly (improved cognition) with vortioxetine before an improvement in depression occurs. I dont know why.
>

Yes. It seems to be related to the action of 5-HT3 agonism.

> Has anyone spoken about lumateperone (Caplyta) for depression here?
>

It does not seem to be available in Europe.

-undopaminergic

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by SLS on December 28, 2022, at 12:01:22

In reply to Re: Finally trying vortioxetine -- initial impressions, posted by undopaminergic on December 28, 2022, at 10:52:39

Hi.

> > Around the same time vortioxetine was approved, there was an increased interest in the properties of the 5-HT7 receptor as a site to exploit to treat depression as an antagonist. To my knowledge, vortioxetine is the only antidepressant possessing this property. Another drug with this property is lurasidone, an antipsychotic. Lurasidone has been advertised as a treatment of bipolar II depression. However, I have not seen any great successes with lurasidone for this indication. I dont know how well it has proven to treat schizophrenia.
> >
>
> I tried lurasidone, and it was a disappointment. It didn't have any notable adverse effects though.
>
> > People with depression often report being able to think more clearly (improved cognition) with vortioxetine before an improvement in depression occurs. I dont know why.
> >
>
> Yes. It seems to be related to the action of 5-HT3 agonism.
>
> > Has anyone spoken about lumateperone (Caplyta) for depression here?
> >
>
> It does not seem to be available in Europe.
>
> -undopaminergic


Is this something that would appear in any kind of EU formulary? Nowhere in Europe?

What about France? In the 1980s, France was the leader in developing novel psychotropic compounds for treating depression and making them available to the public. I would call the France of the 1980s as being the biggest source of novel antidepressants compounds and a liberal mindset to get them to market. One French antidepressant stands out: amineptine. Amineptine is a selective dopamine reuptake inhibitor. It worked. Unfortunately, it was also used recreationally and for enhancing athletic performance. After it was banned from the Olympics, amineptine became a villain, and was taken off the market in France. The problem was that amineptine was available nowhere else. The tragedy is that many of the people for whom no other drugs worked were condemned to return to life of depression and hardship.

Something similar happened with nomifensine (Merital). When it was approved in the United States, many previously treatment-refractory cases of depression responded robustly to it. The main mechanism of action for nomifensine dopamine reuptake inhibition. Nomifensine has been around for a very long time. It was used as the gold standard for biological probes assaying dopamine function in the brain. Within a year, there were reports in Germany that hemolytic anemia appeared in association with nomifensine use. From what I understand, the incidence was rare, and may not have really been sufficient cause for its withdrawal from market. However, I imagine the company didnt want nomifensine to become the next thalidomide.
The first true SSRI was introduced to Europe in 1982. It was called zimelidine (Zelmid). It had one major problem, though. There were reports of GuillainBarré syndrome developing early in treatment. Zimelidine was withdrawn in 1983.

Fluoxetine (Prozac) was originally one of a series of compounds synthesized from diphenhydramine (Benadryl). It was announced in 1972 by Eli Lilly and patented. It hit the market in 1988. In my opinion it is a tragically underutilized drug in 2022.


- Scott

 

Re: Finally trying vortioxetine -- initial impressions » SLS

Posted by undopaminergic on December 28, 2022, at 12:58:03

In reply to Re: Finally trying vortioxetine -- initial impressions » undopaminergic, posted by SLS on December 28, 2022, at 12:01:22

> >
> > > Has anyone spoken about lumateperone (Caplyta) for depression here?
> > >
> >
> > It does not seem to be available in Europe.
> >
> > -undopaminergic
>
>
> Is this something that would appear in any kind of EU formulary? Nowhere in Europe?
>

I cannot say for sure. But here is one that *is* available:

https://www.ema.europa.eu/en/medicines/human/EPAR/reagila

and I imagine there would be a corresponding page for lumateperone if it were approved.

The EMA (European Medicines Agency) is a kind of EU "FDA".

> What about France? In the 1980s, France was the leader in developing novel psychotropic compounds for treating depression and making them available to the public. I would call the France of the 1980s as being the biggest source of novel antidepressants compounds and a liberal mindset to get them to market. One French antidepressant stands out: amineptine. Amineptine is a selective dopamine reuptake inhibitor. It worked. Unfortunately, it was also used recreationally and for enhancing athletic performance. After it was banned from the Olympics, amineptine became a villain, and was taken off the market in France. The problem was that amineptine was available nowhere else. The tragedy is that many of the people for whom no other drugs worked were condemned to return to life of depression and hardship.
>

Yes, France is interesting from a psychopharmacological point of view. David Pearce (author of The Good Drug Guide) is a great fan of amineptine. It's my understanding that he was able to acquire a load of Survector (brand amineptine) from Brazil, but I think he is now using amineptine from the chemical market.

Tianeptine, a drug structurally related to amineptine, is also from France. I haven't seen it mentioned here but it probably has been.

Both amineptine and tianeptine are tricyclics, but are not generally meant to be included when the term "TCA" is used, as they have little (beyond their structure) in common with typical tricyclics.

> Something similar happened with nomifensine (Merital). When it was approved in the United States, many previously treatment-refractory cases of depression responded robustly to it. The main mechanism of action for nomifensine dopamine reuptake inhibition. Nomifensine has been around for a very long time. It was used as the gold standard for biological probes assaying dopamine function in the brain.
>

Really? I don't recall seeing nomifensine mentioned much in neuroscience. Usual probes are amfonelic acid and GBR-12909, but even cocaine is often used, despite its lack of selectivity.

>
> Fluoxetine (Prozac) was originally one of a series of compounds synthesized from diphenhydramine (Benadryl). It was announced in 1972 by Eli Lilly and patented. It hit the market in 1988. In my opinion it is a tragically underutilized drug in 2022.
>

In my experience, fluoxetine is the least apathising SSRI.

-undopaminergic

 

Re: Finally trying vortioxetine -- initial impressions » undopaminergic

Posted by SLS on December 28, 2022, at 14:27:42

In reply to Re: Finally trying vortioxetine -- initial impressions » SLS, posted by undopaminergic on December 28, 2022, at 12:58:03

Hi, UD.

I had been following cariprazine for a few years while it was under development. I really wanted the the increased ratio of dopamine D3/D2 receptor binding. It hurt more than it helped for my bipolar depression.

For me, the following antipsychotics produced an improvement in depression:

risperidone
aripiprazole
asenapine
olanzapine


- Scott

 

Re: Finally trying vortioxetine -- initial impressions » SLS

Posted by undopaminergic on December 28, 2022, at 16:11:51

In reply to Re: Finally trying vortioxetine -- initial impressions » undopaminergic, posted by SLS on December 28, 2022, at 14:27:42

> Hi, UD.
>

Hi SLS.

> I had been following cariprazine for a few years while it was under development. I really wanted the the increased ratio of dopamine D3/D2 receptor binding. It hurt more than it helped for my bipolar depression.
>
> For me, the following antipsychotics produced an improvement in depression:
>
> risperidone
> aripiprazole
> asenapine
> olanzapine
>

Risperidone was the worst I've tried, but that was in a different era (beginning of 2000s decade). I might react differently to it now.

Aripiprazole was without benefit, but stimulated salivation and induced an (eye) accommodation disorder. I had better luck with dopamine pure agonists (pramipexole), but the initial (and unique) anti-anhedonic effect was quickly lost, and I did not try high doses.

Asenapine is one I'd like to try.

Olanzapine has sometimes had a short lived beneficial (less apathy) effect at first. Otherwise it makes me tired and has a tendency to stimulate appetite.

I've also tried other antipsychotics. Sulpiride is the most impressive of them. At first (at low doses) it was a stronger stimulant than methylphenidate. This effect was quickly lost, and did not come back after a considerable period of abstinence.

-undopaminergic


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