![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by SLS on August 17, 2021, at 8:21:06
Hi.
> I added Nardil about a year ago. The onset of improvement was rapid at first. But I found myself needing to play with the dosage constantly. Then, I became suspicions that my dosage of nortriptyline was TOO HIGH. I had been taking 100 mg/day for a bunch of years, assuming that my being within the right range of therapeutic blood levels indicated that I was being dosed properly. Nortriptyline is the ONLY tricyclic for which there is a narrow therapeutic window that one must be within. If you go above a certain dosage, you relapse. After stopping nortriptyline completely for one day and leaving the Nardil dosage the same at 90 mg/day I was pleasantly surprised, to say the least. Bullseye - almost. My doctor advised me to restart nortriptyline at 50 mg/day. That was the right move, but I ended up relapsing. 75 mg/day is the magic number for me. I am now improving rapidly at a steady rate and at a steady dosage of Nardil.
* I just wanted to add that the range of nortriptyline therapeutic blood levels is between 50-150 ng/mL. However this is merely a guide, not an absolute index. When I was tested while taking 150 mg/day of nortriptyline, my blood level was 153 ng/mL. We figured that reducing the dosage from 150 mg/day to 100 mg/day would be sufficient to put me within the dosage window. I never had my blood level tested at 100 mg/day, but I will ask my doctor to take one once I stabilize at 75 mg/day.Response to nortriptyline is bimodal. From what I have observed over the years, low dosage responders take between 50-75 mg/day. High dosage responders take between 125-150 mg/day.
- Scott
Posted by undopaminergic on August 18, 2021, at 11:02:02
In reply to Nortriptyline dosing., posted by SLS on August 17, 2021, at 8:21:06
Thanks for the scoop on nortriptyline. It clearly underlines that more is not always merrier.
This is making me wonder if there is an analogous therapeutic dose window with trimipramine (Surmontil). I'm on 150 mg now. The conventional maximum dose seems to be 300 mg, but I can't say the 150 mg is better than 100 mg, or even slightly worse.
-undopaminergic
Posted by SLS on August 20, 2021, at 16:21:54
In reply to Re: Nortriptyline dosing. » SLS, posted by undopaminergic on August 18, 2021, at 11:02:02
> Thanks for the scoop on nortriptyline. It clearly underlines that more is not always merrier.
>
> This is making me wonder if there is an analogous therapeutic dose window with trimipramine (Surmontil). I'm on 150 mg now. The conventional maximum dose seems to be 300 mg, but I can't say the 150 mg is better than 100 mg, or even slightly worse.
>
> -undopaminergic
>
That's an old drug for which there is no generic. The last time I looked in on it, it was not a reuptake inhibitor of any monoamine.I was on it, but my doctor never mentioned a therapeutic window. Perhaps you should treat the dosage range of trimipramine as if it were imipramine. The accepted top-end of imipramine is 300 mg/day. I think most people are kept at about 150 mg/day. Trimipramine is the one tricyclic that does not act deleteriously on sleep architecture. It might even enhance it. I have some vague recollection of that, but I'm not sure. Trimipramine was the first drug my present doctor tried on me 20 years ago. I don't recall having any side effects. Linkadge once said that imipramine and trimipramine (maybe clomipramine to?) were genotoxic. You would have to ask him about the details.
- Scott
Posted by Jay2112 on August 21, 2021, at 0:18:00
In reply to Nortriptyline dosing., posted by SLS on August 17, 2021, at 8:21:06
Hi Scott
Well, I believe you said you were bipolar? I or II?
I am type II, but my psychiatrist and I were talking recently, and the research always seems to point to the addition of a noradrenergic antidepressant, like nortriptyline, utilization, rather than a serotonergic one, to a mood stabilizer. Which you are, sort of, doing...but, like me, you are also using a serotonin based med.Ok...bear with me...I do have a point..lol. (Along with my fragmented sentences.)
Now, I respond extremely well to lithium, which blocks noradrenaline. I tried nortriptyline (Aventyl) a few times, and I eventually had a few psychotic, manic episodes. See, there is a type of mania called dysphoric mania, which is like taking a boiling hot shower just after falling onto a thousand razorblades. Most people think mania is some euphoric spending spree, having sex with strangers, type of thing. I think you likely know what I am getting at. The noradrenaline is a huge factor in mania...but in your case, it could be an anomaly. Or, like many bipolar people, who respond to, say, Wellbutrin, it may not be an anomaly..lol.
So,have you had any type of very negative episodes on the Aventyl? See, I am *also* an anomaly, lol, because I take 60mg of Vyvanse daily, on top of 225mg of Effexor, 600mg of lithium, and 10mg of Abilify. Now, you also take Lamictal, correct?
I mean this with all due respect, but blood levels, as suggested in pharmacology, I think, can be the exception more than the rule. Yes, it may be based on sound research, but the real-world evidence, versus a randomized controlled trial, and their concordance, are being highly recognized in the scientific community. According to the research, you nor I should not be taking high doses of a serotonergic antidepressant, right? And, I should not be taking a stimulant, especially after a psychotic episode.
I think there is also a bit of an art, with the science, is really what I am getting at. And the metric used for the Aventyl is a very general guide. I am honestly not trying to argue...I respect your thoughts greatly. I *hope* that makes sense..lol.
:)Jay
Posted by undopaminergic on August 21, 2021, at 2:04:06
In reply to Re: Nortriptyline dosing. » undopaminergic, posted by SLS on August 20, 2021, at 16:21:54
> > Thanks for the scoop on nortriptyline. It clearly underlines that more is not always merrier.
> >
> > This is making me wonder if there is an analogous therapeutic dose window with trimipramine (Surmontil). I'm on 150 mg now. The conventional maximum dose seems to be 300 mg, but I can't say the 150 mg is better than 100 mg, or even slightly worse.
> >
> > -undopaminergic
> >
>
>
> That's an old drug for which there is no generic. The last time I looked in on it, it was not a reuptake inhibitor of any monoamine.
>Yes, that is correct.
> I was on it, but my doctor never mentioned a therapeutic window. Perhaps you should treat the dosage range of trimipramine as if it were imipramine. The accepted top-end of imipramine is 300 mg/day. I think most people are kept at about 150 mg/day. Trimipramine is the one tricyclic that does not act deleteriously on sleep architecture. It might even enhance it. I have some vague recollection of that, but I'm not sure.
>Yes, you are correct. I read it several times when I was researching trimipramine.
> Trimipramine was the first drug my present doctor tried on me 20 years ago. I don't recall having any side effects.
>I think maybe, as an anticholinergic, it impairs long term memory, but I don't notice that subjectively.
> Linkadge once said that imipramine and trimipramine (maybe clomipramine to?) were genotoxic. You would have to ask him about the details.
>Yes, I read that too, in one of his posts. He said trimipramine worked well for him, but the genotoxicity was a show stopper. For me, it's more like "big deal".
-undopaminergic
Posted by undopaminergic on August 21, 2021, at 2:11:51
In reply to Re: Nortriptyline dosing. » SLS, posted by Jay2112 on August 21, 2021, at 0:18:00
>
> Now, I respond extremely well to lithium, which blocks noradrenaline.
>I'm not aware of such an effect. Maybe you mean glutamate?
> I tried nortriptyline (Aventyl) a few times, and I eventually had a few psychotic, manic episodes. See, there is a type of mania called dysphoric mania, which is like taking a boiling hot shower just after falling onto a thousand razorblades. Most people think mania is some euphoric spending spree, having sex with strangers, type of thing.
>For me it was euphoria and spending sprees. So, at least in some respects, I've been lucky.
> I think you likely know what I am getting at. The noradrenaline is a huge factor in mania...
>For me, it felt a lot more like dopamine.
-undopaminergic
Posted by SLS on August 21, 2021, at 7:52:57
In reply to Re: Nortriptyline dosing. » SLS, posted by Jay2112 on August 21, 2021, at 0:18:00
> Hi Scott
Hi, Jay.
> Well, I believe you said you were bipolar? I or II?
I was first hit with depression at age 17. From the day that the paroxysmal switch into depression occurred, I had not one day without depression. For a two-year period beginning at age 20, My illness developed into an "ultra-rapid cycling" presentation. The period was 11 days, and so regular, I kept a social calendar around it. 8 days depressed followed by 3 days spent just short of normothymia, followed by 8 days, followed by 3 days, followed by 8 days etc. In August of 1982, I was screened for entry into the depression research program at Columbia-Presbyterian (Now part of New York-Cornell). Michael Liebowitz diagnosed me as having unipolar depression. Once they gave me lithium 1200 mg/day, the cycling stopped, never to return. I was stuck in depression. Throughout a period of nine months, several TCAs MAOIs and trazodone were tried and found to be ineffective, although my first few weeks on imipramine (de novo treatment) produced a total remission lasting about 2 weeks. MAOIs were partially effective at first, but faded within a week. In March, they told me that there was nothing more they could do for me. That's when I rushed to the Rutgers medical school library to find that they were wrong. I asked for bromocriptine or Wellbutrin. The doctor laughed at my theories regarding dopamine. I proceeded to indulge myself into giving a short monologue that resulted in her shedding tears. Words matter.
In 1987, I responded robustly and consistently for a period of six months while taking a combination of Parnate 60 mg/day + desipramine 150 mg/day. However, severe MANIA emerged that was delusional and borderline psychotic. This occurred maybe another 3-4 times. Each time the severity reached well beyond psychotic. Still, the diagnosis remained unipolar. In 1992, I entered the clinical pharmacology department at the NIH. My objective was to take what they then considered to be the most effective antidepressant in the world, clorgyline. Clorgyline is an irreversible and *specific* (not selective) inhibitor of MAO-A. It is the only drug capable of breaking through a truly impenetrable severe anergic depression. I agree with the opinion of the NIH regarding clorgyline. The NIH was the only source of clorgyline for human consumption in the United States. When I entered the program, they reviewed my history, and William Z. Potter told me that I was bipolar. He put me on lithium so that they wouldn't have a mad-man on their hands. This was the point when I realized that I was indeed bipolar, despite never having had a spontaneous manic episode.
The DSM-5 includes in its diagnostic scheme "qualifiers". One qualifier is drug-induced mania. Another is depression only. Think of it like this: Someone's first episode of bipolar disorder presents as depression. It is caused by a bipolar diathesis (underlying brain pathology) rather than a unipolar diathesis. It is literally bipolar depression. Now, lets pretend that this person's brain lacks the strong switching mechanism seen in Bipolar I. This person never switches. They are stuck with experiencing only the depressive phase of the illness.
> I am type II, but my psychiatrist and I were talking recently, and the research always seems to point to the addition of a noradrenergic antidepressant, like nortriptyline, utilization, rather than a serotonergic one, to a mood stabilizer. Which you are, sort of, doing...but, like me, you are also using a serotonin based med.
Excellent conclusion. At the moment, I can see several alternatives.
1. If you have found any relief at all with your current regime, you might consider remaining on it and simply add desipramine or nortriptyline. Desipramine is a stronger and somewhat more selective NE reuptake inhibitor than is nortriptyline. You can even do this if you are currently on, and plan to continue with MAOI. In this case, you are limited to desipramine and nortriptyline and possibly trimipramine and doxepin. Doxepin, however, is a more potent as an antihistamine than it is as an antidepressant .
> Ok...bear with me...I do have a point..lol. (Along with my fragmented sentences.)
>
> Now, I respond extremely well to lithium, which blocks nor adrenaline.Lithium does so many things. Right now, I see it as a glutamate releaser at 300-450 mg/day and can be a capable antidepressant at these low dosages. However, lithium's effects on glutamate are bimodal. Over 450 mg/day, lithium begins to have the opposite effect on glutamate and inhibits its release. Higher dosages of lithium are required to have an anti-manic effect as it then inhibits glutamate release. Personally, I found this to be true, but the cut-off for me is 300 mg/day. Above this, my depression becomes worse and I become passive, flat, and unmotivated. This bimodal behavior of lithium and glutamate activity has been documented. However, there is no medical literature that I could find reporting an association between lithium, glutamate levels, and mood state. This heinous act was mine alone, so don't take me too seriously. It's a rather simple hypothesis though.
> I tried nortriptyline (Aventyl) a few times, and I eventually had a few psychotic, manic episodes. See, there is a type of mania called dysphoric mania, which is like taking a boiling hot shower just after falling onto a thousand razorblades.
All of my manias were dysphoric. There was nothing euphoric about them. Much of the content was expressed as religiosity - Jesus versus the Devil. It was brutal.
> Most people think mania is some euphoric spending spree, having sex with strangers, type of thing. I think you likely know what I am getting at. The noradrenaline is a huge factor in mania...but in your case, it could be an anomaly. Or, like many bipolar people, who respond to, say, Wellbutrin, it may not be an anomaly..lol.
One treatment that I have seen others have success with is the combining of Wellbutrin with Effexor or Pristiq. Some people also do well with a combination of Wellbutrin with Zoloft (Welloft).
> So ,have you had any type of very negative episodes on the Aventyl?
I have never had a manic episode without the involvement of a MAOI - either Parnate or Nardil.
> See, I am *also* an anomaly, lol, because I take 60mg of Vyvanse daily, on top of 225mg of Effexor, 600mg of lithium, and 10mg of Abilify. Now, you also take Lamictal, correct?
Yes. I don't get the maximal positive response to Lamictal (aborigine) until I reach 300 mg/day. That dosage might be worth exploring. If you tolerate that dosage well, I would keep it at 300 mg/day and not miss an opportunity when you add other drugs. If you experience and emergence of persistent sedation or cognitivie / memory impairments at 300 mg/day, the dosage is obviously too high. Does Lamictal help at all? Any side effects. My experience with Lamictal was that I noticed trouble with memory and word-finding for the first 1-2 weeks. It then disappeared entirely.
> I mean this with all due respect, but blood levels, as suggested in pharmacology, I think, can be the exception more than the rule. Yes, it may be based on sound research, but the real-world evidence, versus a randomized controlled trial, and their concordance, are being highly recognized in the scientific community
That is an incredibly astute summation. At 150 mg/day of nortriptyline, my blood level was 153 ng/mL. When I was cut back to 100 mg/day, it was assumed that I would then fall within the reported dosage window. It turns out that 100 mg/day was too high, and it prevented me from gaining a stable robust improvement. I always found myself increasing and decreasing the dosage of Nardil in an effort to finesse it in order to yield the return of a potent response. How I isolated nortriptyline as the culprit is a fun story that involves ice hockey.
> According to the research, you nor I should not be taking high doses of a serotonergic antidepressant, right? And, I should not be taking a stimulant, especially after a psychotic episode.
I really don't think that taking amphetamines or methylphenidate represent a high risk for mania. In fact, Linkadge correctly cites literature indicating that stimulants (I don't know which ones in particular) can actually have an anti-manic effect. I have not poured over the literature looking to verify this, but I think you should. I have had amphetamine and methylphenidate added to ongoing treatment with Parnate 120 mg/day + desipramine. Not one incident of treatment-emergent mania. However, I never did this immediately after a drug-induced mania, so I can't offer any insight regarding that scenario.
No selective serotonin reuptake inhibitor ever provided me with substantial long-term benefit. However, Effexor and Cymbalta have produced a mild improvement. Effexor produced a mild improvement that allowed me to read whole paragraphs when I never could get beyond 2-3 consecutive sentences previously.
> I think there is also a bit of an art, with the science, is really what I am getting at.
Absolutely. I can't think of any field of medicine that relies more on art than psychiatry.
> And the metric used for the Aventyl is a very general guide. I am honestly not trying to argue.
You are trying to get us both closer to the truth. I never felt that it was an argument. I totally agree with you, as my personal description above attests to.
> I respect your thoughts greatly.
Isn't respecting Scott's thoughts the cardinal symptom of insanity?
The feeling is mutual, and try not to pass up an opportunity to read your posts.
> I *hope* that makes sense..lol.
It does make sense, obviously, but even if it didn't, it could still easily be the true.
I find that accepting uncertainty reaps huge rewards.
> :)
>
> JaySincerely,
Scott
Posted by SLS on August 21, 2021, at 8:36:43
In reply to Re: Nortriptyline dosing., posted by undopaminergic on August 21, 2021, at 2:11:51
Hi, UD.
> >
> > Now, I respond extremely well to lithium, which blocks noradrenaline.
> >
>
> I'm not aware of such an effect. Maybe you mean glutamate?
Read my post to Jay regarding lithium and its bimodal effects on glutamate activity.
> > I tried nortriptyline (Aventyl) a few times, and I eventually had a few psychotic, manic episodes. See, there is a type of mania called dysphoric mania, which is like taking a boiling hot shower just after falling onto a thousand razorblades. Most people think mania is some euphoric spending spree, having sex with strangers, type of thing.
> For me it was euphoria and spending sprees. So, at least in some respects, I've been lucky.
>
> > I think you likely know what I am getting at. The noradrenaline is a huge factor in mania...
> >
>
> For me, it felt a lot more like dopamine.
>
> -undopaminergic
I can't really offer any comments regarding your experiences and conclusions. I just don't know enough about it. One of my *older* doctors said that he knows of no effective antidepressant that hasn't precipitated a manic reaction in at least some people. I found that even Wellbutrin, once thought to be immune from producing mania, does indeed trigger it.Ugly stuff, even if it feels like a better high than cocaine. One episode of mania can ruin a life in days that had taken decades to build. The aftermath of a psychotic mania includes embarrassment, being forever remembered as a mentally imbalanced and potentially dangerous mental patient, being ostracized and abandoned by almost everyone, self-inflicted poverty, the loss of respect by friends who become the target of personal insults and rage, etc. Years of depression really doesn't do this - with the exception of poverty.
I know from experience.
- Scott
Posted by undopaminergic on August 21, 2021, at 12:22:54
In reply to Re: Nortriptyline dosing. » undopaminergic, posted by SLS on August 21, 2021, at 8:36:43
> Hi, UD.
Hi SLS!
[... mania ...]
>
> Ugly stuff, even if it feels like a better high than cocaine. One episode of mania can ruin a life in days that had taken decades to build. The aftermath of a psychotic mania includes embarrassment, being forever remembered as a mentally imbalanced and potentially dangerous mental patient, being ostracized and abandoned by almost everyone, self-inflicted poverty, the loss of respect by friends who become the target of personal insults and rage, etc. Years of depression really doesn't do this - with the exception of poverty.
>
> I know from experience.I almost killed myself and ended up in intensive care. I nearly destroyed my kidneys probably from rhabdomyolysis. On other occasions I ended up in the mental hospital. So, I'm not saying mania is worth it.
Only my first, and most intense, episode had a happy ending, other than coming to an end and a descent back into depression.
If I am saying something, it is that classic, euphoric mania is better than mixed or dysphoric mania, if only because it feels better -- but that alone may keep you from attempting suicide.
-undopaminergic
Posted by undopaminergic on August 21, 2021, at 13:47:12
In reply to Nortriptyline dosing and other subjects (long). » Jay2112, posted by SLS on August 21, 2021, at 7:52:57
> > Hi Scott
>
> Hi, Jay.Hi Jay and Scott.
Thanks for your story SLS, it was entertaining, even a bit inspiring for some reason I can't pinpoint.
> I asked for bromocriptine or Wellbutrin. The doctor laughed at my theories regarding dopamine. I proceeded to indulge myself into giving a short monologue that resulted in her shedding tears. Words matter.
>Can you expand a bit on that? I'm curious.
> In 1992, I entered the clinical pharmacology department at the NIH. My objective was to take what they then considered to be the most effective antidepressant in the world, clorgyline. Clorgyline is an irreversible and *specific* (not selective) inhibitor of MAO-A.
>I think you mean "not *just* selective". Obviously it is selective if it inhibits only MAO-A. I assume you mean it doesn't inhibit MAO-B at all even at higher doses?
> It is the only drug capable of breaking through a truly impenetrable severe anergic depression. I agree with the opinion of the NIH regarding clorgyline. The NIH was the only source of clorgyline for human consumption in the United States.
>How come you haven't pursued clorgyline more recently? At worst, you'd have to pay for a custom synthesis, and I don't know what you might end up having to pay for it.
I don't understand, however, why inhibiting only MAO-A would be so much better than inhibiting both of them. Or maybe that's not what you're trying to say?
> When I entered the program, they reviewed my history, and William Z. Potter told me that I was bipolar. He put me on lithium so that they wouldn't have a mad-man on their hands. This was the point when I realized that I was indeed bipolar, despite never having had a spontaneous manic episode.
>I've had spontaneous episodes.
> The DSM-5 includes in its diagnostic scheme "qualifiers". One qualifier is drug-induced mania. Another is depression only. Think of it like this: Someone's first episode of bipolar disorder presents as depression. It is caused by a bipolar diathesis (underlying brain pathology) rather than a unipolar diathesis. It is literally bipolar depression. Now, lets pretend that this person's brain lacks the strong switching mechanism seen in Bipolar I. This person never switches. They are stuck with experiencing only the depressive phase of the illness.
>Could you somehow have a "unipolar diathesis" and for some reason experience (endogenous) manic episodes? Perhaps more importantly, could you have a mixture of both unipolar and bipolar?
> 1. If you have found any relief at all with your current regime, you might consider remaining on it and simply add desipramine or nortriptyline. Desipramine is a stronger and somewhat more selective NE reuptake inhibitor than is nortriptyline. You can even do this if you are currently on, and plan to continue with MAOI. In this case, you are limited to desipramine and nortriptyline and possibly trimipramine and doxepin.
>I partially disagree, based on Ken Gillman's Psychotropical Research:
https://psychotropical.com/overview_maoi_and_tca_interactions/Cite: "We now understand that the only serious interaction between MAOIs and TCAs is caused by excessive elevations of serotonin.".
And: "Of the TCAs the only ones that possess significant SRI potency are clomipramine and imipramine: however, imipramine is weak and only occasionally causes a severe ST interaction.".
Elsewhere, Gillman documents that nortriptyline is the most selective noradrenaline reuptake inhibitor amongst the TCAs.
> > Ok...bear with me...I do have a point..lol. (Along with my fragmented sentences.)
> >
> > Now, I respond extremely well to lithium, which blocks nor adrenaline.
>
> Lithium does so many things. Right now, I see it as a glutamate releaser at 300-450 mg/day and can be a capable antidepressant at these low dosages.
>I tend to view antagonism of glutamate, at least the NMDA-subtype receptors, as being more antidepressive than the opposite. Consider ketamine, laughing gas, and, underrecognised, memantine. Lamotrigine is also supposed to be antiglutamatergic, which may explain it's potency as an anticonvulsant.
> All of my manias were dysphoric. There was nothing euphoric about them. Much of the content was expressed as religiosity - Jesus versus the Devil. It was brutal.
>Wow, that beats my delusions, and I'm (mis)diagnosed with schizophrenia!
> One treatment that I have seen others have success with is the combining of Wellbutrin with Effexor or Pristiq. Some people also do well with a combination of Wellbutrin with Zoloft (Welloft).
>Those are a couple of options I haven't pursued. May come in handy.
> I have never had a manic episode without the involvement of a MAOI - either Parnate or Nardil.
>I got manic on memantine.
> Yes. I don't get the maximal positive response to Lamictal (aborigine) until I reach 300 mg/day. That dosage might be worth exploring.
>There's another idea on my list.
> Does Lamictal help at all? Any side effects.
No effects at all for me. I'm on 200 mg. I shall consider 300 mg.
> > According to the research, you nor I should not be taking high doses of a serotonergic antidepressant, right? And, I should not be taking a stimulant, especially after a psychotic episode.
>
> I really don't think that taking amphetamines or methylphenidate represent a high risk for mania. In fact, Linkadge correctly cites literature indicating that stimulants (I don't know which ones in particular) can actually have an anti-manic effect.
>I tend to agree based on personal experience. I never totally "lost it" while I was taking a stimulant. I was paranoid, all right, but the psychotic breakdown with auditory hallucinations came after I stopped the stimulants. However, stimulants can be abused in a way that leads to accumulating sleep deficit, which can produce psychosis; I think that was what happened to me -- I still could not sleep even after stopping the stimulants.
> No selective serotonin reuptake inhibitor ever provided me with substantial long-term benefit. However, Effexor and Cymbalta have produced a mild improvement. Effexor produced a mild improvement that allowed me to read whole paragraphs when I never could get beyond 2-3 consecutive sentences previously.
>Interesting. Surprisingly, I have never tried Effexor. I thought having tried 4 SSRIs, I had "been there, done that". I did try Cymbalta without noticeable benefit.
> > I think there is also a bit of an art, with the science, is really what I am getting at.
>
> Absolutely. I can't think of any field of medicine that relies more on art than psychiatry.
>Yes, absolutely!
-undopaminergic
Posted by SLS on August 22, 2021, at 20:23:27
In reply to Re: Nortriptyline dosing and other subjects (long). » SLS, posted by undopaminergic on August 21, 2021, at 13:47:12
Hi, UD.
You ask great questions. I'll have to come back to this. I can see a book coming on...
:-)
As far as the difference between "selective" versus "specific" is concerned: With regard to MAO-A inhibition and MAO-B inhibition is concerned, a selective MAOI inhibits both enzymes, but to varying degrees at varying dosages. As an example, selegiline, at low dosages, is selective for MAO-B, but inhibits MAO-A to a small degree. At high dosages, selegiline loses its selectivity and inhibits both enzymes equally. A specific MAOI inhibits only one enzyme without affecting the other, regardless of dosage.
Right now, clorgyline is used only as a biological probe. The NIH stopped treating people with it when there were some reports of their patients having cardiac events during treatment in the 1990s. They had to withdraw it from people for whom it was the only drug that ever worked for them. This was also the scenario with nomifensine (Merital). Nomifensine had been played around with in the 1980s because it was a potent reuptake inhibitor of dopamine, and I think some NE, too. It was approved by the FDA as an antidepressant. However, there were a handful of reports coming from Germany that it produced fatal hemolytic anemia. Hoecht Roussel voluntarily took it off the market worldwide. The thing is, it was the only drug that ever worked for people. Because of my suspicions regarding dopamine, I had to cry in front of Baron Shopsin (MD) to beg him to treat me with it. He relented. When I went back to him two weeks later, it was the only time he ever saw me dramatically improved. Unfortunately, it lasted for less than a week. Par for the course with me. In actuality, the incidence of this reaction was rare.
- Scott
Posted by undopaminergic on August 23, 2021, at 2:18:18
In reply to Re: Nortriptyline dosing and other subjects (long). » undopaminergic, posted by SLS on August 22, 2021, at 20:23:27
> Hi, UD.
Hi SLS!
>
> You ask great questions. I'll have to come back to this. I can see a book coming on...
>
> :-)That is not necessarily a bad idea. There are many people who enjoy reading about other people's struggle.
> As far as the difference between "selective" versus "specific" is concerned: With regard to MAO-A inhibition and MAO-B inhibition is concerned, a selective MAOI inhibits both enzymes, but to varying degrees at varying dosages. As an example, selegiline, at low dosages, is selective for MAO-B, but inhibits MAO-A to a small degree. At high dosages, selegiline loses its selectivity and inhibits both enzymes equally. A specific MAOI inhibits only one enzyme without affecting the other, regardless of dosage.
>Like I thought.
> Right now, clorgyline is used only as a biological probe. The NIH stopped treating people with it when there were some reports of their patients having cardiac events during treatment in the 1990s. They had to withdraw it from people for whom it was the only drug that ever worked for them. This was also the scenario with nomifensine (Merital). Nomifensine had been played around with in the 1980s because it was a potent reuptake inhibitor of dopamine, and I think some NE, too. It was approved by the FDA as an antidepressant. However, there were a handful of reports coming from Germany that it produced fatal hemolytic anemia. Hoecht Roussel voluntarily took it off the market worldwide. The thing is, it was the only drug that ever worked for people. Because of my suspicions regarding dopamine, I had to cry in front of Baron Shopsin (MD) to beg him to treat me with it. He relented. When I went back to him two weeks later, it was the only time he ever saw me dramatically improved. Unfortunately, it lasted for less than a week. Par for the course with me. In actuality, the incidence of this reaction was rare.
>I know they are not clinically available, but it is still possible to acquire them on your own and use them with or without a doctor's supervision. It would be legal, because they aren't controlled substances (or *is* nomifensine?).
Nowadays, there is a whole industry and subculture around research chemicals, none of which are clinically available for prescription, and most of which have only been tested in animals. I've used some of them myself, including desoxypipradrol and ethylphenidate.
-undopaminergic
This is the end of the thread.
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