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Re: Nortriptyline dosing and other subjects (long). SLS

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:

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 (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!





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