Nortriptyline dosing and other subjects (long). » Jay2112

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.

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).

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.

The feeling is mutual, and try not to pass up an opportunity to read your posts.

It does make sense, obviously, but even if it didn't, it could still easily be the true.

Some see things as they are and ask why.
I dream of things that never were and ask why not.

The only thing necessary for the triumph of evil is that good men do nothing.

Nortriptyline dosing and other subjects (long). » Jay2112

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