Re: My frustration in watching you. I apologize. » linkadge

Please read this entire post giving it your full attention. The decisions are yours, not mine. They are not even your doctors.

This is the regime that I thought was better than running back to Effexor - a drug that you can't tolerate at dosages that most people respond to (150-300 mg/day). NO NARDIL is necessary. I never said that it would be. Are you exquisitely sensitive to side-effects of Effexor? Right now, it seems that you are. Did you experience these same side effects to the same degree the very first time you took Effexor? What dosage of Effexor were you able to tolerate the first time you took it?

You have never tried combining the drugs that I listed above, right? (Different is different). I should think that it is worth trying at this juncture. At the very least, it would require you to abstain from taking SRIs for a few months. (3 seems to be the magic number).

Not even close. It is simple and logical. Why did you stop taking nortriptyline if it gave you a 75% improvement? That's a HUGE number. Is it logical that you did this? Keeping nortriptyline on board indefinitely while you build a regime around it is a no-brainer.

Wellbutrin helped you to an unsatisfactory degree. But it did help you. Adding it is another no-brainer.

Lithium continues to improve your condition at 300 mg/day. Dont change it. Keep it exactly at 300 mg/day. Doing this is another no-brainer.

Lamotrigine? Unless you had intolerable side effects in the past, taking lamotrigine at a dosage between 200-300 mg/day might be a necessary component of your treatment regime. You reported in the past that you had suspicions that there was a bipolar component of your depressive illness. Isn't there a first-degree relative that is bipolar or schizoid? If so, then adding lamotrigine is another no-brainer.

If you can tolerate lamotrigine at 200 mg/day, It makes little sense to discontinue it as you go through subsequent drug trials. Adding lamotrigine as an adjunct to treat TRD unipolar depression is pretty close to being a no-brainer. If you are experiencing side effect that are of great magnitude and persistent, just discontinue it. Be aware that side effects often disappear over the course of weeks or months. Responding well to *any one dosage* often takes 3-4 weeks, so wait before increasing the dosage. For me, this was true of cognitive and memory impairments. I found them to be more of a startup side effect than a persistent one. START LOW and GO SLOW. Don't allow a rapid titration to *trigger* side effects.

One of the first tidbits of wisdom bestowed upon me as a patient at Columbia Presbyterian was that "pulsing" antidepressants is perhaps the worst thing you can do (Frederick Quitkin). It makes people less responsive to antidepressants and often produces a sensitivity to side effects. Use Quitkin's advice - not mine. Stay away from SRIs for 3 months. This is another no-brainer.

Pulsing is just one of the things that you *seem* to be unaware of. You can't talk to Quitkin or any of the other research clinicians I saw. They are all dead.

Do you think for one second that I would settle for a merely palliative treatment? I decided to leave Columbia when, after much research into the dopamine system, I decided that Wellbutrin was a logical next step. It was still investigational at the time. Quitkin refused my request. This was on top of telling me that I was likely to be in the 85% who were not treatable (Michael Liebowitz). I made a phone call to Donald Sweeney. I forgot how I found him. He had been using Wellbutrin in a clinical trial. When I spoke to him, I described my rationale for using pro-dopaminergic drugs. He told me that Wellbutrin didn't work the way I thought it did, even though it was listed as a dopamine reuptake inhibitor. However, he said that the drug looked good. Sweeney's clinical trial of Wellbutrin had been completed. So, he recommended that I try Baron Shopsin.

Baron Shopsin was one of the first investigators of lithium in America, and a protege of Nathan Klein when they were both at NYU.

Shopsin also went on to help describe schizoaffective disorder as a single illness. His books are still out there somewhere.

Shopsin was one of the psychopharmacologists who asked me to help him write a paper for publication. Interestingly, it was to be about amoxapine and the unethical practices of the FDA in approving it. After poking around the medical school library at Rutgers, I discovered evidence to corroborate Shopsin's thesis. Unfortunately, Shopsin relocated from NYU in Manhattan to Indianapolis, so the project remained incomplete. That was in 1986.

The only drug that Shopsin saw me very much improved on was nomifensine. It was an investigational drug that was a potent dopamine reuptake inhibitor. It was used as the "gold standard" biological probe to investigate dopamine function.

Shopsin insisted that nomifensine (later to be approved as Merital) was "a piece of sh*t", but he eventually relented. It was the only drug that he ever saw me significantly improved on. However, the antidepressant response to nomifensine didn't last for more than a week. Shopsin was an investigator of Wellbutrin, and treated me with it using a dosage of 900 mg/day. It exacerbated my depression to a moderate, but very perceptible degree. When I discontinued it, I experienced a discontinuation rebound-improvement. This was a common reaction for me with tricyclics and MAOIs. However, this never occurred when discontinuing SSRIs. I can't remember it happening with SNRIs either.

An extremely important example of how the same drug can affect the same person in very different ways is represented by my experience with Effexor. I have been on Effexor at least a handful of times with some success at a dosage of 300 mg/day. 225 mg/day was ineffective. The last time I tried Effexor, things were very different. I had just switched to Effexor immediately after a trial of Trintellix. Trintellix effectively played the role of an experimental pretreatment to Effexor. Upon starting Effexor, I reacted to it in a very different way. It exacerbated my condition and gave me some pretty severe zombie brain-fog effects. It felt very strange and resembled dissociation.

Effexor, then, is one drug that produces different clinical effects, depending upon which drug(s) preceded it. Stay away from SRIs during these drug trials (experiments). Use all of your tricks to ameliorate your depression as you move from drug trial to drug trial. Keep your head above water. These are palliative measures only, since that seems to be the limit to what they are capable of helping you.

* And for God's sake, restart nortriptyline and leave it there indefinitely (if you did indeed experience a 75% improvement on it).

Once your trial of above drugs is complete, you will probably be at the 3 month mark. Then you can reintroduce a SRIs. I would add either Effexor or Pristiq before going with any other SRIs. KEEP IN PLACE the above drugs if you reach dosages that are normally therapeutic.

If you reach another dead end, then make phone calls to doctors and ask them (through their secretaries) if they use Nardil to treat depression. If you turn up empty after calling as many doctors you can find locally (1-2 hours by car), then contact university psychiatric departments. Either they will place you into a research study or treat you outright. I would expect them to provide you with Nardil if they feel its warranted.

I am absolutely sure that you will think of alternative strategies to find treatments outside the sphere you have been stuck in for decades.

Searching for expert clinicians who will treat you with a MAOI if necessary should take up *all* of your time - not studying neuropsychopharmacology. Let the medical community do that.

This the best that I can contribute right now. Oh yeah. Moclobemide is a sh*tty drug for *most* people. I've described why in the past. Descriptions of my experience with moclobemide was clinical and observational rather than being biological guesses. Psychiatrists in clinical practice often give greater weight to their observations and those of their colleagues.

Let the doctors determine if you are an odd-ball that responds only to sub-therapeutic dosages of standard antidepressants. Personally, I am dubious of this. You may have developed an alteration in the dynamics of your serotonin system(s). Although this might be your current reactivity to SRIs, this could be the result of pulsing these drugs repeatedly.

Let the doctor be your doctor as long as he or she is a good one and has your confidence. Whether or not a doctor uses MAOIs is a good index of experience and competence.

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.

Re: My frustration in watching you. I apologize. » linkadge

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