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Re: Augment Effexor or go to Parnate nelag

Posted by SLS on April 25, 2012, at 1:07:44

In reply to Augment Effexor or go to Parnate, posted by nelag on April 24, 2012, at 22:53:07

Dear Nelag.

First of all, thank you for your generous mention of me. It is nice to be appreciated, although it is even nicer to see people get well.

I have never heard of anyone taking as much Effexor as you do. I thought 600 mg was as high as anyone went. Yet you actually need twice that dosage to respond. What I find most obvious is that Effexor doesn't really hit norepinephrine (NE) nearly as much as it does serotonin (5-HT). The ratio most often quoted is 1:30. Your brain might be telling you that you need huge doses of Effexor in order to get enough NE reuptake inhibition to glean an antidepressant response. Perhaps adding a secondary-structure tricyclic (TCA) like desipramine or nortriptyline would give you the NE activity you are attempting to fill with high-dosage Effexor, but without adding any more 5-HT activity. Both tricyclics are selective for NE; with desipramine being the most potent. You might then be able to reduce your dosage of Effexor once you add a TCA. Have you had an EKG? It might be a good idea, especially if you intend to go with desipramine. I am a little uncomfortable with your adding any drug while you are still taking so much Effexor. Would you be able to lower Effexor before you begin taking the tricyclic? I don't know that this is necessary, but this is uncharted territory. I found the combination of Effexor and nortriptyline to be partially effective when neither one alone did anything. At the time, I was taking 75 mg of nortriptyline. I later discovered during a subsequent drug trial that 150 mg was the optimum dosage of nortriptyline for me. I am a rapid metabolizer of tricyclics. It seems to me that people will either respond to 75 mg or they will respond to 150 mg, but not respond to anything in between. Nortriptyline is the TCA studied most for associating blood levels with clinical response. I would suggest starting at a low dosage and work your way up to 75 mg first. Take a blood test to assess your nortriptyline levels, and make decisions using the results as a guideline. Too much nortriptyline is no good. When you exceed your therapeutic window, it becomes less effective. The range of effective therapeutic blood levels for nortriptylne is 50 - 150 ng/ml. At 150 mg, my level approaches 150 ng/ml.

I prefer nortripytline to desipramine because its side effects are milder, although you might need the punch of desipramine to respond. An individual can respond to one TCA, but not the other. I also don't like the idea of adding a potent NE drug like desipramine to your treatment regime while you are taking so much Effexor. 300 mg would be safe. You might want to take a EKG (ECG) before adding the tricyclic, and repeat the test at some point while titrating. I am concerned about cardiotoxicity when adding a TCA to such high dosages of Effexor.

Effexor + Wellbutrin = good response
Effexor + nortriptyline = good response
Wellbutin + nortripytline = ?
Effexor + Wellbutin + nortripytline = ?

It might be interesting to leave the Wellbutrin in place, just in case there is some therapeutic dynamic occurring between it and the nortriptyline. I would really like to see the Effexor come down first. Despite my belief in the great value to be found in rational polypharmacy, I try to remain wary of dangerous adverse effects. The problem is that I simply don't know enough about these drugs to be able to predict the outcome of the many permutations of drugs possible. I am more conservative than many people give me credit for. They think I am some sort of cavalier cowboy shooting bullets in all directions indiscriminantly.

I feel pretty strongly that you will find something that works. You have demonstrated that your brain is not dead or immoveable.

I currently take:

Parnate 80 mg
nortriptyline 150 mg
Lamictal 200 mg
Abilify 10 mg
lithium 300 mg
prazosin 12 mg

You'll get there.

- Scott

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

- George Bernard Shaw




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