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Medicating based on receptors


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So, one night I decided to try and figure out the neurochemistry of what had helped my depression in the past (Cymbalta, Abilify, Lamictal, Lithium) and come up with a cocktail based on the receptors hit and blocked. The following is what I came up with.. and yes, I mean NE where I wrote NA - again, written late at night.

Does this make any sense or am I just being desperate? Am I getting anything wrong? Can this work?

Page1.jpg

Page2.jpg

On the second page: number 1 is what worked before, number 2 is what I'm on now.

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I can't tell the chemistry of all that, but Elivil is a good med, so is Remeron.

B.

PS you do your homework!

Yeah, the Elivil has kept away the suicidal urges and Remeron is great for regulating my sleep - doesn't knock me out, just improves the quality of the sleep I get. Though, I'm not on the Remeron at the moment. I was actually surprised at the max dose for Remeron & am curious as to the affect it would have to go that high.

Thanks.. I do try, though I'm no expert. Trying to be, but I'm not quite there yet..lol.

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Wow, Cetkat - I'm impressed. My concentration is shot today, so I'm not going to try to understand all of that. I'm no expert either, but from what I do about neuroscience and psychopharmacology can be summed up with this - nobody knows jack about the brain and most especially, nobody knows how all these head meds work. For example, for years people thought that SSRIs only hit serotonin, and now realize it's not that simple.

Another wrinkle in all of this - nobody knows how your particular receptors work. Idiosyncratic reactions are definately possible. Remeron has been investigated as an agent to help akathisia - and I can't take it because in me, it causes akathisia.

Psychopharmacology is still like throwing darts at a dart board.

I know you've had a rough go at it, and what you are proposing could theoretically work. Unfortunately, reality does not always match theory.

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See Persephone's response above. I really don't think that our knowledge of the subject is sufficient to be able to accurately make such an analysis. For instance, you failed to take into account receptor reserve, which could make any increases in drug concentration moot (especially for direct agonists), or changes in receptor expression and neurotransmitter release. These things are not predictable or knowable in every (any?) patient with our current knowledge.

That doesn't mean that you shouldn't try the changes you've proposed, or that such an analysis isn't a useful guide, but it's far from a crystal ball.

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I don't think we're really at the point where we can solve MI like a math problem. Each drug has particular qualities beyond their known chemical effects and we really don't know how the chemical effects relate to depression.

One thing we do know is that Miraplex and Strattera have both undergone clinical testing for use as antidepressants and failed to show any separation from placebo.

Where I'd be doing to my detective work isn't in PI sheets but in published case histories and journal articles.

The question you should be asking isn't "Does this make sense on paper?" but rather "is there any evidence something like this has ever helped anyone else?"

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I'm a thinker and a planner, like you. But to be really honest with you, you aren't going to know how these meds are going to react with and on you until you try them.

The one thing you forgot to take into accout (forgive me if I'm wrong, it's late) is side effects.

I suggest taking your list to your pdoc and starting on the meds, *one at a time* so you can see if you tolerate each one and have no adverse side effects from any of them. And if they help you. Then, slowly, you can try getting on your "perfect combo".

Good luck.

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Cetkat,

What your doing sounds like what I imagine myself doing with therapy - or with meds if I was back on them - IF my effing brain would work!

But all the posts above really say perfectly what I think about it.

You sort of need to be able to do this based on personal experience, not on paper - not even, I think, from other peoples experience.

Unfortunately that would mean taking a hell of a lot of meds!

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Sorry that I can't open your linkies (I'm tied to an office network that bans media sharing/streaming sites, among myriad others...bastards). But I have a hunch as to what you are trying to accomplish. There are some pretty loose algorithms out there and it's not Totally a matter of throwing darts at a board. But as others above have said, it just ain't so cut and dried. From the nature of your post, I'll guess that you've done some laps on the med-go-round and finally landing on a cocktail that works for you. That's a sad reality in the MI world. Everyone envies those few who respond well on the first try or two. Our brains all work from the same substrate of cells and chemicals. But they all work somewhat differently and this remains a daunting issue in neuroscience and psychiatry. Personally, I believe it has lots to do with genes turning or turning off (or not turning on or off). But that's for another board.

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See Persephone's response above. I really don't think that our knowledge of the subject is sufficient to be able to accurately make such an analysis. For instance, you failed to take into account receptor reserve, which could make any increases in drug concentration moot (especially for direct agonists), or changes in receptor expression and neurotransmitter release. These things are not predictable or knowable in every (any?) patient with our current knowledge.

That doesn't mean that you shouldn't try the changes you've proposed, or that such an analysis isn't a useful guide, but it's far from a crystal ball.

Yes, there definitely are variables which I have no way to predict. Plus my mind's chemistry has changed from when I first started when those meds worked (obviously, or else they would help), so I may need something completely different now. The unfortunate truth is that I've been on my past meds more than one time and have yet to be able to make a dent in my depression - so no matter what my current brain chemistry is, it's still not in a place where I can get results.

I don't think we're really at the point where we can solve MI like a math problem. Each drug has particular qualities beyond their known chemical effects and we really don't know how the chemical effects relate to depression.

One thing we do know is that Miraplex and Strattera have both undergone clinical testing for use as antidepressants and failed to show any separation from placebo.

Where I'd be doing to my detective work isn't in PI sheets but in published case histories and journal articles.

The question you should be asking isn't "Does this make sense on paper?" but rather "is there any evidence something like this has ever helped anyone else?"

Yeah, I know that we only understand a small amount of what these drugs actually do.. so it's still a hit-or-miss operation. I'm only trying to use what we do know to my advantage so I have a greater chance for a hit. Doesn't necessarily mean it'll work. I just think that if I do make decisions based on receptors the math should at least be right and as potent as possible (meaning choosing the best med for the job).

I'm not surprised to hear that the studies haven't shown results - those drugs, from what we do know, seem very limited in what they do in the brain. I am curious as to whether those studies were on the individual drug or as add-ons to another cocktail. Do you happen to recall?

I'm not so sure the case studies can actually help me. My situation is uncommon (in that the depression never goes away & I'm getting no response at all from the majority of the meds - not even side-effects) so I don't really jibe with the sample group. Not to say that case studies can't be useful, but my research into them has yet to result in an improvement. Anyway, I think both questions are relevant.

I'm a thinker and a planner, like you. But to be really honest with you, you aren't going to know how these meds are going to react with and on you until you try them.

The one thing you forgot to take into accout (forgive me if I'm wrong, it's late) is side effects.

I suggest taking your list to your pdoc and starting on the meds, *one at a time* so you can see if you tolerate each one and have no adverse side effects from any of them. And if they help you. Then, slowly, you can try getting on your "perfect combo".

Good luck.

Yes, I would definitely only make one change at a time. That in and of itself pretty much takes care of the side-effects question because I'll be able to pinpoint what's causing what (right now I'm not really having any negative side-effects, so I can almost leave my current meds out of the equation). Plus at this point I don't really care so much what negative effects they have as long as they relieve my depression.

You sort of need to be able to do this based on personal experience, not on paper - not even, I think, from other peoples experience.

Unfortunately that would mean taking a hell of a lot of meds!

Well the only personal experience I really have is my own, because (you're right) everyone is different - so I'm trying to replicate what I had in the past. And, yeah, I've been through the med-go-round many times.. individual at first, then cocktail. It has definitely been alot of meds. I would take them all at the same time if it would work though. I'm past the point of caring how many different ones I'm on at once as long as they're not contraindicated.

There are some pretty loose algorithms out there and it's not Totally a matter of throwing darts at a board. But as others above have said, it just ain't so cut and dried. From the nature of your post, I'll guess that you've done some laps on the med-go-round and finally landing on a cocktail that works for you. That's a sad reality in the MI world. Everyone envies those few who respond well on the first try or two. Our brains all work from the same substrate of cells and chemicals. But they all work somewhat differently and this remains a daunting issue in neuroscience and psychiatry. Personally, I believe it has lots to do with genes turning or turning off (or not turning on or off). But that's for another board.

I think genes have a hand in who develops what too. To what extent, I don't know. I wish we knew more about it all, but I've just got to go with what's given to me - which isn't always that helpful, or correct.

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Ok, I've had time to check your siggy and profile. I see you are on a thyroid med. Have you had your levels checked? You've pretty much run the gamut of antidepressants. If the Dysthymia dx is accurate that could also be your enemy. Dysthymics often just don't respond to antidepressants to any significant extent. An MAOI for mi'lady? You've certainly got a case for refractory depression. That opens the doors to ECT, TMS, Vagus Nerve Stimulation. They may chafe at your age, though.

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Ok, I've had time to check your siggy and profile. I see you are on a thyroid med. Have you had your levels checked? You've pretty much run the gamut of antidepressants. If the Dysthymia dx is accurate that could also be your enemy. Dysthymics often just don't respond to antidepressants to any significant extent. An MAOI for mi'lady? You've certainly got a case for refractory depression. That opens the doors to ECT, TMS, Vagus Nerve Stimulation. They may chafe at your age, though.

Had blood drawn for my TSH today actually - will know the result Friday. I can tell that I'm within the range though..a little high perhaps, but ok. Unfortunately my Thyroid has nothing to do with my depression. I ended up hyperthyroid for a bit when the Cytomel was added & I was still down in the dumps. Figures.. I did get some energy back though.

An MAOI is certainly something to try. I want to go through the other meds as throughly as possible before resulting to that, but I'll definitely take it when the time comes - which is soon. My second pdoc added the Dysthymia years ago.. haven't seen anything to discount it yet, so I think she was right.

As for the ECT/TMS/VNS, I want to try the ECT, but I'm without insurance. In two years I can get Medicare since I now have SSDI - but when I looked up ECT & Medicare it said that coverage was discontinued in '03. That may change.. or I may be able to purchase insurance later for the sole purpose of getting one or more of those done, but the removal of the preexisting condition clause wont happen till 2012. One good thing is one of my old pdocs wanted me to get ECT and knew someone who'd sign off on it.. so I probably wouldn't have any trouble getting it rx'd.

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First of all, MAOIs aren't as scary as they are made out to be. Definately a good idea before ECT.

Another thing that struck me - you aren't having any side effects. Is your pdoc putting any thought into you may be an ultra-rapid metabolizer and need higher than standard doses?

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Another thing that struck me - you aren't having any side effects. Is your pdoc putting any thought into you may be an ultra-rapid metabolizer and need higher than standard doses?

Well the thing is, I used to have side effects. Never many - in fact the med that actually worked for me (Cymbalta) seemed like nothing but a sugar pill until the first day of the third week came around & it worked like magic. However the other drugs did have something & a couple had alot. Now, when I try the same drugs, I get nothing. In fact I had to stop Abilify and Lamictal before due to side effects.. but this time I haven't had that response. I really think I'm just getting used to having my head played with like I've gotten used to Antihistamines and Painkillers (way too much surgery/physical therapy stuff). Even my midol eventually had to be combined with pamprin and naproxen.

As for upping the dosage, for the Cymbalta I did go up to 120mg and thought about testing levels for, but the lab didn't have it. The other meds have stayed within therapeutic dosages. The tests I have had done for Lithium and Tegretol came back normal for the amount taken.

Actually, now that I think about it.. the Trazodone & Elivil are sedating & that's technically a side-effect. So that's something. (But of course the Elivil had to go from 75 to 100 & then the Traz was tacked on in order to keep it working for sleep - thou obviously sleep wasn't the sole reason for upping the Elivil.)

It still makes sense to go as high as I can safely go on what I'm on now though & see if that makes any difference.

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Persephone makes a good point about you possibly being a rapid metabolizer. There are tests for some members of the CYP family, but this is quite new, not widely available and almost certainly way expensive. Pushing dosages may be the best solution for now, absent a run at Emsam. Be wary, though of pushing Elavil. It has a wildly variable half life and I've seen a couple of inadvertent overdoses in my years. Not good. Luckily, your current dosage leaves lots of wiggle room for your doc.

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There are tests for some members of the CYP family, but this is quite new, not widely available and almost certainly way expensive.

Hmm.. tests, plural. Is there such a thing as a partial ultra-rapid metabolizer - meaning one member has it, another doesn't? That's never occurred to me..

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There are tests for some members of the CYP family, but this is quite new, not widely available and almost certainly way expensive.

Hmm.. tests, plural. Is there such a thing as a partial ultra-rapid metabolizer - meaning one member has it, another doesn't? That's never occurred to me..

Over at Crazy Meds Talk there was an interesting topic that eventually got pinned. It's in the "Other Common Stuff" segment of the Neurologic Meds board. It's entitled "Metabolyzing Meds: CYP 450, UTG...." It wanders all over the place, was initiated by a post about a bad reaction to Effexor, strayed into a strident exchange about misquotation, the usual. Still, an interesting read, and a crash course on conjugation vs induction and other matters.

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Over at Crazy Meds Talk there was an interesting topic that eventually got pinned. It's in the "Other Common Stuff" segment of the Neurologic Meds board. It's entitled "Metabolyzing Meds: CYP 450, UTG...." It wanders all over the place, was initiated by a post about a bad reaction to Effexor, strayed into a strident exchange about misquotation, the usual. Still, an interesting read, and a crash course on conjugation vs induction and other matters.

Thank you! That definitely sounds like something to check out. ;)

As for what's going on now with me..

Went to see my pdoc today. Got Abilify increased to 15mg (from 10mg), and got the go-ahead to titrate from 100mg Lamictal to 200mg (with a stop for two weeks at 150mg before increasing all the way). My plan is to raise the Abilify tommorow, wait two weeks, then go to the 150mg Lamictal. My next appt is a month away so that'll put me at the 15mg/150mg - at which point I'll most likely do the 200mg increase & either stay there for the month or up the Abilify again halfway through. (Of course this all depends on how I react to the 15mg Abilify increase.)

My pdoc was surprisingly optimistic & wholly supportive about this.. pretty strange, especially since I had to sell the 10mg-15mg Abilify increase to him last month. Perhaps I just caught him in a good mood. *shrugs*

Feels good to have the meds in hand & have a game plan.

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