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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by iforgotmypassword on September 21, 2006, at 20:55:19
I was wondering if anyone knew if there is any way some people just don't get the proper level of drugs in their blood to be effective, and when their doctor does not feel okay with increasing, they lose out? Is there a condition? Is there an actual way to measure it?
I have only gotten one drug tested in blood and it was desipramine. Even at 200mg, my blood did not show therapeutic levels. At 300mg, I finally did, but that is the absolute highest you can go with the drug.
Extrapolating from this, is it possible my non-response to so many medications is due to not reaching or maintaining proper therapeutic levels in my blood? Is there a condition that describes this and is there a test for it? And if so, what can I do?
Posted by Jost on September 21, 2006, at 21:19:07
In reply to how to know if i reach/maintain therapeutic levels, posted by iforgotmypassword on September 21, 2006, at 20:55:19
Is there any established correlation for most psych drugs between blood levels of the active ingredients and any therapeutic effect? My impression was that there's not.
How did you establish what a "therapeutic" level for blood testing was?
Jost
Posted by iforgotmypassword on September 21, 2006, at 22:03:18
In reply to Re: how to know if i reach/maintain therapeutic le » iforgotmypassword, posted by Jost on September 21, 2006, at 21:19:07
that's how my desipramine test was discussed with me. that i had not hit the therapeutic range yet at 200mg. but at 300mg i did.
surely if you don't have high enough blood levels the effect must be weaker, if effective at all, right?
Posted by Emily Elizabeth on September 21, 2006, at 22:16:23
In reply to Re: how to know if i reach/maintain therapeutic le » Jost, posted by iforgotmypassword on September 21, 2006, at 22:03:18
I have similar problems w/ meds. I always need a higher level for an effect. When I was tested for desipramine level I also was suprisingly low for the dose. My pdoc didn't seem all that concerned b/c it isn't a perfect measure and we were deciding where to stop my dose based on side effects.
Many meds, like SSRI's (prozac, paxil, zoloft, etc.) and SNRI's (effexor, cymbalta) don't have clear blood levels. Others do, like TCA's (desipramine, imipramine, etc.) and lithium. I believe that blood levels are established by medical research just like any other sort of blood test would be (thyroid, blood sugar, etc.)
I think this condition (if it can be called that) is generally called being a "rapid metabolizer." I do not know of a test for it. You may need to augment with multiple medications to get an adequate effect. You need a somewhat aggressive pdoc.
Best,
EE
Posted by Phillipa on September 21, 2006, at 22:27:01
In reply to Re: how to know if i reach/maintain therapeutic le, posted by Emily Elizabeth on September 21, 2006, at 22:16:23
Emily is right. Love Phillipa
Posted by Racer on September 22, 2006, at 2:22:28
In reply to Re: how to know if i reach/maintain therapeutic le » iforgotmypassword, posted by Jost on September 21, 2006, at 21:19:07
Most of the newer drugs don't, and there's maybe some evidence that the older drugs weren't as clear as they seemed... The TCAs mostly can be tested. Blood levels will usually indicate effective levels. When I took nortriptyline, back at the dawn of time, it took about three times what the doctor expected before I reached the therapeutic window.
That's not a "condition," though. That's just individual variation. It was explained to me a while back, but of course I can't remember it all. (I think I can remember where to find my bed... That's where I needed to be two hours ago...) What I do remember is that poor metabolizers get a higher level of some drugs, and a lower level of others. And, of course, vice versa.
The bottom line, though, is that some people require higher doses than others. And that TCAs generally have known therapeutic windows, so they can be tested for. It's unfortunate that the newer drugs don't have those, since it might help with knowing when to throw in the towel with them...
Posted by Jost on September 22, 2006, at 17:44:47
In reply to how to know if i reach/maintain therapeutic levels, posted by iforgotmypassword on September 21, 2006, at 20:55:19
I found a couple of references:
One from "Have You Phenotyped Your Patient Lately?"
SHELDON H. PRESKORN, MD
Journal of Practical Psychiatry and Behavioral Health, March 1996,115-117
"I then ask if they have ever used therapeutic drug monitoring (TDM) to determine what plasma level of a tricyclic antidepressant (TCA) a patient has developed on a given done of a TCA. Most answer: "Yes."
I then point out that using TDM with such drugs is tantamount to assessing (i.e., phenotyping) the functional status of CYP 2D6 activity in that patient since that activity is the principal factor that determines what plasma TCA level the patient will develop on a given dose of a TCA. Note that dose here refers to the dose the patient is actually taking, not what the physician is prescribing. (For a detailed discussion of cytochrome P450 enzymes, see my November 1995 column.)
In this column, I continue a series devoted to understanding why different patients respond differently to the same dose of the same drug. Here I focus on the role of TDM, which is a refinement of the standard dose-response strategy and involves measuring the concentration of the drug achieved in a specific patient on a specific dose. The concentration in plasma is typically used as a surrogate for the concentration at the site of action because it is relatively easy to obtain and is correlated with concentration in other body compartments (e.g., a specific receptor in the brain). The goal of TDM is typically to ensure that the patient is on a dose that will produce a plasma drug concentration within a range that usually provides a therapeutically desired response in the majority of patients without undue adverse effects. Advances such as TDM have been made possible by research in clinical pharmacology and pharmacogenetics. They can help clinicians detect the reasons behind the interindividual differences that determine much of the variance in response among patients receiving the same dose of the same drug."
Another reference is a more comprehensive discussion:
I guess it's hard to know whether you've come close to a dose that could produce adverse reactions-- although for TCAs, it seems that the information is more reliable than for many more recent ADs.
Jost
Posted by SLS on September 24, 2006, at 7:45:40
In reply to how to know if i reach/maintain therapeutic levels, posted by iforgotmypassword on September 21, 2006, at 20:55:19
> I was wondering if anyone knew if there is any way some people just don't get the proper level of drugs in their blood to be effective, and when their doctor does not feel okay with increasing, they lose out? Is there a condition? Is there an actual way to measure it?
I am unaware of therapeutic testing of blood levels of antidepressant drugs other than tricyclics. I am not saying that they don't exist.
As someone indicated, you need to have an aggressive doctor who is at least familiar with the precedents set for the highest dosages used. For instance, there are plenty of instances reported of the use of 600mg of Effexor, but how many doctors are aware of them? It can be a tricky thing to titrate a dosage of a drug clinically.
Which drugs are you concerned with that you think you might not have explored dosages thoroughly enough? What dosages did you reach?
- Scott
Posted by Jost on September 24, 2006, at 11:07:47
In reply to Re: how to know if i reach/maintain therapeutic le » iforgotmypassword, posted by SLS on September 24, 2006, at 7:45:40
Btw, I agree with Scott about this.
Even where there are established doses, a pdoc could decide to try a little more.
eg, the established dose (not with a blood level, but pretty common) for Parnate is 30-60 mg. I went up to 100 mg and never had any type of hypertensive crisis, or even hypertensive reaction. I've heard of people who used as much as 120 mg.
So individual reactions--and side effect profiles-- can vary considerably. The discussions of dose and blood testing all make that point-- at least, the perhaps somewhat different, but related point, that the ranges don't predict individual reactions.
Jost
Posted by Jost on September 24, 2006, at 11:13:14
In reply to Re: how to know if i reach/maintain therapeutic le » iforgotmypassword, posted by SLS on September 24, 2006, at 7:45:40
Also: the discussions of blood testing and TDM confuse (or discuss in a rather overly co-mingles way) two (and even three) issues:
1. therapeutic levels
2. harmful levels
3. compliance issues
Leaving out compliance issues, though, it's one thing to say that you believe that above a certain level of drug may cause harmful effects (which is more true of lithium, in the discussions than tricyclics, although I don't know enough about TCA to know if it applies there, too).
It's an entirely different thing to say that there'a level that should (or does) cause a therapeutic effect. Clearly, you aren't getting a therapeutic effect-- so no matter what your blood level, that level doesn't correlate with one.
I assume that your pdoc is afraid of some harmful reaction, and that this is the reason for not giving you a higher dose.
Has s/he mentioned what specifically the problem/s might be? Because then possibly you could take more, at a slow upward titration, with more careful monitoring for the SE.
Jost
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