Posted by Elizabeth on March 22, 2002, at 21:00:33
In reply to Article on treatment resistant depression, posted by OldSchool on March 18, 2002, at 15:11:13
Agree with Zo that it probably would have been better just to post the link. But it's a nice little article; thanks for bringing it to our attention here.
The authors point out some interesting stuff that patients and psychiatrists often don't seem to be aware of. A few things I thought were especially noteworthy:
* Patients often are labelled nonresponders to a drug when they really haven't had anything that reasonably could be considered an adequate trial. Similarly, patients can be identified as "treatment-resistant" when they really haven't had adequate trials of many treatments at all. This makes research on TRD difficult because it's hard to make sure that all the patients in the study are actually treatment-resistant (using a standardized definition of "treatment-resistant").
* It's crucial to define "treatment-resistant." TRD used to be defined in a fairly simplistic way, as a failure to respond to adequate trials of perhaps two ADs of different classes; this isn't sufficient now that there are so many "novel" ADs and augmentation strategies. As we see from reading this review article, most research has involved the efficacy of treatment B in nonresponders to treatment A, rather than examining new or novel treatments in people who have tried most of the typical treatments without success.
* Speaking of definitions, "major depressive disorder" covers a lot of different types of symptoms (and probably etiologies). We haven't really been able to find many predictors of response to specific treatments. I think that clinical research and practice could benefit greatly from finer distinctions between types of depression. I hope that advances in neurobiology may offer new clues about different types of "major depression."
* Comorbidity can also affect response to different treatments. Again, not a lot is known about this, but there is some evidence that anxiety disorders, personality disorders, and bipolarity can contribute to treatment resistance. This may be one of the reasons why pdocs are so gung-ho about diagnosing bipolar disorder these days. :-} A problem is that there isn't much research on the treatment of depression associated with these other conditions; the diagnosis of bipolar disorder has also gotten fuzzy of late.
* It's a good idea to maintain a healthy skepticism of rapid responses, because they often turn out to be transient nonspecific (i.e., "placebo") responses. I think that a lot of the time, when people report that a medication "poops out" shortly after it had started (apparently) working, what's really happening is just a natural relapse following a brief placebo response. Personally, I would never assume that I was really "responding" to a drug treatment until the response had persisted for a few months. (There are other factors that can help in identifying placebo responses, although I don't recall what they are -- something to do with the pattern of response. Anyone have more info on this?)
* There are quite a few people who respond to antidepressants but who take much longer to achieve a full response than the expected 6 weeks. (I don't think I'd ever heard this before, and it's always nice to learn new stuff.) So if you're responding partially by week 6, it's often worthwhile to keep waiting to see if things continue to improve.
* Although most ADs generally work for most responders within 6 weeks, this does depend on which AD and who is taking it. Some people can take a little shorter or a little longer to respond. Effexor and the MAOIs seem to work faster for some people; Prozac and Buspar may take more like 8 weeks to work. Also, some people may respond sooner than others. For example, I've generally found that if an AD is going to work for me, I usually start seeing some improvement around 2-3 weeks. YMMV.
* They also mention the peculiar dose-response curves seen with nortriptyline (and amitriptyline). Serum level monitoring is especially important if you're taking one of these ADs, because after a certain point they start becoming *less* effective as the dose is raised. It's possible that this problem also exists with some of the newer ADs; right now we don't know.
* A lot of people who were first treated in the '60s or '70s have tried a lot of different TCAs. But it turns out that the TCAs really don't differ much, except in their side effect profiles (e.g., sedation, anticholinergic side effects, cardiotoxicity). There are a couple that have some noteworthy features: clomipramine inhibits serotonin reuptake to a great extent and is more effective for OCD and panic disorder than the other TCAs; amoxapine, a dopamine antagonist and NE reuptake inhibitor, has demonstrated efficacy in psychotic depression and may have uses in other neuroleptic-responsive depressions (it also causes fewer EPS than the typical neuroleptics; not sure how it compares to the atypicals). In general, though, it doesn't pay off to keep trying different TCAs. (Maprotiline, incidentally, is pretty much another TCA for practical purposes, despite its so-called "tetracyclic" chemical structure.) Switching to another class of AD is much likelier to yield good results.
I was surprised to read that nomifensine (Merital) didn't seem especially effective for TCA-resistant depression; it seems like there are a lot of people out there who were very impressed by it and who've had a history of many medication failures. I would at least have expected it to have a better response rate than trazodone, of all things. (Does anybody even use trazodone as an AD anymore?)
FWIW, I recall reading somewhere-or-other that about 80% of depressed patients will respond to one of the first three ADs tried (assuming that adequate doses and trial durations are used and that the ADs are selected rationally, based on what limited information is available). That's pretty good, and maybe the variety of ADs now available improves it further. But it still leaves a lot of room for improvement.
-elizabeth
poster:Elizabeth
thread:98605
URL: http://www.dr-bob.org/babble/20020322/msgs/99548.html