Posted by detroitpistons on March 18, 2010, at 15:21:20
In reply to Re: My letter to the FDA, posted by SLS on March 18, 2010, at 0:25:09
Scott and Bob,
The "Cerebral blood volume and clinical changes on the third day of placebo substitution for SSRI treatment." is totally fascinating. Wow! I overlooked that yesterday. So all along (since at least 2003), we apparently had pretty convincing evidence that there are actual biological/ physiological changes related to discontinuation. I wonder what kind of impact this study had on the medical/ psychiatric community, if any.
I agree that we need these drugs. I'm not anti-pharmaceuticals. I'm not totally against pharmaceutical companies, but there's a reason why they have developed a bad reputation and why there is a general, popular mistrust of them and/or skepticism about their intentions. Whether that's warranted or not is another issue.
If the FDA completely writes me off or thinks I'm a pain in the butt or some kind of "ranting whack job," then they are guilty of faulty reasoning and they are continuing to avoid the issue. I am asking them very, very specific questions and I'm citing very, very specific information. I am asking them for a fairly specific solution or set of solutions. Therefore, there's not much ambiguity in what I'm saying. If they discard my questions, or if my inquiries don't even spark a little interest in somebody's brain, then it's because they have no answers. All I want is some acknowledgment of the issue.
It took a long time just to get pharmaceutical companies and physicians to admit to the existence of "discontinuation syndrome"!! They told us, "it's in your head." Yeah, it is "in our heads" if you look at the brain scans! That's why I like that study about cerebral blood flow so much. It was placebo controlled. Nobody can rationally say that it's "in our heads" any longer, yet I think some people still don't get it. It took class action lawsuits. I'm not really familiar with the class action Paxil case, but that sort of opened some peoples eyes, but not nearly enough. I believe the main outcomes were money settlements and a labeling change. A labeling change! That really doesn't help much. So really, the issue continued to ignored, by and large.
Today we know that this really exists, but there doesn't seem to be any protocol for dealing with it. There's some research, but is anything actually being done with it? I mean, we have evidence of changes in blood flow in the brain! What more do we really need?!! We have developed protocols for safe alcohol detoxification and safe detox methods for illegal drugs but nobody "owns" alcohol or illegal drugs. So to put it in perspective, we've paid a lot of attention and put a lot of effort and research into detox of illegal drugs (and rightfully so), but we have nothing for legal drugs? What kind of excrement is that? Doesn't this fall into the purview of the FDA? Perhaps the FDA could mandate that approval of certain drugs be contingent upon the completion of specific studies providing discontinuation data, protocols, and tools for discontinuation. Actually, I don't care who does it, as long as somebody does. I just want a plan, plain and simple. In order to come up with a plan, you need statistical means, distributions, correlation coefficients, etc.
Lastly, we need tools to implement plans. My suggestions to the FDA are very specific. I'm asking for smaller dose sizes. What's so hard about that? I guess that would just be too much of a hassle and extra work for everybody, so why not just ignore it? Somebody would have to call their buddies at the pharma companies, and then things would be all awkward, so....let's try to sidestep the issue. OK, that's not completely fair of me to say, but I do believe that there are people within the government and FDA who are perhaps not completely objective due to their relationships with certain other individuals. That's just human nature, but I think it may affect the way things happen. A lot of this is just politics.
At the very least, can we at least try to do some trials where we use Prozac at the very end of discontinuation? Something? Anything?
Right now in argument and philosophy, I feel like I OWN the FDA on this issue. Maybe I don't. Maybe they would turn my argument upside down and make me look like a complete fool. That's possible, but first they have to actually respond to me. But you know what? I'm a nobody, and they don't talk to nobodies. After all, they are doctors MDs and PhDs and I'm just a mental patient, no matter how many FACTS or logical ideas that I bring up. They are public servants, and in this regard, I don't think they're serving the public very well!
Bam! That felt good to get out.
> > The SSRI discontinuation syndrome is no longer completely ignored. Studies are being designed to explore the phenomenon more closely. Recently, a study of SSRI discontinuation syndrome using paroxetine and fMRI demonstrated a set of functional differences in brain activity during symptomatic episodes. The syndrome is now recognized by science, although it may not be by all clinical practitioners. Drug companies know about this stuff. I imagine they would rather not call any attention to it. Hopefully, letters to the FDA will not fall upon deaf ears. I just hope that the populace does not use the existence of this discontinuation syndrome to further fuel the backlash against antidepressants in general. We still need these drugs.
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> Here are two studies indicating significant changes in brain function associated with the emergence of SRI drug discontinuation symptoms. It is interesting that a DS rating scale has been devised.
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> These studies might prove useful in demonstrating a physiological basis for DS to addressees of petition letters.
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> - Scott
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> Biol Psychiatry. 2003 Jan 1;53(1):100-5.
> Cerebral blood volume and clinical changes on the third day of placebo substitution for SSRI treatment.
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> Henry ME, Kaufman MJ, Hennen J, Michelson D, Schmidt ME, Stoddard E, Vukovic AJ, Barreira PJ, Cohen BM, Renshaw PF.
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> Brain Imaging Center, McLean Hospital and Department of Psychiatry, Harvard Medical School, Belmont, Massachusetts 02478, USA.
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> BACKGROUND: Interruptions in SSRI treatment have been associated with adverse effects that can resemble depressive illness. We hypothesized that brain regions implicated in depression, with extensive serotonergic innervation, would exhibit changes in activity associated with emergence of symptoms following drug discontinuation. METHODS: Subjects meeting DSM-IV criteria for remitted major depression on 20 mg/day of either fluoxetine or paroxetine were recruited into this 6-week study. During weeks 2 and 6, subjects underwent a 3-day period in which either active drug or placebo was substituted for their medication under double-blind conditions. Cerebral blood volume (CBV) maps were obtained via dynamic susceptibility magnetic resonance imaging at the end of each double-blind period. RESULTS: In the paroxetine group, change in CBV in left medial superior frontal region and left caudate nucleus correlated significantly with change in Discontinuation Emergent Symptom Scale and Hamilton Depression Rating Scale (HDRS; R2 = 0.66, p =.0007; R2 = 0.51, p =.006; and R2 = 0.43, p =.015; R2 = 0.32, p =.043, respectively). CONCLUSIONS: These data demonstrate that changes in regional CBV of left prefrontal cortex and left caudate nucleus correlate with the emergence of discontinuation symptoms and increased HDRS after interruption of paroxetine treatment.
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> Biol Psychiatry. 2003 Sep 1;54(5):534-9.
> Selective serotonin reuptake inhibitor discontinuation syndrome is associated with a rostral anterior cingulate choline metabolite decrease: a proton magnetic resonance spectroscopic imaging study.
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> Kaufman MJ, Henry ME, Frederick B, Hennen J, Villafuerte RA, Stoddard EP, Schmidt ME, Cohen BM, Renshaw PF.
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> Brain Imaging Center, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
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> The selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome (DS) is an important potential complication of treatment for major depression. We hypothesized that SSRI treatment discontinuation, resulting in change in clinical state, would be associated with reduced rostral anterior cingulate choline (Cho) metabolite ratios. Individuals with a DSM-III-R diagnosis of unipolar major depression who had been stabilized on paroxetine (n = 13) or fluoxetine (n = 13) were study subjects. They were monitored for change in clinical state (mood ratings, discontinuation symptoms) and underwent proton magnetic resonance spectroscopic imaging of the rostral anterior cingulate 3 days after medication substitution with active SSRI and placebo.Placebo-day Cho/Cre (choline/total creatine) metabolite ratios were decreased in four paroxetine and two fluoxetine subjects meeting DS criteria, as compared with asymptomatic subjects (Mann-Whitney z = -2.31, p =.021). Discontinuation syndrome is associated with a rostral anterior cingulate Cho/Cre metabolite ratio decrease that may reflect dynamics of rostral anterior cingulate function.
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> PMID: 12946882 [PubMed - indexed for MEDLINE]
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URL: http://www.dr-bob.org/babble/20100318/msgs/939950.html