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Recently, Prozac and related SSRI antidepressants were dealt a blow when it was made public that Eli Lilly, Glaxo-SmithKline and the other manufacturers of the drugs had failed to disclose data from unfavorable clinical studies that showed patients using SSRIs had an increase as much as four to one in suicide risk. Now, a new study from Hull University, using the data submitted to the FDA to gain approval for the drugs, has found that for most patients, SSRIs are no more effective than a placebo.
Eli Lilly, of course, defends the drugs' effectiveness; and another researcher, the head of psychopharmacology at Bristol University, says that "if they provide some sort of placebo benefit, this shouldn't be discounted."
Now, the thing that immediately occurs to me is this: If you have the choice between a placebo that is medically inert, and has no side effects that aren't psychosomatic, or a drug that performs no better than the placebo, but has a vicious side-effect profile and may quadruple your likelihood of suicide ... aren't you better off with the placebo?
Clarification:
I should point out that I have not read the studies cited; I have only read summaries. My intention here was not to discuss the studies per se, but rather to question the idea that it's still a good idea to use a drug with known severe side-effects for it's placebo-like effect if it's (allegedly) no better than a placebo.
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I haven't read the actual Hull meta-study, just a critique of it, but apparently there's a lot there to critique.
For another thing, sometimes there are significant reasons other than "we didn't like the results" for not including a study in the FDA trials such as tinkering in studies to try to find the right effective doses or serious methodological or design flaws in the excluded study. Apparently this wasn't covered to the satisfaction of the person whose review I read.
"Most patients"---again, I could show easily that for most patients with an upper respiratory infection, antibiotics are no more effective than a placebo. If a whole lot of those patients had colds as opposed to a bacterial infection, I'd get that result---but antibiotics are effective in people who have the condition for which they should be prescribed.
The guy from Bristol is just an example of someone making a lousy argument in defense of his position on an issue. I could argue that clouds cause rain because anything up in the sky when it rains is a partial cause of the rain. It's a lousy argument, but clouds still cause rain.
The increase in suicide risk is common to all antidepressants in the initial phase because when you have someone who is extremely depressed, they frequently want very much to kill themselves but don't have the energy or willpower to follow through with it. Because the energy and willpower often kick back in before the will to live does as depression lifts, these people start feeling better enough to follow through with killing themselves, so they do. It's a problem with all antidepressants, including the ones in use for decades.
The drugs wouldn't be increasing suicide risk if they weren't lifting severe depressions--because the lifting of the depression itself is what increases risk.
After patients get past those first weeks where their antidepressants start to kick in and get to where they've fully kicked in, they're out of the woods as far as antidepressant-related suicide risk goes, and their suicide risk is lower overall because their depression is lifted.
It's a study with some very sensationalist conclusions that got a lot of press. It just happens that not all of their conclusions logically follow from what they actually studied.
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I'm really not a fan of the SSRIs. But anytime I bring this up with people who take them, they tell me I don't know what I'm talking about.
And, maybe I don't.
What I've found in those people, is they had to, via trial and error, find the one that worked for them. Taking months, or even a year or two to find the drug, and to basically titrate the dosage.
(Part of my objection to this concept is it's really no better than witch doctoring. "Here, try this. That help? Ok, lemme put a leech here. Feel better yet? Ok, how about eat this frog. Better yet? Hey!")
If we extend the benefit of the doubt - that each drug has a part of the population that it helps - but that we can't ID which one works for any particular person, then a standard double-blind (where you issue the drug and placebo at random) wouldn't be very useful.
(A tangential point to this is the lack of a real standard and control possible when you spread these studies out among random populations, with potentially very variable routines, body chemistries, and diets. Especially diets.)
On the other hand... If the placebo effect is what's really happening...
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It's about as much a "placebo" as morphine is. It directly affects the balance of neurotransmitters in someone's brain. So does sugar (placebo), but not in the same ways.
They divined their conclusions from the effects of the drug, or lack, on less depressed patients, then said their conclusions also applied to more depressed patients.
Switching around by trial and error isn't so much to find a drug that "works" in the sense of changing your brain chemistry. They change your brain chemistry alright. They do have to titrate the dose. Trial and error is to find the drug with the most effect paired with the fewest objectionable side effects. Not to mention that many of these drugs have a significant potential for allergies.
People switch SSRIs because of weight gain, anorgasmia, allergy, triggered mania, or other significant patient-specific adverse side effect. Thing is, adverse side effects don't mean the drug doesn't work for you, and it doesn't mean the side effects wouldn't lessen over time and you couldn't tolerate the drug if there weren't less objectionable choices. What happens is that when you have significant unpleasant side effects, the doctor usually goes ahead and switches you to another drug in the same class to see if it has fewer side effects for you.
In my case, the Lamictal and Seroquel are mood stabilizers. The Lamictal is my main mood stabilizer because it has fewer exec function side effects than others and may even help exec function problems a little--other drugs don't even touch them. A lot of people can't take it because a lot of people get allergic--allergies to it can be fatal like penicillin allergies. I take a small dose of seroquel at night to help me sleep--mood stabilizer with sedating side effect. Regulating sleep in bipolars is important.
Because I have type II bipolar, I can't take a mood stabilizer as a mono-therapy. I have to have anti-depressants added in. The Paxil gives a small bump to serotonin, the Welbutrin gives a bump to dopamine.
Antidepressant therapy, across all antidepressants, is extremely well studied. There used to be a large, large debate over the effectiveness of therapy versus drugs, so there were some heavy duty longitudinal studies done on people with multiple episodes of clinical depression. They knew antidepressants kick someone loose from a severe depression, but there were long term questions. A low maintenance dose of an antidepressant was the single most effective way of preventing recurring depressive episodes.
Cognitive Behavioral Therapy is also well validated as an effective treatment, but the kicker is what percentage of patients respond to each kind of treatment, and how much of their "issues" are left over.
Like treating heart disease or cancer, treatment is complicated and must be tailored to the patient. You can't just go on WebMD and say, "Hrms. Looks like I've got cancer. I need to go to pharmacy now and order a big bottle of xylophonene. It says here that if I take two of those three times a day my cancer will be gone in three months. Yippee."
Bipolar disorder has a 20% fatality rate untreated, and an 11% fatality rate treated. Most of that risk is front-loaded into the first 3 years post diagnosis. The fatality rates vary based on whose studies you look at, but those are the numbers typically quoted by the Child and Adolescent Bipolar Foundation.
Standard treatment is drugs. It's well established to be biological problem. Therapy can help, but the only people who go into treatment, and comply, who don't take drugs for it are the percentage of sad unfortunates who aren't "medication responders."
I think a 45% drop in fatalities is pretty good evidence that psychiatric drugs work, even though yes, they do have to take a couple of years on the medication merry-go-round as the doctor finds the best medication combination to stabilize a particular patient.
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But not necessarily for everyone. That's why you have (hopefully) large double-blind studies.
Like treating heart disease or cancer, treatment is complicated and must be tailored to the patient.
My ambivalence comes from seeing people who literally walked into the doctors office and said "I want prozac|zoloft|etc", and the doc said "OK" and wrote the script. No therapy, no examination.
Hell, one friend of mine was on SSRI's in college. Not that she was depressed, she just didn't want to be the ONLY girl in the Sorority not on an antidepressant.
It's well established to be biological problem.
I can't agree with that. I'm speaking more of depression than bipolar (which I have almost no personal experience with), but until we can actually diagnose for it - accurately, and through blind studies, I'll have to remain skeptical.
But I do know that people - such as you - disagree strongly based on their personal experience. And I can't gainsay you - either I'm not affected by the depression, or I deal with it in a different way. That's the problem with problems in the brain. Thus my ambivalence.
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As for your friend and her doctor that settled on Prozac, that's their problem and should not reflect upon those that need and have benefited from pharmacological treatment, nor the manufacturers that they depend upon. This anecdata adds nothing to the debate.
House_pundit speaks to bipolar disorder, I speak for biologic depression. Please don't confuse situational with biological depression. I can't speak for your history, but it seems that if you deal with depression "in a different way" perhaps you deal with situational depression... which can be dealt with more effectively than biological. While it is very difficult to overcome any depression, it's a far sight easier to identify depression that is situational (I lost my SO, my job, and everything is going wrong) than if one can only identify exacerbating circumstances to one's lifelong feelings of worthlessness, apathy, and despair.
I don't trust big pharma any more than I trust that the government has "my" best interests at heart. I do know that I wouldn't be here to reply to you if it weren't for the Wellbutrin I have taken off and on (off by my misdirected choice) for many many years.
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One of the things I'm researching these days is the link between niacin and nicotine....and wellbutrin and zyban.
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If we toss anecdotes - (which is fine by me; I use them to point out systematic flaws, not ones with the drugs per se) - then ... we have to toss yours and house_pundit's as well. That was really my complaint - success stories are anecdotal.
That's the problem with this issue - too many people want to toss the anecdotes from the other side, while celebrating the ones from the side they support. That's many things, but scientific isn't one of them.
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Ugh. That's sad in several distinct ways.
The basic factor at work here, I think, is that not all brains are created equal, and not everyone reacts identically to any given medication. It seems they work very well for
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Technically?
No, of course not.
But it is a failure of the system that's dispensing those medications, leaving that system's credibility strained when other claims are made.
It's the same issue right now with Ritalyn and Adderol with kids. One of my at-the-time-coworker's kid was sent to the doctor because he couldn't sit still and pay attention during reading. (Math he was great, everything but reading he was stellar.) You can guess where I'm going - Ritalyn within 5 minutes of the doctor walking in the office.
The kid had never even been tested for dyslexia. (Failure on multiple levels, and I hold the parents in particular scorn, especially when at least I and my boss (who had identical symptoms when he was that age - and has dyslexia) insisted that a dyslexia test was well overdue.
Nope. Drugged him up, and he was sitting still, all right.
What percentage of kids have been on "ADD" and "ADHD" drugs now?
Not the fault of Ritalyn, or Adderol at all. I think they have a place. Just as antidepressants and the other mental drugs do. But the brain is the least understood organ we've got. (Even the organs and systems that are "well understood" still have a lot of "Wow. Wonder why THAT's happening" issues.) We're currently mucking around it with damn near the sophistication of tropical witch doctors trying to find cures.
(And like the witch doctors, or "native healers" I suppose is PC now, cures and palliatives (or poisons and other useful compounds) can be discovered and isolated that way. It is a method. But it's not scientific - and it's a nit of mine when non-science tries to take the scientific mantle.)
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There you go again, putting the patient's needs ahead of the pharmaceutical companies.
Why do you hate America?
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Because I've got eyes?
--or--
I just like to fit in.
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Of course, this is complicated by the fact that if it becomes common knowledge that you may be issued a placebo first, there's the risk that the placebo won't work because the patient knows it's a placebo, and there's even the risk of reverse placebo effect reducing the effectiveness of a real drug that the patient believes to be a placebo.
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And not all the drugs in the survey were SSRIs, either.
FTR, I'm saying this as someone for whom Prozac worked wonderfully, with _no_ side-effects. Yes, I know I was lucky. No, I'm not on the Prozac any more. Yes, I'm glad I took it, and I would do so again in the same situation.
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As noted in my reply to
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I'd also add that it's possible that the study isn't set up correctly, or has variables that we don't know or can't test for. (Which is still an incorrect study, but I think a different sort.)
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The question no one has been able to answer is how they work. If it were just Seretonin, the effect would happen within minutes to an hour, yet it takes a few weeks before the effects show up. I have seen one or two theories as to why that is, (the one I like involves increasing brain cell count.) yet no one can explain how the SSRI's work. (Or what else they effect.)
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Placebo effect is stronger in people with psychological/neurological problems. So the SSRIs still work, it's just more difficult to prove by comparing against placebo.
This still leaves open the issue of whether or not SSRIs should be prescribed if a sugar pill works just as well, on average.
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I don't see that it can do any harm to try the placebo first in cases where the doctor believes it prudent. I'm pretty certain the major drug company reps would even agree, provided the patient buys the sugar pills from them at the same price as the actual drug.... :p
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