There was a study published in The New England Journal of Medicine that has gotten much media attention. I believe the lead author has said that in the media and general public the results have been largely misinterpreted. The study did a meta-analysis of all the pre approval clinical trials done between 1987 and 2004 and covered 12 antidepressants compared to placebo.
The main gist of the study is that big pharma and the FDA cheat. Studies that show positive results are pushed to the fore and published and studies that show negative results are hidden. There is corruption that exists between big pharma and the FDA and I might add Congress too. No big surprise there. That is the main point of the article and what it proves. It doesn’t say anything about why antidepressants work or don’t work. It shows that the original trials don’t paint such a glowing picture. It does not mean antidepressants are ineffective.
In my opinion all of those initial clinical trials whether they were positive or negative are useless because how can you do a 6 to 8 week trial on a drug we now know takes 6 to 8 weeks to work. It tells you nothing about efficacy but does tell you something about safety.
You may see articles titled-
“Why Antidepressants Don’t Work for Treating Depression”
And pointing to the study as the sole source for that statement. This is very misleading and not at all true. In the first place it doesn’t say anything about “why” and it just flatly says they don’t work.
Why Antidepressants Don?t Work for Treating Depression - Dr. Mark Hyman
There are many similar articles that site the study.
New England Journal of Medicine published article on “Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy”
Here is the full article-
MMS: Error
The overall meta-analysis showed efficacy to be superior to placebo just not as good as one would have originally been led to believe.
From the article
Quote:
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We wish to clarify that nonsignificance in a single trial does not necessarily indicate lack of efficacy. Each drug, when subjected to meta-analysis, was shown to be superior to placebo. On the other hand, the true magnitude of each drug's superiority to placebo was less than a diligent literature review would indicate.
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Interview with lead author by ScienceWatch
Erick Turner - ScienceWatch.com
Quote:
SW- If the drug is only superior to the placebo in only half of clinical trials, does the drug actually work?
That's where meta-analysis comes in. Meta-analysis lets you combine trials that show a statistically significant difference between drug and placebo with trials that don't. Then you can see whether, for all trials combined, the drug-placebo difference is statistically significant. For each of the 12 drugs we looked at, it was.
Getting back to the point that drug efficacy is not an all-or-none phenomenon, meta-analysis also tells you how big that difference is. In other words, it allows you to put its efficacy somewhere along a continuum. The effect sizes we calculated for each drug based on the FDA data were substantially less than the effect sizes based on the published literature. Whether those effect sizes are clinically significant, in addition to statistically significant, is a matter of debate.
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Interview of lead author by Psych Central
This Month?s Expert: Understanding Antidepressant Research by Erick Turner, MD | Psych Central Professional
Quote:
TCPR: Looking at your paper, some readers, seeing that only half of the studies submitted showed the antidepressant to be effective, might wonder, “Does this mean that these antidepressants basically aren’t effective at all, that it is just a flip of a coin whether a study shows a drug to be effective?” Is that a proper way of looking at it or no?
Dr. Turner: That question comes up a lot. No, that would not be a proper interpretation, because if the drug does not separate from placebo statistically, it might still be numerically better than placebo. In almost every trial we looked at, the drug still had a numerical edge over placebo (there were a few exceptions, trials in which the drug actually did worse than placebo), just not a big enough edge to be statistically significant. Now if you have a lot of trials like that and you combine them through meta-analysis, you get more statistical power, and the overall difference can become significant. And that’s what we found, that each of the 12 drugs, overall, was statistically superior to placebo.The other caveat would be that the results of these trials get reported as means, but each mean value is based upon thousands of individuals, some with very good responses and others with lousy responses. So when you think about how an individual patient in your practice might respond, remember the old saying, “Your mileage may vary.”
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To me what really matters is the results after a drug has been on the market for a while. Like I said I don’t give much credence to the original clinical trials. They are too short and have flaws to begin with. We are largely left with our own experience, the anecdotal experience of others, and the anecdotal experience of psychiatrists. The biggest and best study I know of that looked at real world practice and results is the StarD study. It has the problem of not comparing to placebo. There is a very large international study currently being conducted. I think the best evidence so far shows they work in 50 to 60% of cases especially for severe depression.
NIMH · Antidepressants: A complicated picture
Quote:
But what about long-term effectiveness and true remission of symptoms? In the NIMH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study, the outcome measure was remission of depressive symptoms, e.g., becoming symptom-free. This outcome was selected because people who reach this goal generally function better socially and at work, and have a better chance of staying well than do people who only achieve a response but not a remission. STAR*D reported remission rates of 31 percent after 14 weeks and 65 percent at six months. These results may seem modest (placebo response rates are often over 30 percent in antidepressant trials). But STAR*D was not a good test of efficacy or effectiveness because it did not have a placebo comparison. While STAR*D was helpful for comparing antidepressants, in the absence of placebo, one does not know how many people would have been in remission without active medication.
Perhaps the best evidence for efficacy comes from patients who have been treated successfully with antidepressants and are switched in a blinded fashion to placebo. In a meta-analysis of 31 withdrawal studies among more than 4,000 patients, Geddes and colleagues found that 41 percent of patients who were switched to placebo relapsed, compared to 18 percent who remained on an antidepressant.xiii These studies provide compelling evidence that antidepressants are effective for some people.
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More on the topic.
Effectiveness of Antidepressants
NIMH · Antidepressants: A complicated picture
Antidepressants: Effectiveness, Trials, Realistic Expectations
NIMH · Questions and Answers about the NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study ? All Medication Levels
Are antidepressants really no better than sugar pills? | The Johns Hopkins News-Letter
Robert DeRubeis on anti-depressants | News Center | Stanford Medicine
http://www.nytimes.com/2011/07/10/op...anted=all&_r=0
Study confirms antidepressant efficacy | Yale Daily News
Mild depression: Are antidepressants effective? - Mayo Clinic
Antidepressants
Antidepressants - NHS Choices
Neurogenesis and antidepressants. This means promotion of new neuron growth and new connections. A very promising area of research.
Unraveling the Mystery of How Antidepression Drugs Work - Scientific American
Neuropsychopharmacology - Fluoxetine-Induced Cortical Adult Neurogenesis
Fluoxetine-induced cortical adult neurogenesis. - PubMed - NCBI
Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor
Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus
The Future of Depression Treatment: The Neurogenesis Theory
Promoting adult hippocampal neurogenesis: a novel strategy for anti... - PubMed - NCBI
The Neural Plasticity Theory of Depression: Assessing the Roles of Adult Neurogenesis and PSA-NCAM within the Hippocampus
Depression
A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor
How antidepressants spur brain growth
http://www.biologicalpsychiatryjourn...581-6/abstract
http://www.cell.com/trends/pharmacol...2814%2900165-5
Depression, antidepressants and new brain cells