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Protest Emails Sent: (If no response is listed, no response was received.
Dear Dr. Biederman: 10/16/05
I am very troubled by the tremendous damage that the publication of open trials have recently done to the field of psychiatry. It is my understanding that open trial are very susceptible to bias and thus do not prove anything, at least not without a randomized (blood tests, x-rays, etc.) rather than subjective measures (questionnaires, verbalized reports of symptoms, impressions of researchers).
The recent scandals involving dozens of open trial publications, almost all aided by the manufacturers, praising gabapentin and topiramate for bipolar disorder leading to thousands of American psychiatrists prescribing these medications only to later find that 5 out of 5 double-blind trials with topiramate and 3 out of 3 with gabapentin have proven they are of no value for treating bipolar symptoms. These are both medications with serious side-effects including death. Thase spoke at the APA in 2003 stating that an anti-depressant manufacturer had only one of eight DB PC studies find the anti-depressant to do significantly better than placebo, so the manufacturer had to go back and fund more studies in order to get FDA approval. Those 7 "failed" double-blind trials were never published.
I read your risperidone open trial with bipolar children (J Child Adolesc Psychopharmacol. 2005 Apr;15(2):311-7). While is was phrased much more cautiously than the large majority of open trials, it still said that a double-blind trial was needed to "confirm" the results, which implies that the open trial found some evidence of benefit. I find this wording misleading and dangerous. While I think, based on adult research with atypicals and bipolars and double-blind studies with risperidone on children, that risperidone will be found of some value for bipolar children, your open trial publication will lead many psychiatrists to prescribe more risperidone to children despite its total lack of scientific evidence.
I am sure that you are well aware that the medical literature is loaded with hundreds of treatments claimed to be of benefit in open trials only to be found worthless in double-blind studies. While I might accept that researchers often need open trials before double-blind studies in order to save expenses, I personally think that open trials of the type you did should never be published.
Please enlighten me. What social good and scientific benefit did the publication of your above noted study result in? Could you have not simply taken the results to the manufacturer of risperidone and lobbied them for funding without publication. What social harm would there be if all such open trials were banned from publication? In fact, manufacturers ban, temporarily or permanently many double-blind trials from publication when they don't yield the results they wish, e.g. the topiramate trials.
While I have a high esteem for Harvard and also for the tremendous volume of good research which you have done, I have seen a lot of open trial publications and heard public speeches by Harvard psychiatrist researchers that seemed more oriented toward currying the favor of drug manufacturers than serving any public good.
Am I wrong about gabapentin and topiramate for bipolar disorder being embarrassing episodes in the history of American psychiatry? Am I wrong about open trials being misleading? Am I wrong about most psychiatrists being unable to appreciate the difference between science and fluff? I can tell you that out here in the trenches, "evidence-based medicine" doesn't exist. We are controlled by "free lunch-based medicine." If it's not brand-name and still patent-protected, forget it.
Sincerely,
Tom Radecki, M.D., J.D., psychiatrist, Clarion, PA
modern-psychiatry.com
Dear Dr. McIntyre: 10/15/05
I have read your study in the June, 2005, issue of the Canadian Journal of Psychiatry of Bipolar I and II patients. I fail to understand how, based on your open-label observations, you can conclude "Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms."
I have always been taught that open-label studies are extremely prone to bias. Despite this, they influence huge numbers of doctors, which is why drug manufacturers continue to fund them. Am I wrong or how do you know that your open-label study is different?
Tom Radecki, M.D., psychiatrist, Clarion, PA
Dr. McIntyre's response: 10/16/05
Hi Tom your right in suggesting that open label is not definitive. thanks
Roger M Dr. Roger S. McIntyre, MD, FRCPC Assistant Professor
Department of Psychiatry, University of Toronto Head, Mood Disorders Psychopharmacology Unit, University Health Network 399 Bathurst Street, MP 9-325, Toronto, ON, Canada M5T 2S8 Telephone: # 416 603 5279 Fax: #416 603 5368 Email: [email protected]
Dr. Radecki responds:
Hi Roger: 10/16/05
Suicide attempts were impressively increased in the company's own research with 13 attempts in 3999 patient-years vs. 0 attempts in 1430 patient-years on placebo. One was a completed suicide. Since December, 2003, suicide attempts are now listed as a "frequent" side-effect, i.e. occurring in at least 1% of patients (added 12/03 to FDA required labelling). Depression in considerably increased in people taking Topamax when compared to placebo (13% vs. 3% at the top dosage), again in the company's own research.
I apologize to you, but I am attempting at this late date to try to find a way to publish a comment letter in the Canadian Journal of Psychiatry disagreeing with the claim that your study showed that "Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms" in bipolar patients. Open trial studies can never prove any degree (i.e. "suggest") of cause-effect, and yet the statement in your article is a clear cause-effect conclusion. The inability of open trials to prove cause-effect is especially true when there is no randomization to placebo and/or comparator controls and when the illness is measured subjectively rather than by objective measures not able to be influenced by patients, doctors, or researchers.
Of course, the Journal may not accept comment letters or it may be too late, but I do hope that you will join with me in protesting any future publication of open trials in the field of psychiatry. Again, I apologize for the fact that I disagree with the publication of your article.
Tom Radecki, M.D., J.D.
Dear Professor Nutt: 9/21/05
I was very disappointed to see the publication of the results of a small, open trial of mirtazazepine given to generalized anxiety patients. (J Psychopharmacol. 2005 Sep;19(5):483-487). The research is extremely clear that open trials are rife with bias. The wording of the study claims that such an open trial can investigate the efficacy of a treatment for generalized anxiety disorder. Such a claim is untrue. The article claims that mirtazazepine had a 79% "response rate," strongly suggesting that the patients had responded to mirtazazepine. Such wording is seriously misleading. The study claimed that the study "supports the notion that mirtazapine is an efficacious." This is also untrue, since only a proper double-blind study can support such a notion.
The publication of such open trials for psychiatric conditions should simply not occur. That is especially true for a condition such as generalized anxiety disorder for which there are numerous treatments which have already been proven to have some efficacy in proper double-blind random assignment studies.
You know as well as I do that most of these open trials are supported by pharmaceutical companies either directly or indirectly as a cheap way to promote their drugs. Unfortunately, it is a very successful strategy as evidenced by the over 40 open trial papers published on gabapentin for bipolar disorder which led to thousands of American psychiatrists to give gabapentin to tens of thousands of American patients, only to have later DB PC studies show that gabapentin was of no value. In fact, in one study it did worse than the placebo. A large review of open trial and later DB studies of treatments for alcoholism in the 1960s showed that the vast majority of treatments which had been claimed to work in open trials failed in the DB studies.
I think that your journal has committed a serious unethical act in publishing this study. Just because many other journals also publish such open trials is no excuse. You know as well as I do that modern academic psychiatry has been seriously corrupted by drug company money which has had a powerful influence on every step of our afflicted field from researchers to the clinical offices.
Of course, it is very likely that mirtazazepine would do better than placebo for GAD. I am unaware of any anti-depressant which hasn't done better and at least of dozen have one or more double-blind studies published.
I don't know if your journal accepts letters to the editor, but I will happily write one if it does. More importantly, I would like to know why your journal persists in this misguided practice and what I can do to help academic journals clean up their own shop.
Sincerely,
Thomas E. Radecki, M.D., J.D.
Clinical psychiatrist, Clarion, Pennsylvania, U.S.A. A similar email was sent to Dr. Gambi. No responses were received.
Thomas E. Radecki, M.D., J.D.
modern-psychiatry.com
Email: [email protected]
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