Corruption Grips the Field of Medicine
This is an odd section indeed. It may shock the reader to know, but the field of psychiatry and the entire field of medicine is heavily polluted by financial self-interests and a lack of scientific honesty. For instance, in September, 2003, a study documented that in the previous 10 years a huge treatment shift of bipolar patients from lithium to divalproex (Depakote) had exposed hundreds of thousands of patients to a 170% increased risk of suicide. That means hundreds, if not thousands, of actual deaths occurred! The author of the JAMA article attributes the shift to the financial influence of the pharmaceutical industry on the educational programs of the field of psychiatry. Having attended last year's American Psychiatric Association conference and visiting the offices of quite a few psychiatrists and mental health centers in the Midwest in the past year, I can say with certainty that the profit motives of drug companies have a powerful influence on the medications patients actually receive. The APA convention is virtually controlled by drug company money.
Drug companies hide failed studies; medical school researchers put a spin on the results of studies to exaggerate any benefit found; academics take money from drug companies to turn out articles on "open trials" and claim to have found the drug in question beneficial, something impossible in an open trial. Medical journals knowingly publish the bogus "open trial research." No one bothers to calculate the costs of the benefits. The Bush FDA is strongly influenced by drug company contributions to politicians. Even the way the FDA operates guarantees that only expensive brand-name treatments will ever be "FDA approved" for a particular disease. Even though a vitamin, mineral, supplement, or older generic medication might be scientifically proven to be better, it will never be "FDA approved."
Most of the material below has nothing to do with psychiatry directly. However, if you want to read about how thousands of psychiatrists from 2000 to 2003 flocked to using two new and expensive seizure medications to treat almost every known psychiatric condition, especially Bipolar Disorder, only to have double-blind research later find that the medicines are almost worthless as a psychiatric medications. The manufacturer was fined $200,000,000 by the FDA, but its academic psychiatrist drug pushers got away. See the Gabapentin (Neurontin) Scandal. Topiramate (Topamax) is the second medication. Psychiatrists from Harvard, Duke, Stanford, and UCLA all wrote articles praising gabapentin based only on their own "open trial" experience with the medications. Many of the psychiatrists were receiving money from the manufacturer! Influenced by these articles and marketing campaigns using the articles, thousands of psychiatrists have given given gabapentin and topiramate to tens of thousands of bipolar patients with absolutely no scientific evidence that they are of any value. Now, I have read that the first double-blind studies have found that neither is of any value for bipolar patients! We have treated these patients worse than guinea pigs. Most of these studies have been kept unpublished by the manufacturers because the results weren't favorable!
Federal prosecutors investigated Topamax manufacturer Johnson & Johnson in regards to possible illegal marketing practices in promoting Topamax (Knight Ridder 12/15/03). The $200,000,000 fine for illegally promoting gabapentin for bipolar disorder was the largest fine in FDA history, but investment analysts pointed out that the company earned $2 billion in just one year from gabapentin and could easily afford the fine.
Why were thousands of psychiatrists taken in. To read examples of studies where academic psychiatrists made false and exaggerated claims of effectiveness based on open trials and misled community psychiatrists around the nation, see Open Trial Claims.
The distortions of good practice and fairness in life caused by others trying to make money is commonplace and something we all need to guard against. Also, many individual physicians honestly believe they are seeing benefit and forget that no one can trust his clinical impression. The fields of medicine and mental health are no different from any other area of life. Most of the distortions are not caused by sinister intents. Some is caused by wishful thinking, others by an exaggerated sense of importance of one's particular area. People who work in the clothing industry usually think that we need to dress better and spend more on clothing. Accountants usually think that we need more accounting services. Lawn care specialists think we need to have more beautiful lawns. Teachers are sure we need more teachers and have to be in school longer (as long as they are paid more).
Doctors and politicians are the same way. We are spending an incredibly huge amount of money on medical care. Most of it is spent with very minimal or no real health gain. If it was our own money, we would often opt to try out a less expensive medicine, avoid a test and take a little more of a chance of dying a little sooner, not have an expensive surgery and die a month earlier. Most of us have other areas in life that get short-changed because so much of our money is being spent on medical care. The shame of it is that so much of it is needless. Inefficiencies abound in the area of medicine. Many treatments cost over $100,000 per year of life saved, sometimes as much as $20 million per year of life saved. Most of us couldn't afford to spend our own money this way. If it was our own money and we were given the option of taking even half the money and losing a year of life, many of us would take the money. Of course, indirectly, it is our own money.
I may be overly pessimistic, but I think that we are all living in a bubble economy. The U.S. and state governments will not be able to continuing borrowing money at their current incredible rates. We continue to steal from social security funds even though we know that they are going to run out and that we will have far fewer workers per retiree to do anything about the short fall. Medicare is rapidly going broke. The U.S. cannot forever run massive trade deficits. While the rapid advances of science are a bright spot, I fear that they will not be able to offset the forces of deterioration. Even though few people really care about saving money so long as they can make Uncle Sam or someone else pay for it, I can't help but think we should be trying to save money and be cost-conscious.
Even managed care is not at all efficient. A lot is wasted on administration and valuable services are sometimes denied. Also, managed care doesn't really care about saving money, only making a profit. If doctors can be forced to earn less money, managed care looks good, but there is no real efficiency and bright people may choose, in fact they are choosing to go into different fields. If the cost of managed care insurance can be raised, the managed care corporations are happy approving even extremely costly treatments. Managed care is often pressured into paying for unreasonably expensive interventions. Of course, mental health care is often short changed because no one wants to admit that they might some day need such care.
Many articles and comments on this and related issues are scattered through this website.
Three Cheers for the National Institute of Health: The US National Institutes of Health has asked all investigators who receive federal funds to make their results freely available to the public. Dr Robert Steinbrook of the New England Journal of Medicine predicts that some journal editors and publishers will be "riled" (BMJ 2005;352:1739). Dr Zerhouni of the NIH has asked researchers whose work was supported by public funding to voluntarily submit an electronic copy of their manuscripts, when they are accepted for publication, to PubMed Central, a free internet service. A similar initiative in the United Kingdom led to controversy recently when some editors and publishers said that free online dissemination of research articles might cause some medical journals to "go broke and close" (BMJ 2005;330:923, 23 Apr). Dr Michael Wilkes, vice dean for medical education and professor of medicine at the University of California School of Medicine at Davis, reacted to the charge that some medical journals might be forced to close by asking, "So what?" He said, "How is the world going to be any poorer if [some journals] go out of business? Publicly funded studies belong to the public. I don't think there should be a system where a middleman makes a profit at the public's expense. If journals are going to survive, they have to have added value." NIH Improved Their Ethics Rules in 2005.
Industry Sponsorship Powerful Effect: Studies of 1140 research reports found industry sponsorship increased finding results favorable to the industry by an OR of 3.60. Disgusting but true: 68% of academic institutions have stock in the very pharmaceutical companies for whom they are doing research! Industry sponsored research is much more likely to reach conclusions favorable to industry than independently funded research. In 61 industry sponsored trials of non-steroidal anti-inflammatory drugs, not a single trial found the comparison drug superior to the sponsor's drug. Nationally, 23% to 28% of academic researchers received funding from industry, 43% received gifts such as biomaterials and discretionary funds, and a third had personal financial ties with industry sponsors. The financial ties included paid speaking engagements, consulting arrangements, positions on advisory boards, and equity in the sponsoring company. Scope and impact of financial conflicts of interest in biomedical research: a systematic review. Bekelman JE, Li Y, Gross CP. JAMA 2003 Jan 22;289(4):454-65; Yale
Funding Source Biases Research: A meta-analysis of 370 double-blind trials for various diseases found that 50% of the studies funded by for-profit organizations recommended the study drug as the treatment of choice vs. 35% where studies were funded by other sources. The three factors that predicted recommending the drug were the drug effect size, the use of a double-blind methodology, and funding by a for-profit entity. Industry-funded studies also reported more side-effects. Als-Nielsen B, et al: Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? JAMA 2003;290:921-8. Copenhagen Univ.
More Proof of Drug Company Corruption of Academic Psychiatry: A systematic review of all double-blind, randomized clinical trials comparing fluoxetine with any other antidepressant drug in patients suffering from depression found 37 studies meeting the inclusion criteria. A metaregression analysis indicated that, after adjusting for possible confounders, studies where fluoxetine was the experimental agent were positively associated with treatment effect, indicating a significant advantage for fluoxetine. The evidence that the outcome of fluoxetine trials varied according to whether this drug was used as a new compound or a reference one suggests the presence of bias. "Wish bias" in antidepressant drug trials? Barbui C, Cipriani A, Brambilla P, Hotopf M. University of Verona, Italy. J Clin Psychopharmacol. 2004 Apr;24(2):126-30. Ed: These are mostly studies done for drug companies by American and international academic psychiatrists. The research found that if the producer of fluoxetine was funding the study, fluoxetine tended to do better. If another drug company was paying to have their own medication to fluoxetine, the academic psychiatrists found the other medication doing better.
Published SSRI Research Biased: Five SSRIs were approved in Sweden between 1989 and 1994 for treating major depression. Forty two short term (4-8 weeks) placebo controlled clinical trials with the approved doses were submitted to the Swedish drug regulatory authority and formed the basis for the approvals. When applying for marketing authorization, the applicants are obliged to submit full reports of all studies performed by the applicants as well as all available information on any study not performed by the applicants. Studies showing significant differences between efficacy of drug and placebo were three times more likely to appear as stand alone publications than were studies with non-significant results. Although both intention to treat analyses and per protocol analyses were available in the submissions to the regulatory agency, only 24% of the stand alone publications reported the usually less favorable intention to treat results. "For anyone who relies on published data alone to choose a specific drug, our results should be a cause for concern. Without access to all studies (positive as well as negative, published as well as unpublished) and without access to alternative analyses (intention to treat as well as per protocol), any attempt to recommend a specific drug is likely to be based on biased evidence. "Evidence b(i)ased medicine—selective reporting from studies sponsored by pharmaceutical industry: review of studies in new drug applications Hans Melander, Jane Ahlqvist-Rastad, Gertie Meijer, Björn Beermann. BMJ 2003;326:1171-1173 (31 May), Uppsala
Bogus "Research" from Depression and Anxiety Journal & Bristol-Myers-Squibb: A supposed "Research Article" funded by the drug manufacturer with one of the two authors apparently an employee of the manufacturer is entitled "The efficacy of nefazodone augmentation for treatment-resistant depression with anxiety symptoms or anxiety disorder" by Fletcher Taylor and Maureen Prather. Depression and Anxiety 18:83-8, 9/2003. It is an open study of only 11 patients using only one measure for improvement, the Clinical Global Impression of Improvement Scale. It claims that all 11 patients improved thanks to the nefazodone with no significant side-effect. The authors write, "Nefazodone’s unique pharmacologic profile may explain its unusual efficacy in these cases of treatment-resistant major depression." The very small number of patients had quite a mixture of diagnoses in addition to Major Depressive Disorder without Psychosis. Three were diagnosed ADHD. According to the authors, none had responded to at least two anti-depressant trials. The 11 patients were put on nefazodone in addition to their other medications which hadn't worked for as long as 9 months. Some patients were already on two anti-depressants and had nefazodone added as a third, e.g. fluoxetine, mirtazapine and nefazodone or bupropion, lithium and nefazodone. At least four were on stimulants and three on minor tranquilizers. One patient was on a total of five psychotropic medicines and three were on four psychotropics. For example, a patient diagnosed as suffering from both Major Depressive Disorder and Generalized Anxiety Disorder was on nefazodone, venlafaxine, lithium, and mirtazapine. All but one patient was 42-55yos. Nefazodone was started at 50mg/d and increased in steps up to 300mg/d if needed.
Editor: and the clinical science editor Alan Schatzberg of Stanford. An email was sent 9/28/03 to ask about the wisdom of publishing this type of industry funded material and calling it research. Uhde responded in a very polite and encouraging way, but he has not yet explained how such extremely low quality articles get published. It is something I just don't understand. While this article may be an extreme example, hundreds of other open trials with unsubstantiated claims of efficacy are appearing in numerous psychiatric journals.
One reason I think this study should never have been published is that open trials, especially very small open trials, can never measure efficacy. And this is the messiest open trial I have ever seen with so many different medicines all given at the same time. Who could possibly tell what is having what effect? The glowing promotional language used by the author with the approval of the journal’s reviewers goes far beyond any findings and has no place in a supposedly scientific journal. It’s clear that the pharmaceutical company got its money’s worth. This report is an example of the troubling psychiatric polypharmacy which has become much more common in the past 15 years.
Tiagabine Called Highly Effective Based on Very Small Open Label Study. Tiagabine, a fairly expensive anti-epilepsy medicine costing $50-100/month, is a selective inhibitor of GAT-1 GABA transporter system which reuptakes GABA from synaptic clefts in presynaptic neurons and glia in the brain. In another, very small open trial, ten patients with chronic anxiety and a huge mix in diagnoses (GAD, PTSD, BD, MDD, DTS disorganized schizophrenia) and considered refractory to treatment were given tiagabine 2mg HS and increased up to 8mg HS for four weeks. Five were on and continued on risperidone, clomipramine, paroxetine, or citalopram. Five were not on any medicine. All patients were at least much improved at 4 weeks, usually within the first week. All were still doing well at 3 months and none reported any side-effects. The authors call tiagabine "highly effective." At the end of the article, the authors make the usual genuflection in the direction of established science by saying placebo controlled trials are warranted. But with the authors already declaring tiagabine "high effective" one wonders why there is any need for DB PC trials. Daniel Crane, Tiagabine for the treatment of anxiety. Depr Anx 1:51-2, 2003. (Ed: While this is a more accept open trial, open trials should never claim to prove efficacy. This is especially true of very small open trials of patients with a wide range of diagnoses.)
Psychiatric Research: Drug Company Funding Huge Effect on Results of Research: Meta-analysis of 30 studies comparing research funded by drug companies vs. others. Research funded by drug companies was less likely to be published or presented than research funded by other sources. Research funded by drug companies was also more likely to be published in the proceedings of symposiums than non-industry sponsored research. 18 different comparisons (15 studies) of the outcomes of industry funded and non-industry funded studies—seven from pharmacoeconomic analyses and 11 from clinical trials or meta-analyses of clinical trials. The summary odds ratio was 4.05 for industry funded studies getting positive results. Of the nine that provided statistical analyses, four found that drug company sponsored research had better quality scores. One study evaluated the appropriateness of the comparators in clinical trials and found that a greater proportion of industry sponsored studies compared innovative treatment to either placebo or no therapy than did studies sponsored by public resources (60% v 21%; P < 0.001). "In the past few years, manufacturers have attempted to prevent studies which are unfavorable to their products from being published in several high profile cases." Pharmaceutical industry sponsorship and research outcome and quality: systematic review. Joel Lexchin, Lisa A Bero, Benjamin Djulbegovic, Otavio Clark. BMJ 2003;326:1167-1170 (31 May), York Univ & UCSF
Clozapine May Not Be as Superior as Claimed: Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine. The benefits of clozapine compared with conventional treatment may not be substantial. Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination. University College London. Moncrieff J. Br J Psychiatry. 2003 Aug;183:161-6
Topiramate Said to Fail in DB Study Not Yet Published: There are negative, as yet unpublished, controlled studies on topiramate for mania according to a mention in a recent review article. RW Licht, Acta Psychiatrica Scand 2003;419:108 (suppl pg 13), although in three open trial reports, researchers claimed benefit (J Clin Psychiatry 2001;62:464-8; Biol Psychiatry 2000;47:1025-33; J Clin Psychopharm 2001;21:340-2). (Ed: Thousands of psychiatrists have been prescribing Topamax to bipolar patients with absolutely no scientific evidence that it helps Bipolar Affective Disorder. When will doctors learn that "open trials" prove nothing. Tens of thousands of patients have suffered needless side-effects and lack of effective care. The patients have been guinea pigs without even signed consent of an experimental treatment. They have been exposed to risks without any benefit to science.)
How Did Psychiatry Miss SSRI Sexual Dysfunction?: When Prozac first came out 15 years ago or so, and when the other SSRIs first came out, there was little talk about how frequent their sexual side-effects were. Now, we read that "erectile dysfunction and associated sexual dysfunction secondary to antidepressant therapy may occur in up to 90% of men with antidepressant-emergent sexual side effects." (Prevalence of antidepressant-associated erectile dysfunction. Rosen RC, Marin H. J Clin Psychiatry. 2003;64 Suppl 10:5-10). How can you miss an important side-effect that occurs in such a large percentage of patients. I wonder how many psychiatrists even now warn male patients about the high frequency of such side-effects.
Insurance Boosts Medical Care Spending Unwisely: We all like to have medical care insurance coverage to pay for our bills. Of course, people with insurance consume far more medical care than those without insurance. They go to the doctor more often and for more minor problems. They are more likely to ask for the expensive medicines they have seen advertised. They want every test possible and the best possible care no matter what the cost. And, of course, we all gripe when the cost of insurance goes up or when our employer won't raise our pay as much because health care insurance is eating up the profits that could fund a fatter paycheck. And we all complain when corporations move their factories to other countries because the cost of manufacturing is too high.
Malpractice Suits Boost Medical Care Costs: A large fraction of what doctors get paid goes directly to malpractice insurance companies to pay for more lawyers. Doctors practice defensive medicine, ordering more tests than necessary and giving in to expensive patient requests more readily than advisable.
FDA Secretive; Said to Act Precipitously: Droperidol has been a standard treatment since 1970 for sedating severely agitated patients. It was faster and less expensive then haloperidol IM. FDA now requires a black box dysrhythmia warning for a quinidine-like effect on the QT interval. UCSD researchers report treating 12,000 patients without a significant dysrhythmia and found no consistent pattern of harm. The FDA refuses to release its data without going through FOIA. The manufacturer has ceased production due to liability concerns created by the black box warning. The authors state, "One must also ask whether droperidol would have a black box warning today if it were still under patent to a pharmaceutical industry leader." They point out that ziprasidone (Geodon) had research funded by Pfizer to show there was no clinically significant QT prolongation and it has no black box. The authors conclude that the "FDA was precipitous to issue their warning on droperidol without the opportunity for public discussion." John H. Shale, et al: A review of the safety and efficacy of droperidol for the rapid sedation of severely agitated and violent patients. J Clin Psychiatry 2003;64:500-5
Thomas E. Radecki, M.D., J.D.