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By now, the reader may be asking, How does the Food and Drug Administration (FDA) allow such dangerous and often ineffective psychiatric drugs to reach the market? In reality, the FDA has been subject to considerable criticism and scrutiny over the years from the U.S. Congress and the media (summarized in Shulman et al., 1995 [1177]), including allegations that the FDA is becoming more protective of drug companies (Skrzycki, 1996 [1186]).
Since the publication of the 1997 edition of this book, criticism of the FDA has heated up considerably. In the past few years, a series of regulatory failures, highlighted by the discovery that the pain medication rofecoxib (Vioxx) and the diabetes treatment rosiglitazone (Avandia) boost the risk of heart disease, has led to increased criticism of the FDA.
A New York Times article was aptly headlined "At F.D.A., Strong Drug Ties and Less Monitoring" (Harris, 2004 [598]). Describing the travail of FDA whistle-blower David Graham concerning Vioxx, the editor of the British Medical Journal asked, Is drug regulation failing in the United States (Abbasi, 2004 [3])? In 2004, the FDA came under fire from Congress for its handling of SSRI-induced suicidality, especially in children and youth (Rosack, 2004 [1097]).
In 2005 [76], Jerry Avorn wrote a prospective in the New England Journal of Medicine titled "FDA Standards-Good Enough for Government Work?" Avorn pointed out that most of the FDA's energy was wasted on forcing the industry to jump through hoops on issues that had little to do with whether or not the drugs would help people. Then, in September 2006, the Institute of Medicine of the National Academy of Sciences, a government-sponsored organization, criticized the unresponsiveness of the agency to potential drug risks and recommended, for example, that the FDA review the postmarketing safety data of each drug every 5 years. It also sought to give the agency more power to force companies to "complete required safety studies" (Harris, 2006b [600]). The FDA itself, after decades of criticism, is reexamining the issue of how many of its advisory committee members have drug company ties (Harris, 2006a [599]), but it seems unlikely that the agency can disentangle these ties without unraveling the entire psychopharmaceutical complex.
The FDA responded by proposing a few minor changes, including an experimental program to review the safety of two or three drugs each year after they have been on the market for 18 months. The agency also declared its intention to start an online newsletter that would publish the safety reviews generated by the pilot program. Meanwhile, the FDA plans to continue its policy of withholding confidential, commercial data - that is, the sealed information necessary to determine if the companies are telling the truth about their commercial products. The Wall Street Journal commented that this is "a move likely to please the drug industry" (Mathews, 2007a [887]). Unfortunately, the drug industry's pleasure comes at the expense of human lives.
In March 2007, a study commissioned by the FDA came out with similar conclusions to mine. The FDA had hoped the study would exonerate the agency, but instead it lamented the culture of conflict, avoidance, and waste inside the FDA when it comes to tracking adverse drug reactions (Mathews, 2007b [888]).
Marcia Angell (2007) [54], former editor of the New England Journal of Medicine and now senior lecturer at Harvard Medical School, raised the basic question: Who does the FDA represent, consumers or industry? In a column titled "Taking Back the FDA" in the Boston Globe on February 26, 2007, she concluded that the FDA was becoming more dedicated to serving the companies than to serving the consumer of psychiatric drugs.
The public may be catching on. A recent USA Today editorial headline summed up the national outcry: "Our View on Pharmaceutical Safety: Latest Drug Scare Shows Need for FDA Overhaul" (Our view on pharmaceutical safety, 2007 [1015]). Americans need to know that the FDA is not their friend. It is the friend of the pharmaceutical industry.
Much of the tightening of FDA regulations over the years has been in reaction to disasters and tragedies. For example, in 1937, over 100 people, mostly children, died due to poisoning with an organic solvent used in the liquid form of the antibiotic sulfanilamide. In the following year, Congress passed the federal Food, Drug, and Cosmetic Act. The early legislation made requirements for safety, but not for efficacy.
In the early 1960s, thalidomide, a sleeping medication with no special advantages in regard to efficacy, caused an epidemic of birth defects. In 1962, the Kefauver-Harris amendment strengthened the FDA drug approval process to include controlled trials to demonstrate clinical efficacy. The amendment also required manufacturers to submit proof of efficacy for all drugs marketed between 1938 and 1962. In The Therapeutic Nightmare, Mintz (1965) [932] provided a critical analysis of FDA functioning up to that period of time. In short, criticism of federal drug monitoring has been going on for a long time, with mixed success in reforming the agency, which too often panders to the needs of industry.
The FDA has evolved a complex plan for each drug application, beginning with animal experimentation and proceeding through four phases of human experimentation (Food and Drug Administration [FDA], 1977 [455]; Jorgensen et al., 1992 [701]). Phase 1 and Phase 2 involve experimentation with animals and human volunteers and early clinical testing to determine if larger and more elaborate clinical trials are warranted or safe.
In Phase 3, controlled clinical trials are used to compare the drug to placebo and to previously approved, similar medications. At least two of the controlled studies must show a statistically significant positive effect from the drug. A few thousand patients are usually involved in the total database developed during the psychiatric drug approval process, but this number is misleading. It includes almost everyone who has taken even one dose of the drug. Only a few hundred patients may be involved in the Phase 3 controlled clinical trails that the FDA finds adequate for evaluating efficacy, and many of these subjects have usually dropped out before completion of the trials (Breggin et al., 1994a [219]).
The entire drug development process in the past could easily take 10-12 years, giving the public and the profession the misleading impression that the actual clinical studies were themselves very lengthy. Most of these years were spent completing various FDA requirements that did not directly pertain to clinical studies. Several years were often spent by the FDA itself in evaluating the company's new drug application (NDA)25, a process the FDA is now speeding up (see DiMasi et al., 1994 [365]). But the actual clinical trials for psychiatric drugs usually last a mere 4-6 weeks.
All of the studies involved in the FDA approval process are designated completely by the drug companies and conducted by physicians hired and paid for by them. Would physicians be rehired if they regulary failed to churn out positive results? In complex studies involving human beings, statistics can, of course, be endlessly massaged until a seemingly significant result is generated irrespective of what actually occurred. To prove that a drug is an effective antidepressant, for example, the company needs only to develop two positive studies, even if innumerable others are entirely negative. This regulatory policy is not consistent with the canons of science or statistical analysis. As we found in chapter 7 in regard to the testing of antidepressants, when all of the trials are taken into account, antidepressants do not prove to be significantly better than placebo.
The main concern of this book is safety, rather than efficacy, but the flaws in these trials (see subsequent discussion) will obviously affect both.
The FDA approval process is about creating and obtaining a label for the marketing of the drug. The approval of the label by the FDA is the final step in the process before the government allows the drug to go to market.
Before approval of the label, the FDA negotiates with the pharmaceutical company conceming its contents. After approval, the label appears in package inserts. It is published by the drug companies in the Physicians' Desk Reference (PDR) [1034], a commercial book sent free to all practicing physicians and found in most treatment facilities and doctors' offices. A shortened form of the label with emphasis on adverse effects must be included in advertising and promotional materials.
The FDA-approved drug label is very important, especially in regard to defining dangerous side effects. Physicians often use the PDR to alert themselves to the dangers of drugs. Typically, it is the first place that physicians look when they have a question about a drug. Reviews in the literature are frequently based on it as well.
Phase 4 spans the entire period of time after the drug has bee approved and entered the market. Phase 4 studies are implemented when the FDA requests a drug company to examine newly discovered drug hazards. In my interviews with FDA officials, they agreed that this crucial process tends to be given relatively low priority compared to the approval process. They attribute this to congressional and consumer priorities (see Government Accounting Office [GAO], 1990 [551]). On occasion, drug companies simply neglect to pursue Phase 4 trials suggested to them by the FDA. For example, Eli Lilly never conducted Phase 4 trials on Prozac-induced suicidality, even though the agency had required it and the drug company had agreed to it. The FDA, in turn, did nothing to force Eli Lilly to comply with its demand.
After the drug has been marketed, the FDA remains responsible for reacting to new information. It can remove a drug from the market if it proves too hazardous. It can also require a drug manufacturer to add newly recognized adverse drug reactions to a label or to strengthen the information concerning known adverse reactions.
The American Medical Association lobbied Congress to make sure that after a drug is approved, physicians are not legally bound to follow the FDA guidelines. In the case of Prozac, for example, physicians quickly began giving it to children, even though it was not approved for them. Drug companies are not allowed to promote their drugs for unapproved purposes but often do so on the sly through their sales forces.
After the FDA approves a drug, the companies have continuing responsibility to inform the FDA about adverse drug reactions discovered after marketing of the drug. The drug companies are also required to monitor the scientific literature concerning their medications and to report adverse drug reactions found in that source as well.
In some product liability cases in which I have been a medical expert for the plaintiff, drug companies have tried to claim that the FDA holds ultimate responsibility for the information that the company places on its label and, in particular, that the drug company cannot make changes to a drug's label without prior FDA approval. This is not true. Every pharmaceutical company is empowered by law to make changes to its drug labels without prior FDA approval, provided that the changes will "add or strengthen a contraindication, warning, precaution, or adverse reaction" or "add or strengthen a statement about drug abuse, dependence, or overdosage". The company can also "delete false, misleading, or unsupported indications for use or claims for effectiveness" (Code of Federal Regulations, 1995, 314.70c, p. 124 [291]) without prior FDA approval. Thus each drug company retains responsibility for making sure that its drug labels are as current and accurate as possible concerning risks and hazards, even to taking unilateral action to upgrade safety aspects of its labels without prior FDA approval. After the company has made and published the change, the agency may then evaluate it to its own satisfaction.
The media often treat the pronouncements of scientists and the results of scientific research with an aura of naive and undue respect. Scientific endeavors are conducted by ordinary human beings, many of whom come burdened with heavy biases and overwhelming financial interests. Especially in the field of human sciences, where complexity is made infinite by the interaction between human nature and society, bias easily runs rampant. Nearly all the research conducted in the are a of psychiatric drugs is funded, designed, and conducted by drug companies or their close associates and allies, eliminating any hope of obtaining unbiased results.
Fortunately, there are signs of a growing awareness in the media that science per se cannot necessarily be trusted (Hotz, 2007 [633]). Researchers have also begun to challenge the myth of scientific objectivity. John Loannidis (2005) [849] published an essay titled "Why Most Published Research Findings Are False". He pointed out, in effect, that most research findings do not reflect reality as much as they reflect "prevailing bias" in their field. This is nowhere truer than in psychiatry, where bias rules and drug-company and professional interests reign triumphant.
Focusing on a scientific issue that is critical to psychiatric drug treatment, too much faith can be placed in premarketing clinical trials as a method of detecting adverse drug reactions. For example, it can be mistakenly assumed that controlled clinical trials are the paradigm of scientific investigation. In my forensic experience, drug companies have defended themselves in product liability cases by arguing that only a controlled clinical trial can prove the existence of an adverse drug reaction. This is a mistaken interpretation of the nature of science and scientific conclusions. (For an extensive review of drug product liability issues, including FDA-manufacturer relationships and responsibilities, see Dixon, 1995. [368])
In reality, proving safety in clinical trials for FDA drug approval is an even more flawed process than proving efficacy. Often, serious and even fatal reactions will not be detected in the studies used for drug approval.
In the past, the FDA (1995) [463] itself has been vocal about the limits of premarketing testing and about the importance of the supposedly less scientific postmarketing spontaneous reporting system (SRS) in which professionals like doctors and pharmacists, as well as concerned consumers, send in reports of possible adverse drug reactions. In the mid-1990s, the agency briefly stepped up its efforts to inform physicians and other members of the health community that drug approval by no means guarantees that all serious side effects have been detected and that more attention needs to be given to spontaneous reports generated after the drug has reached the market. The FDA distributed a dramatic white on black poster with the following point emblazoned on it:
"When a drug goes to market, we know everything about its safety. Wrong."
The FDA's June 1995 publication [463] "A MedWatch Continuing Education Article" replicated the poster and made the following points in a section called Limitations of Premarketing Clinical Trials:
Short duration - effects that develop with chronic use or those that have a long latency period are impossible to detect
Narrow papulation - generally don't include special groups, (e.g., children, elderly), to a large degree and are not always representative of the population that may be exposed to the drug after approval
Narrow set of indications - those for which efficacy is being studied and don't cover actual evolving use
Small size (generally include 3,000 to 4,000 subjects) - effects that occur rarely are very difficult to detect.
The FDA (1995) [463] made the following point concerning the probability of detecting an adverse reaction:
"Clinical trials are effective tools primarily designed for assessing efficacy and risk-benefit ratio, but in most cases they are neither large enough nor long enough to provide all information on a drug's safety. Ar the time of approval for marketing, the safety database for a new drug will often include 3,000 to 4,000 exposed individuals, an insufficient number to detect rare adverse events. For example, in order to have a 95% chance of detecting an adverse event with an incidence of 1 per 10,000 patients, an exposed population of 30,000 patients would be required."
The director of the FDA's MedWatch program, Dianne Kennedy (Kennedy et al., 1993 [752]), wrote:
"The safety profile of a drug continually evolves over time. Clinical triais that precede product approval typically include safety data on only a few thousand patients. New information is expected to be discovered as a drug is used in larger and larger populations, in subgroups not studied during the clinical trials (e.g., pregnant women, the elderly), or in patients with numerous medical conditions taking multiple other medications."
Writing in the Journal of the American Medical Association on behalf of the FDA, former Commissioner David Kessler (1993) [754] declared:
"Even the large, well-designed clinical trials that are conducted to gain premarket approval cannot uncover every problem that can come to light once a product is widely used ... If an adverse event occurs in perhaps one in 5000 or even in 1000 users, it could be missed m clinical trials but pose a serious safety problem when released to the market."
In The Pharmacalagic Basis of Therapeutics, Alan Nies (1996) [989] made a similar point:
"Since only a few thousand patients are exposed to experimental drugs in more or less controlled and well-defined circumstances during drug development, adverse drug effects that occur as frequently as 1 in 1,000 may not be detected prior to marketing. Postmarketing surveillance oi drug usage is thus impera tive to detect infrequent but significant adverse effects." (p. 57)
To pursue Kessler and Nies's point, assume as a hypothetical example that Prozac causes suicide in 1 in 1,000 patients. If this were true, among the first 5 million patients to take the drug, 5,000 would die by suicide. Yet the problem could have gone wholly undetected in the trials. This, of course, gives even more weight to the actual finding of Prozac-induced suicidality in the controlled clinical trials (chapter 6).
Paul Leber (1992) [821], at the time director of the FDA's Division of Neuropharmacological Drug Products, addressed the limitations of premarket testing and the importance of postmarketing surveillance. He pointed out that "even the best designed and well-executed premarketing evaluation programs may fail to detect risks that can have extremely serious consequences for the public health". Again using the illustration of a drug testing program involving 1,000 patients, he observed, "There remains a 5% chance that the drug, upon marketing, might regularly cause serious, even fatal, injury to one in every 333 or so patients" treated.
Thomas Laughren (1992) [815], then the group leader of the psychiatric drugs section in Leber's division, reviewed the standards and also the limitations or problems inherent in using clinical trials to determine adverse drug effects. (The standards can be found in Center for Drug Evaluation and Research, 1988 [267]; see also Castle, 1986 [264]; Leber, 1992 [821]; Peace, 1987 [1024].) After describing the small size and short duration of the premarketing clinical trials, Laughren (1992) [815] concluded:
"It is important to acknowledge this limitation of the typical developent programs and to recognize that careful postmarketing surveillance is the most feasible method for detecting the more infrequent adverse events occurring with the use of a new drug."
Because the trials err toward missing adverse reactions, Laughren suggested that the FDA should lean toward assuming a drug connection when adverse events occur in association with it.
Paul Leber (1992) [821] also pointed out that the risks may be even greater statistical analysis indicates. Additional factors include the following:
In regard to the final point, Leber stated:
"In any event, whatever the reasons, it is likely that Phase III testing ordinarily fails to reproduce the conditions of illness and polypharmacy that occur in actual clinical practice with market drugs, and this may generate a misleadingly reassuring picture of a drug's safety in use."
Leber (1992) [821] concluded, "In sum, at the time a new drug is first marketed, a great deal of uncertainty invariably remains about the identity, nature, and frequency of all but the most common and acutely expressed risks associated with its use."
Karl E. Peace (1987) [1024], Director, Research Statistics, SmithKline and French Laboratories, pointed out that "it is frequently impossible to design trials to provide definitive information about safety-particularly about adverse events". He described occasions when it has been possible to design adequate safety studies, but concluded, "However, for most new drugs in clinical development it is not possible."
In recent years, the FDA has become increasingly defensive about its approval process and increasingly protective of the drug companies when they are accused of overlooking or hiding data concerning adverse drug reactions. As a result, the FDA has stopped emphasizing and publicizing the limits of the controlled clinical trials used to obtain the agency's approval.
There are other difficulties that further compromise the clinical trials used for FDA approval. For example, the FDA routinely allows the drug companies to winnow out patients who might respond to placebo before placing them randomly in either the drug or the control group of the placebo-controlled clinical trial. During this so-called washout period, all of the potential subjects for the study are given placebo. If any of them improve on the placebo, and many usually do, they are dropped from the study. This then gives the drug an unfair advantage in comparison to the placebo in the subsequent placebo-controlled clinical trial, because the known placebo responders have been eliminated. Because placebo responders have been thrown out in advance, the drug is likely to look better in comparison to placebo than it really is. When I first discovered and wrote about this (Breggin et al., 1994 [195]), I could not believe that the FDA allowed this deceptive practice in testing psychiatric drugs and that drug "experts," all of them in the pocket of the drug companies, universally went along with the ruse. To this day, the FDA continues to condone this fraudulent science.
The numbers of subjects included in clinical trials is not nearly as large as the drug companies sometimes claim and doctors sometime believe. While a thousand or more patients may enter the controlled clinical trials, the FDA will throw out many of the studies as scientifically invalid. In addition, not all of the patients will finish the trials that the FDA considers valid. Many subjects will drop out because they haven't been helped or because they have experienced distressing side effects.
The gap between drug company claims and reality can be enormous in regard to the numbers of patients tested. Eli Lilly, for example, gave the impression that between 6,000 and 11,000 patients had been given Prozac during the FDA approval process. When I laboriously reviewed each of the Prozac studies that the FDA considered valid enough to use for approval, I discovered that a total of only 286 patients had completed them (Breggin et al., 1994 [195]).
The ability to discern adverse effects is compromised by the fact that many of the individual studies may be relatively small, involving only a few dozen patients or less. One principal investigator, for example, may supervise a project involving only 20 or 30 patients, half of whom are taking the placebo. He or she then sends in a report to the drug company, where its staff takes on the ultimate task of looking over the entire database from all of the investigators in search of patterns of adverse drug reactions. Even in the smaller clinical trials, the patients are not all taking the drug at the same time. Patients are included in the trial as they become available and sign up over a period of weeks or months. Some are starting the trial long after others have finished it. The principal investigator and associates are therefore not able to survey the group altogether or all at once but must rely on memory and on records to discern patterns of adverse drug reactions. They must do this over an extended period of many months while preoccupied with many other unrelated professional activities.
If an unexpected adverse reaction were to appear only once in one of the smaller projects, the local clinical investigator might easily miss its significance. He might not even bother to report it. For example, worsening of depression might easily be attributed to the patient's illness, rather than to the antidepressant drug, and go unreported as an adverse drug reaction. A seemingly bizarre abnormal movement may be attributed to the patient's schizophrenia, rather than to a drug-induced neurological disorder, and again go unreported.
Individual projects and investigators will also vary in their approach to evaluating adverse reactions. The ultimate database is not drawn from one consistent source, but from the variable efforts of different investigators often operating under somewhat different experimental protocols and with markedly different subjective perceptions26.
Leber (1992) [821] addressed some of these issues when he stated:
"Finally, of course, clinical testing during premarket development may fail to detect drug associated risks for any number of commonplace reasons: poor or careless technique, uncooperative patients, incompetent professional staff, clerical mistakes, etc. Indeed, even in closely monitored inpatient environments, it would be naive to believe that every adverse event that occurs is observed. Further, even if an untoward clinical event is observed, there is no certainty that it will be recognized as drug related, or if it is, that it will be subsequently recorded author reported."
Especially for readers who have not been exposed to scientic research, the phrase controlled clinical trials is likely to conjure up something much more rigorous than individual patients signing up at various times in a doctor's office or in a clinic for an opportunity to participate in a project that is probably being supervised and conducted by the doctor's assistant or nurse.
The treatment subjects in most controlled clinical trials used for FDA approval are not sequestered on a hospital ward. They return home to their everyday lives, including whatever undisclosed psychological or physical problems they may harbor and any legal or illegal drugs which they may take without informing the investigator.
Clinical experience and various studies have shown that patient compliance is spotty in regard to taking drugs at home. Rarely can the investigator be sure that the patient is taking the drug in question at all, let alone in the prescribed fashion. Efforts are sei dom made to detect the drug in the subject's blood or urine to confirm that it has been taken. If an individual has signed up for the study to earn money rather than to seek a cure, he or she may have little motivation to risk taking the potentially dangerous drug.
The pool of individuals who sign up for drug testing has not been given adequate consideration in evaluating the usefulness of clinical trials. Often, the subjects are obtained from newspaper and radio advertisements that invite members of the public to sign up for a clinical trial for a new drug for anxiety, depression, phobia, or some other named disorder. Sometimes flyers for the trial are distributed at meetings or conferences of patients who suffer chronically from these disorders. The individuals to whom these promotions will appeal may be desperate for money, desperate for therapeutic relief, or both. Why else would they go into an unfamiliar setting to risk taking an experimental drug whose safety and efficacy have not been demonstrated? Their need to be in the experiment may influence what these subjects tell the investigators about their past histories as well as their responses to the drugs. Their hope for a cure or their desire to please the doctors may influence their own perceptions and communications (see subsequent discussion for recent pertinent disclosures).
The placebo control does not ensure that either patients or doctors will in fact remain blind to what the patients are getting. A drug like Prozac or Paxil, for example, often causes stimulating side effects such as nervousness and insomnia, enabling the investigator to guess that the individual is taking the drug rather than the placebo. Similarly, a drug like Zyprexa or Risperdal will cause patients to become inexpressive and sluggish, again making it easy to distinguish those who are taking the drug from those who are not. Fisher and Greenberg (1989) [444] made the point that there are very few truly blind studies, even when controls are carefully implemented. The failure to keep the study blind may easily play into the patient's or the investigator's need to make a positive evaluation of the drug in regard to both safety and efficacy.
Since the individual drug trials are too small, too short, and otherwise inadequare to the task, it remains the ultimate responsibility of the drug company to go rhrough the complete, combined data base in search of patterns of adverse drug reactions. Even if drug companies were properly motivared, there is no foolproof way to oversee the entire group of several thousand patients.
Controlled clinical trials are not inevitably scientific. They may meet the canons of science, or they may not, depending on their structure and on how they are carried out. But even if they are performed to a high standard, they still do not by themselves prove anything. Their data must be cientifically interpreted - that is, subjected to reasoned analysis.
As the FDA has made clear, a reasoned analysis discloses that the controlled clinical trials used in the FDA process have grave limitations in regard to the detection of adverse drug effects. The FDA came to this conclusion without discussing some of the more subtle issues I have raised this chapter.
There are some obvious oversights in the FDA requirements imposed on drug companies, including some specific areas that are wholly neglected. First, the FDA does not require drug manufacturers to demonstrate through animal (or human) research that the brain recovers from any of the various biochemical imbalances and other malfunctions produced by every psychiatric medication. Information is frequently provided to the FDA concerning the impact of the drug on neurotransmitters and other brain functions in animals, while no information is provided concerning the potential for recovery. All of the neuroleptics and antidepressants as well as lithium produce profound changes in brain function during treatment, but to this day, there has been little research on the recovery of these functions (see chapter 6 in regard to Prozac; see also Breggin et al., 1994a [219]).
Second, the FDA does not require intensive neuropsychological testing of human subjects to document cognitive impairment or other brain dysfunction associated with drug treatment. There is no follow-up to determine if cognitive and other functions return to normal after termination of drug treatment. For example, ir took independenr postmarketing studies to show that antidepressants (chapter 6) and lithium (chapter 8) can impair cognition.
Third, the FDA does not require the drug company to show that any patients actually recover from their psychiatric disorders as a result of drug treatment. Instead, all measures aim at demonstrating relative degrees of improvement in comparison to placebo or other medications. To get into an antidepressant study, subjects typically must be shown to suffer from major depression, and to get into a neuroleptic study, they must be shown to suffer from schizophrenia. However, they are not usually evaluated at the end of the study to determine whether or not they have partially, largely, or fully recovered from depression or schizophrenia. Instead, improvement on a few items on a symptom checklist is usually sufficient to determine a positive outcome. Thus the drug companies avoid asking potentially embarrassing questions about actual recovery. In reality, drug treatment almost never leads to recovery, and that is why the drug companies never use recovery as one of the standards for evaluating treatment.
Fourth, for a drug to be approved, there is no requirement that the patients rate themselves improved as a result of it. Checklist ratings by outside observers, that is, drug company-paid researchers, are sufficient evidence for FDA approval, even if the patients rate themselves no more improved on the drug than on placebo. In many instances, psychiatric drugs are approved despite the fact that patient self-ratings do not indicate improvement.
Fifth, where there are known and even extreme risks in association with a particular class of drugs, the FDA does not require that the drug company specifically determine the new drug's risk in regard to these known dangers. For example, neuroleptics cause tardive dyskinesia (TD) and neuroleptic malignant syndrome (NMS). Yet, during the approval process of new neuroleptics, the companies are not required to demonstrate the specific risk that the new drug poses in regard to TD or NMS. A class warning may be required, for example, for TD or NMS, but there will be no requirement to test for the possibility of an increased risk with the new agent.
Finally, the FDA does not conduct any drug studies on its own. It relies entirely on research produced, monitored, and financed by the pharmaceutical companies. In the old days, thousands of hard-copy pages would be submitted in numerous cartons to the FDA for the agency to examine while hundreds and hundreds of cartons of background material remained unexamined at the company headquarters. Nowadays, the material is sent to the FDA in digital form, but the effect is the same. The FDA is inundated with pages of information, but a mountain more remains untouched by agency eyes. In Talking Back to Prozac (Breggin et al., 1994a [219]), and more recently in my reports about Paxil (Breggin, 2006a-c [213]) I have documented the far-reaching negative consequences of the FDA's dependence on data generated, collected, and analyzed exclusively by drug companies themselves.
While the FDA has procedures for monitoring the drug companies during their application for new drug approval, the validity of the process nonetheless rests on the ethical and scientific integrity of the corporations. Drug companies have a strong financial incentive not to focus their attention on discovering or reporting adverse drug reactions that might threaten the approval of their product or cause future legal liability. They often fight hard against the passage of tougher FDA regulations and sometimes try to evade them after they are put into effect.
In reading drug company in-house communications and depositions, it is apparent that the overriding concern is to market a drug that makes a profit. When an adverse drug reaction becomes a public scandal, for example, the tendency is to campaign against the bad image, instead of evaluating the actual danger. A researcher, marketing representative, publicist, attorney, or CEO does not overnight become devoted to the public good simply because he or she takes a job with a drug company. Some product liability attorneys have told me, to the contrary, that the highly competitive pharmaceutical industry seems especially self-pratective.
For example, in reviewing an NDA for a product liability suit against a drug manufacturer, I discovered that a company official had written a memo recommending a comparative study between the company's drug and older one. In the hope that his company's drug was safer, he wanted to compare the frequency with which the two drugs caused the same serious side effect. Penciled into one corner of his memo was a note from another company executive stating that it was a bad idea to ask questions whose answers might prove embarrassing. The study was never done.
Bias may affect a drug company's overall analysis of the patterns of adverse reports from the clinical trials. In my forensic experience, the methodology of the analyses may deviate drastically from the scientific process. In addtion, if the conclusions seem to threaten the future of the drug, the conclusions may be modified or kept secret (see chapter 14). In general, drug companies have learned to employ many of what Scott (2006) [1147] called tricks of the trade to make clinical trials produce exaggeratedly good results.
By 1969, the FDA developed a systematic approach to collecting and maintaining adverse drug reactions after marketing. For many years, it was called the SRS. The regulations were updated in 1985, and the system has been renamed MedWatch (for the basic regulations, see Johnson et al., 1991 [695]; for critiques, see the various citations below). Anyone, including patients, can initiate an adverse report by writing to the drug company or the FDA. In the past, the vast majority came from physicians and from hospital pharmacists, but increasingly, consumers have been sending in reports.
Unlike in England, in America, there is no formal requirement or readily available mechanism for health professionals to make these postmarketing reports. Nies (1996) [989] estimated that over 40% of doctors do not even know that they can report adverse effects directly to the FDA.
In addition to the larger numbers of patients involved and the longer treatment periods, the postmarketing SRS has a number of advantages over the premarketing clinical trials.
First of all, most of the pharmacists and physicians making the reports from the field, unlike those conducting the clinical trials, are not being directly paid by the drug companies. They are likely to have much less vested interest in retaining the drug company's goodwill.
Second, the largest portion of those who send in spontaneous reports are hospital pharmacists. They are working in institutional settings, where they can overview hundreds of patient experiences with the drug. They are in an especially good position to spot something requiring scrutinity.
Third, spontaneous reports are sent in by professionals who are evaluating the drug under more natural field conditions. These patients have not been prescreened by the drug company as they are before clinical trials. Many of the patients are receiving other drugs; suffering from physical illnesses; or taking large, and sometimes excessive, dosages of the drug. Adverse drug reactions are more likely to show up under these complex and often more hazardous conditions. For example, adverse drug reactions typically occur more frequently at doses in excess of those used in the clinical trials. Reactions to excessive dosages can provide a signal that these reactions are in all probability occurring at more standard doses as well, although less frequently or less intensively. Advanced age and infirmity, usually screened out and hence untested factors in clinical trials, are more likely to be encountered in general practiee and can be bellwethers. Tricyclic antidepressants, for example, will cause life-threatning cardiovascular problems much more frequently in the elderly. Similarly, neuroleptics cause TD much more frequently among the elderly. Because the SRS includes a larger variety of patients taking a broader spectrum of doses, it is much more likely to disclose adverse reactions than a controlled clinical trial conducted for FDA approval of the drug.
Fourth, the professionals making the reports have been alerted, through their own experience and through reports in the literature, to initially unexpected adverse reactions. They have the benefit of increased clinical awareness as well as hindsight in identifying adverse drug reactions. Physicians are also more likely to know their patients well compared to clinical trial investigators and, like family members, may be better able to notice personality changes and other more subtle adverse drug reactions. Also, physicians are more likely to be in touch with family members who are largely ignored during controlled clinical trials.
In describing the impact of the MedWatch spontaneous reporting system (SRS), the FDA's Kessler (1993) [754] said:
"In response to voluntary reports from physicians to the FDA or the manufacturer, the FDA has issued warnings, made label changes, required manufacturers to conduct postmarketing studies, and ordered product withdrawals that have ultimately prevented patient deaths and suffering."
The FDA (1995) [463] MedWatch publication makes clear that the SRS is the most important source of postmarketing information on adverse drug reactions. It frequently leads to scientific determinations for the need to modify drug labels or to withdraw drugs from the market. According to a 1990 Government Accounting Office report [551], more than 50% of all drugs approved by the FDA between 1976 and 1985 were found during postmarketing to have previously undetected serious side effects, sometimes requiring removal from the market. Fifteen psychopharmaceuticals were approved during this period, nine of which turned out to have serious risks during postmarketing, leading, in one case, to removal from the market (GAO, 1990 [551]). Since then, additional psychiatric drugs have been withdrawn from the market. For example, the antidepressant nomifensine (Merital) was found to cause massive intravascular hemolytic anemia - but only after it had been on the market worldwide for 8 or 9 years (Leber, 1992 [821]). As another example, the widely used antidepressant nefazodone (Serzone) was approved in December 1994 and not withdrawn from the market for another 10 years because of causing fatal liver failure. At that point, the FDA had received 55 reports of severe liver failure, 39 cases of less severe liver failure, and 20 deaths attributable to Serzone (Rosack, 2004 [1097]). Even then, the company and not the FDA made the decision to stop manufacturing the drug, in part due to a flood of product liability lawsuits against it. As a third example, pemoline (Cylert) was approved by the FDA for the treatment of ADHD in 1975 but was not removed from the market by the agency until 2005 - a period of three decades. By that time it had already been removed from the market in Great Britain in 1997 and in Canada two years later. Like Serzone, Cylert causes death due to liver failure.
In each of the above three cases, the FDA decision to withdraw the drug had nothing to do with data generated by controlled clinical trials. The decision was based on reports made to the FDA's spontaneous reporting system and clinical reports in the scientific literature.
In addition to the three more recent withdrawals of Merital, Serzone, and Cylert, I have also reviewed the entire list of serious adverse reactions to psychiatric drugs detected during the postmarketing period in the GAO (1990) [551] study. It seems probable that every one of them was discovered and confirmed through a combination of the SRS, individual case reports, and general clinical experience. As far as I can ascertain, not one of these adverse reactions was primarily, if at all, identified by means of a controlled clinical trial. As a result of postmarket discoveries, alprazolam (Xanax) had rage added to the label as a paradoxical reaction, and amoxapine (Asendin) had NMS added.
More recently, the FDA did use controlled clinical trials to verify that antidepressants cause suicidality in children, adolescents, and young adults. However, glaringly bright signals already existed from multiple sources (chapters 6 and 7) before the FDA turned to the clinical trial data. Furthermore, the drug companies failed to detect a signal in these same clinical trials until forced to reevaluate them under FDA supervision in 2004-2006.
There are a number of approaches that can be used to confirm from spontaneous reports that a drug is actually causing the adverse reaction. Chapter 12 described how several FDA officials went about confirming for themselves a possible or probable causal relationship between Halcion (and Xanax) and various behavioral abnormalities, including violence. To confirm causality, some of the following factors are useful:
The Federal Judicial Center (Bailey et al., 1994 [86]) has proposed a series of criteria that compact many of the points I have made. The difference in approach is, in part, due to their epidemiological emphasis in contrast to my clinical emphasis. Drawing on Koch's postulates, they stated, "Seven factors should be considered when an epidemiologist determines whether the association between an agent and a disease is causal." Put in the form of questions, they list the following factors:
None of the above individual criteria is an absolute requirement for coming to a scientiflc conclusion. One must weigh the best available evidence and come to as sound a conclusion as possible. Commonly, or even typically, decisions with a high degree of probability will be made with an incomplete set of data.
While it would be helpful to have conflrmation from controlled clinical trials, it is typically impossible to obtain it, even in regard to known or proven adverse drug reactions. As we have already seen, the absence of findings from controlled clinical trials involving a drug cannot be used to rule out a causal connection between a drug and an adverse reaction. To illustrate this again, we turn, in the next section, to the stories of NMS and TD.
Earlier in the chapter, I examined several dramatic failures on the part of the FDA to withdraw drugs from the market until the passage of years and even decades, despite mounting reports of potentially fatal adverse effects. This section examines how long it can take before flagrant adverse effects are even noted in the drug label.
NMS (see chapter 4) provides an example of how a devastating, common disorder can be wholly missed in the clinical trials during the approval process. It also illustrates how long it can take drug companies and the FDA to give formal recognition to such a disorder.
NMS is a potentially fatal reaction to neuroleptic drugs such as Haldol, Prolixin, Risperdal, Zyprexa, Seroquel, and Abilify. It occurs at a relatively high rate, developing in somewhere from 1.4% to 2.4% of patients exposed to the older neuroleptics and at significant rates to patients exposed to the newer ones (chapter 4). By contrast, a reaction that occurs 1% of the time is considered common or frequent by FDA standards. This particular reaction is extremely dramatic and therefore not easily overlooked. Yet NMS was entirely missed in one study after another conducted by drug companies when applying for FDA approval of neuroleptic drugs.
The failure to detect NMS in clinical trials cannot be attributed to the need for longer studies since an estimated 80% of NMS reactions develop within the first few weeks of treatment (Davis et al., 1991 [336]). Nor can the failure be forgiven on the basis of inadequate knowledge about the disorder. Suggestions of its existence began soon after the neuroleptic drugs went into use, and it was clearly identified in the English language literature by 1968 (chapter 4).
In 1986, nearly two decades after NMS had become an identifiable syndrome, the FDA at last began to force the drug companies to add the adverse drug reaction to their neuroleptic labels. Since the disease is fatal in approximately 20% of cases when it goes unrecognized and untreated, the failure to properly inform physicians cost many lives and untold suffering.
There are important lessons from the history of NMS. First, for many years, neither the FDA nor the drug companies came close to fulfilling their ethical and legal obligations by warning physicians and by adding the disorder to the neuroleptic label. The drug companies did almost nothing until forced to act by the FDA. Both the FDA and the drug companies were much too late, causing unnecessary death and suffering. Second, the history confirms that clinical trials cannot be relied on by themselves to identify even common, obvious hazards such as NMS.
TD occurs with extreme frequency in neuroleptic-treated patients, including both the older neuroleptics and the newer so-called atypicals (chapter 4). Research on the older drugs has shown that in relatively young, physically healthy adults, 4% to 7% per year will develop the disease. After a total of 5 years' exposure, at least one-third will develop this largely irreversible, disfiguring, and potentially disabling movement disorder. In older patients, the rate may exceed an astronomical 20% or more per year. Patients taking the drug for a lifetime will approach a 100% risk. While the rates for TD from the newer neuroleptics remain controversial, there is no doubt that they frequently cause the disorder (chapter 4). In the face of such an astronomically frequent risk, why is there nothing in the current FDA-required warning label for neuroleptics to alert a physician or patient to the extraordinary frequency of the risk of TD?
The neuroleptic drugs were in widespread use by 1954, and TD was documented within the first few years (chapter 4). Yet, for nearly 20 additional years, the drug companies and the FDA failed to provide an appropriate warning on the label of neuroleptic drugs. In the early 1970s, the agency finally forced a very weak uniform label statement about TD on the drug companies. It gave no hint about the frequency of the disorder, mentioning only that "some patients" might get it.
Even as the tragic news about TD accumulated, the drug companies did little or nothing to update their labels. Then, on February 24, 1984, Paul Leber called a meeting of the FDA's Psychopharmacologic Drugs Advisory Committee (FDA, 1984 [456]) to discuss the agency's proposal for an updated uniform class warning label for all neuroleptics. Leber explained to the committee that public pressure had caused the FDA to re-examine the problem. This public concern about TD had been generated in large part by a CBS-TV Dan Rather report. I had given CBS an advanced manuscript copy of my 1983 book on psychiatric drugs. It inspired the Dan Rather show, and I consulted on planning the program. Along with the publication of my book, I had also done my best to flood the general media with information, including many personal appearances on radio and TV to discuss the danger of TD.
In the 1984 meeting, Leber proposed a version of the label that included specific numerical estimates to underscore the very high rates. Seven expert drug consultants confirmed the need for mentioning actual numbers, and an eighth sent in a report taking the same viewpoint On the basis of the American Psychiatric Association (1980b) [35] task force report, some of the experts recommended citing a 20% risk in routine neuroleptic exposure. Others suggested a figure of 15% in the first 4 years. Leber himself observed that extrapolating from the data indicated that over a lifetime, "100% of patients may in fact develop the disorder" (FDA, 1984, p. 54 [456]). These are most extraordinary estimates for the rate of contracting a drug-induced, irreversible, and potentially severe disorder.
Approximately 5 months after the meeting, in the summer of 1984, Leber sent a formalletter to all neuroleptic manufacturers, suggesting a revision of the proposed class warning label. By then, almost surely in response to industry pressure, the proposed language had already been watered down. Without mentioning any figures, Leber's proposed label stated that TD would develop in a "substantial portion of patients treated with neuroleptics" (P. Leber, unpublished letter, 1984, p. 3). The meaning of substantial was left up to interpretation.
The FDA's Pharmacologic Drugs Advisory Committee met a second time on January 31, 1985, to discuss TD. Leber again mentioned the impact of the "clamor from the press" in the fall of 1983 - the date of Dan Rather's TV report and the simultaneous publication of my book.
Leber told the assembled representatives of the drug companies that he would not act without their endorsement or approval. He stated that he had been through "a year and a half of trying to bring about change in the labeling of neuroleptic products that would be fair and that would be acceptable to everyone" (FDA, 1985b [458], emphasis added).
Leber described to the meeting participants the elaborate back and forth negotiating that had already gone on between the FDA and industry. He said that one of his aims was to obtain "equitable labeling that did not cause injury to industry, as much as it also should not cause injury to patients or physicians who have to use neuroleptics under trying circumstances" (FDA, 1985b [458], p. 9, emphasis added).
Can the FDA perform a watchdog function without biting industry? Without even growling at them? If the process of identifying dangerous drug effects were painless to industry ("should not cause injury to industry"), industry would not need the FDA to regulate it. A properly functioning FDA would at times have to cause injury to industry through diminished revenues and other sanctions related to marketing dangerous drugs. The neuroleptics were being prescribed with too little regard for their devastating adverse effects; if the new warning label had done its job, neuroleptic sales would, of necessity, have dropped. There is nothing in the FDA legislation that urges the agency to protect industry. It is supposed to protect patients, despite the inevitable painful results for industry.
By this second meeting, Leber and the FDA had surrendered to industry. The somewhat ominous phrase substantial proportion was replaced by the entirely innocuous phrase some patients, implying a minimal risk. Ironically, it was the same phrase that appeared on the outdated 1973 label. No change had been made.
Ultimately, some patients was also dropped. The warning on the current neuroleptic label states that TD "may develop in patients" treated with neuroleptics - not even a hint of a serious risk, let alone an astronomical one, with millions of victims. In the critical arena of TD rates, the class warning label is possibly weaker, although more detailed, than the old one.
Partly owing to the persistently inadequate label, too many ill informed physicians and their patients continue to believe that the risk of TD is insignificant. Leber succeeded in causing little or no injury to industry - but at what cost to patients, their families, and the health care system? Since that time, Leber has retired and become a consultant to the pharmaceutical industry.
The story of the FDA's handling of warning labels for NMS and TD leads to a dismal conclusion. When it comes to warning about the dangers of psychiatric drugs, the FDA is more responsive to the profit needs of industry than to the safety needs of patients.
In Talking Back to Prozac (Breggin et al., 1994a [219]), I examined the overall FDA approval process in regard to Prozac, reconfirming that in regard to psychiatric drugs, the FDA is more concerned about industry goodwill than the public good. What follows is a small taste of what went wrong in the Prozac approval process.
As noted earlier in the chapter, although several thousand patients were involved in studies of various kinds, I counted only 286 who actually finished the three placebo-controlled protocols (groups of studies) used for approval. Many patients dropped out because of adverse stimulant reactions. Prozac seldom proved any better than placebo and was not as good as the older antidepressants. It was so stimulating that sedatives were often given along with it.
In perhaps the most important study, called Protocol 27, the results indicated that Prozac by itself had no efficacy. To get a positive result, the FDA had to allow the drug companies to include all the patients who, against the rules, were also given sedative and tranquilizing medications with their Prozac.
Protocol 27 was conducted by several separate investigators at sites in different cities. The individual study sites could not show that Prozac was any better than placebo, so the FDA allowed the negative results be pooled and manipulated until a positive result was barely achieved.
The FDA's Laughren (1992) [815], in an analysis of the drug approval process, observed, "Pooling of effectiveness data from independent studies is not standard and must be done with great care." Protocol 27 was not only made up of independent studies conducted at separate centers, but almost all of them had negative results. Furthermore, in the pooling process, one center was dropped entirely, eliminating 25% of the original data.
Lilly employees Stark and Hardison (1985) [1214] eventually published Protocol 27 in the Journal of Clinical Psychiatry. They did so without mentioning (a) that four of the five individual centers produced negative results before the data were pruned and pooled, (b) that even the pooled data were negative when Prozac patients taking sedatives and tranquilizers were excluded, (c) that the FDA had many criticisms of the study and its practices, or (d) that even the apparent success of the drug was marginal. The publication by Stark and Hardison claimed that Prozac was comparable to Tofranil in efficacy - a myth that gained considerable currency in the profession - when in fact, the older tricyclic outperfored Prozac most of the time.
The general perception in America is that the FDA is far tougher on drug companies than comparable European authorities. If that was ever true, it is not anymore, at least in the arena of psychiatric drugs where I have my greatest familiarity. As described earlier in the chapter, regulatory agencies in both Great Britain and Canada have at times been quicker than the FDA to take lethal psychiatric drugs off the market. In addition, as noted in chapter 6 in regard to antidepressants, the British and Canadian agencies were also ahead of the FDA in responding to the risk of suicide and, in regard to the Canadians, to the risk of harm to self and others.
On December 10, 1991 [814], Thomas Laughren, then group leader for Psychiatric Drug Products, wrote amemo concerning Zoloft's upcoming approval. Laughren listed a series of concerns about the antidepressant drug expressed by several European nations as well as by FDA advisors. These included "failure to provide data on depressed inpatients, severely depressed patients, `major depression,' etc.; failure to provide long term data, relapse efficacy, etc.; failure to provide comparative data, i.e., for alternative antidepressant agents". Despite these problems with Zoloft, he concluded that "the data were sufficiently persuasive to justify approval of this product".
Spurred on by Laughren's (1991) [814] critique, an exchange of memos occurred between Paul Leber and his boss, Robert Temple [1247], Director, Office of Drug Evaluation 1. The continuing subject was the approval of Zoloft, whose efficacy as an antidepressant remained in doubt up to the last minute. Temple noted that Zoloft was not being approved in some European countries because of its "lack of robustness" in the efficacy trials. Zoloft often failed to do any better than placebo in studies in the United States and never did as well as the older antidepressant amitriptyline. Despite these pervasive failures, one positive study and two supportive studies were found sufficient to earn approval.
On December 24 - a mere 6 days before the official approval letter was written for Zoloft - Leber (1991) [820] responded to Temple's concerns about approving the drug. About the tougher standards in the European countries, Leber wrote:
"This turn of events may seem somewhat surprising in view of the fact that the agency is traditionally more conserva tive than its European counterparts. Obviously, changes are underway throughout Western Europe, perhaps in response to EEC's [European Economic Community] harmonization initiatives. In any case, with the exception of the UK's [drug approval authority], standards for antidepressant drug product approval seem to be becoming more demanding in regard to (1) the duration of controlled trials serving as sources of evidence of efficacy, (2) the need to document efficacy in hospitalized depressed patients (because these are presumed, arguably, to be more severely depressed), (3) the need to show efficacy in maintaining remission, (4) the need to show efficacy in preventing relapse in euthymic [normal mood] patients with a history of recurrent episodes of affective illness, and (5) a need to establish equivalency andJor superiority of a new antidepressant to already marketed products."
Having outlined these standards, Leber acknowledged their merit but stated that they could not be implemented in America's current political climate:
"Many of these foreign regulatory initiatives have potential merit, but, given the perceived urgency we express as an institution for expediting the public's access to new, potentially promising drugs, I do not believe we can successfully introduce similar, more demanding, requirements domestically, at least until there is a significant `sea change' in our society's collective attitude toward Federal regulation of new drugs."
Leber (1991) [820] believed that Zoloft, despite its relative ineffectiveness, had met the FDA's official requirements for approval. He then concluded his memo with the following warning:
"Approval [of Zoloft] may, however, for the reasons enumerated above, come under attack by constituencies that do not believe the agency is as demanding as it ought to be in regard to its standard for establishing the efficacy of antidepressant drug products."
It is striking that these concerns and misgivings are being expressed less than a week before final approval of the drug. Temple did not respond for another week, until December 31, 1991 - 1 day after the date on the final approval letter. He agreed that the drug should be approved but concluded, "I would, however, strongly encourage formal thinking, in which I would be pleased to participate, about whether we should modify the advice we give to companies to assure that they examine aspects of their drug's effectiveness that are not being well enough studied."
Leber's claim, quoted above, that the FDA is stymied by "our society's collective attitude toward Federal regulation of new drugs" is disingenuous and self-serving. Above all others, Leber was personally in a position at the FDA to stand up for truth and honesty in drug regulalation, but instead he constantly pandered to the drug companies, for example, by delaying for years FDA recognition of antidepressant-induced suicidality and by watering down the warnings on TD. This permissive and even promotional attitude toward drug company interests then allowed him, after retirement from the FDA, to develop a second career. He now owns a consulting firm that helps drug companies get their products approved by the FDA (Dolan and Altimari, 2003 [369]).
A significant portion of the public believes that the FDA moves too slowly and places too many barriers in the way of new drug products. Despite all the bureaucratic time it wastes, in the arena of psychiatric drugs, the FDA is nowhere near thorough enough. The approval of a psychiatric drug does not in reality demonstrate either its efficacy or safety. The postmarketing surveillance is equally flawed. Not only is the system too haphazard, the division responsible for psychiatric drugs often fails to make an appropriate response to the most extreme drug-induced reactions, such as NMS and TD, produced by neuroleptics like Risperdal and Zyprexa and suicidal, violent, and manic behavior caused by antidepressants like Prozac, Zoloft, Paxil, and Celexa.
The FDA is hampered not only by its own internal failures, but also by its reliance on the potentially fraudulent activities of the pharmaceutical companies in developing and marketing their products. Because the FDA never evaluates the primary data generated by the drug companies, instead relying on the scientific integrity and ethics of each company, the agency often ends up evaluating fraudulent scientific data. Chapter 14 looks further at examples of drug company deception.
The NIMH is the federal agency funded to respond to so-called mental illness in America. When I was a full-time consultant to NIMH (1966-1968), it was fundamentally a psychosocial and educationally oriented institution. It sought ways to improve the nation's mental health through psychological, social, educational, and economic means. For example, it was greatly concerned with improving our schools and reducing poverty.
When I was on the staff at NIMH, biological psychiatry was relegated to a relatively small center in the larger psychosocial contexto But then, with the shift in the political wind toward medicalizing psychiatry that I document in Toxic Psychiatry (Breggin, 1991c [190]), NIMH was transformed in the 1970s into an institution for the promotion of biological psychiatry and drugs.
Eventually, NIMH completely shucked off its patient-service wing and became a research institute on behalf of biological psychiatry and the drug companies. As described in chapter 6, nowadays, NIMH conducts extremely expensive controlled clinical trials on behalf of the drug companies, trying to demonstrate the effectiveness of their products. Again, as previously described, when the antidepressants came under fire, the direction of NIMH spoke out in their defense.
In the mid-1990s, my wife Ginger and I discovered that NIMH and NIH, and even the Centers for Disease Control (CDC), were promoting an interagency racist biopsychiatric program aimed at identifying innercity children as suffering from violence-inducing brain disorders. In addition to funding research, the aim was to conduct mass screening and treatment of potentially violent children who supposedly suffered from genetic and biological abnormalities. Fortunately, our national campaign caused the federal agencies to stop their attempts to fund the program (Breggin and Breggin, 1994b [220]; Breggin and Breggin, 1998 [221]).
The NIMH puts out an enormous amount of literature on behalf of biological psychiatry and the drug companies. One example is its booklet Schizophrenia, available on its Web site (http://www.nimh.nih.gov; National Institute of Mental Health [NIMH], 2007 [975]). It promoted every myth of schizophrenia favorable to the use of drugs. Breggin (1991c [190]), Cohen and Cohen (1986) [294], Harding and Zahniser, (1994) [597], Irwin (2004a&b [653] & [654]), Joseph (2004a [704], 2006 [706]), Karon and Widener (1999) [743], Lidz (1981) [841], Mosher and Burti (1989) [954], Read and Ross (2003) [1074], Read et al. (2005) [1075] and Siebert (1999) [1179] provide analyses of the myths of schizophrenia.
The booklet (NIMH, 2007 [975]) declared, "Schizophrenia is a chronic, severe, and disabling brain disorder that has been recognized throughout recorded history." It certainly has not been recognized as a brain disorder since recorded history. In fact, it was often seen as a spiritual gift. Nor is there any substantial evidence that it is a brain disorder (chapter 5). It does not act like any other known brain disorder. It has no identifiable underlying pathology, it does not lead to deterioration in mental or neurological processes, and it responds to psychosocial interventions. That schizophrenia is a brain disorder is speculation, but one that biological psychiatry and the drug companies have turned into a battle cry on behalf of their authority, power, and economic success.
The NIMH (2007) [975] booklet admitted that psychosocial interventions can help, but with a caveat: "Numerous studies have found that psychosocial treatments can help patients who are already stabilized on antipsychotic medication deal with certain aspects of schizophrenia." Given that NIMH estimates that 1% of the population suffers from this disorder, that is an enormous number of people who allegedly cannot live without psychiatric drugs.
In deference to drug company interests, NIMH makes no mention of the World Health Organization studies showing that patients diagnosed with schizophrenia actually do better in Third World countries, where they receive little or no drugs and are supported by an extended family (de Girolamo, 1996 [338]), as well as the many studies of psychosocial approaches to deeply disturbed persons cited in chapter 16.
Somewhat to its credit, NIMH (2007) [975] does not claim that schizophrenia is a proven genetically determined disorder. The following may come as a surprise to readers who are convinced that schizophrenia, above all other psychiatric disorders, is known to be genetic:
"Several of these genes are thought to be associated with an increased risk of schizophrenia, but scientists currently believe that each gene has a very small effect and is not responsible for causing the disease by itself."
Then, to save the day, the government booklet (NIMH, 2007 [975]) added, "Although there is a genetic risk for schizophrenia, genes alone are not likely to be sufficient to cause the disorder. Interactions between genes and the environment are thought to be necessary for schizophrenia to develop." The careful reader may be able to discern that all of this is speculation, laced with hope for the discovery of some kind of genetic component. In fact, decades of research have failed to reveal a genetic component, while instead confirming an environmental one (see Breggin, 1991b [189]; see also Joseph, 1999 [703], 2004a&b [704] & [705], 2006 [706], and the discussion in chapter 1).
Meanwhile, recent research indicates that "childhood abuse is a causal factor for psychosis and 'schizophrenia' and, more specifically, for hallucinations, particularly voices commenting and command hallucinaioos" (Read et al., 2005 [1075]). But even more to the point is a simple summary from Medical News Today ("Schizophrenia," 2005 [1133]), paraphrasing the conclusions of Richard Bental, Professor in Experimental Clinical Psychology at the University of Manchester:
"Schizophrenia has been attributed to everything from genetic predisposition, brain chemistry, sufferers' home environment and even catborne viruses, but no consistent causal pattern has ever been identified. As a result, treatment outcomes for today's patients are not very different from those of patients treated 100 years ago."
No such honest skepticism in our government agencies. Both the FDA and NIMH are now agents of the psychopharmaceutical complex. They do virtually everything in their power to promote biologically oriented psychiatry and the products of the psychopharmaceutical industry.