To Phil and Jean Ross,
Our Loving Parents
Acknowledgments
Our assistant, Melissa Magruder, has been indispensable in copyediting and maintaining and retrieving the complex materials required for the completion of this book and in handling innumerable daily activities around the office. She has made this project run smoothly. Chad Alden joined us as an intern at precisely the moment we needed research assistance and we appreciate his generous help.
We are grateful to our friends who read portions of the manuscript, especially Kevin McCready and David Cohen, who reviewed it cover to cover, and offered many valuable suggestions. Helpful comments were made by Robert Grimm on neurological aspects and David Whitford on statistical issues. We also thank Paul Sleven for his untiring, admirable legal vetting. We, of course, remain wholly and exclusively responsible for the final product.
We wish to thank the more than one hundred members of the Board of Directors and the Advisory Council of the Center for the Study of Psychiatry. Founded more than twenty years ago by Peter Breggin, this network of medical and mental health professionals, attorneys, patient advocates, and members of Congress continues to provide enormous moral and professional support. More than two dozen board and advisory council members are psychiatrists, and another dozen are drawn from other medical specialties, including internal medicine, neurology, and pediatrics. We especially wish to acknowledge John George and Michael Valentine, co-directors of the Center’s new membership division, Children First!
We are grateful for the mutual support we have shared with groups and individuals who identify themselves as survivors of psychiatry and psychiatric drugs. In areas related to this book, we have worked particularly closely with Guy McConnell, national director of the Prozac Survivors Support Group, Inc., and state directors Bonnie Leitsch (Kentucky), Ann Tracy (Utah), and Dwight Harlor III (Ohio).
This is the third book of ours published by St. Martin’s Press, the first two being Toxic Psychiatry (1991) and Beyond Conflict (1992) by Peter Breggin. It will be followed by a fourth, The War Against Children (fall 1994), coauthored by Peter and Ginger Breggin. Barbara Anderson is the very competent, congenial editor of this book and we look forward to a long relationship with her.
Our agent, Richard Curtis, supported us from the beginning when it was as yet difficult to get published. Richard, thanks for your continued help!
This book is co-created, but Peter Breggin did the actual writing, and he alone is responsible for any observations or opinions on medicine, psychiatry, the FDA, psychiatric drugs, and pharmaceutical company practices. Ginger Breggin provided important concepts and directions, edited the entire manuscript several times, and organized and supervised the vast amount of activity required to develop the research and background material, to maintain the files, and to work with resource persons.
The awkward problem of how to refer to the authors in the text has been resolved by using “I” to refer to Peter Breggin, since it is to his activities as a physician and psychiatrist that the text most frequently refers. The word “we” will be used to designate both authors. Ginger Breggin will be referred to by name when describing her specific activities.
Acronyms of Organizations
AAAS —American Association for the Advancement of Science
ADAMHA —Alcohol, Drug Abuse, and Mental Health Administration (now absorbed into NIH)
AMA—American Medical Association
APA—American Psychiatric Association or American Psychological Association
CH.A.D.D.—Children with Attention-Deficit Disorders
DHHS—Department of Health and Human Services (includes the FDA, the NIH, and the CDC)
FAES—Foundation for Advanced Education in the Sciences
FDA—Food and Drug Administration
GAO-U.S. General Accounting Office
HHS-same as DHHS
NAMI—National Alliance for the Mentally 111
NAS—National Academy of Sciences (also see NRC)
NIH—National Institutes of Health
NIAA—National Institute of Alcoholism and Alcohol Abuse (formerly part of ADAMHA; now part of the NIH)
NIDA —National Institute of Drug Abuse (formerly part of ADAMHA; now part of the NIH)
NIMH —National Institute of Mental Health (formerly part of ADAMHA; now part of the NIH)
NRC—National Research Council (part of NAS)
NSF—National Science Foundation
PHS-U.S. Public Health Service
How to Use This Book
First, an important warning:
When trying to withdraw from many psychiatric drugs, patients can develop serious and even life-threatening emotional and physical reactions. In short, it is dangerous not only to start taking psychiatric drugs but also can be hazardous to stop taking them. Therefore, withdrawal from psychiatric drugs should be done under medical and clinical supervision.
Most books about psychiatric drugs provide the kind of information that drug advocates and pharmaceutical companies want the public to have. At best, they offer a watered-down version of information that is at the fingertips of most physicians and other professionals.
This book is different. It provides information not readily available, even to most experts in the field. Much of it, in fact, has been systematically withheld from physicians and patients alike. Nonetheless, this book cannot be used as a treatment handbook. We suggest instead that you share it with your personal physician or mental health professional. Almost certainly, he or she will be unfamiliar with some if not much of what it contains.
We have provided an extensive bibliography that lists every author, article, or project mentioned in the book. If the reference cannot be located easily by the name of the author, the numbered chapter note will help you find the source in the bibliography. The appendix to the book contains information on psychiatric reform organizations, self-help support groups, therapy resources, legal resources, and standard sources of drug information.
In most cases we have provided identifying information about the professionals whose work we cite in the book. Psychiatrists are physicians; they have medical degrees. As medical doctors, they have the right to prescribe medications. Some psychiatrists are also trained in psychotherapy or “talking therapy,” but many of them lack these skills. While psychiatrists take leadership roles in promoting psychiatric drugs, many family physicians and other medical specialists also prescribe these medications. Psychologists are trained in a variety of disciplines, including research, psychological testing, and psychotherapy. They have Ph.D., rather than M.D., degrees and cannot prescribe medications.
Many biologically oriented psychiatrists argue that medication is the best or only approach to the problems they diagnose and treat, but there is a great diversity of opinion about this in the field of mental health and within the public. While some psychologists are lobbying for the right to prescribe medication, they have not as yet obtained this dubious power. Like many mental health professionals, however, some psychologists support the pharmacological approach that we criticize, while many others do not. In seeking help from mental health professionals—including psychiatrists, psychologists, clinical social workers, counselors, and family therapists—it is best to inquire in advance about their views on psychiatric drugs.
Introduction:1
Science and the FDA Have Confirmed the Findings of this Book;
Even the Drug Companies Have Uncovered No Errors
By Peter R. Breggin, M.D.
How good is the science in this book? How valid and convincing is it—even to the drug companies that I am criticizing?
I have now been a medical expert in dozens of product liability suits against pharmaceutical companies, including the manufacturers of drugs examined in this book: Prozac, Paxil and Zoloft. Most of the lawsuits have centered on the main issues in this book: antidepressant-induced violence, suicide and mania. In most of these cases, the plaintiffs or the plaintiffs’ families have hired me after individuals have committed suicide, perpetrated crimes, or otherwise ruined their lives while under the influence of an antidepressant.
Most of the antidepressant cases in which I have been an expert have been settled to the satisfaction of the people who brought the suit against the drug company. Sometimes the drug companies have given a million, or even many millions of dollars, to the plaintiffs—of course, always without admitting guilt. Except for one case that was settled for millions of dollars during the trial2, in no case has an antidepressant manufacturer chosen to go to court in a case in which I have been a medical expert. The reason, I believe, is that the science I have presented is solid and even incontrovertible. The drug companies don’t want the evidence coming out in open court and they don’t want to risk losing a high-profile case.
As a result of my work as a medical expert against the drug companies, teams of opposing lawyers and opposing medical experts have scrutinized my medical opinions and this book in particular. This high-powered critical assault has been going on for years and it has turned up no errors in this book. None of the original book needs correction. It would be difficult to exaggerate how much financial investment and manpower the drug companies have devoted to examining Talking Back to Prozac without finding any scientific or factual errors.
In addition to its unsullied record as a scientific work, Talking Back to Prozac remains worthwhile reading as a demonstration that objective analyses—i.e., analyses done by a scientist independent of the Psychopharmaceutical Complex—can come to clear conclusions years ahead of the medical establishment with its ties to the drug companies.
Talking Back to Prozac continues to provide a model for how to go about examining the actual adverse effects and efficacy of psychiatric drugs, or the risk/benefit ratio. The rich detail in this book remains relevant and useful to a variety of researchers as well as to medical experts and attorneys involved in product liability litigation against pharmaceutical companies.
If you were to read this book by itself, you would know more about the risks of the newer antidepressants than most physicians. Ideally, you should also read my two most recent books, Brain-Disabling Treatments in Psychiatry, the Second Edition (2008) and Medication Madness: A Psychiatrist Exposes the Dangers of Mood Altering Drugs (2008).
This introduction is based on Chapter 6 of the second edition of Brain-Disabling Treatments in Psychiatry (2008) and examines the evolution of the drug labels for SSRI antidepressants including Prozac, Paxil and Zoloft. The evolution of the drug label allows an in-depth look at the FDA’s acknowledged hazards of the newer antidepressants. A more detailed analysis of the background scientific literature can be found in Chapter 7 of Brain-Disabling Treatments in Psychiatry (2008).
My most recent book, Medication Madness: A Psychiatrist Exposes the Dangers of Mood-Altering Drugs (2008), presents dozens of new cases of individuals driven to take out-of-character and sometimes horrendously destructive actions while under the influence of the newer antidepressants. It introduces the concept of medication spellbinding which helps to explain how people fail to appreciate the negative emotional and psychological effects of psychoactive agents while they are taking them; how they can feel better than ever when they are in reality doing worse than ever; and how they will sometimes commit harmful actions that they would never have perpetrated except for the spellbinding drug effect.
A Huge Market
In recent years, the market for antidepressants has become huge. In the United States in 2001, an estimated 24.5 million patient visits were made for depression, with 69% of these visits resulting in prescriptions for SSRIs (Fergusson et al., 2005; Stafford et al., 2001). In 2002, about 6% of all boys were taking antidepressants, and the number has continued to grow. By 2004, an estimated 1 in 10 women was taking one of the newer antidepressants (Vedantam, 2004).
The antidepressants generate gigantic revenues for the drug companies. In 2006, according to IMS Health (2007), antidepressants were the most prescribed among all classes of drugs, with a total of 227.3 million prescriptions in the United States. They were third in revenue, with a total of $13.5 billion. To give perspective to these figures, the widely prescribed lipid regulators like Lipitor were second as a class, with 203.0 million prescriptions, and first in revenue, at $21.6 billion.
Antidepressants have, however, been taking something of a licking from the Food and Drug Administration (FDA) and the media in the last few years, culminating in 2004–2005 with a black-box warning about antidepressant-induced suicidality in children and then in 2007 by another black-box warning about increased suicidality in young adults. But in reality, there was little impact on the prescription of these drugs. U.S. sales of antidepressants declined 1.4% in 2004 and 6% in 2005, followed by a 2% recovery in 2006, with industry determining that the black-box warnings were ultimately “unlikely to significantly threaten sales” (McManus, 2007). And as already mentioned, they are still number one when it comes to sales.
The FDA Begins to Catch Up with Talking Back to Prozac
In 2004 the FDA began issuing a series of label changes and public health warnings for the newer antidepressants that have confirmed the most important conclusions drawn ten years earlier in Talking Back to Prozac. The FDA now requires extensive warnings in the labels for antidepressants describing most of the problems first documented in detail in this book, including the increased risk of suicidality, and the over-stimulation or activation syndrome with irritability, aggression, hostility, mood instability, hypomania and mania. The FDA has also acknowledged that the drugs are ineffective in children and further research has confirmed that they lack efficacy in adults as well, once again confirming observations made years earlier in this book.
The FDA’s conclusions have been accompanied by an enormous amount of research that further confirms the conclusions made in Talking Back to Prozac. Thus, the scientific analyses in Talking Back to Prozac have held up under the test of time.
Warning Signs from the Beginning
Soon after the introduction of the first SSRI, fluoxetine (Prozac), into the United States marketplace in January 1988, published reports began describing fluoxetine-induced violence against self and others.
In 1990, Teicher et al. published their classic article “Emergence of Intense Suicidal Preoccupations During Fluoxetine Treatment” in the American Journal of Psychiatry, describing five patients who developed akathisia and became obsessively suicidal on Prozac, who felt relief when the medication was stopped, and then a resumption of their agitation when it was resumed. In May 1990, the FDA required the manufacturer of Prozac, Eli Lilly and Company, to add suicidal ideation and violent behaviors to the Post-introduction Reports section of its label. The section that listed violence and suicide as possible adverse drug reactions began with a caveat that the reported reactions “may have no causal relationship with the drug.”
On August 11, 1990, an editorial in The Lancet (“5-HT Blockers,” 1990) included “the promotion of suicidal thoughts and behaviour” (p. 346) among the adverse effects of fluoxetine. The journal was ahead of its time in its cautions:
Fluoxetine represents US know-how at its best and has been aired in the media at a time when biological psychiatry has become supreme in North America. However, we do not know whether the drug is better than earlier antidepressants, whether 5-HT is the main neurotransmitter in depression, and whether the 5-HT uptake blockers have acceptable side effects.
The following year, the British National Formulary, a joint publication of the British Medical Association and Royal Pharmaceutical Society of Great Britain (1991), listed suicidal ideation and violent behavior as fluoxetine side effects. Also in 1991, I published Toxic Psychiatry, in which I observed for the first time that Prozac was producing a continuum of overstimulation that included akathisia, agitation, anxiety, insomnia, depression and mania, and, in the extreme, suicide and violence. I drew on previously sequestered FDA premarketing data on Prozac, the scientific literature, and my own clinical and forensic cases.
Subsequently, many books and reports have dealt with the subject of SSRI-induced violence and suicide (e.g., Breggin, 1992b, 1997, 2001a; Breggin et al., 1994a; Glenmullen, 2000; Healy, 2000; Teicher et al., 1993).
The Class of SSRIs
These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft.
A number of other antidepressants share most of the risks associated with the SSRIs, including suicidality, aggression, and over-stimulation with mania. One group includes the nonselective serotonin reuptake inhibitors (NSRIs) such as venlafaxine (Effexor) and the tricyclic clomipramine (Anafranil). Buproprion (Wellbutrin, Zyban) is a very stimulating drug. Duloxetine (Cymbalta) also shares many characteristics with SSRIs. Nefazodone (Serzone) was not as stimulating, and it has been withdrawn from the market due to liver damage.
When observations are made in clinical practice and in the scientific literature concerning the impact of SSRIs, they are typically treated as a single category or class of pharmacological agents. It is generally recognized that an adverse mental or behavioral reaction, such as agitation or mania, that is observed in regard to one SSRI is likely to be found with all the other SSRIs. When I initially testified about this reality in deposition and trial as a medical expert, drug company lawyers ridiculed my position, claiming that I could not use data about one SSRI to draw conclusions about other SSRIs. Then, in 2004–2007, the FDA began issuing required class warnings on adverse psychiatric reactions such as suicidality, hostility, irritability, and mania that are identical for the entire class of SSRIs.
FDA Confirms Antidepressant-Induced Suicidality in Children
On February 2, 2004, the FDA held an open meeting of the joint Psychopharmacological Drugs Advisory Committee and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee to hear public testimony and explore the risk of suicidality associated with antidepressants in children. During September 13–14, 2004, the FDA met again to present a reevaluation of data on 4,582 pediatric patients from 24 antidepressant controlled clinical trials of 4–16 weeks in duration. With one exception, the studies were drawn from 23 industry-sponsored trials. The exception was one National Institute of Mental Health (NIMH) study, the Treatment for Adolescents With Depression Study (TADS), a 12-week trial involving 439 children age 12–17, comparing Prozac alone, cognitive therapy alone, combined therapy, and placebo (March et al., 2004). Thus industry-sponsored studies dominated the data.
Despite the handicap that the studies were largely developed and conducted with the aim of proving the value of industry products, a meta-analysis of the combined data indicated that antidepressants in children and youth increase the suicide attempt rate and that an estimated 1% to 3% of patients would be at risk of antidepressant-induced suicidality (Hammad et al., 2006). On October 15, 2004, the FDA mandated a black-box warning, and in early 2005, it was finalized (FDA, 2005a). According to FDA requirements for describing adverse drug reactions, a risk of 1% or more is considered common.
Easy to Show Serious Harmful Effects;
Hard to Show Effectiveness
We will find that the psychiatric establishment continues to minimize the FDA findings. Even the FDA recently described the finding as “modest” (see subsequent discussion). Thomas Insel, director of NIMH, weighed in on the side of drugs, describing them as “medications of known benefit and of questionable risks” (Vedantam, 2005), when the scientific research actually shows them to be medications of no benefit and grave risk.
The New England Journal of Medicine asked one of the panel members of the FDA Psychopharmacological Drug Advisory Committee, physician and epidemiologist Thomas B. Newman (2004), to comment on the results of the studies conducted in the controlled clinical trials to determine the risk of suicidality. He wrote,
The results were striking. When all the pediatric trials were pooled, the rate of definite or possible suicidality among children assigned to receive antidepressants was twice that in the placebo group. (The summary risk ratio was 2.19; 95 percent confidence interval.) Although the FDA staff did not provide this information to the committee, according to my own calculations, such a dramatic result could be expected to occur by chance only 1 time in 20,000 (p = 0.00005)…. The fact that an association emerged from a meta-analysis with a P value of 0.00005, for an outcome that the sponsors of the trials were not looking for, and presumably did not wish to find, was quite convincing.
Notice that the FDA itself failed to provide the p value that made the result so stunning! The panel member had to calculate it for himself.
Newman (2004) also made the point that the FDA found that only 3 of the 15 available controlled clinical trials showed efficacy for antidepressants in treating depressed children. He said that several FDA committee members spoke in favor of the antidepressants, citing either their own experience or the TADS conducted by NIMH; “however, others and I found the evidence of efficacy much less convincing than the evidence of harm.” According to Newman,
In reviewing TADS we were struck by the small size of the difference between fluoxetine and placebo as compared with the effect of placebo alone…. It is easy to see why the personal experience of clinicians and patients would lead them to believe the drug to be effective, since they would have no way of knowing that more than 85% of the benefit they observed would have also occurred with placebo.Randomized trials other than TADS have had less favorable results. The FDA indicated that only 3 of 15 trials of antidepressant use in children with depression had found a statistically significant benefit. The agency also provided us with a meta-analysis that showed that the estimated efficacy of antidepressants in children was minimal and likely to have been overestimated, because published studies have much more favorable results than unpublished studies. Thus, both clinical experience and published trials are likely to lead to inflated estimates of the efficacy of these drugs.
The critique provided by the FDA was by Whittington et al. (2004) (see chapter 7 in Peter Breggin, Brain-Disabling Treatments in Psychiatry, 2008).
Newman (2004) also found many unanswered questions: “The FDA’s meta-analysis suggested that the new antidepressants double the risk of suicidality, about 2.5 percent to 5 percent, in trials lasting two or three months. But what happens if you take them for a year?”
Epidemiologist Newman’s (2004) comments summarize the essential problem of psychiatric drugs in general: easy to show their serious adverse effects; difficult to show their effectiveness.
Recent FDA Admissions and Findings
Thus, in 2004, the FDA began to catch up with observations I had begun making in 1991 in Toxic Psychiatry and more elaborately documented in the 1997 edition of this book, concerning the risks of antidepressant-induced suicide, at least in children, and later, the FDA would also affirm the risk in adults, at least young ones. However, in some ways more important, and almost entirely ignored in the press and the medical community, the FDA also confirmed my major critique of the newer antidepressants: that they produce a stimulant-like syndrome or activation that causes a whole array of disorders, from agitation, anger, and hostility to outright mania.
Following public hearings in early 2004, the FDA issued a press release for a Public Health Advisory in regard to children and adults, in which it stated, “The agency is also advising that these patients be observed for certain behaviors that are known to be associated with these drugs, such as, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia (severe restlessness), hypomania, and mania.”
The FDA’s description and its final label changes closely parallel what I had been saying for more than a decade and mimicked language from my 2003 report “Suicide, Violence and Mania Caused by Selective Serotonin Reuptake Inhibitors,” in which I concluded, “Mania with psychosis is the extreme end of a stimulant continuum that often begins with lesser degrees of insomnia, nervousness, anxiety, hyperactivity and irritability and then progresses toward more severe agitation, aggression, and varying degrees of mania.” In that report, I also discussed akathisia and described the antidepressant-induced stimulant syndrome, including “hypomania/mania, insomnia, nervousness, anxiety, agitation, central nervous system stimulation, emotional lability … as well as paranoid reaction, psychosis, hostility, and euphoria.”
The Final Class Label on Suicidality in Children and Adolescents
The FDA published its final version of the class label for all antidepressants on January 26, 2005. The FDA applied the new label changes to all 34 antidepressants on the market, including older, more sedating antidepressants such as amoxapine (Asendin), trazodone (Desyrel), amitriptyline (Elavil), doxepin (Sinequan), and imipramine (Tofranil). The last-minute inclusion of the older antidepressants was an act of deference to the manufacturers of the newer antidepressants, in effect tarring all antidepressants with a brush meant only for the newer ones.
However, the agency’s conclusions were based on a limited number of new antidepressants, including bupropion, citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, escitalopram, and venlafaxine, according to an FDA Talk Paper (2004a). These were the drugs most often cited by the public at the two FDA hearings.
Although the labels are currently being updated by the FDA to include a warning about antidepressant-induced suicidality in young adults, every antidepressant label until recently had a black-box warning at the top titled “Suicidality in Children and Adolescents” that begins with the following statement:
Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders.
This statement was already a compromise between the FDA’s original proposal and drug company feedback. The FDA’s original, stronger draft read, “A causal role for antidepressants in inducing suicidality has been established in pediatric patients” (Lenzer, 2005). The draft statement went beyond the clinical trials themselves to say that suicidality had been established in general. It also used the dread phrase causal role. In every case in which I have testified against the drug companies in deposition, the defendant companies have tried to dismiss any scientific conclusions about drugs inducing suicidality, unless the conclusion used the term causal. In reality, scientific articles and FDA-approved labels rarely use the concept of causation, giving much relief to the drug companies, who can then claim, however falsely, that causality has not been established.
Meanwhile, referring to the decision made by the FDA Psychopharmacological Drugs Advisory Committee, even staunch advocates of antidepressants have to admit that “the committee concluded that a causal link exists between antidepressant treatment and pediatric suicidality and advised that policies be implemented” (Pfeffer, 2007).
The Stimulant Syndrome
Beneath the black box, a headline reads “WARNINGS—Clinical Worsening and Suicide Risk.” Without identifying it as such, this section contains a warning about the stimulant or activation syndrome that I first described in Toxic Psychiatry in 1991:
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric.
Note the specific references to “irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania,” a virtual prescription for violence. This new addition to the label, the implications of which having been largely overlooked, refers to children and adults. By indicating that nonpsychiatric patients can develop these reactions, the FDA class label challenges the commonly held belief that only patients with a bipolar history or vulnerability are at risk for developing antidepressant overstimulation.
The new label addresses information that should be given to patients who take the newer antidepressants and their caregivers:
Clinical Worsening and Suicide Risk: Patients, their families and caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, and other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
Most of the symptoms described in my previous publications and by the FDA in its new label are the result of activation or stimulation, a syndrome similar to that caused by stimulants such as amphetamine, methamphetamine, and methylphenidate, especially in high doses. Compared to antidepressant-induced suicidality, activation is bolstered by a much larger scientific literature and poses a far more common, and often disastrous, level of risk (see subsequent discussion).
Activation should be at the top of the differential diagnosis list when a patient’s condition deteriorates while taking antidepressants. If the physician misidentifies drug-induced activation as caused by the patient’s original psychiatric disorder, the doctor is likely to continue, or even increase, the antidepressant dose, ultimately causing mania and psychosis.
The New FDA Medication Guide
Simultaneously with the new warnings, the FDA required physicians to provide the families of children receiving antidepressants with a sheet of information titled “Medication Guide: About Using Antidepressants in Children and Teenagers” (Food and Drug Administration, 2005e). The label is currently being updated by the FDA to include young adults but otherwise remains largely unchanged.
In a section titled “You Should Watch for Certain Signs If Your Child Is Taking an Antidepressant,” the information sheet states, “Contact your child’s healthcare provider right away if your child exhibits any of the following signs for the first time, or if they seem worse, worry you, your children, or your child’s teacher.” It lists the following danger signs:
Thoughts about suicide or dying
Attempts to commit suicide
New or worse depression
New or worse anxiety
Feeling very agitated or restless
Panic attacks
Difficulty sleeping (insomnia)
New or worse irritability
Acting aggressive, being angry, or violent
Acting on dangerous impulses
An extreme increase in activity and talking
Other unusual changes in behavior or mood
Recently, the FDA has expanded the target group for these warnings to include adults.
Except for suicidality, the medication guide does not specifically state that there is a causal link between this list of reactions and the medications but clearly implies that these reactions are associated with taking medication. Each symptom is consistent with the activation or stimulation syndrome. The inclusion of anger, aggression, and violence shows the FDA’s well-justified concern about antidepressants posing a serious danger to others.
The FDA’s Final Word on Antidepressant-Induced Suicidality in Children
In March 2006, Hammad et al. from the FDA Division of Neuropharmacological Drug Products Center for Drug Evaluation and Research published a summary of the agency’s methods and findings. Their conclusion minimized the importance of their findings: “Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.”
Compare this conclusion of a “modestly increased risk of suicidality” to the previously mentioned observations of the epidemiologist on the FDA’s Psychopharmacological Drugs Advisory Committee, Thomas Newman (2004), who said, “The results were striking…. The fact that an association emerged from a meta-analysis with a P value of 0.00005, for an outcome that the sponsors of the trials were not looking for, and presumably did not wish to find, was quite convincing.”
In reality, since the short-term, company-run clinical trials were wholly unsuited to detecting suicidality, the risk had to be much more than “modest” to show up at all. In addition, Hammad et al. (2006) admitted to a fact that I had been insisting on for years in publications and testimony: that the drug company’s premier measure of suicidality, typically the Hamilton Depression (Ham-D) Scale, is useless in that regard. The investigator asks the subject questions from the scale, only one of which is related to suicidality. Obviously, the answers will depend on how seriously the question is asked, and rote questions are likely to elicit rote answers. The inventor of the Ham-D Scale did not himself believe that it could be used as a scientific tool in the manner that the drug companies have utilized it (Hamilton, 1960).
Why There Are No Completed Suicides in the Controlled Clinical Trials
The FDA report also mentioned that no completed suicides were recorded among all the trial subjects. The agency failed to emphasize that no suicides occurred on placebo either. Leaving depressed children drug-free did not produce a single suicide. This wholly contradicts the tendency to give drugs to prevent suicides.
The drug companies, and their promoters at the American Psychiatric Association (APA), have tried to emphasize that the clinical trials evaluated by the FDA produced “suicidality” but no actual suicides (Lenzer, 2005). Although I have never seen this point made before, it is important to realize that in general, depressed people do not commit suicide during clinical trials. Depression is essentially a loss of hope. During clinical trials, the participants are given hope that a new medication may finally relieve their suffering, they are given professional attention on at least a weekly basis, and they are monitored for any deterioration in their condition. Thus clinical trials provide the essential elements of any good therapy for depression: hope, professional attention, and close monitoring. No wonder placebo turns out to be as good as the drug; participating in the trial is itself therapeutic, at least during its brief duration.
In addition, actively suicidal patients are excluded from clinical trials. They are the most vulnerable and therefore the ones that the drugs are most likely to push into committing suicide.
The FDA authors concluded their report with an acknowledgment to “the drug companies that supplied the data needed for this work.” At no point do they respond to the massive evidence that some drug companies, including the manufacturers of Prozac and Paxil, purposely provide junk data calculated to mislead, and especially to minimize, the risks associated with their drugs.
Canadian and British Regulatory Agency Warnings
On June 3, 2004, before the FDA issued its formal label changes concerning children, Health Canada (2004)—the Canadian drug regulatory agency—issued “stronger warnings” for SSRIs and other newer antidepressants that were more encompassing than the U.S. version: “These new warnings indicate that patients of all ages taking these drugs may experience behavioural and/or emotional changes that may put them at increased risk of self-harm or harm to others.” In dramatic contrast to the FDA, Health Canada applied the warning to children and adults in regard to suicidality, and it further warned about harm to self and to others (violence):
Patients, their families and caregivers should note that a small number of patients taking drugs of this type may feel worse instead of better, particularly within the first few weeks of treatment or when doses are adjusted. For example, they may experience unusual feelings of agitation, hostility or anxiety, or have impulsive or disturbing thoughts that could involve self-harm or harm to others (emphasis added).
This is consistent with my testimony and publications, beginning with Toxic Psychiatry in 1991, in which I warned about both suicide and violence caused by SSRIs and with my book Medication Madness (2008), which presents dozens of case histories illustrating harm to self and to others induced by the SSRIs. The FDA continues to lag behind, however, mentioning hostility and aggression in the new labels as problems associated with SSRIs but without giving these dire outcomes sufficient emphasis.
In Great Britain, all SSRI antidepressants, except fluoxetine, have been banned for use in treating depression in children. The main concern surrounded suicidality that was increased with SSRIs in general, including fluoxetine.
Expanding the Suicide Warning to Young Adults
I warned the public and the health professions about the risk of SSRI antidepressant-induced suicidality in adults in Toxic Psychiatry (1991) and again in 1997 with a lengthy discussion in the first edition of this book. I elaborate in much greater detail on risk in 2003 in my scientific journal article “Suicidality, Violence and Mania Caused by Selective Serotonin Reuptake Inhibitors (SSRIs): A Review and Analysis.”
In the meantime, in 2001, Houston, Texas, attorney Andy Vickery won a product liability suit against GlaxoSmithKline in a Paxil murder—suicide suit (Tobin v. SmithKline Beecham, 2001). Donald Schell, age 60, had taken two doses of Paxil before shooting his wife, their daughter, and his granddaughter to death. The jury awarded $6.4 million to two surviving family members (Josefson, 2001).
In fighting the case, GlaxoSmithKline claimed that there was no substantial evidence connecting Paxil to suicide. After reviewing evidence presented by both sides, the judge found that there was sufficient scientific evidence for Paxil-induced suicide to proceed with the case. Under intense pressure from the FDA to reevaluate its existing data, it would take the drug company 5 more years to come around to the same conclusion. Growing concern about antidepressant-induced suicidality led the FDA to require the drug companies to revaluate their earlier controlled clinical trials based on FDA standards for categorizing and reanalyzing data. In May GlaxoSmithKline (2006b) published a “Dear Healthcare Provider” announcement concerning Paxil-induced suicidality in depressed adults. The letter emphasized the supposedly slight increase in suicidality among young adults (through age 30) who take Paxil for a variety of conditions, including depression, panic attacks, anxiety, and obsessive—compulsive disorder.
Far more important was the drug company’s description of a statistically significant increase in suicidality in all ages of adults in the controlled clinical trials for major depression. Depressed patients receiving Paxil were 6.4 times more likely to display suicidal thoughts and behavior than depressed patients taking a sugar pill. In regard to suicide—the most devastating risk associated with antidepressants—it is safer for depressed persons to stay off Paxil.
The FDA allowed the Paxil manufacturer to soft-pedal the findings by claiming, for example, that the results could be compounded by the fact that suicide is an aspect of “psychiatric illnesses.” This is nonsense— and every scientist knows it. Since both groups were depressed, and since they differed only in the substances they were given to take in the blinded trials, Paxil, and not depression, was the cause of this astronomical increase in the rate of suicidality.
If depression had caused the increased suicidality, then the placebo patients—who lacked the supposed benefit of an antidepressant effect—would have suffered a much higher rate of suicidality than the Paxil patients. Instead, they had a much lower rate. In other words, because the antidepressants were supposed to be helping the depressed patients, the relative ineffectiveness of the sugar pill should have led to more suicidality than the drug, not less. The FDA, the drug company, and the media ignored this important fact. Conventional assumptions would have predicted increased suicidality on placebo, instead of increased suicidality on Paxil. It is a complete reversal of the expected outcome, underscoring the seriousness of finding increased suicidality in patients on the drug.
Finally, in December 2006, the FDA held hearings concerning the potential addition of an adult suicide warning to all antidepressant labels. The data generated in older controlled clinical trials indicated that not only children but also young adults to age 24 were developing increased suicidal thoughts and actions when taking the newer antidepressants. The FDA’s panel ended up recommending a black-box warning about increased suicidality in the 18-to-24-year-old age group. The FDA’s committee was rife with conflicts of interest (Pringle, 2007).
Note that this conclusion concerning antidepressants in general ignored the Paxil data published in May 2006 by GlaxoSmithKline indicating an increase in suicidality in all ages for adults suffering from Major Depressive Disorder.
In May 2007, the FDA gave published notice of its intention to add a warning about increased suicidality aimed at “young adults” taking antidepressants. The FDA’s new warnings required at the top of each antidepressant label are contained in a black box with the title “Suicidality and Antidepressant Drugs.” The warning begins, “Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders” (GlaxoSmithKline, 2007).
The FDA Helps Out the Drug Companies
The FDA’s parsing of the suicidality warning into various age brackets meets drug company needs to obscure the basic reality that antidepressants cause suicide in children and adults. I don’t know of another example in which a signal for a serious effect like suicidality has been divided up by age brackets, including some and excluding others. The distinctions are too fine to be made on the basis of controlled clinical trials that, at best, can provide a gross signal of a problem.
Once again, to dilute its impact on market for the newer antidepressants, the warning will be required for every drug approved for the treatment of depression, when in fact the data were generated entirely from clinical trials using the newer and more stimulating antidepressants. Because every antidepressant will carry the new warning, many doctors will be misled into believing that the older antidepressants have a similar risk to the newer ones. These doctors will conclude that there are no safer choices than the big moneymakers like Prozac, Paxil, Zoloft, Celexa, and Effexor.
The FDA not only limited its suicidality warnings to children, adolescents and young adults in the new warning but also declared that there was no increase in antidepressant-induced suicidality in adults beyond age 24 and, furthermore, that “there was a reduction in risk with antidepressants compared to placebo in adults age 65 and older” (GlaxoSmithKline, 2007). The FDA is inviting doctors to believe, based on a small number of elderly patients in short-term clinical trials, that antidepressants might even reduce the suicide rate among older patients.
When insensitive clinical trials signal a suicide risk in both children and younger adults, it is time to admit flat out that antidepressants cause suicidality in all age groups. Besides, the numbers of patients 65 and older who were tested was very small.
Meanwhile, there is scientific data contradicting the FDA’s suggestion that antidepressants might protect older adults against suicidality. A study published a few months before the FDA hearings evaluated coroners’ records, prescription data, physician billing claims, and hospitalization data for more than 1.2 million Ontario residents age 66 and older from 1992 to 2000 (Juurlink et al., 2006). After evaluating more than 1,000 deaths by suicide, they found that “SSRI antidepressants were associated with a nearly five-fold higher risk of completed suicide than other antidepressants” (p. 813). This makes the FDA even more unscrupulous in acting as if antidepressants are safer in the older population.
As already mentioned, the FDA’s new warning is actually weaker than the “Dear Healthcare Provider” letter sent out by GlaxoSmithKline earlier in May 2006. The Paxil trials as disclosed in the letter showed an increased rate of suicidality in all ages of adults with major depressive disorder.
Paxil Is the Most Dangerous for Adults
The FDA’s own analysis of all the adult controlled clinical trials found that Paxil was the most dangerous in regard to causing suicide attempts (Stone and Jones, 2006, p. 26). With the exception of Paxil, the individual antidepressants did not show a statistically significant increase in adult suicidality. The significant result came only after the data were pooled for all antidepressants. But in regard to Paxil, in adults of all ages and in all psychiatric disorders, there was a statistically significant increase in suicidality (OR 2.76, 95% CI 1.16-6.60, p = 0.02).
Paxil stood out from the pack in terms of dangerousness despite GlaxoSmithKline’s efforts over many years to hide cases of Paxil-induced suicidality, to misidentify suicide attempts as emotional lability in their computerized coding system, and to manipulate the suicidality data to make it seem less menacing (chapter 14; Breggin 2006a—c). Despite the company’s efforts to thwart the truth, even in short-term controlled clinical trials that were skewed to avoid demonstrating Paxil-induced suicidality, there was a statistically significant increased rate of suicidality in patients taking the drug compared to patients taking the placebo in all ages and all diagnostic categories.
The Real-Life Risk Is Much Greater Than Described
Keep in mind that controlled clinical trials are planned by the drug companies, supervised by the drug companies, and carried out by paid doctors known to cooperate with the drug companies. Keep in mind that all the data analysis is done at drug company headquarters by drug company executives. Independent scientists play no role anywhere along the process. Keep in mind that the trials are constructed to prove the usefulness of the drug and to minimize adverse effects such as suicidality. Keep in mind that the controlled clinical trials are very short, usually 4–6 weeks long, and that prescreening excludes suicidal and psychotic patients from participating in the studies. Given these caveats, it is surprising that the suicidal signal was so strong that it could shine in the context of these trials.