「うつが病気であるという神話─薬物治療の限界と代替策」1-3

Pocket

Allan M. Leventhal and Christopher R. Martell, The Myth of Depression as Disease: Limitations and Alternatives to Drug Treatment (Praeger Publishers, 2005)読了。

The Myth of Depression

著者の2人はともに心理学者です。Allan M. LeventhalはAmerican Universityの名誉教授(2004年に退任)、Christopher R. Martellはシアトル在住のうつ研究の心理学者。まえがきを寄稿しているMarsha M. Linehan教授(University of Washington)は自らが境界性パーソナリティー障害であった非常に著名な心理学者です。弁証法的行動療法(dialectical behavior therapy)は彼女が開発した認知行動療法です。New York Timesが連載特集でひどい精神病を克服した人たちをとりあげていますが、最初に登場したのがリネハンです(写真右側)。Expert on Mental Illness Reveals Her Own Fight (June 23, 2011)

linehan

本書の章立ては以下の通り。
1. Societal Views of Mental Disorder
2. Welcome to the Brave New World
3. The Context of Depression and Anxiety
4. Psychology as a Science
5. Behavior Therapy
6. Behavioral Analysis, Behavior Therapy, and Outcome Research
7. Summary and Conclusions

本書のメインポイントは2つあります。1つ目はうつが脳の問題を起因とする「病気」であるというのは間違いであるという事。2つ目は「病気」ではないので薬物治療は害があるだけであり、うつには認知行動療法(cognitive behavior therapy, CBT)が効果的であることを示していること。今回は1つ目を取り上げます。

第1章で1980年頃までの臨床心理学と精神病治療を概観し、第2章で製薬会社がいかにしてうつ病を抗うつ剤で治せる「病気」であるという認識を構築化したかを探ります。これがタイトルにもなっている「うつが病気であるという神話」です。第3章ではうつ病の主原因が「回避行動」(avoidance behavior)にあることを示し、「科学としての心理学」というタイトルの第4章に続き、第5章では行動療法について詳しく説明します。そして第6章で「負の強化」(negative reinforcement)について詳しく分析した後、様々な行動療法を紹介します。
本書が意義深いのは、抗うつ剤の危険性を指摘するだけでなく、薬を使わない代替治療の有効性を示していることです。
If you have been feeling depressed, are worried about yourself and thinking of going to see a doctor for help, this book has been written for you. The chances are that you think there is something wrong with you and that you should be taking a pill to feel better. After all, that is what you are told in ads on television and probably have read about in many magazines and newspaper articles.
This book is aimed at informing you about what is wrong with that idea. We want you to know what alternatives you have.  (p. xiii)

People have a choice in the matter of how to help themselves. Too little is said in the popular press about non-pharmaceutical choices for dealing with depression and anxiety. Certainly, CBT and other approaches have not been shown to be a fast fix, but they have demonstrated efficacy and endurance over time. Medication, on the other hand, while bringing about rapid improvement in some cases, does not produce enduring effects when the medication is discontinued and can be associated with negative side effects. Learning stays with us, and behavior therapies, based on learning principles, are designed to endure over time and in multiple situations. We believe that to be the outcome of choice. (p.133)

Kadison, R., & DiGeronimo, T. F. (2004). College of the overwhelmed: The campus mental health crisis and what to do about it. San Francisco: Jossey-Bass.
によれば、
2万9千人以上の大学生を調査したところ、7%の男子学生と14%の女子学生がうつであると病院で診断され、その内の28%の男子学生と38%の女子学生が抗うつ剤(一番多いのがプロザック。[注]プロザックは世界で一番有名な抗うつ剤ですが日本では認可されていません)を飲んでいるそうです。(p.108)

病院でうつ病と診断され、抗うつ剤が処方される患者が急激に増え始めたのは1980年以降からです。なぜ、突然うつ病患者が増えたのでしょうか。脱工業化社会ではうつ病が蔓延するのか。それともうつ病を発見するのが容易になったのか。本書は、4段階のプロセスを経て、うつ病と診断される人が増え、抗うつ剤が大量に処方されるようになったと主張します。
(1) 医学の分野で人気がなくなっていた精神科の医師たちが心理的療法だけに頼るのをやめ、精神疾患は脳のバランスが壊れたから生じるという生化学的基盤に基づく論を展開することで失墜の回復を求めた。
(2) 製薬会社が巧妙なマーケティング戦略により、うつは向精神薬を飲めば治るという幻想を大衆に植え付け、大量の薬を売り、莫大な利益を得るようになった。
(3) 多くの医師や医療関係者が、うつは脳内の化学成分の欠陥から生じる病気であり、薬によって元に戻して治すことができるという考えを受け入れるようになった。
(4) 大衆やメディアもこの説明を受け入れるようになった。
The last 20 years have seen an enormous increase in the diagnosis and pharmacological treatment of depression. A recent survey showed that one out of three office visits by women includes prescription of an antidepressant drug. How should we explain this phenomenon? One possible explanation is that we are in the midst of an unprecedented epidemic of depression. Another is that we have suddenly become very good at detecting depression. Neither explanation has merit, and there is reason to be concerned that we don’t know what we are doing.
The answers to what is driving this are to be found in (l) adoption by the field of psychiatry of a belief in a biochemical basis for depression that has enabled psychiatry to recover from a state of alarming decline by the 1980s into becoming a robust medical specialty; (2) the highly sophisticated marketing by the pharmaceutical industry to doctors and the general public of psychotropic drugs that has led to enormous profits for the industry; (3) acceptance within the professional community by medical doctors (internists, family physicians, gynecologists) and most mental health practitioners (psychologists and social workers, as well as psychiatrists) of a biological explanation for depression as a disease that is the result of a defect in brain chemistry and as a disorder that can be fixed by a drug; and (4) a similar acceptance by the general public and the media of this explanation. (p.135)

まずは神経科学(neuroscience)の登場。人間の思考と行動は脳をコントロールすることで変えられるという考えが広まります。
One of the more exciting advances in recent years is the emergence of the neurosciences as a partner with the behavioral sciences in both developing new treatment paradigms and in researching the mechanisms of action among current effective treatments. In considering the wedding of neuroscience with behavioral science and its impact on mental health treatments, a number of factors must be remembered. First, all human action and reaction, including observable behaviors, emotional responses, thoughts, images, and sensations, are biological events. That is, there is nothing human (or animal of any kind) that is not biological. Nor is there any human activity that does not involve some sort of neural firing in the brain. With the advent of the newer and more powerful methodologies of the neurosciences emerging over the last several decades, the intimate relationship of neural firing of the brain with thought, emotion, and action became clear to both the scientific community and the public. The 1990s were called the decade of the brain. The promise was that with these new sciences, we would be able to control our actions, reactions, moods, and perhaps even our ultimate happiness and destiny by controlling our brains. No doubt it is true: if one can find a way to exert control over one’s own brain, one could control much if not all of one’s own actions and reactions. (pp.ix-x)

神経科学に基づくうつ治療はメディカルモデルに基づきます。脳内化学物質が不安定になる(例えば、セロトニンが不足する)と精神疾患が生じるという考えです。その対処法は不足した脳内物質を補うための薬物治療です。
More popular, currently, are biological explanations for mental disorder based upon the medical model. These theories hold that mental disorder is the result of an imbalance in brain chemistry; for example, an insufficiency of the neurotransmitter serotonin (a biogenic amine) is postulated to explain depression. Other neurotransmitters are cited to explain schizophrenia, eating disorders, alcoholism, violence, and shyness. Administering a chemical boost to the deficient neurotransmitter is the treatment of choice. (pp.6-7)

しかし、脳内化学物質の不足がうつ病を生じさせるという考えが「事実」であるといまだ証明されておらず、単なる「意見」にすぎません。
The main point to remember is that, although the study of biochemical processes in the brain as they relate to human behavior is interesting and will in all likelihood continue to increase our understanding of human functioning, the facts do not equal the claims made regarding depression (or other problems such as social anxiety, for example) resulting from a [chemical imbalance in the brain.] Labeling depression an illness or disease is more in the realm of opinion than fact. (p.7)

Many biological therapies have been discovered by accident. Sometimes an explanation or theory of the cause of the disorder follows. This is typified in the field of psychiatry, where so little is known about brain chemistry and where there is a strong desire to offer a biological explanation for mental disorder. The interested reader is referred to Valenstein (1998) for a comprehensive review and critique of the various drugs that were discovered accidentally in pursuit of treatments for other purposes that then were noticed to have properties that could be applied to explaining and treating mental disorders. (p.34)
注: Valenstein, E.S. (1998). Blaming the brain: The truth about drugs and mental health. New York: Free Press.

For example, in 1962, Stein speculated that depression may arise from a deficiency in the reward system in the brain since many people become depressed even when the environment [supplies a normal amount of rewarding stimulation] (Valenstein, 1998, p. 66). This starts as a testable theory from observation of depressed patients. However, because antidepressant medications seemed to have positive effects for some people, and because it was known that the neurotransmitter system (the chemicals that are emitted between nerves in the brain as a method of [communication]) had an effect on the experience of reward, it was then argued that depression was caused by an [imbalance] of the brain’s neurotransmitters. This hypothesis seemingly was supported by the finding that the neurotransmitters norepinephrine, serotonin, and dopamine are all decreased by the drug reserpine, which was used in the 1950s and 1960s to treat schizophrenia and anxiety. Because reserpine decreased these three neurotransmitters and caused sedation and lethargy in patients, it was hypothesized that depression was caused by low levels of these neurotransmitters. Some theorists believed norepinephrine was most closely associated with depression, while others thought serotonin was most important. However, it was later discovered that reserpine does not precipitate clinical depression, although it may exacerbate symptoms in those already predisposed to depression. Despite the popularity of the theory that depression is caused by chemical imbalances, there is no definitive support for this conclusion (Akiskal, 1995; Valenstein, 1998). (pp.35-6)
注:
Akiskal, H.S. (1995). Mood disorders: Introduction and overview. In H. I. Kaplan & B.J. Sadock (Eds.), Comprehensive textbook of psychiatry: Vol. 4 (6th ed.). Baltimore: Williams & Wilkins.

1970~1980頃にかけてメディカルスクールで精神科を専門とする医師が減少します。一番の理由は、心理学部出身の臨床心理学者や臨床心理士との競争にさらされたことです。
The middle of the twentieth century witnessed the emergence of clinical psychology. The need during World War II for large numbers of mental health personnel led to the military training of psychologists, principally to do diagnostic testing. Prior to the war, psychologists had developed tests for measuring intelligence, personality, and brain injury that were very useful in the diagnosis and treatment of military personnel. With the blossoming of interest in mental health following the war, departments of psychology at universities across the country began educating a far larger number of psychology graduate students. Unlike psychiatrists who were trained in university professional programs (medical schools) and earned medical degrees, psychologists received their training in graduate schools whose core curriculum emphasized research methodology leading to the Doctor of Philosophy (Ph.D.) degree. (pp.14-5)

Psychology departments had been educating psychologists as researchers since the late 1800s and a good deal of basic and applied research had been accomplished by the mid–1900s, but the great influx of new students, many of whom were as interested in applied research as they were in basic research, led to the rapid development of the field of clinical psychology. The research efforts of this new cadre of mental health personnel not only began to provide a scientific base for understanding and controlling human behavior, it also produced a desire by psychologists for recognition as an independent profession within which they could provide treatments based on their training and research. Although the fields of psychology, sociology, and social work had much to say about human problems, psychiatry maintained a monopoly on psychotherapy until the early 1960s (Valenstein, 1998). Non-physicians were prevented from attending psychoanalytic institutes, and psychologists or social workers practicing psychotherapy were accused of practicing medicine without a license. In the 1950s, conflict emerged when psychologists mounted an effort for legislation to grant state licensure in order to free them of control by psychiatry. Despite bitter opposition from medicine and psychiatry that psychotherapy was medical practice that required medical training, the growing power of psychology together with the predominance of Freud’s psychological theory of mental disorder enabled psychologists to succeed in gaining independent status. (p.15)

For a long time psychiatrists were viewed with suspicion by the rest of medicine as not being real doctors. In fact, for a period of time in the 1970s the medical internship year was eliminated for those specializing in psychiatry. By the 1980s fewer and fewer medical students were pursuing psychiatry as a specialty. Psychiatrists found themselves increasingly rejected by their patients in favor of other practitioners, and many psychiatrists grew concerned that the continued existence of psychiatry as a medical specialty was endangered. An article in the New York Times in 1982 described the situation:

American psychiatrists are increasingly distressed because they believe too few medical school students are being attracted to the profession to keep psychiatry vital and to meet the nation’s mental health needs.… From 1970 to 1980 the percentage of medical students drawn to psychiatry fell from above 11 percent to less than half that proportion … [E]fforts are underway to raise the scientific quality of psychiatric education in medical schools, to promote recruitment into the field and to improve the public’s esteem for psychiatry…[C]areer interest in psychiatry has plunged just when many medical experts say the nation is facing a shortage of psychiatrists.…The reluctance of medical students to enter the field is especially galling and demoralizing to psychiatrists who remember their discipline as the fastest-growing medical specialty in the heady years after World War II …What the waning enthusiasm for their field has forced psychiatrists to confront more directly is their low position on the medical profession’s totem pole …The students have been disconcerted by the large influx of people into the therapy business from a variety of other backgrounds—including psychology, social work and pastoral counseling. Not only do these often highly trained professionals offer economic competition, but they can make the student wonder why an arduous medical education is needed to do similar work.… Dr. Stuart C. Yudolfsky, vice chairman of the psychiatry department at Columbia University’s College of Physicians and Surgeons, said, [There was too much emphasis on social theory rather than on the biological and pharmacological triumphs in psychiatry.] (Nelson, 1982) (pp.16-7)

カウンセリングであれば心理学部出身の心理カウンセラーと差別化が図れません。医学部精神科が復権するためのカギが薬物治療でした。米国国立精神保健研究所(NIMH)は1980年代初めに心理療法から薬理学的研究に方向転換します。
Although at this time there existed within psychiatry a minority who had continued to advocate a biological viewpoint, they tended to be psychiatrists who treated only very serious cases or served as adjuncts to patients seen by others (including psychiatrists) for psychotherapy. Most psychiatrists treated a general clientele and considered the use of drugs as secondary in their treatment, which was based on a psychological (psychoanalytic) point of view. Now, however, with the field of psychiatry in economic trouble, the biologically oriented psychiatrists took control as the field sought to remake itself and utilize medical expertise in the treatment of a broader array of human problems. They argued vigorously and successfully for a return to an organic orientation and for the importance of adopting a single voice on this issue. As one writer put it in the American Journal of Psychiatry in 1981, [There are two political influences of great power: insurers and bureaucrats want clear definitions and agreed-upon entities. Moreover, psychiatry wants to speak with a unified voice not only to secure their support but to buttress its own position against numerous other mental health professionals seeking patients and prestige] (Havens, 1981). (p.17)

Central to this transformation of the field of psychiatry was redirection of the research effort at the National Institute of Mental Health (NIMH), founded in 1948 as a part of the National Institutes of Health (NIH) to be the prime agency for funding research on mental disorder. Research at the NIMH had been under two umbrellas: one to support grants for pharmacological research and one to support grants for psychotherapy research. A reorganization in the early 1980s simply eliminated the latter branch. Clinical trials according to diagnostic categories treated via drugs was firmly established. (p.17)

そこに目をつけたのが製薬会社。多額な宣伝費を使って、抗うつ剤の有用性を印象づけようとします。
In 2000 the pharmaceutical industry spent 14 percent of sales on research and development and 31 percent on marketing and administration; that is, almost two-and-a-half times what it spent on research and development (Angell, 2004, 48). (p.28)
注:
Angell, M. (2004). The Truth About the Drug Companies: How They Deceive Us and What to Do About It. New York: Random House.

A very important question about the widespread use of antidepressants is why they are so popular, given the body of scientific evidence that shows that the effect of these drugs can barely be distinguished from the effects of taking a placebo (Moore, 1999). The primary answer to this question is to be found in the enormous amount of money the pharmaceutical industry spends on advertising and the expertise they have demonstrated in how they spend this money. Drug companies spend $100 million a day on advertising (Wolfe, 2003). Just as advertising has created a great demand for many products, it has achieved a similar effect in promoting a desire for psychiatric drugs by persuading people that these drugs are the best means of relieving their suffering. (p.40)
注: Moore, T. (1999). It’s what’s in your head. The Washingtonian, October, 45–49;
Wolfe, S. (2003). Sweetening the pill. Health Letter, September 19, 1–10.

製薬会社の抗うつ剤販売はthe 10–20–30 Year Patternという経過をたどります。まず発売後10年間は「画期的な」治療薬として販売されます。次の十年間は様々な問題が明らかになる中、製薬会社とお抱え医師が問題を指摘する論文や医師を批判し問題を隠し続けます。そして次の十年は非有効性を示すデータが蓄積され守り切れなくなったと判断した製薬会社が新たな「画期的な」と称する治療薬を開発・販売します。抗うつ剤治療薬としておなじみのプロザック、ゾロフト、パキシル、ルボックスはすべてこのパターンに従っています。
Joseph Glenmullen, a Harvard psychiatrist, has described what he calls the 10–20–30 Year Pattern of psychiatric drug usage, which begins with the discovery of a new drug that is highly touted and aggressively marketed as a miraculous breakthrough far superior to its predecessors. In the beginning, a few doctors are ardent advocates, sometimes aided by celebrities endorsing the drugs as having been amazingly helpful. General practitioners then begin prescribing the drug to large numbers of people for more and more conditions. It takes about 10 years for development of recognition that there are problems with these drugs, during which period they are heavily defended by the drug companies and physicians advocating the drugs. After about 20 years, enough data have accumulated that doubts begin to take hold, and it takes another 10 years before the drug is abandoned in favor of a new miracle drug. He describes this pattern as a historical one that has unfolded in the prescribing of cocaine, amphetamines, barbiturates, tranquilizers, the tricyclics, and now has begun to play out with the selective serotonin reuptake inhibitors (SSRIs) of Prozac, Zoloft, Paxil, and Luvox. (pp.36-7)

メンタルヘルスの消費者擁護団体の多くが抗うつ剤治療を支持していますが、これらの団体は製薬会社からの寄付金で賄われています。
A number of mental health consumer advocacy groups, all of which endorse a biological viewpoint in explaining psychiatric disorder, are heavily funded by drug companies. For example, the Anxiety Disorders Association of America, which has as its aim [the prevention and cure of anxiety disorders,] has received 75 percent of its income from pharmaceutical companies; the National Depressive and Manic Depressive Association, whose purpose is to provide education about [depressive and manic-depressive illness as medical diseases,] has received 91 percent of its income from pharmaceutical companies; the National Mental Illness Screening Project, which sponsors such events as [National Depression Screening Day] in schools, received 48 percent of its income from Eli Lilly (Duncan, Miller, and Sparks, 2000). Thus, the nature of the advocacy offered by these groups appears to have been largely financed by the pharmaceutical industry. (pp.47-8)

うつ病の人に対する薬物治療は糖尿病のメタファーをよく用います。糖尿病患者が血管内の化学的インバランスをインシュリンで調整するように、うつ病患者に対しては抗うつ剤投与により脳内の化学的インバランスを回復させるというメタファーです。しかし、脳の不都合が原因でうつが生じるという科学的証拠はいまだ提出されていません。
Again, the basic premise of the medical model is that there are underlying causes for behaviors that are viewed as symptoms. Diabetes is an often-cited metaphor in explaining the biological basis for depression. It is argued that just like the fatigue or frequent urination of the diabetic is the symptom of the underlying disease, the sadness, lethargy, and hopelessness of the depressed person are symptoms of an underlying biochemical or psychological process. (pp.7-8)

Psychiatry’s promotion of psychotropic drugs to treat mental disorder is based upon a rationale that these drugs correct a chemical imbalance in the brain that is the cause of mental disorder. As we have indicated, frequently the analogy is made to the chemical imbalance in diabetes that is treated with insulin. The description provided earlier in this chapter regarding the research history that led to the understanding and treatment of diabetes makes clear that the use of insulin followed a series of objective findings having to do with a chemical imbalance that can be measured in the blood of diabetics. No such definitive findings or measurements exist of a chemical imbalance in the blood or brains of people with mental disorders when compared with normal people. Thus, in this analogy, a theory has been presented as if it is an established finding when it is not and does not fit the facts as we know them. Mental health practitioners, physicians, and the general public have been persuaded by a great deal of hype that something exists when there is, at least as yet, no good scientific basis for the claim. (pp.23-4)

この「糖尿病メタファー」は2つの点で間違っています。まず第1にうつはある特徴をもった気分状態であり、病気ではないこと。第2に病気である糖尿病も薬を使わないダイエットや運動などでコントロール可能であること。
In Chapter 1, we looked at how diabetes often is used as a metaphor for the [disease] of mental disorder. Depressed patients are told that, [Just like diabetics need to take insulin, people who ‘have depression’ need to take medication.] But, as we discussed earlier, there is no comparable imbalance in the blood of depressed patients and, as discussed in later chapters, depression is not something that one [has.] Depression is more accurately conceptualized as a mood state with biological, cognitive, and behavioral manifestations, not a disease. However, if we consider the diabetes metaphor and look at the reality of the illness of diabetes, while there is a small minority of people who have early-onset diabetes treated only with insulin, the vast majority of people who develop diabetes do so not solely because of genetic or biological factors, but also as a result of a poor diet, improper exercise, and obesity. In fact, diabetes is often controllable through diet and exercise. Thus, the diabetes metaphor that we reject as an example of a biological cause for depression, in this sense becomes an apt metaphor for depression. (p.32)

うつはアレルギーとの類推でみるのが適切です。誰もがアレルギーを持ちますが、外的環境の刺激物に接触しない限りアレルギーの症状は生じません。同じように、うつの症状が起きやすい人と起きにくい人という個人差はありますが、うつになりやすいタイプの人も何かのきっかけがない限りうつにはなりません。
A more apt analogy for depression would be allergies and allergic reactions. Some individuals are born with certain vulnerabilities to environmental stimuli that cause a reaction. Others become sensitized to certain allergens over a lifespan, and develop allergies later in life. (p.32)

Without the environmental exposure, however, the person would not have an allergic reaction. For those that become depressed the same may very well hold true. Some people may be born with or develop the vulnerability to experience negative life events in a way that makes them more anxious and depressed. When childhood environments provide toxic rather than ameliorative experiences, depression becomes potentially chronic with all of the psychological, biological, and behavioral systems maintaining it. Others become sensitized over a longer period of time, through lifetimes of disappointment, loss, or bombardment with adversity. Without the interaction of the person and the environment, however, there is no [disease] entity waiting to pounce. However, just like allergies, depression can cause great suffering and needs to be addressed appropriately to improve the person’s life. (p.33)

抗うつ剤がうつに効くという科学的証拠は出ていません。薬の効果といわれるものの80%はプラシーボ効果です。
You have lived long enough to know that quick fixes, no matter how tempting they may be, are not to be trusted. Unfortunately, there has been a great deal of hype about the effectiveness of antidepressant drugs that implies that simply taking a pill will be the solution. Similarly, there is widespread belief that taking drugs is necessary because depression is caused by your biology. The fact is there is little or no scientific backing for either of these claims. The explanation of depression as something you are born with is a theory that exists without sound backing. And the science that allegedly supports the use of antidepressant drugs to correct such a biological condition is woefully weak. As the old saying goes, even though it walks like a duck and quacks like a duck, that doesn’t means it is a duck. Recent careful studies have made it clear that the great bulk of the effect of these drugs is a placebo effect. They often don’t work any better than a sugar pill, but you wouldn’t know it because the pharmaceutical industry has spent a great deal of money to convince you of the value of their products. (p. xiv)

It is a simple fact that the biological explanation on which all of this is based is missing a sound scientific basis. There is much window dressing, but not much substance to the claims that have been made and widely accepted. Scrutiny of the research on antidepressant drugs reveals that the great bulk of the effect (at least 80 percent) is likely due to a placebo effect, with reason to suspect that the unaccounted for portion may be a specious contribution attributable to the intrusive practices of the drug companies that support almost all of the reported results. (p.137)

うつ病の人に抗うつ剤を処方することは2つの点で問題があります。第1に、抗うつ剤を飲んでもうつは治らないこと。抗うつ剤を飲むことで生じた反応の82%はプラシーボ効果であり、残りの18%も単なるバイアスにすぎません。
Several investigators have questioned this enthusiasm about the effectiveness of antidepressant medications. In 1998, Kirsch and Saperstein conducted a meta-analysis of 20 studies comparing antidepressant medications to pill-placebo representing data on 2,328 patients. Meta-analysis is a mathematical technique for comparing the data from multiple studies that meet certain selection criteria, allowing the investigators to make rational comparisons between studies that are similar in design. Based on their analyses, they concluded that 75 percent of the effect of antidepressant medications is accounted for by the placebo effect that accompanies taking medication. In a more recent meta-analysis, Kirsch, Moore, Scoboria, and Nicholls (2002) re-analyzed the efficacy data reported to the Food and Drug Administration (FDA) for approval of six widely prescribed antidepressant medications: Prozac, Paxil, Zoloft, Effexor, Serzone, and Celexa. The analysis included 47 randomized placebo controlled trials for the six drugs. A randomized placebo controlled trial assigns patients to drug or placebo conditions at random and uses double-blind procedures whereby supposedly neither the patient nor the prescriber knows whether the patient is on the active drug or the placebo. Kirsch, Moore, Scoboria, and Nicholls analyzed the differences as reported by means of a commonly used physician administered assessment for depression (the Hamilton Depression Scale). In efficacy studies, the average change on the scale was about two points, which was not clinically significant. The authors concluded that 82 percent of the drug response was due to placebo effects. While the authors concluded that about 18 percent of the drug response was due to the pharmacological agent in the medication, even this small number is open to question given the intrusiveness of the drug companies in this research. Valenstein (1998) and others we will cite later in this chapter have described how the drug industry influences what research is done, what is and is not reported, sampling problems, and the selectivity that occurs in determining which investigators are supported. Consequently, it is reasonable to question how much of this remaining 18 percent is due to artifacts attributable to bias. (pp.38-9)
注: Kirsch, I., Moore, T., Scoboria A., & Nicholls, S. S. (2002). The emperor’s new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration. Prevention & Treatment, 5, Article 23.

In fact, Moore, who was one of the authors of this analysis, has since provided additional information on the study he did with Kirsch. He states that it is likely that the drug effect of 18 percent is an inflated figure because investigators did not have access to unpublished studies from FDA files that failed to show any drug effect. When he and Kirsch included these 40 studies, the difference between drugs and placebos was even smaller. For Prozac, the placebo accounted for 89 percent of the antidepressant effect. Looking at 1,500 patients in five studies, the Prozac patients improved about eight points compared with seven points for those on placebo (Moore, 1999). (p.39)

2つの臨床試験で抗うつ剤のサーゾーン(ネフェゾドン)の有効性が示されたという文献を調べたところ、著者は8つの臨床試験を行い、6つの臨床試験では何ら効果がなかったということが判明しました。
The drug companies employ 87,000 sales representatives who visit doctors’ offices to sell doctors on the virtues of their products, backed up with favorable literature selected by the drug companies. Moore (1999) did some checking on this literature by looking into what is printed with the packaging of the antidepressant Serzone, which is touted as having significantly helped two-thirds of patients. He discovered that the insert that accompanied the drug declared the drug to have been proven superior over placebo in two clinical trials. However, when he looked into this claim, he found that Bristol-Myers had done eight studies of Serzone, not two. In the six studies that were not mentioned, the drug had no measurable effect. In addition, in one of the two studies cited, the drug effect was found only after some of the patients who improved on the placebo or did poorly on the drug were dropped from the study. (pp.40-1)

抗うつ剤を飲むことの2つ目の問題点はその副作用です。とくに問題なのは、抗うつ剤を飲むことで自殺が増えることです。
Although severe side effects were reported by the drug companies as infrequent with the tricyclic antidepressants, in fact they routinely produce side effects that make them difficult for many patients to tolerate. Furthermore, tricyclic antidepressants, and monoamine oxidase inhibitors are potentially lethal if taken in overdose. Antidepressant medications are the most common agent involved in suicide by drug overdose (Kapur, Mieczkowski, & Mann, 1992). The SSRIs may be less likely to be lethal if taken in overdose. However, there is a finding with children and with adults that SSRIs increase suicidal thinking and impulses in some individuals. In his 2000 book, Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Effective Alternatives, Dr. Joseph Glenmullen reports many published and anecdotal case studies of SSRIs in which adults had increased agitation, suicidality, or homicidal urges. The possibility of adverse side effects that take many years to develop should be a matter of particular concern when it comes to the use of these drugs by children and adolescents. The drugs they are taking are powerful agents, being taken at a time in their lives when their brains and bodies are still developing. They have many more years of life ahead of them, offering opportunity for the expression of unknown effects that might only show up years later. (p.51)

自殺願望以外の副作用に、下痢、吐き気、不眠、頭痛、性機能障害がよく生じます。肝臓障害、発作、アカシジア(静座不能症)。製薬会社はプロザックを飲むことで性機能障害が生じる確率は2~5%と主張していますが、多くの研究では60 percent程度であると報告されています。
Even though suicidality or homicidal tendencies should not be of grave concern for most people taking antidepressant medications, other side effects are consistently underestimated by the drug companies. The advantage of SSRIs over older antidepressant drugs in lessened production of side effects is marginal. Diarrhea, nausea, insomnia, headaches, and sexual problems are common. On rarer occasions, taking SSRIs has also led to liver damage, seizures, and a condition called akathisia, which is terrible tension that can produce suicidal and homicidal impulses. … The underestimation by the drug companies of adverse side effects of antidepressant drugs has been substantial. For example, Lilly’s literature reports that 2 to 5 percent suffer sexual side effects from Prozac, whereas many studies indicate that 60 percent experience significant sexual side effects (Glenmullen, 2000). Similarly, the literature on Paxil reports adverse side effects in 2 percent of users, when studies suggest the true figure to be anywhere from 20 percent to 60 percent. (pp.52-3)
注:
Glenmullen, J. (2000). Prozac backlash: Overcoming the dangers of Prozac, Zoloft, Paxil and other antidepressants with safe, effective alternatives. New York: Simon & Schuster

さらに抗うつ剤が問題なのは、いったん抗うつ剤を常用すると薬からの離脱が困難になることです。
Withdrawal is another issue of concern. Not infrequently, when people attempt to withdraw from antidepressant drugs they experience distressing emotional reactions. And, not infrequently, people misinterpret their distress as a recurrence of their problems caused by going off the medication. This leads them to return to full usage of the drug because they do not recognize their response to be a withdrawal effect. As a result, there is reason to be concerned that many people have become chemically and psychologically dependent on these drugs. And this is not a small matter. Withdrawal effects are so common that the drug companies, because of the negative implications to the term, have invented a euphemism called [discontinuation syndrome] and have urged doctors to use this term rather than [withdrawal] when speaking with patients.
注: http://www.ncbi.nlm.nih.gov/pubmed/8889907

次回、薬物治療に変わる行動療法に関する議論を見てみます。

10月 30, 2014 · Pukuro · No Comments
Posted in: ☆医療系

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