抑鬱症是一種非常普遍的疾病，在其一生中的某個時間影響五分之一的女性和十分之一的男性。 在任何時間點，5% 至 10% 的成年人患有臨床抑鬱症，另有 10% 至 15% 的人經歷亞臨床水平或更輕微的抑鬱症。Depression is a highly prevalent disorder that affects 1 in 5 women and 1 in 10 men at some time in their lives. At any point in time, 5% to 10% of adults are clinically depressed, and another 10% to 15% experience subclinical levels or milder forms of depression.
像上面這樣的陳述，來自 Johnson 和 Flake（2007 年）的陳述，在心理健康領域很常見，而且一般來說，它們都是從表面上看的。沒有人問：“抑鬱與不快樂有什麼不同嗎，因為我知道很多人，也許是大多數人，在他們的生活中都有不快樂的時光？”或者，如果提出問題，將參考官方診斷手冊（美國精神病學協會，2000 年）中的標準來回答，好像完成一個項目清單以某種方式將一個人從人類不幸的領域提升到重度抑鬱症紊亂。很少有人會意識到，像這樣的數字是為了增強心理健康專業人員的能力而捏造和推廣的。即使特定的專業人士沒有推銷毒品，而約翰遜和弗萊克也沒有，這些數字最初是為了促進精神科藥物市場而產生的。為了擴大市場，發明了亞臨床抑鬱症的概念，以證明向不符合重度抑鬱症標準的人開抗抑鬱藥是合理的。
Statements like the above, this one from Johnson and Flake (2007), are frequent in the mental health fi eld, and generally, they are taken at face value. No one asks, “Is depression different from unhappiness, because I know a lot of people, maybe most, have unhappy times in their lives?” Or if the question is asked, it will be answered with a reference to the criteria in the official diagnostic manual (American Psychiatric Association, 2000), as if fulfilling a checklist of items somehow elevates a person from the realm of human unhappiness to major depressive disorder. Few stop to realize that figures like these are concocted and generally promoted in the interest of empowering mental health professionals. And even if the particular professionals are not pushing drugs, and Johnson and Flake are not, the figures were originally generated to promote the market for psychiatric drugs. In an effort to enlarge the market, the concept of subclinical depression was invented to justify prescribing antidepressants to people who do not meet the standard criteria for major depressive disorder.
市場變得巨大。 在美國，2001 年估計有 2450 萬患者因抑鬱症就診，其中 69% 的患者開具了 SSRI 的處方（Fergusson 等，2005；Stafford 等，2001）。 2002 年，大約 6% 的男孩正在服用抗抑鬱藥，而且這個數字還在繼續增長。 到 2004 年，估計有十分之一的女性正在服用一種較新的抗抑鬱藥（Vedantam，2004）。
The market 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).
抗抑鬱藥為製藥公司帶來巨額收入。 2006 年，根據 IMS Health (2007)，抗抑鬱藥是所有類別藥物中處方最多的，在美國共有 2.273 億張處方。 他們的收入排名第三，總收入為 135 億美元。 從這些數據來看，像立普妥這樣廣泛使用的血脂調節劑在同類產品中排名第二，有 2.03 億張處方，收入第一，為 216 億美元。
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.
然而，抗抑鬱藥在過去幾年中一直受到美國食品和藥物管理局 (FDA) 和媒體的批評，最終在 2004 年至 2005 年出現了關於抗抑鬱藥導致兒童自殺的黑框警告，然後在 2007 年，另一個關於年輕人自殺率增加的黑框警告。 但實際上，這些藥物的處方幾乎沒有影響。 美國抗抑鬱藥的銷售額在 2004 年下降了 1.4%，在 2005 年下降了 6%，隨後在 2006 年恢復了 2%，行業認為黑匣子警告最終“不太可能顯著威脅銷售”（McManus，2007 年）。 正如已經提到的，它們在銷售方面仍然是第一名。
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.
從一開始的警告標誌（第 116 頁）
WARNING SIGNS FROM THE BEGINNING (p. 116)
1988 年 1 月第一個 SSRI 氟西汀（百憂解）進入美國市場後不久，已發表的報告開始描述氟西汀引起的針對自己和他人的暴力行為。
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.
1990 年，Teicher 等人。 在美國精神病學雜誌上發表了他們的經典文章“氟西汀治療期間出現強烈的自殺傾向”，描述了 5 名患者出現靜坐不能並在使用百憂解時變得痴迷於自殺，當停藥後他們感到如釋重負，然後又恢復了躁動 當它恢復時。 1990 年 5 月，FDA 要求百憂解、禮來公司的製造商在其標籤的“引入後報告”部分添加自殺意念和暴力行為。 將暴力和自殺列為可能的藥物不良反應的部分一開始就警告說，報告的反應“可能與藥物沒有因果關係”。
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 Postintroduction 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.”
1990 年 8 月 11 日，《柳葉刀》(5-HT Blockers, 1990) 的一篇社論將“促進自殺念頭和行為” (p. 346) 列入氟西汀的不良反應中。 該雜誌在警告方面領先於時代：
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:
氟西汀代表了美國最好的技術訣竅，並在生物精神病學在北美成為至高無上的時候在媒體上播出。 然而，我們不知道該藥物是否比早期的抗抑鬱藥更好，5-HT 是否是抑鬱症的主要神經遞質，以及 5-HT 攝取阻滯劑是否具有可接受的副作用。
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.
次年，英國醫學協會和英國皇家藥學會聯合出版的英國國家處方集（1991 年）將自殺意念和暴力行為列為氟西汀的副作用。 同樣在 1991 年，我出版了《有毒精神病學》，在其中我第一次觀察到百憂解正在產生一系列過度刺激，包括靜坐不能、激動、焦慮、失眠、抑鬱和躁狂症，極端情況下，還有自殺和暴力。 我利用了以前被隔離的 FDA 關於百憂解的上市前數據、科學文獻以及我自己的臨床和法醫案例。
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.
隨後，許多書籍和報告都討論了 SSRI 引發的暴力和自殺這一主題（例如，Breggin, 1992b, 1997, 2001a; Breggin et al., 1994a; Glenmullen, 2000; Healy, 2000; Teicher et al., 1993 ）。
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).
第 7 章將對有關抗抑鬱藥引起的精神和行為異常的文獻進行廣泛的回顧和分析。 本章將探討當前抗抑鬱藥標籤變化的演變和重要性。
Chapter 7 will present an extensive review and analysis of the literature on antidepressant-induced mental and behavior abnormalities. This chapter will look at the evolution and importance of current changes in antidepressant labels.
SSRI 類別
THE CLASS OF SSRIs
這些選擇性 5-羥色胺再攝取抑製劑 (SSRI) 包括氟西汀 (Prozac)、舍曲林 (Zoloft)、帕羅西汀 (Paxil)、氟伏沙明 (Luvox)、西酞普蘭 (Celexa)，以及最近的依他普崙(escitalopram) (Lexapro；見附錄)。 這些藥物阻止神經遞質血清素從突觸間隙中去除。 許多其他抗抑鬱藥是有效的非選擇性血清素再攝取抑製劑 (NSRI)。 這些包括非典型文拉法辛（Effexor）和三環氯米帕明（Anafranil）。 奈法唑酮（Serzone）因肝損傷已退出市場。
These selective serotonin reuptake inhibitors (SSRIs) include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and, most recently, escitalopram (Lexapro; see the appendix). These drugs block the removal of the neurotransmitter serotonin from the synaptic cleft. A number of other antidepressants are potent nonselective serotonin reuptake inhibitors (NSRIs). These include the atypical venlafaxine (Effexor) and the tricyclic clomipramine (Anafranil). Nefazodone (Serzone) has been withdrawn from the market due to liver damage.
當在臨床實踐和科學文獻中對 SSRIs 的影響進行觀察時，它們通常被視為單一類別或類別的藥物。 人們普遍認為，在一種 SSRI 中觀察到的不良心理或行為反應，例如激動或躁狂，很可能在所有其他 SSRI 中都存在。 當我最初以醫學專家的身份在證詞和審判中就這一現實作證時，製藥公司的律師和專家批評了我的立場，聲稱我不能使用關於一個 SSRI 的數據得出關於其他 SSRI 的結論。 然後，在 2004 年至 2007 年，FDA 開始針對不良精神反應（如自殺、敵意、易怒和躁狂）發布所需的類別警告，這些警告對於整個 SSRI 類別都是相同的。
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 and experts criticized 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.
雖然通常作為單獨類別的抗抑鬱藥進行檢查，但像 Effexor 這樣的 NSRIs 也與 SSRIs 有許多共同特徵，包括誘導刺激、焦慮、激動和躁狂的能力。
While usually examined as separate classes of antidepressants, the NSRIs like Effexor also share many characteristics with the SSRIs, including the capacity to induce stimulation, anxiety, agitation, and mania.
FDA 發現接觸抗抑鬱藥的兒童自殺率增加 (p. 118)
FDA FINDS INCREASED SUICIDALITY IN CHILDREN EXPOSED TO ANTIDEPRESSANTS
2004 年 2 月 2 日，FDA 召開了聯合精神藥理學藥物諮詢委員會和抗感染藥物諮詢委員會兒科小組委員會的公開會議，聽取公眾的證詞並探討與兒童抗抑鬱藥相關的自殺風險。 2004 年 9 月 13 日至 14 日期間，FDA 再次召開會議，對 24 項為期 4 至 16 週的抗抑鬱藥對照臨床試驗的 4,582 名兒科患者的數據進行了重新評估。 除了一個例外，這些研究來自 23 個行業贊助的試驗。 一個例外是美國國家心理健康研究所 (NIMH) 的一項研究，即青少年抑鬱症治療研究 (TADS)，這是一項為期 12 週的試驗，涉及 439 名 12-17 歲的兒童，比較了單獨的百憂解、單獨的認知療法、聯合療法和 安慰劑（March 等人，2004 年）。 因此，行業贊助的研究主導了數據。
On February 2, 2004, the FDA held an open meeting of the joint Psychopharmacological Drugs Advisory Committee and the Pediatric Sub-committee 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.
儘管這些研究主要是為了證明工業產品的價值而開發和進行的，但對綜合數據的薈萃分析表明，兒童和青少年的抗抑鬱藥增加了自殺未遂率，估計有 1% 到 3 % 的患者有抗抑鬱藥誘發的自殺風險（Hammad 等，2006）。 2004 年 10 月 15 日，FDA 要求發布黑框警告，並在 2005 年初完成（FDA，2005a）。 根據 FDA 描述藥物不良反應的要求，1% 或更高的風險被認為是常見的。
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.
容易顯示嚴重的不良反應；難以顯示療效（第 119 頁）
EASY TO SHOW SERIOUS ADVERSE EFFECTS;DIFFICULT TO SHOW EFFICACY (p. 119)
我們會發現精神病院繼續盡量減少 FDA 的調查結果。 甚至 FDA 最近也將這一發現描述為“適度的”（見後續討論）。 NIMH 主任 Thomas Insel 對藥物進行了權衡，將它們描述為“已知益處和可疑風險的藥物”（Vedantam，2005 年），而科學研究實際上表明它們是沒有益處和嚴重風險的藥物 .
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.
《新英格蘭醫學雜誌》要求 FDA 精神藥理學藥物諮詢委員會的一名專家組成員、醫師和流行病學家 Thomas B. Newman（2004 年）對對照臨床試驗中進行的研究結果發表評論，以確定風險 自殺。 他寫了，
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,
結果是驚人的。 當匯總所有兒科試驗時，被分配接受抗抑鬱藥治療的兒童的明確或可能自殺率是安慰劑組的兩倍。 （總結風險比為 2.19；95% 的置信區間。）雖然 FDA 工作人員沒有向委員會提供這些信息，但根據我自己的計算，預計這種戲劇性的結果只會在 20,000 人中偶然發生 1 次（ p = 0.00005)。 . . . 一項 P 值為 0.00005 的薈萃分析出現了一個關聯，該關聯是試驗的申辦者沒有尋找的，並且可能不希望找到的結果，這一事實非常令人信服。
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.
請注意，FDA 本身未能提供使結果如此驚人的 p 值！ 小組成員必須自己計算。
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) 還指出，FDA 發現在 15 項可用的對照臨床試驗中，只有 3 項顯示抗抑鬱藥對治療抑鬱兒童有效。 他說，幾位 FDA 委員會成員表示支持抗抑鬱藥，引用了他們自己的經驗或 NIMH 進行的 TADS； “然而，我和其他人發現功效的證據遠不如傷害的證據令人信服。” 據紐曼介紹，
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,
在審查 TADS 時，與單獨使用安慰劑的效果相比，氟西汀和安慰劑之間的差異很小，這讓我們感到震驚。 . . . 很容易理解為什麼臨床醫生和患者的個人經歷會讓他們相信這種藥物是有效的，因為他們無法知道他們觀察到的超過 85% 的益處也會發生在安慰劑上。
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.
TADS 以外的隨機試驗的結果不太理想。 FDA 指出，在抑鬱症兒童使用抗抑鬱藥的 15 項試驗中，只有 3 項發現具有統計學意義的益處。 該機構還向我們提供了一項薈萃分析，該分析表明，抗抑鬱藥對兒童的估計療效微乎其微，而且可能被高估了，因為已發表的研究比未發表的研究有更好的結果。 因此，臨床經驗和已發表的試驗都可能導致對這些藥物療效的誇大估計。
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.
FDA 提供的批評來自 Whittington 等人。 （2004 年），在第 7 章中進行了描述。
The critique provided by the FDA was by Whittington et al. (2004), described in chapter 7.
Newman (2004) 還發現了許多懸而未決的問題：“FDA 的薈萃分析表明，在持續兩三個月的試驗中，新型抗抑鬱藥使自殺風險增加一倍，約為 2.5% 至 5%。 但如果你服用它們一年會發生什麼？”
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?”
流行病學家 Newman (2004) 的評論概括了精神科藥物的本質問題：容易表現出嚴重的不良反應； 很難顯示它們的有效性。
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.
最近的 FDA 錄取和警告（第 120 頁）
RECENT FDA ADMISSIONS AND WARNINGS (p. 120)
因此，在 2004 年，FDA 開始追趕我在 1991 年開始在 Toxic Psychiatry 中所做的觀察，並在本書 1997 版中更詳細地記錄了關於抗抑鬱藥引起的自殺風險，至少在兒童中，以及後來 ，FDA 還將確認成年人的風險，至少是年輕人。 然而，在某些更重要的方面，媒體和醫學界幾乎完全忽略了，FDA 還證實了我對新型抗抑鬱藥的主要批評：它們會產生類似興奮劑的綜合徵或激活，從而導致一系列疾病， 從激動、憤怒和敵意到徹底的狂熱。
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.
在 2004 年初的公開聽證會之後，FDA 發布了一份關於兒童和成人的公共衛生諮詢新聞稿，其中指出：“該機構還建議觀察這些患者的某些已知相關的行為。 使用這些藥物，例如激動、驚恐發作、失眠、易怒、敵意、衝動、靜坐不能（嚴重的躁動）、輕躁狂和躁狂症。”
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.”
FDA 的描述及其最終標籤的變化與我十多年來所說的非常相似，並且模仿了我 2003 年報告“選擇性血清素再攝取抑製劑引起的自殺、暴力和躁狂症”中的語言，我在其中總結道，“精神病躁狂症 是興奮劑連續體的極端，通常以較輕程度的失眠、緊張、焦慮、多動和易怒開始，然後發展為更嚴重的激動、攻擊性和不同程度的躁狂症。” 在該報告中，我還討論了靜坐不能並描述了抗抑鬱藥引起的興奮劑綜合徵，包括“輕躁狂/躁狂症、失眠、緊張、焦慮、激動、中樞神經系統刺激、情緒不穩”。 . . 以及偏執反應、精神病、敵意和欣快感。”
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.”
兒童和青少年自殺的最終類別標籤 (p. 121)
The Final Class Label on Suicidality in Children and Adolescents
FDA 於 2005 年 1 月 26 日發布了所有抗抑鬱藥類別標籤的最終版本。FDA 將新標籤更改應用於市場上的所有 34 種抗抑鬱藥，包括較老的、更鎮靜的抗抑鬱藥，如阿莫沙平 (Asendin)、曲唑酮 (Desyrel) )、阿米替林 (Elavil)、多塞平 (Sinequan) 和丙咪嗪 (Tofranil)。 最後一分鐘加入較舊的抗抑鬱藥是對新型抗抑鬱藥製造商的尊重，實際上是用僅適用於較新抗抑鬱藥的刷子塗抹所有抗抑鬱藥。
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 antidepressant 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.
然而，根據 FDA 談話文件 (2004a)，該機構的結論是基於數量有限的新型抗抑鬱藥，包括安非他酮、西酞普蘭、氟西汀、氟伏沙明、米氮平、奈法唑酮、帕羅西汀、舍曲林、依他普崙和文拉法辛。 這些是公眾在兩次 FDA 聽證會上最常引用的藥物。
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.
儘管 FDA 目前正在對標籤進行更新，以包括關於抗抑鬱藥誘發年輕人自殺的警告，但直到最近，每個抗抑鬱藥標籤的頂部都有一個黑框警告，標題為“兒童和青少年的自殺”，開頭如下 陳述：
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:
在患有重度抑鬱症 (MDD) 和其他精神疾病的兒童和青少年的短期研究中，抗抑鬱藥增加了自殺思維和行為（自殺）的風險。
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.
這一聲明已經是 FDA 最初的提議和製藥公司反饋之間的妥協。 FDA 最初的、更強有力的草案內容為：“抗抑鬱藥在兒童患者中誘發自殺的因果作用已經確定”（Lenzer，2005 年）。 聲明草案超出了臨床試驗本身的範圍，說總體上已經確定了自殺。 它還使用了可怕的短語因果作用。 在我作證反對製藥公司的每一個案件中，被告公司都試圖駁回任何關於藥物誘導自殺的科學結論，除非該結論使用了因果關係這個詞。 實際上，科學文章和 FDA 批准的標籤很少使用因果關係的概念，這讓製藥公司鬆了一口氣，他們可以聲稱，無論多麼錯誤，因果關係尚未確定。
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.
同時，參考 FDA 精神藥理學藥物諮詢委員會的決定，即使是抗抑鬱藥的堅定擁護者也不得不承認，“委員會得出結論認為，抗抑鬱藥治療與兒科自殺之間存在因果關係，並建議實施相關政策”（Pfeffer，2007 ）。
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).
興奮劑綜合症（第 122 頁）
The Stimulant Syndrome (p. 122)
在黑框下方，標題是“警告——臨床惡化和自殺風險”。 在沒有明確指出的情況下，本節包含一個關於我在 1991 年在有毒精神病學中首次描述的興奮劑或激活綜合症的警告：
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:
以下症狀，焦慮，激動，驚恐發作，失眠，易怒，敵意，攻擊性，衝動，靜坐不能（精神運動性躁動），輕躁狂和躁狂症，在接受抗抑鬱藥治療的重度抑鬱症的成人和兒童患者中也有報導 至於其他適應症，包括精神病和非精神病。
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.
請注意對“易怒、敵意、攻擊性、衝動、靜坐不能（精神運動性躁動）、輕躁狂和躁狂症”的具體提及，這是對暴力的虛擬處方。 這個標籤的新增內容，其含義在很大程度上被忽視了，指的是兒童和成人。 通過表明非精神病患者可以發生這些反應，FDA 類別標籤挑戰了人們普遍持有的信念，即只有具有雙相情感病史或脆弱性的患者才有發生抗抑鬱藥過度刺激的風險。
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.
新標籤提供了應提供給服用新型抗抑鬱藥的患者及其護理人員的信息：
The new label addresses information that should be given to patients and their caregivers who take the newer antidepressants:
臨床惡化和自殺風險：應鼓勵患者、他們的家人和護理人員警惕焦慮、激動、驚恐發作、失眠、易怒、敵意、攻擊性、衝動、靜坐不能（精神運動性躁動）、輕躁狂、躁狂和 其他不尋常的行為變化、抑鬱症惡化和自殺意念，尤其是在抗抑鬱藥治療的早期以及劑量調高或調低時。 應建議患者的家人和護理人員每天觀察此類症狀的出現，因為變化可能是突然的。 此類症狀應報告給患者的開藥者或醫療保健專業人員，特別是如果它們是嚴重的、突然發作的或不是患者表現症狀的一部分。
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.
我之前的出版物和 FDA 在其新標籤中描述的大多數症狀都是激活或刺激的結果，這種綜合徵類似於苯丙胺、甲基苯丙胺和哌醋甲酯等興奮劑引起的綜合徵，尤其是在高劑量時。 與抗抑鬱藥引起的自殺相比，激活得到了更廣泛的科學文獻的支持，並且構成了更為常見且通常是災難性的風險水平（見後續討論）。
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).
當患者在服用抗抑鬱藥時病情惡化時，激活應該放在鑑別診斷列表的頂部。 如果醫生將藥物誘發的激活誤認為是由患者原有的精神疾病引起的，醫生很可能會繼續甚至增加抗抑鬱藥的劑量，最終導致躁狂(mania)和精神病(psychosis)。
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.
新的 FDA 藥物指南 (P. 123)
The New FDA Medication Guide (P. 123)
在發布新警告的同時，FDA 要求醫生向接受抗抑鬱藥的兒童家庭提供一份題為“藥物指南：關於在兒童和青少年中使用抗抑鬱藥”的信息表（食品和藥物管理局，2005e）。 該標籤目前正在由 FDA 更新，以包括年輕人，但其他方面基本保持不變。
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.
在標題為“如果您的孩子正在服用抗抑鬱藥，您應該注意某些跡象”的部分中，信息表指出，“如果您的孩子第一次出現以下任何跡象，或者如果他們 看起來更糟，擔心你，你的孩子，或者你孩子的老師。” 它列出了以下危險信號：
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:
關於自殺或死亡的想法
企圖自殺
新的或更嚴重的抑鬱症
新的或更嚴重的焦慮
感到非常激動或不安
驚恐發作
睡眠困難（失眠）
新的或更嚴重的煩躁
表現出攻擊性、憤怒或暴力
對危險的衝動採取行動
活動和談話的極端增加
其他不尋常的行為或情緒變化
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
除自殺外，藥物指南並未明確說明此反應列表與藥物之間存在因果關係，但明確暗示這些反應與服藥有關。 每個症狀都與激活或刺激綜合症一致。 包含憤怒、侵略和暴力表明 FDA 對抗抑鬱藥對其他人構成嚴重危險的擔憂是有道理的。
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.
FDA 關於抗抑鬱藥誘發兒童自殺的最終決定（第 124 頁）
The FDA’s Final Word on Antidepressant-Induced Suicidality in Children (p. 124)
2006 年 3 月，Hammad 等人。 FDA 神經藥理學藥物產品部藥物評估和研究中心發表了該機構方法和發現的摘要。 他們的結論最小化了他們的發現的重要性：“在兒科患者中使用抗抑鬱藥物與適度增加的自殺風險有關。”
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 fi ndings: “Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.”
將“自殺風險適度增加”這一結論與之前提到的 FDA 精神藥理學藥物諮詢委員會流行病學家 Thomas Newman（2004 年）的觀察結果進行比較，後者說：“結果令人震驚。 . . . 一項 P 值為 0.00005 的薈萃分析出現了一個關聯，該關聯是試驗的申辦者沒有尋找的，並且可能不希望找到的結果，這一事實非常令人信服。”
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.”
實際上，由於公司開展的短期臨床試驗完全不適合檢測自殺，因此風險必須遠遠超過“適度”才能出現。 此外，哈馬德等人。 （2006 年）承認我多年來在出版物和證詞中一直堅持的一個事實：製藥公司衡量自殺的首要指標，漢密爾頓抑鬱 (Ham-D) 量表，在這方面毫無用處。 調查員從量表中詢問受試者問題，其中只有一個與自殺有關。 顯然，答案將取決於問題的嚴肅程度，而死記硬背的問題可能會引出死記硬背的答案。 Ham-D 量表的發明者本人並不認為它可以像製藥公司那樣用作科學工具（漢密爾頓，1960 年）。
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, 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).
在臨床試驗中沒有完成自殺(p. 124)
No Completed Suicides in the Clinical Trials
FDA 報告還提到，在所有試驗對像中沒有記錄到完成自殺。 該機構沒有強調安慰劑也沒有發生自殺事件。 讓抑鬱的孩子遠離毒品並沒有導致一次自殺。 這與使用藥物預防自殺的趨勢完全矛盾。
The FDA report also mentioned that no completed suicides were recorded among all the trial subjects. The agency failed to emphasize that the 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.
製藥公司及其在美國精神病學協會 (APA) 的發起人試圖強調 FDA 評估的臨床試驗產生了“自殺性”，但沒有實際自殺（Lenzer，2005 年）。 雖然我以前從未見過這一點，但重要的是要認識到，一般而言，抑鬱症患者在臨床試驗期間不會自殺。 抑鬱症本質上是失去希望。 在臨床試驗期間，參與者希望一種新的藥物最終可以減輕他們的痛苦，他們至少每週得到專業的關注，並監測他們的病情是否有任何惡化。 因此，臨床試驗為抑鬱症的任何良好療法提供了基本要素：希望、專業關注和密切監測。 難怪安慰劑和藥物一樣好。 參與試驗本身就是治療性的，至少在其短暫的時間內是這樣。
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.
此外，積極自殺的患者被排除在臨床試驗之外。 他們是最脆弱的，因此是藥物最有可能推動自殺的人。
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.
FDA 作者在報告結束時感謝“提供這項工作所需數據的製藥公司”。 大量證據表明，包括 Prozac 和 Paxil 的製造商在內的一些製藥公司故意提供垃圾數據，以誤導，尤其是盡量減少與其藥物相關的風險（見第 14 章），他們在任何時候都沒有回應。
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 (see chapter 14).
加拿大和英國監管警告（第 125 頁）
Canadian and British Regulatory Warnings (p. 125)
2004 年 6 月 3 日，在 FDA 發布關於兒童的正式標籤變更之前，加拿大藥品監管機構加拿大衛生部 (2004) 對 SSRI 和其他比美國版本更全面的新型抗抑鬱藥發出了“更強烈的警告”：“ 這些新的警告表明，服用這些藥物的所有年齡段的患者都可能會經歷行為和/或情緒變化，這可能會使他們自殘或傷害他人的風險增加。” 與 FDA 形成鮮明對比的是，加拿大衛生部向兒童和成人發出了關於自殺的警告，並進一步警告對自己和他人的傷害（暴力）：
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):
患者、他們的家人和護理人員應注意，少數服用此類藥物的患者可能感覺更糟而不是更好，特別是在治療的最初幾週內或調整劑量時。 例如，他們可能會經歷不尋常的激動、敵意或焦慮感，或者有可能涉及自殘或傷害他人的衝動或令人不安的想法（強調）。
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).
這與我的證詞和出版物是一致的，從 1991 年的 Toxic Psychiatry 開始，其中我警告過 SSRI 引起的自殺和暴力以及我的書 Medication Madness（出版中），其中將展示數十個案例歷史，說明對自我的傷害 以及由 SSRI 引起的其他人。 然而，FDA 繼續落後，在新標籤中提到敵意和侵略是與 SSRI 相關的問題，但沒有充分強調這些可怕的結果。
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 (in press), which will present 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.
在英國，除氟西汀外，所有 SSRI 抗抑鬱藥都被禁止用於治療兒童抑鬱症。 主要關注的問題是總體上隨著 SSRIs 增加的自殺率，包括氟西汀（藥物安全委員會，2003 年）。
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 (Committee on Safety of Medicines, 2003).
將自殺警告擴大到年輕人（第 126 頁）
Expanding the Suicide Warning to Young Adults (p. 126)
我在有毒精神病學（1991 年）和 1997 年再次警告公眾和衛生專業人員關於 SSRI 抗抑鬱藥引起的成人自殺風險，並在本書的第一版中進行了冗長的討論。 我在 2003 年的科學期刊文章“選擇性血清素再攝取抑製劑 (SSRIs) 引起的自殺、暴力和躁狂症：回顧與分析”中更詳細地闡述了風險。
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.”
與此同時，2001 年，在德克薩斯州休斯頓，律師 Andy Vickery 在 Paxil 謀殺自殺訴訟中贏得了針對 GlaxoSmithKline 的產品責任訴訟（Tobin v. SmithKline Beecham, 2001）。 60 歲的唐納德·謝爾 (Donald Schell) 在射殺妻子、女兒和孫女之前服用了兩劑 Paxil。 陪審團判給兩個倖存的家庭成員 640 萬美元（Josefson，2001）。
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).
在打官司的過程中，葛蘭素史克聲稱沒有實質性證據將 Paxil 與自殺聯繫起來。 法官在審查了雙方提交的證據後，認為有足夠的科學證據證明帕西爾自殺，可以繼續審理此案。
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.
在 FDA 重新評估其現有數據的巨大壓力下，這家製藥公司需要 5 年多的時間才能得出同樣的結論。對抗抑鬱藥引起的自殺的日益關注導致 FDA 要求製藥公司根據 FDA 對數據進行分類和重新分析的標準重新評估其早期的對照臨床試驗。 5 月 GlaxoSmithKline (2006b) 發表了一篇“尊敬的醫療保健提供者”公告，內容涉及 Paxil 誘導的抑鬱成人自殺。這封信強調了服用 Paxil 治療各種疾病（包括抑鬱症、驚恐發作、焦慮症和強迫症）的年輕人（至 30 歲）的自殺率可能略有增加。更重要的是製藥公司描述了在嚴重抑鬱症的對照臨床試驗中，所有年齡段的成年人的自殺率都有統計學意義的增加。接受 Paxil 的抑鬱症患者出現自殺念頭和行為的可能性是服用糖丸的抑鬱症患者的 6.4 倍。關於自殺——與抗抑鬱藥相關的最具破壞性的風險——抑鬱症患者遠離 Paxil 更安全。
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.
FDA 允許 Paxil 製造商軟化調查結果，例如聲稱自殺是“精神疾病”的一個方面這一事實可能會使結果更加複雜。 這是胡說八道——每個科學家都知道。 由於兩組都患有抑鬱症，並且由於他們僅在盲法試驗中服用的物質有所不同，因此Paxil而不是抑鬱症是導致自殺率呈天文數字增加的原因。
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.
如果抑鬱症導致自殺率增加，那麼缺乏抗抑鬱作用的安慰劑患者的自殺率將比 Paxil 患者高得多。 相反，他們的利率要低得多。 換句話說，因為抗抑鬱藥本應幫助抑鬱症患者，糖丸的相對無效應該導致比藥物更多的自殺率，而不是更少。 FDA、製藥公司和媒體忽略了這一重要事實。 傳統假設會預測安慰劑會增加自殺率，而不是 Paxil 會增加自殺率。 這是對預期結果的完全逆轉，強調了發現藥物增加自殺率的嚴重性。
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 on the drug.
最後，在 2006 年 12 月，FDA 就可能在所有抗抑鬱藥標籤中添加成人自殺警告舉行了聽證會。 在較早的對照臨床試驗中產生的數據表明，在服用新型抗抑鬱藥時，不僅兒童而且 24 歲以下的年輕人都出現了更多的自殺念頭和行動。 FDA 的小組最終建議對 18 至 24 歲年齡組的自殺率增加發出黑框警告。 FDA 的委員會充斥著利益衝突（Pringle，2007）。
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).
請注意，這一關於抗抑鬱藥的結論總體上忽略了葛蘭素史克公司 2006 年 5 月發布的 Paxil 數據，該數據表明患有重度抑鬱症的成年人在所有年齡段的自殺率都有所增加。
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.
2007 年 5 月，FDA 發佈公告，表示其打算增加針對服用抗抑鬱藥的“年輕人”的自殺率增加的警告。 FDA 要求在每個抗抑鬱藥標籤頂部的新警告包含在一個標題為“自殺和抗抑鬱藥”的黑盒子中。 警告開始時，“與安慰劑相比，在重度抑鬱症 (MDD) 和其他精神疾病的短期研究中，抗抑鬱藥增加了兒童、青少年和年輕人的自殺思維和行為（自殺）風險”（葛蘭素史克，2007 年） .
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).
FDA 幫助製藥公司 (p.128)
The FDA Helps Out the Drug Companies (p.128)
FDA 將自殺警告解析為各個年齡段，這符合製藥公司掩蓋抗抑鬱藥導致兒童和成人自殺這一基本現實的需要。 我不知道另一個例子，其中像自殺這樣的嚴重影響的信號已按年齡段劃分，包括一些和排除其他的。 這些區別太精細了，無法在對照臨床試驗的基礎上做出，而對照臨床試驗充其量只能提供問題的總體信號。
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 fi ne to be made on the basis of controlled clinical trials that, at best, can provide a gross signal of a problem.
再一次，為了淡化其對新型抗抑鬱藥市場的影響，每一種被批准用於治療抑鬱症的藥物都需要發出警告，而實際上這些數據完全來自使用新型和更具刺激性的抗抑鬱藥的臨床試驗。
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.
因為每一種抗抑鬱藥都會帶有新的警告，許多醫生會被誤導，認為舊的抗抑鬱藥與新的抗抑鬱藥有相似的風險。 這些醫生會得出結論，沒有比像 Prozac、Paxil、Zoloft、Celexa 和 Effexor 這樣的大賺錢者更安全的選擇了。
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.
FDA 不僅在新的警告中將其自殺警告限制在兒童、青少年和年輕人，而且還宣布 24 歲以上的成年人因抗抑鬱藥引起的自殺率沒有增加，此外，“風險降低了 與安慰劑相比，在 65 歲及以上的成年人中使用抗抑鬱藥”（葛蘭素史克，2007 年）。 FDA 正在邀請醫生根據短期臨床試驗中的少數老年患者相信，抗抑鬱藥甚至可能降低老年患者的自殺率。
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.
當不敏感的臨床試驗表明兒童和年輕人都有自殺風險時，是時候承認抗抑鬱藥會導致所有年齡段的人自殺。 此外，接受檢測的 65 歲及以上患者數量非常少。
When insensitive clinical trials signal a suicide risk in both children and younger adults, it is time to admit fl at out that antidepressants cause suicidality in all age groups. Besides, the number of patients 65 and older who were tested was very small.
與此同時，有科學數據與 FDA 的建議相矛盾，即抗抑鬱藥可能會保護老年人免於自殺。在 FDA 聽證會前幾個月發表的一項研究評估了安大略省超過 120 萬例驗屍官的記錄、處方數據、醫生賬單索賠和住院數據 1992 年至 2000 年 66 歲及以上的居民（Juurlink 等人，2006 年）。 在評估了 1,000 多例自殺死亡後，他們發現“SSRI 抗抑鬱藥與其他抗抑鬱藥相比，導致自殺的風險高出近五倍”（第 813 頁）。 這使得 FDA 更加肆無忌憚地表現得好像抗抑鬱藥在老年人群中更安全。
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 fivefold 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.
如前所述，FDA 的新警告實際上比 2006 年 5 月早些時候 GlaxoSmithKline 發出的“親愛的醫療保健提供者”信要弱。信中披露的 Paxil 試驗表明，所有年齡段的重度抑鬱症患者的自殺率都有所增加 紊亂。
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 對成年人來說是最危險的 (p.129)
Paxil Is the Most Dangerous for Adults (p.129)
FDA 自己對所有成人對照臨床試驗的分析發現，Paxil 在導致自殺未遂方面是最危險的（Stone 和 Jones，2006，第 26 頁）。 除了 Paxil，個別抗抑鬱藥在成人自殺率方面沒有顯示出統計學上的顯著增加。 只有在匯總了所有抗抑鬱藥的數據後，才會出現顯著的結果。 但就 Paxil 而言，在所有年齡的成年人和所有精神疾病中，自殺率都有統計學意義的增加（OR 2.76，95% CI 1.16-6.60，p = 0.02）。
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).
儘管葛蘭素史克多年來一直在努力隱藏由 Paxil 引起的自殺案例，在其計算機編碼系統中將自殺企圖誤認為是情緒不穩定，並操縱自殺數據以使其看起來不那麼具有威脅性，但 Paxil 在危險性方面脫穎而出。 （第 14 章；布雷金 2006a-c）。 儘管該公司努力阻止真相，即使在短期對照臨床試驗中，這些試驗被扭曲以避免證明 Paxil 誘導的自殺，與服用安慰劑的患者相比，服用該藥物的患者的自殺率在統計學上顯著增加 年齡和所有診斷類別。
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.
現實生活中的風險比描述的要大得多（第 129 頁）
The Real-Life Risk Is Much Greater Than Described (p.129)
請記住，受控臨床試驗由製藥公司計劃，由製藥公司監督，並由已知與製藥公司合作的付費醫生進行。 請記住，所有數據分析均由製藥公司高管在製藥公司總部完成。 獨立科學家在這個過程中沒有任何作用。 請記住，這些試驗旨在證明藥物的有效性並儘量減少自殺等副作用。 請記住，對照臨床試驗非常短，通常長達 4-6 週，並且預篩選排除了自殺和精神病患者參與研究。 鑑於這些警告，令人驚訝的是，自殺信號如此強烈，以至於它可以在這些試驗的背景下發光。
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.
在現實生活中的醫療實踐中，藥物引起的自殺率將遠高於以研究為導向的對照臨床試驗。 在實際實踐中，許多患者在開始服用藥物時已經有自殺傾向，這增加了藥物將他們推向自殘行為的可能性。 同樣，在現實生活中的臨床實踐中，與用於研究的對照臨床試驗相比，忙碌的醫生提供的監督或監測要少得多，患者幾乎從未接受過自殺測試或評估，經常同時服用多種藥物，而且醫生知道 幾乎沒有尋找對心靈的不利影響。
In real-life medical practice, the rate of drug-induced suicidality will be much higher than in the research-oriented, controlled clinical trials. In actual practice, many patients are already suicidal when they are started on the drug, increasing the likelihood that the drug will push them over into self-injurious behavior. Similarly, in real-life clinical practice, compared to controlled clinical trials used for research, busy doctors provide much less supervision or monitoring, the patients are almost never tested or evaluated for suicidality, multiple drugs are often given at once, and the doctors know little about looking for adverse effects on the mind.
鑑於Paxil在製藥公司的對照臨床試驗中將自殺率提高了6倍以上，在實際實踐中會大幅增加。 我們無法準確確定臨床實踐中的風險會有多大，但它會比簡短、高度選擇性和密切監測的對照臨床試驗高得多。
Given that Paxil increased the rate of suicidality by more than 6 times in the drug company’s controlled clinical trials, it will be considerably increased in actual practice. We cannot determine exactly how much greater the risk will be in clinical practice, but it will be much higher than in the brief, highly selective, and closely monitored controlled clinical trials.
心理藥物複合體的反應
THE PSYCHOPHARMACEUTICAL COMPLEX RESPONDS
美國神經精神藥理學學院
The American College of Neuropsychopharmacology
美國神經精神藥理學學院 (ACNP) 認為自己是世界上專注於精神科藥物研究和實踐的專業人士的首要組織。 對於兒童抗抑鬱藥對治療抑鬱症無效但會惡化青少年的整體狀況並導致自殺率增加的披露，它有何反應？ 該組織在製藥公司的工資單上充斥著醫生，警告說 FDA 正在造成潛在的災難。 ACNP 在 Psychiatric Services 雜誌所稱的“令人不寒而栗的總結段落”中得出結論（“ACNP Releases”，2006；Mann 等人，2006），
The American College of Neuropsychopharmacology (ACNP) considers itself the premier organization in the world of professionals concerned with research and practice in the fi eld of psychiatric medications. What was its response to the disclosure that antidepressants in children are ineffective in treating depression but that they can worsen the youngsters’ overall condition and cause increased suicidality? This organization, bloated with doctors on the payrolls of drug companies, warned that the FDA was causing a potential disaster. In what the journal Psychiatric Services called a “chilling summary paragraph,” the ACNP concluded (“ACNP Releases,” 2006; Mann et al., 2006),
FDA 最近的黑匣子警告可能有助於啟動一項自然的公共衛生實驗。 標籤的改變可能伴隨著抗抑鬱藥處方的減少，尤其是對年輕人而言。 這項政策的一個意想不到的後果可能是青少年自殺率的增加。 這是一個將在不久的將來檢驗的實證問題。
The FDA’s recent black box warning could serve to initiate a natural public health experiment. The change in labeling may be accompanied by a reduction in antidepressant prescriptions, particularly for youth. An unintended consequence of this policy could be an increase in youth suicide. That is an empirical question to be examined in the near future.
真正令人不寒而栗的實驗是用有毒的所謂抗抑鬱藥給數百萬美國兒童下藥，這些藥物沒有經過證實的功效，而且已經證實有不良反應，包括躁狂和自殺。 當然，應該希望標籤的改變能夠減少接觸這些藥物的兒童人數。 至於關於減少抗抑鬱藥使用可能增加青少年自殺的經驗問題，很難從安慰劑對照的臨床試驗中得出結論，更不用說從社會實驗中得出結論了，其中變量實際上是無限的，主觀性可能猖獗 ，並且控件不存在。 自成人抗抑鬱治療出現以來，已經有大量此類流行病學研究，一些聲稱自殺增加，一些聲稱自殺減少（Van Pragg，2003）。
The real chilling experiment has been the drugging of millions of America’s children with toxic so-called antidepressants, with no proven efficacy and with proven adverse effects, including mania and suicidality. Of course, it should be hoped that the change in label reduces the number of children exposed to these drugs. As for the empirical question concerning any potential increase in youth suicide from a reduction in antidepressant use, it is hard enough to draw conclusions from placebo-controlled clinical trials, let alone from societal experiments, where the variables are literally infinite, subjectivity can run rampant, and the controls are nonexistent. There is already a plethora of such epidemiological studies, some claiming that suicide has increased, and some claiming that it has decreased (Van Pragg, 2003), since the advent of antidepressant treatment for adults.
全社會的流行病學研究不能現實地回答有關藥物療效和副作用的經驗問題； 在嚴格控制的臨床試驗中做到這一點已經夠難的了。 此外，臨床試驗已經回答了經驗問題。 抗抑鬱藥會增加兒童和青少年以及成人的自殺率。 但可以肯定的是，這些所謂的 ACNP 專家將開始進行脆弱甚至荒謬的流行病學研究，以試圖破壞在受控臨床試驗中產生的更可靠的數據。
Society-wide epidemiological studies cannot realistically answer empirical questions about drug efficacy and adverse effects; it is hard enough to do so in carefully controlled clinical trials. And besides, the empirical question has already been answered by the clinical trials. Antidepressants increase suicidality in children and youth as well as adults. But it is guaranteed that these same ACNP so-called experts will start producing flimsy and even ridiculous epidemiological studies in an attempt to undermine the far more reliable data generated in controlled clinical trials.
說 ACNP 代表製藥公司，而不是美國的孩子，這不公平嗎？ 在 ACNP 報告的末尾，有一份工作組成員（報告作者）的名單，以及他們對潛在利益衝突的披露（Mann 等人，2006 年）。 行業從屬關係列表佔一頁和四分之三頁。 在 11 位作者中，只有 1 位，即名單中的第四位作者 William Beardslee，聲稱沒有行業從屬關係。 其他 10 位作者中的每一位都承認與多家製藥公司有關聯，大多數有許多關聯，並且所有 10 位作者都與抗抑鬱藥製造商有聯繫。 這些是專業人士，據說是頂級專家，他們為美國和全世界的精神科藥物處方制定了標準！
Is it unfair to say that the ACNP represents the drug companies, rather than America’s children? At the end of the ACNP report, there is a list of Task Force members (the report authors), with their disclosures concerning potential conflicts of interest (Mann et al., 2006). The list of industry affiliations fills one and three-fourth pages. Of the 11 authors, only 1, William Beardslee, the fourth name in the list, claims no industry affiliation. Every one of the other 10 authors acknowledges several drug company affiliations, most have many affiliations, and all 10 have connections to the manufacturers of antidepressants. And these are the professionals, the supposedly top experts, who set the standards for the prescription of psychiatric drugs in America and worldwide!
由於我在針對製藥公司的產品責任訴訟中擔任醫學專家，因此我熟悉其中的一些人。
例如，主要作者 J. John Mann 列出了與兩家領先的抗抑鬱藥製造商葛蘭素史克 (Paxil) 和輝瑞 (Zoloft) 的隸屬關係。 他指出，他曾代表輝瑞（Pfizer）擔任專家審判證人，我在這方面閱讀了他的前藥公司報告。 但他的工業隸屬關係列表中沒有包括同樣有趣的聯繫：製藥巨頭楊森資助了他在哥倫比亞大學的教授職位。 他是精神病學和放射學轉化神經科學的 Paul Janssen 教授。 楊森現在是強生公司的一部分，強生公司是世界第二大製藥公司，2006 年的收入為 505.14 億美元（CNN Money，2007）。
I am familiar with a number of these men as a result of my work as a medical expert in product liability suits against the drug companies.
For example, the lead author, J. John Mann, listed affiliations with two of the leading manufacturers of antidepressants, GlaxoSmithKline (Paxil) and Pfizer (Zoloft). He noted that he had been an expert trial witness on behalf of Pfizer, and I have read his prodrug company reports in that context. But he does not include an equally interesting connection under his list of industrial affiliations: the pharmaceutical giant, Janssen, funds his professorship at Columbia. He is the Paul Janssen Professor of Transla-tional Neuroscience in Psychiatry and Radiology. Janssen is now a part of Johnson & Johnson, the second largest pharmaceutical company in the world, with revenues of $50.514 billion in 2006 (CNN Money, 2007).
哥倫比亞大學醫學中心的神經科學系（2006 年 12 月）網頁將保羅詹森教授職位和保羅詹森學者計劃描述為該大學與強生公司之間的“合作夥伴關係”。 這是一個可怕的例證，說明製藥業已經深深地融入了美國領先的醫療中心。
The Department of Neuroscience (December 2006) Web page for the Columbia University Medical Center describes the Paul Janssen Professorship and the Paul Janssen Scholars program as resulting from a “partnership” between the university and Johnson & Johnson. It is a frightening illustration of how deeply embedded the pharmaceutical industry has become in the nation’s leading medical centers.
為什麼曼恩不能將他的教授職位列為他的行業隸屬關係之一？ 我相信他對自己的教授職位感到非常自豪，並將其列為他的大學證書。 我懷疑這種與工業的密切聯繫是如此普遍，並且在像曼這樣的人的生活中如此固有，以至於他們幾乎不認為讓你的工作由你的大學之間的合作夥伴資助可能是一種利益衝突 和世界第二大製藥公司，即使這項工作表面上涉及對藥品進行客觀、獨立的評估。
Why would Mann fail to list his professorship as one of his industry affiliations? I am sure he takes great pride in his professorship, and he lists it as his university credential. I suspect that this kind of hand-in-glove connection to industry is so commonplace and so inherent in the lives of men like Mann that they hardly consider that it might be a conflict of interest to have your job funded by a partnership between your university and the world’s second largest pharmaceutical company, even when that job ostensibly involves providing objective, independent evaluations of pharmaceutical products.
作為產品責任專家工作中我熟悉的另一個例子，Jan Fawcett 多年來為製藥公司進行了許多臨床試驗。 他將自己列為十家製藥公司的顧問，八家製藥公司的發言人局成員，以及八家製藥公司的贈款和研究支持的接受者。 奇怪的是，Fawcett 列出了第九個機構，即 NIMH，隸屬於行業，這證實了我的觀點，即 NIMH 現在是精神製藥綜合體的一部分，也可能被視為製藥行業的一個分支。
As another example of someone familiar to me from my work as a product liability expert, Jan Fawcett has conducted numerous clinical trials for drug companies over the years. He lists himself as a consultant to ten pharmaceutical companies, as a Speaker’s Bureau member for eight pharmaceutical companies, and as recipient of grants and research support from eight pharmaceutical companies. Curiously, Fawcett lists a ninth institution, the NIMH, under industry affiliations, confirming my view that NIMH is now a part of the psychopharmaceutical complex and might as well be considered a branch of the pharmaceutical industry.
對於想要查看所有這些內容以及更多內容的讀者，可以通過 Neuropsychopharmacology 網站 (http://www.nature.com/npp) 找到這篇文章，包括行業附屬機構列表。
For readers who want to see all this, and more, for themselves, the article, including the list of industrial affiliations, can be found through the Neuropsychopharmacology Web site (http://www.nature.com/npp).
美國精神病學協會（第 132 頁）
The American Psychiatric Association (p. 132)
APA 也一直忙於試圖抑制甚至消除 FDA 黑匣子警告的影響。 2007 年 6 月，該協會的美國精神病學雜誌（Pfeffer，2007 年）發表的一篇社論感嘆道，“這些政策行動可能產生了意想不到的效果，即不鼓勵為兒科患者開抗抑鬱藥處方，也不鼓勵兒科使用抗抑鬱藥，而沒有補償性增加其他特定治療。” （第 845 頁）。 如果不是為了阻止使用抗抑鬱藥，那麼警告自殺的目的是什麼？
The APA has also been busy trying to dampen, and even to obliterate, the effects of the FDA black-box warnings. A June 2007 editorial in the association’s American Journal of Psychiatry (Pfeffer, 2007) lamented, “these policy actions may have had the unintended effect of discouraging the prescription of antidepressants for pediatric patients and pediatric utilization of antidepressants without compensatory increases in other specific treatments” (p. 845). What was the purpose of warning about suicidality, if not to discourage the use of antidepressants?
社論的觀點如此扭曲，甚至沒有提到 FDA 還發現絕大多數臨床試驗表明抗抑鬱藥對治療兒童抑鬱症無效。 如前所述，15 項安慰劑對照臨床試驗中只有 3 項顯示出任何療效。 （三項陽性研究中的兩項由禮來公司贊助，禮來公司的密切合作者 Graham Emlsie 為第一作者；見後續討論。）還請記住 FDA 委員會成員和流行病學家 Thomas Newman（2004 年）的觀察，即 抗抑鬱藥的療效比它們的療效要好得多，這在很大程度上可以歸因於安慰劑效應。
The viewpoint of the editorial is so warped that it does not even mention that the FDA also found that the vast majority of clinical trials showed that antidepressants are ineffective in treating depression in children. As already noted, only 3 of 15 placebo-controlled clinical trials showed any efficacy. (Two of the three positive studies were sponsored by Eli Lilly, with Graham Emlsie, a close Lilly collaborator, as the first author; see subsequent discussion.) Also remember FDA committee member and epidemiologist Thomas Newman’s (2004) observations that the adverse effects of the antidepressants were much better established than their efficacy, which could largely be accounted for by the placebo effect.
危險且無效——這應該會阻止對兒童進行治療。
Dangerous and ineffective—that should discourage the use of a treatment in children.
抗抑鬱藥對兒童無效（第 133 頁）
ANTIDEPRESSANTS LACK EFFICACY IN CHILDREN (p. 133)
無需等待 FDA 得出結論，即大多數兒童研究未能顯示出任何抗抑鬱功效。 這個問題早在幾年前就已經在科學文獻中做出了決定，並且在 FDA 聽證會的同時展開了更多的確認。
There was no need to wait for the FDA to conclude that most studies with children fail to display any antidepressant efficacy. The issue had been decided in the scientific literature years earlier, and additional confirmation was unfolding at the same time as the FDA hearings.
我觀察了十多年（Breggin，1991c，1997a），沒有科學證據表明抗抑鬱藥對抑郁兒童有幫助。 但正如十幾年前《臨床精神病學新聞》中的標題所指出的那樣，“儘管缺乏數據，但抗抑鬱藥在兒童中得到了廣泛應用”（Baker，1995 年）。
I have observed for more than a decade (Breggin, 1991c, 1997a) that there is no scientific evidence that antidepressants are helpful for depressed children. But as a headline in Clinical Psychiatry News indicated a dozen years ago, “Though Data Lacking, Antidepressants Used Widely in Children” (Baker, 1995).
Sommers-Flanagan 和 Sommers-Flanagan (1996) 回顧了 1985-1994 年期間發表的所有針對三環類抗抑鬱藥 (TCA) 的雙盲、安慰劑對照療效試驗。 他們總結道：“結果表明，儘管使用旨在使抗抑鬱藥優於安慰劑的研究策略，但 TCA 和 SSRI 在緩解兒童和青少年抑鬱症狀方面的效果均優於安慰劑”（第 145 頁）。
Sommers-Flanagan and Sommers-Flanagan (1996) reviewed all double-blind, placebo-controlled efficacy trials for tricyclic antidepressants (TCAs) with depressed young people published during the period 1985–1994. They summarized, “Results indicate that neither TCAs nor SSRIs have demonstrated greater efficacy than placebo in alleviating depressive symptoms in children and adolescents, despite the use of research strategies designed to give antidepressants an advantage over placebo” (p. 145).
他們得出的結論是：“從未發表過一項雙盲、安慰劑對照研究表明抗抑鬱藥物在治療兒童或青少年抑鬱症方面比安慰劑更有效”（第 151 頁）。
They concluded, “There has never been a double-blind, placebo controlled study published indicating that antidepressant medications are more effective than placebo in treating child or adolescent depression” (p. 151).
Fisher 和 Fisher (1996) 探討了圍繞兒童使用抗抑鬱藥的倫理問題。 他們指出，面對相同出版物中的數據，已發表的使用抗抑鬱藥的建議如何飛行。 他們觀察到，“為兒童開具抗抑鬱藥的處方清楚地說明了一大群從業者（兒童精神科醫生和兒科醫生）如何堅持使用與研究數據實際上相矛盾的程序，同時為這樣做收集正當理由”（p . 101).
Fisher and Fisher (1996) explored the ethical issues surrounding the use of antidepressants in children. They pointed out how published recommendations for the use of antidepressants fly in the face of data within the same publications. They observed, “The prescribing of antidepressants for children clearly illustrates how a significant group of practitioners (child psychiatrists and pediatricians) can persist in using a procedure that is actually contradicted by research data and at the same time muster justifications for doing so” (p. 101).
Whittington 等人的一項薈萃分析研究。 （2004 年）在《柳葉刀》中發現，結合已發表和未發表的研究得出的結論是，除了百憂解之外，沒有跡象表明對兒童的抗抑鬱治療有效。 此外，文章中沒有提到的事實是，有利於百憂解的兩項關鍵研究得到了禮來公司的支持，一項直接支持，另一項通過 NIMH(^1) 提供的資金間接支持，並且這兩項研究的主要作者都是格雷厄姆 埃姆斯利（Graham Emslie 等人，2002 年，1997 年）。 Emslie 是 ACNP 臭名昭著的抗抑鬱藥辯護的工作組聯合主席和第二作者。 Emslie 的行業從屬關係包括“資助/研究支持：禮來、諾華、歐加農”和“顧問/發言人局：百時美施貴寶、禮來、森林實驗室、葛蘭素史克、麥克尼爾、大塚、輝瑞公司和惠氏-艾爾斯特 。”
A meta-analysis study by Whittington et al. (2004) in The Lancet found that the combination of published and unpublished studies led to the conclusion that with the possible exception of Prozac, there was no indication of efficacy for the antidepressant treatment of children. In addition, not noted in the article is the fact that the two key studies in favor of Prozac were supported by Eli Lilly, one directly and the other indirectly through funds funneled through NIMH(^1) and that the lead author in both was Graham Emslie (Emslie et al., 2002, 1997). Emslie was task force cochair and second author of the ACNP’s infamous defense of antidepressants. Emslie’s industry affiliations included “Grants/Research Support: Eli Lilly, Novartis, Organon” and “Consultant/Speaker’s Bureau: Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, McNeil, Otsuka, Pfizer, Inc., and Wyeth-Ayerst.”
Whittington 等人（2004 年）的薈萃分析使《柳葉刀》發表了一篇題為“令人沮喪的研究”（2004 年）的社論，其中世界上最古老的醫學雜誌描述了因自殺而失去孩子的家庭的痛苦。 它繼續：
Whittington et al.’s (2004) meta-analysis led The Lancet to publish an editorial titled “Depressing Research” (2004), in which the world’s oldest medical journal described the anguish of families who lose a child to suicide. It went on:
一種所謂的有益藥物可能引發這樣的事件是一場災難。 這種藥物的使用基於對有利研究的選擇性報告的想法應該是不可想像的。 然而，在本週的《柳葉刀》雜誌上，Craig Whittington 及其同事進行的一項薈萃分析表明，這就是在兒童時期使用抗抑鬱藥的研究中正在發生的事情。 他們的結果表明，患者對醫生的信任被濫用了。
That such an event could be precipitated by a supposedly beneficial drug is a catastrophe. The idea of that drug’s use being based on the selective reporting of favourable research should be unimaginable. In this week’s issue of The Lancet, however, a meta-analysis by Craig Whittington and colleagues suggests that this is what has been happening for research into the use of antidepressants in childhood. Their results illustrate an abuse of the trust patients place in their physicians.
同年，英國醫學雜誌 (BMJ) 發表了另一篇研究綜述和對兒童抗抑鬱藥研究的全面批評 (Jureidini et al., 2004)。 其總結要點如下：
In the same year, the British Medical Journal (BMJ) published another review of studies and an overall critique of antidepressant research in regard to children (Jureidini et al., 2004). Its summary points stated the following:
• 對照組的改善很大； 藥物的額外益處具有可疑的臨床意義。
•Improvement in control groups is strong; additional benefit from drugs is of doubtful clinical significance.
• 不利影響已被淡化。
•Adverse effects have been downplayed.
• 抗抑鬱藥不能被自信地推薦為兒童抑鬱症的治療選擇。
•Antidepressant drugs cannot confidently be recommended as a treatment option for childhood depression.
該報告之後是另一篇社論，這次是在英國精神病學雜誌上（Tonkin 等人，2005 年）。 關於兒童抗抑鬱藥，總結如下：
This report was followed by yet another editorial, this time in the British Journal of Psychiatry (Tonkin et al., 2005). Concerning antidepressants in children, it summed up the following:
有效性的證據很弱。 至少有五項使用安慰劑對照的未發表試驗未能顯示抗抑鬱藥優於安慰劑。 在八項已發表的試驗中，四項發現抗抑鬱藥在任何主要結果指標上均未優於安慰劑，只有約三分之一（17/52）的已發表指標顯示藥物優於安慰劑。 即使是統計學上顯著的改善也具有可疑的臨床重要性。
The evidence for efficacy is weak. At least five unpublished trials using a placebo control have failed to show an advantage of antidepressants over placebo. Among eight published trials, four found no statistically significant advantage for antidepressants over placebo on any primary outcome measure, and only about a third (17/52) of all published measures show an advantage for drug over placebo. Even the statistically significant improvements are of dubious clinical importance.
英國主要精神病學雜誌的這篇社論總結道：“目前可用的證據表明，不應推薦 SSRIs 作為抑鬱症兒童的一線治療。”
This editorial in Britain’s major psychiatric journal concluded, “The currently available evidence indicates that the SSRIs should not be recommended as first-line treatment in children with depression.”
鑑於英國主要期刊上的這些驚人的研究報告和社論，為什麼美國主要精神病學期刊的社論無視 FDA 建議在兒童中使用抗抑鬱藥？ 答案很簡單，美國的精神科醫生比英國的精神科醫生更容易落入製藥公司的腰包。
Given these striking research reports and editorials in major journals in Great Britain, why would an editorial in America’s major psychiatric journal, in defiance of the FDA, recommend the use of antidepressants in children? The answer, simply, is that psychiatrists in the United States are much more in the pocket of the drug companies than psychiatrists in Great Britain.
所謂的替代療法（第 135 頁）
So-Called Alternative Treatments (p. 135)
美國精神病學雜誌的社論對 FDA 警告抗抑鬱藥引起的自殺而沒有提供另一種選擇感到惱火。 但所謂的治療兒童抑鬱症的替代方法——心理社會和教育干預——應該已經成為兒童抑鬱症的唯一治療方法。
The editorial in the American Journal of Psychiatry is miffed that the FDA warned about antidepressant-induced suicidality without providing another alternative. But the so-called alternatives for treating depression in children—psychosocial and educational interventions—should have already become the only treatments for childhood depression.
正如我在《樂於助人的心》（1997b）和《抗抑鬱藥事實手冊》（2001a）中所描述的，抑鬱症最終是失去希望。 對曾經有價值或幸福的生活感到絕望。 一個沮喪、不快樂的孩子失去了希望，開始放棄成功地處理生活。
As I describe in The Heart of Being Helpful (1997b) and in The Antidepressant Fact Book (2001a), depression ultimately is loss of hope. It is despair over ever having a worthwhile or happy life. A depressed, unhappy child has lost hope and begun to give up trying to handle life successfully.
在兒童中，這種絕望和失去希望的原因幾乎總是在第一次諮詢時就很明顯，只要它涉及家庭並包括對孩子學校生活的評估。 在兒童中，抑鬱症幾乎總是圍繞著學校和家庭中的問題，從學校的欺凌和家庭虐待到學業失敗、痛苦的同伴關係以及如何撫養孩子的家庭衝突。 治療兒童抑鬱症首先需要找出孩子抑鬱的原因和原因，其次幫助孩子、家庭、學校和孩子生活中的所有其他參與者恢復孩子的希望。 孩子有很多需求，包括穩定的家庭、理性的管教、無條件的愛、刺激的教育環境、身體安全和情感安全。 治療的目的是識別未滿足的需求並幫助成年人滿足這些需求。
In children, the causes of this despair and loss of hope are almost always apparent in the first consultation session, providing it involves the family and includes an evaluation of the child’s school life. In children, depression almost always revolves around problems at school and in the home, everything from bullying at school and abuse at home to academic school failure, painful peer relationships, and family conflicts over how to raise the child. The treatment of depression in children requires, first, finding out how and why the child became depressed and, second, helping the child, the family, the school, and all the other participants in the child’s life restore hope in the child. Children have many needs, including a stable family, rational discipline, unconditional love, stimulating educational environments, physical security, and emotional safety. The object of therapy is to identify the unmet needs and to help adults meet them.
這篇美國精神病學雜誌社論中沒有關於孩子的基本需求以及如何滿足這些需求的內容。 一切都是為了宣傳藥品(drugs)。 社論中沒有關於兒童作為人類的任何內容。 美國精神病學對藥物的依賴導致了道德破產和治療虛無主義(therapeutic nihilism)。 談到美國的孩子，精神病學弊大於利。
There is nothing in this American Journal of Psychiatry editorial about the child’s basic needs and how to meet them. It is all about promoting drugs. There is nothing about children as human beings in the editorial. American psychiatry’s dependence on drugs has led to moral bankruptcy and therapeutic nihilism. When it comes to America’s children, psychiatry is doing far more harm than good.
結論
CONCLUSION
總體而言，FDA 在向公眾和醫學界警告與抗抑鬱藥相關的風險方面進行了一項重要的運動，但花費的時間太長了，該機構仍然無法掌握以下現實： 抗抑鬱藥是致命且無效的。 與此同時，有組織的精神病學強烈反對做出任何改變或調整，以應對抗抑鬱治療缺乏療效和極端危險的知識增加。 個人醫療保健從業者似乎常常對有關抗抑鬱藥的最新負面信息毫不畏懼。 至少，這些藥物在治療抑鬱症兒童時應該是禁忌的，在一個更理想的世界裡，醫生會停止為兒童或成人開這些藥，而是轉向更有效、風險更低的心理社會干預措施來治療抑鬱症患者。 老少皆宜。
Overall, there has been an important movement at the FDA in the direction of warning the public and the medical profession about the risks associated with antidepressants, but it has taken much too long, and the agency remains unable to come to grips with the reality that antidepressants are lethal and ineffective. Meanwhile, organized psychiatry has fought mightily against making any changes or accommodations in response to increased knowledge about the lack of efficacy and extreme hazards associated with antidepressant treatment. Individual health care practitioners too often seem undaunted by the latest negative information about antidepressants. At the least, these drugs should be contraindicated in the treatment of depressed children, and in a more ideal world, doctors would stop prescribing them for children or adults, instead turning to more effective and less risky psychosocial interventions in the treatment of depressed people of all ages.
筆記
1. Jureidini 等人。 (2004) 表示 Emslie 等人的資金。 （1997 年）在文章中歸因於國家心理健康研究所，但“[食品和藥物管理局] 數據顯示該研究是由禮來公司贊助的”（第 880 頁）。
NOTE
1. Jureidini et al. (2004) stated that the funding for Emslie et al. (1997) was attributed to the National Institute of Mental Health in the article, but “[Food and Drug Administration] data show that study was sponsored by Eli Lilly” (p. 880).