第2章 CHAPTER 2
神經阻滯劑引起的失活綜合症（化學腦葉切除術） (^21)
Deactivation Syndrome (Chemical Lobotomy) Caused by Neuroleptics (^21)
2006 年，所謂的非典型或新型抗精神病藥物在價值 115 億美元的抗精神病藥物業務中佔據主導地位。 作為一個整體，抗精神病藥在所有類別的藥物中排名第四，包括抗膽固醇、抗高血壓和抗抑鬱藥物。 這種用於治療精神病和躁狂症的專用藥物能夠獲得如此巨大的市場份額，這要歸功於製藥公司在說服醫生使用這些藥物治療從兒童行為問題到成人失眠等各種精神疾病方面的宣傳技巧 . 自 2002 年以來，抗精神病藥物的銷售額幾乎翻了一番。
In 2006, the so-called atypical or newer neuroleptics increased their dominance over the $11.5 billion business for antipsychotic drugs. As a group, the antipsychotics placed fourth in sales among all categories of drugs, including anticholesterol, antihypertension, and antidepressant drugs. That such specialized drugs for the treatment of psychosis and mania could garner such a huge market share is a tribute to drug company promotional skills in convincing doctors to use these medications for a wide swath of psychiatric problems, from behavior problems in children to insomnia in adults. Antipsychotic drug sales have nearly doubled since 2002.
個別抗精神病藥物獲得以下市場份額：Seroquel (26%)、Risperdal (22%)、Zyprexa (21%)、Abilify (17%) 和 Geodon (6%)，僅剩下 8% 給其他藥物（Vital Signs , 2007)。 根據 IMS Health (2007)，Seroquel 在 2006 年在美國銷售的所有藥物中排名第九，總收入為 30 億美元。
Individual antipsychotic drugs earned the following market shares: Seroquel (26%), Risperdal (22%), Zyprexa (21%), Abilify (17%), and Geodon (6%), leaving a mere 8% for others (Vital Signs, 2007). According to IMS Health (2007), Seroquel was ninth among all drugs in sales in the United States in 2006, with total revenues of $3 billion.
在美國，思瑞康具有越來越大的市場優勢，不僅被批准用於治療躁狂症，還被批准用於治療雙相情感障礙的抑鬱期。 預計 2008 年“全球雙相情感障礙銷售”將產生 17.6 億美元（“New Hope”，2006 年）。 與此同時，世界其他地區還沒有完全接受 Seroquel 的促銷活動，而 Zyprexa 和 Risperdal 領導了全球抗精神病藥物的銷售額，銷售額分別為 47 億美元和 46 億美元（IMS Health，2007 年）。 它們在所有醫療藥物中排名第七和第八。
In the United States, Seroquel has the growing market advantage of being approved not only to treat mania but also to treat the depression phase of bipolar disorder. It is expected to generate $1.76 billion from “global bipolar disorder sales” in 2008 (“New Hope,” 2006). Meanwhile, the rest of the world has not quite caught on to the Seroquel promotional campaign, and Zyprexa and Risperdal led global sales for antipsychotic drugs, with $4.7 billion and $4.6 billion in sales, respectively (IMS Health, 2007). They were seventh and eighth among all medical drugs.
儘管大肆宣傳相反，但很快就發現這些新藥的危害不亞於舊藥。 研究表明不良反應發生率較低，只是使用了相對較低的劑量（Smith，2001）。 鑑於這些藥物既不比奮乃靜（Trilafon；見後續部分）等老藥更安全也更有效，而且它們的成本更高（Rosenheck 等人，2006 年），這是藥品營銷的又一勝利。
Despite enormous hype to the contrary, it soon became apparent that these newer medications were no less harmful than the older ones. Studies showing a lower rate of adverse effects simply used comparatively lower doses (Smith, 2001). Given that these drugs are neither safer nor more effective than older drugs like perphenazine (Trilafon; see the subsequent sections), and given that they cost a great deal more (Rosenheck et al., 2006), this was another triumph of pharmaceutical marketing.
非典型抗精神病藥物是較弱的 D 受體阻滯劑的神話（第 22 頁）
THE MYTH THAT ATYPICAL ANTIPSYCHOTIC DRUGS ARE WEAKER D BLOCKERS (p. 22)
十幾種藥物，幾乎都是使用多年的藥物，都可以歸類為精神安定藥。 吩噻嗪衍生物最初是最常用的一類精神抑製藥物。 氯丙嗪是原型，在法國開發並於 1953 年由 Heinz Lehmann 引入北美。 它在加拿大和英國的品牌名稱是 Largactil，在美國的品牌名稱是 Thorazine。 抗抑鬱藥阿莫沙平（Asendin）被代謝成一種精神安定藥，具有相似的作用，更重要的是，副作用，如遲發性運動障礙。 所有經典的安定藥都會阻斷多巴胺，但它們也會影響其他神經遞質系統。
More than a dozen drugs, almost all of them in use for many years, can be classified as neuroleptics. The phenothiazine derivatives were originally the most commonly used class of neuroleptic drugs. Chlorpromazine is the prototype, developed in France and introduced into North America in 1953 by Heinz Lehmann. Its brand name in Canada and England is Largactil, and in the United States, Thorazine. The antidepressant amoxapine (Asendin) is metabolized into a neuroleptic and has similar effects and, more important, adverse effects, such as tardive dyskinesia. All the classic neuroleptics block dopamine, but all of them also affect other neurotransmitter systems.
最重要的是，所有較新的抗精神病藥物——阿立哌唑 (Abilify)、齊拉西酮 (Geodon)、帕利哌酮 (Invega)、利培酮 (Risp erdal)、喹硫平 (Seroquel)、奧氮平加百憂解 (Symbyax) 和奧氮平 (Zyprexa)——也可阻斷 多巴胺。 事實上，它們在藥理學上被歸類為對 D2 具有高親和力——這意味著它們與 D2 受體強烈結合，從而導致強烈的阻斷。 普通讀者可以在 Drug Facts and Compares (2007, p. 1280) 及其表“抗精神病受體親和力” (^1) 中找到此信息（另見 Janssen，2007，關於 Risperdal）。
Most important, all of the newer antipsychotics—aripiprazole (Abilify), ziprasidone (Geodon), paliperidone (Invega), risperidone (Risp erdal), quetiapine (Seroquel), olanzapine plus Prozac (Symbyax), and olanzapine (Zyprexa)—also block dopamine. In fact, they are pharmacologically classified as having a high affinity for D2 —meaning that they bind strongly to D2 receptors, causing a strong blockade. The casual reader can find this information in Drug Facts and Comparisons (2007, p. 1280) and its table “Antipsychotic Receptor Affinity” (^1) (see also Janssen, 2007, regarding Risperdal).
除了教科書摘要外，許多對照研究表明，非典型藥物會產生高受體佔有率。在引入奧氮平後不久，Kapur 等人。 (1998) 對 12 名診斷為精神分裂症的患者使用正電子發射地形圖 (PET) 成像來確定由臨床劑量的新型非典型抗精神病藥引起的 D2 受體佔據。 患者服藥直至達到穩態血漿水平。 每天服用 5-20 毫克的患者的入住率為 43% 至 80%，而每天服用 30-40 毫克的患者的入住率為 83% 至 88%。 在其通常的 10-20 mg 臨床劑量範圍內，由抗精神病藥引起的佔用失活綜合徵的發生率從 71% 到 80% 不等。 作者將這種受體佔據程度描述為與利培酮相似。
In addition to textbook summaries, many controlled research studies show that atypicals produce high receptor occupancy. Shortly after olanzapine was introduced, Kapur et al. (1998) used positron emission topography (PET) imaging with 12 patients diagnosed schizophrenic to determine D2 receptor occupancy caused by the new atypical antipsychotic at clinical doses. The patients were medicated until steady state plasma levels were achieved. Patients taking 5–20 mg/day showed 43% to 80% occupancy, while patients taking 30–40 mg/day showed 83% to 88% occupancy. In its usual clinical dose range of 10–20 mg, occupancy Deactivation Syndrome Caused by Neuroleptics varied from 71% to 80%. The authors described this degree of receptor occupancy as similar to that of risperidone.
作為比較，氟哌啶醇（Haldol）通常被認為是最有效的精神安定藥之一，最容易引起錐體外系反應。 在一項對首發精神分裂症患者的雙盲研究中，受試者被隨機分配每天服用 1、2、3 或 5 毫克（Kapur 等，2000）。 如果患者對較低劑量沒有反應，則將他們提高到 5 mg/天的極限。 這些是相對較小的劑量。 中度症狀或老年或虛弱患者的推薦初始劑量為 1-6 毫克/天（Drug Facts and Compares, 2007）。 對於嚴重或慢性患者，為 6-15 毫克/天，為了及時控製而增加更高的劑量。
As a comparison, haloperidol (Haldol) is generally considered to be among the most potent neuroleptics and the most likely to cause extrapyramidal reactions. In a double-blind study of first-episode patients diagnosed with schizophrenia, the subjects were randomly assigned to take 1, 2, 3, or 5 mg/day (Kapur et al., 2000). If the patients did not respond to the lower doses, they were raised to the limit of 5 mg/day. These are relatively small doses. The recommended initial dose for moderate symptoms or geriatric or debilitated patients is 1–6 mg/day ( Drug Facts and Comparisons, 2007). For severe or chronic patients, it is 6–15 mg/day, with higher doses for prompt control.
所有患者均在 4 週時進行評估。 患者表現出廣泛的 D2 佔用率（38% 至 87%）。 當入住率超過 78% 時，錐體外系反應的可能性增加。 請注意，所有這些入住率數據與同一團隊（Kapur 等人，1998 年）為 Zyprexa 和 Risperdal 發現的數據在同一範圍內。 這打破了非典型人群對 D2 受體的佔有率較弱的神話。
All patients were evaluated at 4 weeks. Patients showed a wide range of D2 occupancy (38% to 87%). The likelihood of extrapyramidal reactions increased when occupancy exceeded 78%. Note that all of these occupancy figures are within the same range as those found by the same team (Kapur et al., 1998) for Zyprexa and Risperdal. This explodes the myth that atypicals have weaker occupancy of D2 receptors.
雷明頓等人。 (2006) 對長效注射劑型利培酮進行了類似的 PET 研究，劑量為每 2 週 25、50 或 75 mg。 達到穩定後，9 名診斷為精神分裂症或分裂情感障礙的患者在註射後 3 天和下一次注射前 5 天進行了兩次掃描。 根據雷明頓等人的說法。 （2006 年），“所有三種劑量的可注射利培酮都顯示出高於與最佳臨床反應相關的 65% 閾值的 D(2) 峰值佔用水平； 75 毫克劑量接近與錐體外系反應風險增加相關的 80% 閾值。” 顯然，這一切都在劑量中。 所有非典型藥物都是有效的多巴胺阻滯劑。
Remington et al. (2006) conducted a similar PET study of the long-acting injectable form of risperidone at doses of 25, 50, or 75 mg every 2 weeks. After reaching stabilization, nine patients with a diagnosis of schizophrenia or schizoaffective disorder were scanned twice, 3 days postinjection and 5 days before the next injection. According to Remington et al. (2006), “all three doses of injectable risperidone showed peak D(2) occupancy levels above the 65% threshold associated with optimal clinical response; the 75-mg dose approximated the 80% threshold linked to increased risk of extrapyramidal reactions.” Clearly, it is all in the dose; all of the atypicals are potent dopamine blockers.
事實上，一些較舊的神經安定藥對 D2 的親和力或影響比較新的要小。 例如，莫林酮 (Moban) 對 D2 的親和力明顯較弱（藥物事實和比較，2007 年），但它很少使用。
Indeed, some of the older neuroleptics have less affinity or impact on D2 than the newer ones. Molindone (Moban), for example, has a decidedly weak affinity for D2 ( Drug Facts and Comparisons, 2007), but it is rarely used.
非典型抗精神病藥通常用於兒童。莫蘭蓋茨等人。 （2007 年）來自馬薩諸塞州總醫院和哈佛醫學院的研究人員檢查了用利培酮治療的幼年和成年大鼠的腦組織。他們發現利培酮“在兩個年齡組中都對 D2 受體具有高親和力，這與其他已發表的報告一致”（第 451 頁）。然而，他們發現長期給藥（3 週）對幼年動物的 D2 受體產生更深遠的影響，導致這些受體的數量增加。與成年大鼠 30% 相比，幼年大鼠的 D2 受體結合增加了 90%，“這進一步反映了發育中的動物對長期接觸利培酮的敏感性更高”（第 453 頁）。這種上調（響應於多巴胺阻斷而增加的多巴胺受體）被認為是錐體外系反應和遲發性運動障礙的可能機制。不幸的是，兒童和青少年的抗精神病藥或精神安定藥處方繼續增加。
Atypical neuroleptics are commonly given to children. Moran-Gates et al. (2007) from the Massachusetts General Hospital and Harvard Medical School examined the brain tissue of juvenile and adult rats treated with risperidone. They found that risperidone “has high affinity for D2 receptors in both age groups, which is in agreement with other published reports” (p. 451). However, they found that long-term dosing (3 weeks) had a much more profound impact on the D2 receptors of the juvenil enimals, causing an increase in the number of these receptors. There was a 90% increase in D2 receptor binding in juvenile rats, compared to 30% in adults, “which further reflects the greater sensitivity of developing animals” (p. 453) to longer-term exposure to risperidone. This up-regulation (increased dopamine receptors in response to dopamine blockade) is considered the likely mechanism of extrapyramidal reactions and tardive dyskinesia. Unfortunately, the prescription of antipsychotic or neuroleptic drugs to children and youth continues to rise.
也有很多觀察結果表明，較舊的非典型抗精神病藥對更多種類的神經遞質系統的影響是較新的（例如，Lieberman 等人，2005b）。 然而，沒有理由懷疑對多個神經遞質系統的影響會提高安全性或有效性。 相反，它似乎必然會增加不利影響的範圍。 但即使就它們對多種神經遞質系統的影響而言，非典型性也不是唯一的。 所有較老的精神安定藥都會影響至少三種神經遞質系統，例如血清素和組胺，有幾種會影響其中的四五個。 例如，老式的硫利達嗪（Mellaril）影響至少五個神經遞質系統。
Much is also made of the observation that the newer atypical neuroleptics impact on a greater variety of neurotransmitter systems than the older ones (e.g., Lieberman et al., 2005b). However, there is no reason to suspect that impacting on multiple neurotransmitter systems would improve either safety or efficacy. To the contrary, it would seem bound to increase the spectrum of adverse effects. But even in regard to their impact on multiple neurotransmitter systems, the atypicals are not unique. All of the older neuroleptics affect at least three neurotransmitter systems, such as serotonin and histamine, and several affect four or five of them. For example, old-fashioned thioridazine (Mellaril) impacts at least five neurotransmitter systems.
儘管有這些事實，包括 Lieberman 等人在內的機構精神病學。 （2005a），多年來被引用最多的精神抑製藥研究（見後續段落）——繼續將非典型藥物描述為對 D2 受體具有顯著且臨床上重要的較低親和力。為什麼這麼多專家會接受製藥公司的宣傳，認為非典型藥物對 D2 的親和力相對較低，而且它們對眾多受體的更大影響在某種程度上是一種優勢？因為專家在專業和經濟上與製藥公司及其利益密切相關。正如 Lieberman 等人發起的大型國家心理健康研究所 (NIMH) 贊助的臨床抗精神病干預有效性試驗 (CATIE) 研究一樣。 （2005a），幾乎所有的專家都對製藥公司的“受體”有很高的親和力，他們想方設法作為顧問、研究人員和演講局成員賺取可觀的錢。 CATIE 研究的第一作者 Jeffrey Lieberman 報告說，他收到了來自 AstraZeneca Pharmaceuticals、Bristol-Myers Squib、GlaxoSmithKline、Janssen Pharmaceutica 和 Pfizer 的研究資助，以及來自 AstraZeneca、Bristol-Myers Squid、Eli Lilly、Forest Pharmaceuticals 的諮詢和教育費用，葛蘭素史克、楊森製藥、諾華、輝瑞和索爾維。前七位 CATIE 作者報告說與製藥公司有著廣泛的聯繫，第八位作者 Sonia Davis 是 Quintiles 的員工，該公司是製藥行業的大型支持公司，專門幫助加快藥物進入市場。第九位作者也與製藥公司有聯繫，最後三位為政府工作。令人驚訝的是，NIMH 將完全依靠與製藥公司有聯繫的專家進行其最重要的抗精神病藥物研究。
Despite these facts, establishment psychiatry—including Lieberman et al. (2005a), the most cited neuroleptic study in years (see subsequent paragraphs)—continues to describe the atypicals as possessing a significantly and clinically important lower affinity for D2 receptors. Why would so many experts buy into drug company propaganda that the atypicals have a relatively low affinity for D2 and that their greater impact on numerous receptors is somehow an advantage? Because the experts are closely allied professionally and economically with the drug companies and their interests. As in the giant National Institute of Mental Health (NIMH)-sponsored Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study by Lieberman et al. (2005a), virtually all the experts have a high affinity for drug company “receptors,” finding ways of making considerable money as consultants, researchers, and speakers’ bureau members. Jeffrey Lieberman, first author in the CATIE study, reports having received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squib, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer and consulting and educational fees from AstraZeneca, Bristol-Myers Squid, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Pfizer, and Solvay. The first seven CATIE authors report extensive ties to drug companies, and the eighth, Sonia Davis, is an employee of Quintiles, a giant support fi rm for the drug industry, specializing in helping speed drugs to the market. The ninth author also has ties to drug companies, and the last three worked for the government. It is astonishing that NIMH would conduct its most important study of antipsychotic drugs by relying entirely and exclusively on experts with drug company ties.
儘管大多數藥物處方編寫者似乎已經忘記了這一事實，但所有新型抗精神病藥物的多巴胺阻斷能力意味著它們的不良反應將包括舊精神安定藥的最壞影響，包括遲發性運動障礙和神經安定藥惡性綜合徵的產生 （第 4 章；參見 Physicians’ Desk Reference，1973、1978、1995-2007 中的各個藥物標籤）。 它還有助於解釋其停用的主要影響。 此外，較新的抗精神病藥物會帶來更大的風險，導致潛在的危及生命的疾病，包括顯著肥胖、膽固醇升高以及可能致命的糖尿病、心血管疾病和胰腺炎。
Although this fact seems to have been lost on most medication prescription writers, the dopamine-blocking capacity of all the newer antipsychotic drugs means that their adverse effects will include the worst effects of the older neuroleptics, including the production of tardive dyskinesia and neuroleptic malignant syndrome (chapter 4; see the individual drug labels in the Physicians’ Desk Reference, 1973, 1978, 1995–2007). It also helps to account for their primary effect of deactivation. In addition, the newer antipsychotic drugs pose even greater risks of causing potentially life-threatening disorders, including marked obesity, elevated cholesterol, and potentially lethal diabetes, cardiovascular disease, and pancreatitis.
總體而言，非典型的概念是一種營銷策略，幾乎沒有臨床現實。這些藥物將與較舊的精神抑製藥相關的風險與非常嚴重的新風險結合在一起。儘管如此，醫療保健提供者，包括經驗豐富的醫生，似乎都被這些說法所吸引。例如，Adamou 和 Hale (2004) 對他們的三名患者出現錐體外系反應表示驚訝，其中包括一名嚴重的“眼球上吊(oculogyric crisis)、構音障礙、斜頸、吞嚥困難、震顫和強直”。 （有人想知道他是否有體溫升高和神經阻滯劑惡性綜合徵的漏診病例。）不同的神經阻滯劑需要不同的劑量才能產生類似的效果，並且可能會誇大一種或另一種毒性作用。它們在體內保持活躍的時間長度也有所不同。儘管如此，除了一些例外，這些藥物中的大多數可以被描述為具有相同特徵和副作用的單一組。沒有證據表明這些藥物中的任何一種對心理功能有顯著不同的影響，除了一些產生更多鎮靜作用的傾向。在我的臨床經驗中，例如，Zyprexa、Seroquel、Abilify 和 Risperdal 在抑制意志和動機方面至少與任何較舊的抗精神病藥物一樣有效。
Overall, the concept of atypical is a marketing ploy with little clinical reality. These drugs combine the risks associated with the older neuroleptics with very serious new risks. Nonetheless, health care providers, including sophisticated physicians, seem taken in by the claims. Adamou and Hale (2004), for example, expressed surprise when three of their patients developed extrapyramidal reactions, including one severe case with “oculogyric crisis, dysarthria, torticollis, dysphagia, tremor, and rigidity.” (One wonders if he had an elevated temperature and a missed case of neuroleptic malignant syndrome.) Different neuroleptics require different doses for similar effects and may exaggerate one or another toxic effect. They also vary in the length of time they remain active in the body. Nonetheless, with some exceptions, most of these drugs can be described as a single group sharing the same characteristics and side effects. There is no evidence that any of these drugs has a substantially different impact on mental functioning, other than the tendency for some to produce more sedation. In my clinical experience, Zyprexa, Seroquel, Abilify, and Risperdal, for example, are at least as potent in suppressing the will and motivation as any of the older antipsychotic drugs.
各種精神安定藥也用於非精神病目的，通常以較小的劑量用於較短的持續時間。 然而，這些有限的用途有時會產生嚴重的影響。 利血平 (Serpasil) 是一種精神安定藥，更常用於抑制遲發性運動障礙的症狀（第 4 章）。 丙氯拉嗪 (Compazine) 用作止吐藥，很少用作安定藥。 如果給予足夠劑量以表現出精神活性，這些藥物會產生與其他抗精神病藥物相同的情緒冷漠。
Various neuroleptics are also used for nonpsychiatric purposes, usually in smaller doses for shorter durations. However, severe effects can sometimes develop from these limited uses. Reserpine (Serpasil) is a neuroleptic that is more often used to suppress the symptoms of tardive dyskinesia (chapter 4). Prochlorperazine (Compazine) is used as an antiemetic and rarely as a neuroleptic. If given in sufficient doses to manifest psychoactive effects, these drugs produce the same emotional indifference as the other antipsychotic drugs.
其他具有安定作用的非精神科製劑包括一些抗組胺藥，例如甲地拉嗪 (Tacaryl) 和曲美拉嗪 (Temaril)； 一些止吐藥，如硫乙拉嗪（Torecan）； 以及麻醉輔助劑，例如丙丙嗪 (Largon) 和異丙嗪 (Phenergan)，它們也可用作抗噁心、抗暈車劑。 這些藥物的效力不如精神病學中使用的抗精神病藥，但在足夠的劑量下，它們具有相似的副作用。
Other nonpsychiatric preparations with neuroleptic effects include some antihistamines, such as methdilazine (Tacaryl) and trimeprazine (Temaril); some antinausea drugs, such as thiethylperazine (Torecan); and adjuncts to anesthesia, such as propiomazine (Largon) and promethazine (Phenergan), which is also used as an antinausea, anti-motion-sickness agent. These drugs are less potent than neuroleptics used in psychiatry, but in sufficient doses, they have similar adverse effects.
甲氧氯普胺 (Reglan) 用於胃食管反流、糖尿病胃淤滯症和止吐藥。 Reglan 的作用與較老的精神抑製藥相同。 眾所周知，Reglan 可以引起與常規使用的精神抑製藥相同的不可逆轉的神經系統影響。一些研究人員估計，Reglan 引起的遲發性運動障礙的患病率是《醫師案頭參考》中報導的 0.2% 的 100 倍。
Metoclopramide (Reglan) is used in gastroesophageal reflux, dia-betic gastric stasis, and as an antiemetic. Reglan is identical to older neuroleptics in its effects. It is well established that Reglan can cause irreversible neurological effects identical to the routinely used neuroleptics. Some researchers estimate the prevalence of Reglan-induced tardive dyskinesia to be 100 times more than the 0.2% reported in the Physicians’ Desk Reference.
我評估了許多因胃問題接受 Reglan 治療的嬰兒和兒童的病例，這些病例導致嚴重和多樣的神經系統疾病、冷漠、生長遲緩和發育遲緩。 在我熟悉的案例中，醫生們意識到孩子們的病情正在下降，但未能確定雷格倫是肇事者。 在繼續 Reglan 的同時，他們讓孩子們接受了昂貴、危險和侵入性的醫學檢查，以尋找難以捉摸的原因。 在我的一些法醫案件中，醫生最終指責母親“毒害”了他們的孩子，而實際上，醫生自己正在分配毒藥。
I have evaluated numerous cases of infants and children who have been treated with Reglan for gastric problems, resulting in severe and varied neurological disorders, apathy, retarded growth, and developmental delay. In cases familiar to me, the doctors recognized that the condition of the children was declining but failed to identify Reglan as the offending agent. While continuing the Reglan, they submitted the children to costly, dangerous, and intrusive medical tests in search of the elusive cause. In some of my forensic cases, doctors ended up blaming the mothers for “poisoning” their children when, in reality, the doctors themselves were dispensing the poison.
非典型神經病患者之間的差異示例 (p. 26)
EXAMPLES OF DIFFERENCES AMONG ATYPICAL NEUROLEPTICS (p. 26)
儘管在許多方面它們可以被視為一組藥物，特別是在產生腦葉切開樣激活方面，但抗精神病藥或抗精神病藥之間存在顯著差異。 利培酮和氯氮平就是例子。
Although in many ways they can be treated as a single group of drugs, especially in regard to producing lobotomy-like activation, there are significant differences among the antipsychotic or neuroleptic drugs. Risperidone and clozapine provide examples.
氯氮平（Clozaril）
Clozapine (Clozaril)
唯一對 D2 缺乏高親和力的非典型抗精神病藥物是氯氮平。 它具有相對較弱的阻斷 D2 的傾向，因此它是唯一一種不太可能產生常見的不良神經系統影響（如遲發性運動障礙）的藥物。 然而，氯氮平經常導致白細胞計數（粒細胞缺乏症）危險且可能致命的下降，因此需要通過血液檢查進行持續監測，並且很少開處方。 具有諷刺意味的是，雖然氯氮平被歸類為一種非典型的精神安定藥，但它是一種非常古老的藥物，最初因其毒性而在一些歐洲國家下架，後來在 1989 年大張旗鼓地重新引入美國市場之前，就好像它是 一種前景廣闊的全新藥物。
The only atypical antipsychotic drug that lacks a high affinity for D2 is clozapine. It has a relatively weak tendency to block D2 , and therefore it is the only one that is less likely to produce common adverse neurological effects like tardive dyskinesia. However, clozapine so often produces a dangerous and potentially lethal drop in the white blood cell count (agranulocytosis) that it requires continuous monitoring with blood tests and is infrequently prescribed. Ironically, while classified as an atypical neuroleptic, clozapine is a very old drug that was originally taken off the market in some European countries because of its toxicity, before it was later reintroduced into the U.S. market in 1989 with much fanfare, as if it were a brand new drug with great promise.
氯氮平引起特別高的癲癇發作率，第一年估計為 4% 至 5%。 這是一個非常嚴重的危險。 該藥物經常產生嚴重的低血壓和增加的心率，可能導致心血管衰竭。 它也可能導致高血壓。 它會引起發燒和流感樣綜合徵。 已經報導了呼吸停止（Westlin，1991）。 它對老年人尤其危險，他們可能有跌倒、心血管問題或譫妄的風險（Pitner 等，1995）。
Clozapine causes a particularly high rate of grand mal seizures, estimated at 4% to 5% in the first year. This is a very serious hazard. The drug frequently produces severe low blood pressure and increased heart rate, potentially resulting in cardiovascular collapse. It can also cause hypertension. It can cause fever and a flulike syndrome. Respiratory arrest has been reported (Westlin, 1991). It can be particularly hazardous for the elderly, who may risk falls, cardiovascular problems, or delirium (Pitner et al., 1995).
雖然不是有效的 D2 阻滯劑，但氯氮平在邊緣（情緒調節）系統中似乎比在紋狀體區域（控制情緒和自主運動；Chiodo 等，1983）更有效。 由於該藥物對額葉和邊緣系統的影響更大，人們認為它會產生更多的“治療”效果，同時錐體外系副作用更少。 該藥物可能確實會在某些患者中產生更嚴重的失活或腦葉切除樣綜合徵，這說明它有時比其他神經安定藥效果更好。 因此，它可能有更大的風險產生永久性額葉損傷和遲發性癡呆或遲發性精神病。
Although not a potent D2 blocker, clozapine seems to be more potent in this regard in the limbic (emotion-regulating) system than in the striatal region (which controls both emotion and voluntary movement; Chiodo et al., 1983). Because of the drug’s greater impact on the frontal lobes and limbic system, it was thought that it would produce more “therapeutic” effect with fewer extrapyramidal side effects. The drug probably does produce a more profound deactivation or lobotomy-like syndrome in some patients, accounting for its reputation for sometimes working better than other neuroleptics. As a result, it probably has a greater risk of producing permanent frontal lobe damage and tardive dementia or tardive psychosis.
根據歐洲的經驗，早在 1977 年，Ungerstedt 和 Ljungberg 就表達了對氯氮平對高級腦功能特別有害的影響的擔憂。 Chouinard 和 Jones (1982) 指出了在停用氯氮平後對反應性精神病的觀察，並評論說：“氯氮平能夠誘發超敏性精神病的這一令人信服的證據可能與該藥物的半衰期短及其對中腦邊緣多巴胺的更大親和力有關。受體。”觀察結果還表明，戒斷性精神病可能比老年精神抑製藥更頻繁和更嚴重（見第 5 章）。有報導稱氯氮平戒斷綜合徵包括激動、不安、顫抖、運動障礙、精神錯亂、出汗、攻擊性和自殺行為等新症狀（“氯氮平戒斷綜合徵”，1994 年；Richardson 等人，1993 年）。當抗精神病藥物劑量減少或停止時，會發生超敏感或戒斷性精神病。它可以被視為遲發性運動障礙的心理等價物，因為兩者都可能是由於先前受阻的多巴胺功能的反應性過度活躍所致（第 5 章）。
Concern about clozapine’s especially damaging effect on higher brain function was voiced as early as 1977 by Ungerstedt and Ljungberg, based on the European experience. Chouinard and Jones (1982) pointed to observations on reactive psychoses following withdrawal from clozapine and commented, “This convincing evidence of clozapine’s ability to induce supersensitivity psychosis might be related to both the short half-life of the drug and its greater affinity for mesolimbic dopamine receptors.” Observations have also indicated that withdrawal psychoses may be more frequent and severe than with the older neuroleptics (see chapter 5). There is a report of a clozapine withdrawal syndrome that includes new symptoms of agitation, restlessness, shakiness, dyskinesia, confusion, sweating, aggression, and suicidal behavior (“Clozapine Withdrawal Syndrome,” 1994; Richardson et al., 1993). Supersensitive or withdrawal psychoses occur when the antipsychotic drug dose is reduced or stopped. It can be viewed as the mental equivalent of tardive dyskinesia, since both probably result from a reactive hyperactivity of the previously blocked dopamine functions (chapter 5).
氯氮平的抗膽鹼能作用可引起混亂和譫妄以及鎮靜和嗜睡。 戒斷性精神病的嚴重程度可能是由於膽鹼能反彈。 氯氮平可加重或導致唾液分泌過多、青光眼、便秘和腸梗阻以及尿瀦留（Baldessarini 等，1991）。 體重增加也是一個潛在的非常嚴重的問題。
Clozapine’s anticholinergic effects can cause confusion and delirium as well as sedation and lethargy. The severity of withdrawal psychosis may be due to cholinergic rebound. Clozapine can aggravate or cause hypersalivation, glaucoma, constipation and ileus, and urinary retention (Baldessarini et al., 1991). Weight gain is also a potentially very serious problem.
據報導，雖然產生較少的錐體外系反應，但氯氮平可產生與使用安定藥有關的每一種神經系統反應，包括安定藥惡性綜合徵（Anderson 等人，1991；Dasgupta 等人，1991）和遲發性運動障礙（Weller 等人，1993） ）。
While reportedly producing fewer extrapyramidal reactions, clozapine can produce every one of the neurological reactions associated with neuroleptic use, including neuroleptic malignant syndrome (Anderson et al., 1991; Dasgupta et al., 1991) and tardive dyskinesia (Weller et al., 1993).
氯氮平的功效一直受到公眾的高度吹捧，但實際上是值得懷疑的，即使按照傳統標準（見 Winslow 的精神病學家 Herbert Meltzer 的評論，1990）。 此外，在精神抑製藥領域，與大腦致殘原則一致，更好或更強的藥物實際上是一種更具抑制性和潛在更具破壞性的藥物。
Clozapine’s efficacy has been highly touted to the public but in reality is questionable, even by conventional standards (see comments of psychiatrist Herbert Meltzer in Winslow, 1990). Furthermore, in the arena of neuroleptics, consistent with the brain-disabling principles, a better or stronger drug is in reality a more suppressive and potentially more destructive drug.
大腦致殘原則的一個基本原則是，所有精神科藥物都以類似的方式影響人類和動物，沒有針對任何疾病的特異性。 佐爾格等人。 (2004) 發現氯氮平以相似的方式影響人類和大鼠的生理機能，包括擾亂睡眠-覺醒週期和產生異常的大腦溫度。
A basic tenet of the brain-disabling principles is that all psychiatric drugs affect human beings and animals in a like fashion, without specificity for any disorder. Sorge et al. (2004) found that clozapine affects human and rat physiology in similar ways, including disrupting the sleep–wake cycle and producing abnormal brain temperatures.
利培酮（利培酮） (p. 28)
Risperidone (Risperdal)
第 1 章檢查了三項利培酮研究，這些研究證實了精神科治療中的大腦功能障礙原理，證明該藥物會導致正常人和被診斷患有精神分裂症的患者的額葉和顳葉代謝抑制（失活, deactivation），並且這種禁用 效果與症狀表達的減少相關，例如幻覺和妄想，這需要一個功能齊全的大腦。 如前所述，如果進行測量，該效果還與自發性心理活動和語言表達的總體減少相關，這是對精神抑製藥反應而出現精神運動遲緩的患者的常見臨床現象。
Chapter 1 examined three risperidone studies that confirm the brain-disabling principles of psychiatric treatment by demonstrating that the drug causes a metabolic suppression in the frontal and temporal lobes (deactivation) that occurs in both normal persons and patients diagnosed with schizophrenia, and that this disabling effect correlates with a reduction in the expression of symptoms, such as hallucinations and delusions, that require a fully functioning brain. As previously noted, if measured, the effect would also correlate with an overall reduction in spontaneous mental activity and verbal expressions, which are common clinical phenomena in patients who experience psychomotor retardation in response to neuroleptics.
Risperdal 於 1994 年首次作為非典型神經安定藥上市。臨床試驗大部分持續了幾週，時間太短，無法確定遲發性運動障礙和許多其他不良反應的發生率。事實上，用於批准氯氮平和利培酮的簡短對照臨床試驗並未提供足夠的信息來確定療效或安全性，因為這些藥物將在個別患者中使用數月或數年，而不是數週（見章節13）。未來幾年服用藥物的患者將提供實驗數據。然而，由於 Risperdal 是一種強效的多巴胺阻滯劑，因此應該預料到它會引起與較老的精神抑製藥相似的不良反應。以我自己的經驗，我評估了許多由 Risperdal、Zyprexa 和 Geodon 引起的遲發性運動障礙病例。與此同時，美國食品和藥物管理局 (FDA) 要求氯氮平和利培酮標籤上的遲發性運動障礙和抗精神病藥惡性綜合症警告與舊抗精神病藥標籤上的警告相同。
Risperdal was first marketed in 1994 as an atypical neuroleptic. The clinical trials, most of which lasted a few weeks, were too short to determine the rate of tardive dyskinesia and many other adverse effects. Indeed, the brief controlled clinical trials used for the approval of both clozapine and risperidone do not provide sufficient information to determine either efficacy or safety since the drugs would be used for months and years in individual patients, rather than for a few weeks (see chapter 13). Patients taking the medications over the coming years will provide the experimental data. However, since Risperdal is a potent dopamine blocker, it should have been anticipated that it would cause similar adverse reactions as the older neuroleptics. In my own experience, I have evaluated many cases of tardive dyskinesia caused by Risperdal, Zyprexa, and Geodon. Meanwhile, the Food and Drug Administration (FDA) has required the same tardive dyskinesia and neuroleptic malignant syndrome warnings on the labels of clozapine and risperidone as on the labels of the older neuroleptics.
利培酮特別傾向於產生不良興奮作用，包括失眠、激動和焦慮。 可能由於這些刺激作用，它可能會增加引起躁狂的風險（Dwight 等，1994）。 刺激也可能是利培酮引起的憤怒髮作和恢復濫用藥物的衝動的原因，儘管該報告的作者認為這些反應是由於對增加的心理洞察力感到絕望（Post，1994）。 除了刺激之外，該藥物還經常引起疲勞、嗜睡或失眠。
Risperdal has a particular tendency to produce adverse stimulant effects, including insomnia, agitation, and anxiety. Probably because of these stimulant effects, it may have an increased risk of causing mania (Dwight et al., 1994). Stimulation may also account for risperidone-induced rage attacks and the urge to resume substance abuse, although the author of the report believes that these reactions are due to despair from increased psychological insight (Post, 1994). In addition to stimulation, the drug frequently causes fatigue, sleepiness, or insomnia.
利培酮引起與其他精神安定藥一起發現的所有錐體外系反應，包括遲發性運動障礙（Addington 等，1995）和精神抑制惡性綜合徵（Mahendra，1995；Singer 等，1995；見第 4 章）。 現在判斷遲發性運動障礙的發生率是否與其他精神抑製藥不同還為時過早。
Risperdal causes all the extrapyramidal reactions found with other neuroleptics, including tardive dyskinesia (Addington et al., 1995) and neuroleptic malignant syndrome (Mahendra, 1995; Singer et al., 1995; see chapter 4). It is too early to tell if the rate of tardive dyskinesia will differ from that of other neuroleptics.
一份報告發現，即使是小劑量的利培酮（平均劑量為 1.7 毫克/天）也會在三分之一患有癡呆症的老年人中產生或加重急性錐體外系反應（貝克，1996 年）。 在 41 名患者中，6 人出現新的帕金森病，5 人先前的帕金森病惡化，1 人出現頸肌張力障礙，1 人出現抗精神病藥惡性綜合徵，同時服用 Tegretol 和 Mellaril。
A report found that even small doses of Risperdal (average dose of 1.7 mg/day) produced or worsened acute extrapyramidal reactions in one-third of an elderly population suffering from dementia (Baker, 1996). Among 41 patients, 6 developed new parkinsonism, 5 had a worsening of previous parkinsonism, one developed cervical dystonia, and one developed neuroleptic malignant syndrome while also taking Tegretol and Mellaril.
像大多數抗精神病藥一樣，利培酮會導致大鼠和小鼠患上乳腺癌，但這一發現並沒有得到 FDA 的足夠重視。 或製藥公司。
Like most neuroleptics, Risperdal can cause mammary cancer in rats and mice, but this finding has not been taken seriously enough by the FDA, the profession. or the drug companies.
干預效果的臨床抗精神病試驗 (CATIE) (p. 29)
CLINICAL ANTIPSYCHOTIC TRIALS OF INTERVENTION EFFECTIVENESS (CATIE) (p. 29)
2005 年，一項名為 CATIE 的 NIMH 多中心研究比較了較老的抗精神病藥奮乃靜 (Trilafon) 和非典型抗精神病藥奧氮平 (Zyprexa)、喹硫平 (Seroquel)、利培酮 (Risperdal) 和齊拉西酮 (Geodon；Lieberman 等人，2005a；另見 Nasrallah , 2007; Rosenheck 等人, 2006; Weiden, 2007a)。 第一階段涉及 1,460 名被診斷患有精神分裂症的患者，最初在一項雙盲研究中隨機分配到五種抗精神病藥中的一種。 該研究持續了 18 個月，在 1、3、6、9、12、15 和 18 個月評估了安全性和耐受性結果。
In 2005, an NIMH multisite study called CATIE compared the older neuroleptic perphenazine (Trilafon) and atypical neuroleptics olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon; Lieberman et al., 2005a; see also Nasrallah, 2007; Rosenheck et al., 2006; Weiden, 2007a). Phase I involved 1,460 patients diagnosed with schizophrenia initially randomly assigned in a double-blind study to one of the five neuroleptics. The study lasted 18 months, with safety and tolerability outcomes evaluated at 1, 3, 6, 9, 12, 15, and 18 months.
令臨床醫生和製藥行業同樣震驚的是，各種藥物（包括老式、廉價奮乃靜）在療效的主要標準、患者在隨機分配的初始治療中停留的時間長度方面幾乎沒有區別。 藥物。 總體而言，高達 74% 的人在 18 個月前停用了研究藥物：奧氮平為 64%，利培酮為 74%，奮乃靜為 75%，齊拉西酮為 79%，喹硫平為 82%。 根據 Lieberman (2005a) 的說法，“每組中的大多數患者由於無效或無法忍受的副作用或其他原因而停止了分配的治療。”
In a shock to clinicians and the pharmaceutical industry alike, there was little difference among the various medications, including old-fashioned, inexpensive perphenazine, in regard to the primary criterion for efficacy, the length of period that the patients remained on their randomly assigned initial medication. Overall, a whopping 74% discontinued the study medication before 18 months: 64% for olanzapine, 74% for risperidone, 75% for perphenazine, 79% for ziprasidone, and 82% for quetiapine. According to Lieberman (2005a), “the majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or other reasons.”
請注意奮乃靜（Trilafon）在包裝中間； 它與領先者奧氮平（Zyprexa）之間沒有統計學差異。 但 Zyprexa 的副作用最嚴重（見後續部分）。
Note that perphenazine (Trilafon) is in the middle of the pack; there was no statistical difference between it and the leader, olanzapine (Zyprexa). But Zyprexa had the worst adverse effect profile (see subsequent sections).
此外，在研究期間，根據陽性和陰性症狀量表和臨床總體印象量表測量，所有藥物的治療效果均等。 同樣，較新的抗精神病藥物也沒有優勢。 這兩個量表是最常用於評估這些藥物治療效果的量表。
In addition, over the length of the study, treatment effects equalized among all the medications as measured on the Positive and Negative Syndrome Scale and the Clinical Global Impressions Scale. Again, there was no advantage to the newer antipsychotic drugs. These two scales are among the most commonly used to rate treatment effectiveness of these medications.
耐受性最差的藥物喹硫平（Seroquel）是美國最常用的藥物，並帶來了最大的收入。 它的成功是營銷上的勝利，而不是臨床上的勝利。
The most poorly tolerated drug, quetiapine (Seroquel), is the most commonly used in the United States and brings in the greatest revenues. Its success is a marketing triumph, not a clinical one.
氯氮平（Clozaril）也有研究，但因為需要驗血檢查粒細胞缺乏症，所以不是雙盲的。 再次證明了臨床偏倚的力量，作為唯一沒有被蒙蔽的藥物，氯氮平表現出比其他藥物更大的療效。
Clozapine (Clozaril) was also studied, but because of the requirements for blood testing for agranulocytosis, it was not double blind. Once again demonstrating the power of clinical bias, as the only drug that was not blinded, clozapine demonstrated some greater efficacy than the others.
CATIE再次證實，患者不喜歡服用這些藥物，很大程度上是因為它們的不良反應，也因為它們缺乏幫助。 如前所述，在為期 18 個月的研究完成後，74% 的患者停用了他們的原始藥物。 Nasrallah (2007) 認為這證實了“患者和臨床醫生通常對所取得的結果不滿意”。 有許多替代方法來評估這項研究（例如，Weiden，2007a），但沒有一種方法能夠對任何一種藥物給出特別有利的描述，並且沒有一種方法比老藥奮乃靜更能突出幾種非典型藥物中的任何一種。
CATIE once again confirmed that patients do not like to take these drugs, largely due to their adverse effects, but also because of their lack of helpfulness. As noted, at the completion of the 18-month study, 74% of patients discontinued their original drug. Nasrallah (2007) viewed this as confirmation that “both patients and clinicians are often dissatisfied with the outcome achieved.” There were many alternative methods for evaluating this study (e.g., Weiden, 2007a), but none gave a particularly favorable picture of any of the drugs, and none gave a significant advantage to any of the several atypicals over the older drug, perphenazine.
新的抗精神病藥物引起錐體外系副作用和遲發性運動障礙的風險較小，有很多炒作。然而，如前所述，除氯氮平外，它們都是強效多巴胺阻滯劑（D2 亞型），所有 D2 阻滯劑都會引起錐體外系效應和遲發性運動障礙。 Nasrallah (2007) 總結道，“錐體外系副作用、運動障礙或靜坐不能的發生率之間沒有統計學上的顯著差異”（第 9 頁）。然而，更多接受奮乃靜治療的患者由於錐體外系效應而停止治療（Lieberman 等，2005a），這表明他們更加痛苦。利伯曼等人。 (2005a) 在他們的討論中指出，“在我們的研究中，接受第一代和第二代藥物治療的患者出現錐體外系症狀的比例沒有顯著差異。儘管有這一發現，但由於錐體外系效應，與其他藥物相比，更多的患者停用奮乃靜。” 與其他藥物相比，8% 的奮乃靜患者因錐體外系效應而停藥，而新藥的這一比例為 2% 至 4%。
There has been much hype about the newer antipsychotics posing less risk of causing extrapyramidal side effects and tardive dyskinesia. However, as already discussed, with the exception of clozapine, they are all potent dopamine blockers (subtype D2 ), and all D2 blockers cause extrapyramidal effects and tardive dyskinesia. Nasrallah (2007) summed up, “There were no statistically significant differences between the rates of extrapyramidal side effects, movement disorders, or akathisia” (p. 9). However, more patients treated with perphenazine discontinued treatment because of extrapyramidal effects (Lieberman et al., 2005a), suggesting that they were more distressing. Lieberman et al. (2005a) stated in their discussion that “the proportion of patients with extrapyramidal symptoms did not differ significantly among those who received first-generation and second-generation drugs in our study. Despite this finding, more patients discontinued perphenazine than other medications owing to extrapyramidal effects.” Compared to the other drugs, 8% of perphenazine patients discontinued because of extrapyramidal effects, versus 2% to 4% for the newer drugs.
抗膽鹼能藥物通常給予有錐體外系症狀的患者以提供緩解。 根據利伯曼等人的說法。 （2005a），“接受喹硫平的患者較少接受抗膽鹼能藥物（3% 對 8% 至 10%）。” 真正的消息是，服用舊藥奮乃靜的患者接受的抗膽鹼能藥物量與服用所有新藥（喹硫平除外）的患者大致相同，這再次表明舊藥和新藥之間幾乎沒有差異或沒有差異 一是關於引起錐體外系症狀。
Anticholinergic drugs are typically given to patients with extrapyramidal symptoms in order to provide relief. According to Lieberman et al. (2005a), “fewer patients receiving quetiapine were prescribed anticholinergic drugs (3% vs. 8 to 10%).” The real news is that patients taking the older drug, perphenazine, received roughly the same amount of anticholinergic drugs as patients taking all the newer drugs (except for quetiapine), indicating again that there was little or no difference between the older drug and the newer one in regard to causing extrapyramidal symptoms.
似乎遺漏的一點是，由於較舊的藥物奮乃靜在患者使用該藥物的時間方面處於中間位置，因此錐體外系效應並未使奮乃靜總體上比新型抗精神病藥物的耐受性差。根據利伯曼等人的說法。 （2005a），“由於無法忍受的副作用，直到停藥前，各組之間的時間沒有顯著差異。” CATIE 證實了發生代謝綜合徵的高風險，即一系列與體重增加、血糖升高和膽固醇升高有關的不良反應，同時暴露於非典型的神經安定藥如 Zyprexa、Risperdal 和 Seroquel。 CATIE 測量體重變化、體重增加的患者比例、每月平均體重變化、血糖升高、血紅蛋白 A1c 變化（糖尿病測試）、膽固醇變化和甘油三酯變化。他們沒有測量另一個變量，血壓。代謝綜合症使患者面臨糖尿病和心血管疾病的風險。在對 689 名患者進行的分項測試中，可獲得最佳數據，根據標準，非典型抗精神病藥物的代謝綜合徵患病率高達 40.9% 至 42.7%，令人震驚。令人震驚的是，超過 50% 的女性患上了代謝綜合症。
A point that seems to missed is that since the older drug, perphenazine, was in the middle of the pack in terms of how long patients remained on it, the extrapyramidal effects did not make perphenazine overall less tolerable than the newer antipsychotics. According to Lieberman et al. (2005a), “there were no significant differences between groups in time until discontinuation due to intolerable side effects.” CATIE confirmed the high risk of developing metabolic syndrome, an array of adverse effects related to weight gain, elevated blood sugar, and elevated cholesterol, while exposed to atypical neuroleptics such as Zyprexa, Risperdal, and Seroquel. CATIE measured weight change, proportion of patients gaining weight, average weight change per month, blood glucose increased, hemoglobin A1c change (a diabetes test), cholesterol change, and triglyceride change. They did not measure another variable, blood pressure. The metabolic syndrome puts patients at risk for diabetes and cardiovascular disease. In a subtest of 689 patients, where the best data were available, the prevalence of metabolic syndrome was a shocking 40.9% to 42.7%, depending on the criteria, for the atypical antipsychotic drugs. Shockingly, more than 50% of the females developed metabolic syndrome.
與禮來（Eli Lilly）就 Zyprexa 引起的糖尿病（第 14 章）解決的大量訴訟一致，Zyprexa 是引起代謝綜合症的最嚴重的罪犯。 Zyprexa 患者平均每月增重 2磅(2* 0.45359237公斤)。 這將在 18 個月內增加 36 磅。 Zyprexa 患者在糖基化血紅蛋白、總膽固醇和甘油三酯升高方面也存在更大的問題。 作為針對禮來 (Eli Lilly) 的產品責任案件的醫學專家，我評估了 Zyprexa 導致之前沒有患糖尿病的相對年輕的成年患者突然發生致命糖尿病的案例。
Consistent with the huge numbers of lawsuits being settled by Eli Lilly for Zyprexa-induced diabetes (chapter 14), Zyprexa was the worst offender in regard to causing the metabolic syndrome. Zyprexa patients gained an average of 2 pounds/month. That would add up to 36 pounds in 18 months. Zyprexa patients also had greater problems with elevated glycosylated hemoglobin, total cholesterol, and triglycerides. As a medical expert in product liability cases against Eli Lilly, I have evaluated cases in which Zyprexa caused the sudden onset of lethal diabetes in relatively young adult patients who were previously free of the disorder.
如果這些藥物不開給所謂的精神病患者，尤其是那些被標記為精神分裂症的人，那麼代謝綜合症的研究結果可能會導致 FDA 將它們從市場上撤出。
If these drugs were not being prescribed to so-called mental patients, and especially to those labeled as schizophrenic, the findings on metabolic syndrome would probably lead the FDA to withdraw them from the market.
我們將檢查最近的研究，其中一些涉及非典型神經安定藥，證實抗精神病藥物會縮短壽命。 代謝綜合徵(代謝症候群, metabolic syndrome)的產生無疑會增加死亡風險。 然而，在較老的精神安定藥中也發現了這種風險。 這至少部分是由於對自己的漠不關心，包括缺乏自我照顧，這是由所有的腦葉切除劑引起的，包括精神抑製藥。
We will examine recent studies, some involving atypical neuroleptics, confirming that antipsychotic drugs shorten the life span. The production of a metabolic syndrome undoubtedly contributes to this increased risk of dying. However, this risk was also detected in regard to the older neuroleptics. It is due, at least in part, to the indifference to oneself, including lack of self-care, caused by all lobotomizing agents, including the neuroleptics.
停用綜合症（第 32 頁）
DEACTIVATION SYNDROME (p. 32)
精神病學中的一大神話是神經安定藥的特異性，例如 Thorazine、Haldol、Prolixin、Zyprexa、Risperdal、Seroquel 或 Geodon，用於治療被診斷患有精神分裂症的患者。 (^2) 儘管缺乏驗證性研究（在 Breggin, 1983b, 1991c; Jackson, 2005 進行了綜述），但許多臨床醫生和研究人員假設這些藥物具有特定的抗精神病藥甚至抗精神分裂症的作用。 這個概念被用來證明精神安定治療是一種合法的醫療方法。 相反，安定藥會產生所謂的失活綜合徵或效應，這是腦葉切除綜合徵的核心方面。
One of the great myths within psychiatry is the specificity of neuroleptics such as Thorazine, Haldol, Prolixin, Zyprexa, Risperdal, Seroquel, or Geodon for the treatment of patients diagnosed with schizophrenia. (^2) Despite a lack of confirmatory studies (reviewed in Breggin, 1983b, 1991c; Jackson, 2005), many clinicians and researchers postulate a specific antipsychotic, and even an antischizophrenic, effect for these drugs. The concept is used to justify neuroleptic treatment as a legitimate medical approach. Instead, the neuroleptics produce what can be called a deactivation syndrome or effect, a central aspect of the lobotomy syndrome.
為了幫助組織隨後的臨床材料，從仔細研究失活的概念開始可能會有所幫助（Breggin，1993）：
To help organize the clinical material that follows, it may be helpful to begin with a closer look at the concept of deactivation (Breggin, 1993):
停用一詞將用於指定一系列現象，這些現像被各種描述為不感興趣、冷漠、減少關注、遲鈍、缺乏自發性、減少情緒反應、減少動力或意志、冷漠，以及在極端情況下，一種可喚醒的昏迷。
The term deactivation will be used to designate a continuum of phenomena variously described as disinterest, indifference, diminished concern, blunting, lack of spontaneity, reduced emotional reactivity, reduced motivation or will, apathy, and, in the extreme, a rousable stupor.
失活效應是委婉地稱為抗精神病效應的本質。 與精神科治療的大腦功能障礙原則一致，這種類似腦葉切除術的影響是人們所追求的、主要的、據稱的治療效果。 與明顯且幾乎不變的腦葉切除樣失活作用相比，任何特定的抗精神病作用都是非常推測的。
The deactivation effect is the essence of what is euphemistically called the antipsychotic effect. Consistent with the brain-disabling principles of psychiatric treatment, this lobotomy-like impact is the sought after, primary, and supposedly therapeutic effect. Any specific antipsychotic effect is very speculative compared to the obvious and almost unvarying lobotomy-like deactivation effect.
我們會發現幾乎所有的精神科藥物都能產生某種程度的失活。 即使是興奮劑，如利他林，也會使孩子產生足夠的冷漠或冷漠，使成年人更容易控製或指導孩子（見第 11 章）。 SSRIs，如 Prozac 和 Paxil，也會產生冷漠綜合症（第 7 章）。 然而，失活以其最純粹的形式出現在精神抑制治療中。
We will find that nearly all psychiatric drugs can produce some degree of deactivation. Even stimulants, such as Ritalin, can cause sufficient apathy or indifference in a child to enable adults to more easily control or direct the child (see chapter 11). The SSRIs, such as Prozac and Paxil, can also produce an apathy syndrome (chapter 7). However, deactivation appears in its purest form in neuroleptic treatment.
失活與額葉綜合徵密切相關； 它描述了情感或情緒成分。 Adams 和 Victor（1989）將額葉綜合徵的表現分為（a）認知和智力變化，例如失去抽象推理和計劃，（b）人格惡化，以及（c）“損害或缺乏主動性和自發性”（ 第 333 頁）。 失活是指主動性和自發性的損害，亞當斯和維克多稱之為額葉疾病最常見的影響。
Deactivation is closely related to the frontal lobe syndrome; it describes the affective or emotional component. Adams and Victor (1989) divide the manifestations of frontal lobe syndrome into (a) cognitive and intellectual changes such as loss of abstract reasoning and planning, (b) personality deterioration, and (c) “impairment or lack of initiative and spontaneity” (p. 333). Deactivation refers to the impairment of initiative and spontaneity, which Adams and Victor call the most common effect of frontal lobe disease.
同樣，Stuss 和 Benson (1987) 將兩個基本功能歸因於額葉前部：“順序、設定和整合”和“驅動、動機和意志”（第 241 頁）。 “最常見的改變是冷漠”（第 242 頁）。 神經阻滯劑引起的額葉損傷主要是通過引起冷漠，以及深度的引人入勝。
Similarly, Stuss and Benson (1987) ascribed two basic functions to the anterior portion of the frontal lobes: “sequence, set, and integration” and “drive, motivation, and will” (p. 241). The “most common alteration is apathy” (p. 242). Neuroleptic-induced impairment of the frontal lobes acts primarily by causing apathy, along with a profound degree of spellbinding.
我們對額葉綜合症的大部分了解來自對心理外科效果的研究，其主要臨床效果是產生失活，或 Kalinowsky (1973) 所說的“減少關注”（第 20 頁）。 我的臨床經驗和文獻回顧 (Breggin, 1975, 1980, 1981b) 以及神經心理學研究 (Hansen et al., 1982) 表明，較新的立體定向手術，如扣帶切開術、杏仁核切開術和丘腦切開術，繼續產生 額葉綜合徵，尤其是失活。 漢森等人(1982) 以一種與安定藥失活效應無法區分的方式描述了現代心理外科的影響：
Much of what we know about the frontal lobe syndrome comes from studying the effects of psychosurgery, whose primary clinical effect is the production of deactivation, or what Kalinowsky (1973) called “diminished concern” (p. 20). My clinical experience and reviews of the literature (Breggin, 1975, 1980, 1981b) as well as neuropsychological research (Hansen et al., 1982) indicate that the newer stereotactic procedures, such as cingulotomy, amydalotomy, and thalamotomy, continue to produce a frontal lobe syndrome, especially deactivation. Hansen et al. (1982) described the impact of modern psychosurgery in a way that is indistinguishable from neuroleptic deactivation effects:
患者的行動選擇因主動性和構建情境的能力減弱而減少； 情緒消退，組織得更淺，更依賴於眼前的情況。 與其他人的接觸變得更加平坦，直接的軸承更加機械化。 （第 115 頁）
The patient’s options for action are reduced by a weakening of initiative and ability to structure his situation; emotionality fades, is organized more shallowly and is more dependent upon the immediate situation. Contact with other people becomes more flattened and the immediate bearing more mechanical. (p. 115)
腦葉切開術患者實際上不知道是什麼擊中了他們。 他們被傷害深深地迷住了，以至於他們常常沒有意識到已經對他們做了任何事情。 有些人生活在欣快（表面上愚蠢）的水平上，大多數人陷入深深的冷漠； 沒有人能夠理解發生在他們身上的事情。
腦葉切開術患者實際上不知道是什麼擊中了他們。 他們被傷害深深地迷住了，以至於他們常常沒有意識到已經對他們做了任何事情。 有些人生活在欣快（表面上愚蠢）的水平上，大多數人陷入深深的冷漠； 沒有人能夠理解發生在他們身上的事情。
Lobotomy patients literally do not know what hit them. They are so profoundly spellbound by the injury that they often have no awareness that anything has been done to them. Some live on a euphoric (superficially silly) level, most lapse into deep apathy; none are left with the ability to understand what has happened to them.
正如我們將看到的，使用抗精神病藥物的先驅幾乎一致認為失活是抗精神病藥的主要臨床效果。 正因為如此，臨床醫生經常將安定作用稱為化學腦葉切除術（Haase，1959）。 Bleuler (1978) 觀察到，長期使用安定藥“也經常削弱人的活力和主動性”（第 301 頁）。 他總結道：“因此，我們看到使用抗精神病藥的長期維持充滿了一些與腦葉切除術相同的缺點”（第 301 頁）。 第 5 章將討論這些藥物引起的永久性認知障礙和癡呆。
As we shall see, pioneers in the use of antipsychotic drugs almost uniformly cited deactivation as the main clinical effect of neuroleptics. Because of this, clinicians often referred to the neuroleptic effect as a chemical lobotomy (Haase, 1959). Bleuler (1978) observed that long-term neuroleptic use “also often dampens the vitality and the initiative of the person” (p. 301). He concluded, “So we see that long-term maintenance with neuroleptics is fraught with some of the same disadvantages that are ascribed to lobotomies” (p. 301). Chapter 5 will discuss permanent cognitive impairment and dementia from these drugs.
停用和藥物治療（第 33 頁）
DEACTIVATION AND MEDICATION SPELLBINDING (p. 33)
由於藥物引人入勝的標誌是缺乏對不良心理影響的欣賞或關注，因此任何產生冷漠或冷漠的物質都是高度引人入勝的。 服用安定藥的患者可能會變得如此著迷，以至於他們看起來像機器人或殭屍一樣，對自己或周圍環境幾乎沒有意識或興趣。 他們通常認為自己在藥物上的表現要好一些，儘管事實上他們因帕金森病的情緒平緩和精神運動遲緩而受到嚴重損害（第 4 章）。
Since the hallmark of medication spellbinding is a lack of appreciation or concern about adverse mental effects, any substance that produces indifference or apathy is highly spellbinding. Patients taking neuroleptics can become so spellbound that they appear robotic or zombielike, with little awareness of or interest in themselves or their environment. They commonly think that they are doing somewhat better on the drugs, despite the fact that they are grossly impaired by a parkinsonian emotional flatness and psychomotor retardation (chapter 4).
失活的剖析 (p. 34)
The Anatomy of Deactivation
額葉和邊緣系統（作為額葉綜合徵的一個方面）或基底神經節（作為皮質下癡呆的一個方面）的功能障礙可能導致失活。 它也可以通過抑製網狀激活系統來發生，網狀激活系統是大腦下部的一個網絡，可以為其所有過程提供能量。 所有抗精神病藥，包括較新的非典型藥，都會損害所有這些區域的多巴胺能通路。
Deactivation can result from dysfunction in either the frontal lobes and limbic system (as an aspect of frontal lobe syndrome) or the basal ganglia (as an aspect of subcortical dementia). It can also occur through dampening down the reticular activating system, a network in the lower portion of the brain that energizes all of its processes. All neuroleptics, including the newer atypicals, impair the dopaminergic pathways to all of these regions.
多巴胺是大腦中研究最多的神經遞質系統之一。 它有許多受體亞型，包括 D2，它提供從基底神經節起源區域到邊緣系統、額葉和網狀激活系統的神經乾。 阻斷 D2 是神經阻滯劑作用的關鍵，包括失活和一些更嚴重的不良反應，包括遲發性運動障礙和神經阻滯劑惡性綜合徵。 所有阻斷 D2 的藥物都可能導致這些潛在的災難性影響。
Dopamine is one of the most studied neurotransmitter systems in the brain. It has numerous receptor subtypes, including D2 , which provides nerve trunks from the region of their origin in the basal ganglia to the limbic system, frontal lobes, and reticular activating system. Blockade of D2 is key to neuroleptic effects, including deactivation and some of the more serious adverse effects, including tardive dyskinesia and neuroleptic malignant syndrome. All drugs that block D2 can cause these potentially disastrous effects.
安定藥的失活效應在其臨床影響上與精神外科非常相似，因為它會破壞大腦的相同區域。 例如，經典的腦葉切除術將下行纖維從額葉切割到更深的大腦結構，而安定藥往往會損害上行的多巴胺能纖維。
The neuroleptic deactivation effect so closely resembles psychosurgery in its clinical impact because it disrupts the same regions of the brain. Classical lobotomy, for example, cuts the descending fibers from the frontal lobes to deeper brain structures, while the neuroleptics tend to impair the ascending dopaminergic fibers.
腦葉切開術樣神經阻滯作用（第 34 頁）
Lobotomy-Like Neuroleptic Effects (p. 34)
Any drug that blocks D2, including every newer antipsychotic medication, will, in sufficient doses, produce a lobotomy-like effect.
The very first report on the psychiatric use of chlorpromazine was published in France by Delay and Deniker (1952; translated in Jarvik, 1970). Their article described the actual state of the patient for a medical world that as yet had no familiarity with the drug:
坐著或躺著，病人在床上一動不動，常常臉色蒼白，眼瞼下垂。 他大部分時間都保持沉默。 如果被問到，他會用單調、冷漠的聲音緩慢而刻意地回答； 他用幾句話表達了自己，然後變得沉默了。 （賈維克，1970）
Sitting or lying, the patient is motionless in his bed, often pale and with eyelids lowered. He remains silent most of the time. If he is questioned, he answers slowly and deliberately in a monotonous, indifferent voice; he expresses himself in a few words and becomes silent. (Jarvik, 1970)
他們還將患者描述為“相當合適且適應性強。 . . . 但他很少提出問題，也不會表達他的焦慮、慾望或偏好”（Jarvik，1970）。
They also described the patient as “fairly appropriate and adaptable. . . . But he rarely initiates a question and he does not express his anxieties, desires or preferences” (Jarvik, 1970).
注意這些影響的非特異性。 不僅焦慮等症狀，而且慾望和偏好都被中止或掩埋在冷漠或冷漠之下。 正如 Delay 和 Deniker 所說，存在“對外部刺激的明顯冷漠或反應遲緩”和“主動性和焦慮的減少”（Jarvik，1970）。 再一次，這是醫源性的無助和否認，具有迷人的效果。
Notice the nonspecific nature of these effects. Not only symptoms such as anxiety, but also desires and preferences, are aborted or buried beneath indifference or apathy. As Delay and Deniker put it, there is an “apparent indifference or the slowing of responses to external stimuli” and “the diminution of initiative and anxiety” (Jarvik, 1970). Once again, this is iatrogenic helplessness and denial with spellbinding effects.
Heinz Lehmann 於 1953 年 5 月通過蒙特利爾將氯丙嗪引入北美。Lehmann 和 Hanrahan (1954) 發表了第一篇英文文章，宣傳其在精神病學中的應用。 他們表示，
Heinz Lehmann introduced chlorpromazine into North America via Montreal in May 1953. Lehmann and Hanrahan (1954) published the first article in English promoting its psychiatric use. They stated,
目的是產生運動遲緩、情緒冷漠和嗜睡的狀態，隨著耐受性的發展，劑量必須相應增加。
The aim is to produce a state of motor retardation, emotional indifference, and somnolence, and the dose must be increased accordingly as tolerance develops.
The doses required for achieving “retardation,” “emotional indifference,” and “lethargy” rarely exceeded 800 mg/day, and sometimes did not exceed 100 mg/day. Much larger doses—sometimes thousands of milligrams—were often used in the past and are sometimes used in contemporary treatment by psychiatrists.
萊曼和漢拉漢 (Lehmann and Hanrahan) (1954) 以開拓者特有的坦誠寫作，接著說，
Writing with that burst of honesty so characteristic of pioneers, Lehmann and Hanrahan (1954) go on to say,
接受治療的患者對環境缺乏自發的興趣。 . . 當他們獨自一人時，他們往往保持沉默和不動，並以緩慢單調的方式回答問題。 . . . 一些患者不喜歡這種治療並抱怨他們的嗜睡和虛弱。 一些人說他們感到“被洗掉了”，就像在一場令人筋疲力盡的疾病之後，這種抱怨確實與他們的外表相符。
The patients under treatment display a lack of spontaneous interest in the environment . . . they tend to remain silent and immobile when left alone and to reply to questions in a slow monotone. . . . Some patients dislike the treatment and complain of their drowsiness and weakness. Some state they feel “washed out,” as after an exhausting illness, a complaint which is indeed in keeping with their appearance.
Lehmann and Hanrahan (1954) recognized that they were suppressing their patients without specifically affecting or improving symptoms such as hallucinations and delusions: “We have not observed a direct influence of the drug on delusional symptoms or hallucinatory phenomena.”
次年，Lehmann (1955) 發表了他關於氯丙嗪的第二篇文章。 在相對較小的劑量下，他發現了主要的大腦功能障礙：“許多患者不喜歡由於驅動力和自發性降低而產生的‘空虛感’，這顯然是這種物質最典型的作用之一。” 他還談到了“倦怠”並將其效果與腦葉切除術進行了比較：“在晚期癌症病例的疼痛管理中，氯丙嗪可能被證明是腦葉切除術的藥理學替代品。”
The following year, Lehmann (1955) published his second article on chlorpromazine. With relatively small doses, he found the primary brain-disabling effect: “Many patients dislike the ‘empty feeling’ resulting from the reduction of drive and spontaneity which is apparently one of the most characteristic effects of this substance.” He also spoke of “lassitude” and compared the effects to lobotomy: “In the management of pain in terminal cancer cases, chlorpromazine may prove to be a pharmacological substitute for lobotomy.”
英國第一份關於氯丙嗪作為精神病治療的報告（Anton-Stephens，1954 年）證實了使用小劑量（200 毫克/天）的藥物的影響。 安東-斯蒂芬斯稱其為心理冷漠，並再次將其與腦葉切除術進行比較。
The first British report concerning chlorpromazine as a psychiatric treatment (Anton-Stephens, 1954) confirmed the impact of the drug using small doses (200 mg/day). Anton-Stephens called it psychic indifference and again compared it to lobotomy.
在整個 1950 年代，一些精神病學文獻繼續準確地描述了精神安定藥對大腦的影響。 例如，這裡是 Noyes 和 Kolb 在 1958 年版《現代臨床精神病學》中描述的最大益處的類似腦葉切開術的臨床圖片：
Throughout the 1950s, some psychiatric texts continued to accurately describe the impact of the neuroleptics on the mind. Here, for example, is the lobotomy-like clinical picture of maximum benefit described by Noyes and Kolb in the 1958 edition of Modern Clinical Psychiatry:
如果患者對藥物反應良好，他就會對周圍環境和症狀表現出漠不關心的態度。 他表現出對幻覺體驗的興趣和反應減少，並且對妄想的表達不那麼自信。 （第 654 頁，斜體添加）
If the patient responds well to the drug, he develops an attitude of indifference both to his surroundings and to his symptoms. He shows decreased interest in and response to his hallucinatory experiences and a less assertive expression of his delusional ideas. (p. 654, italics added)
在當代精神病學中，否認抗精神病藥的主要腦葉切除作用已成為一種時尚，但偶爾在文獻中也能找到這種認識。在 1991 年生物精神病學的一篇題為“神經性焦慮症”的社論中，Emerich 和 Sanberg 描述了對 Haldol 和其他精神安定藥的各種不良情緒反應，包括“認知遲鈍”。社論描述了 Belmaker 和 Wald (1977) 對 Haldol 的自我管理，其中每個“正常的實驗對象”都“抱怨意志麻痺，缺乏體力和精神能量。受試者感覺無法閱讀、打電話或執行他們願意做的家務，但如果需要，他們可以執行這些任務。”社論還提到了其他令人心煩意亂的影響的報導，包括“化學緊身衣”、“缺乏動力”和“像陰影一樣落下”的感覺。該社論未能與腦葉切除術進行明顯的比較，但其觀察結果完全符合併證實了第 1 章中描述的精神病治療的大腦功能障礙原則。
It has become fashionable in contemporary psychiatry to deny the primary lobotomizing effects of the neuroleptics, but occasionally, recognition can be found in the literature. In a 1991 editorial in Biological Psychiatry titled “Neuroleptic Dysphoria,” Emerich and Sanberg described various adverse emotional reactions to Haldol and other neuroleptics, including “cognitive blunting.” The editorial describes the self-administration of Haldol by Belmaker and Wald (1977), in which each of these “normal experimental subjects” “complained of a paralysis of volition, lack of physical and psychic energy. The subjects felt unable to read, telephone or perform household tasks of their will, but could perform these tasks if demanded to do so.” The editorial also mentioned reports of other mind-subduing effects, including “chemical straightjacketing,” “lack of motivation,” and a feeling “like a shade coming down.” The editorial failed to make the obvious comparison to lobotomy, but its observations are entirely consistent with and confirm the brain-disabling principles of psychiatric treatment described in chapter 1.
鑑於研究人員如此多地承認神經安定藥通過抑制大腦和思想，有時甚至是身體本身起作用，值得注意的是，精神科藥物倡導者繼續推廣這些藥物，就好像它們對精神病、躁狂症或精神分裂症有特別的改善作用一樣。
Given so many acknowledgments by researchers that neuroleptics work by subduing the brain and mind, and sometimes the body itself, it is remarkable that psychiatric drug advocates continue to promote these drugs as if they have a specifically ameliorating effect on psychosis, mania, or schizophrenia.
在臨床討論中，腦葉切除效應現在有時歸入安定藥誘導的缺陷綜合徵 (NIDS)。 馬爾科姆·拉德 (Malcolm Lader)（1993 年）是該主題國際研討會的主席，他寫道：
In clinical discussions, the lobotomy effect is now sometimes subsumed under neuroleptic-induced deficit syndrome (NIDS). Malcolm Lader (1993), chairperson of an international symposium on the subject, wrote,
然而，使用經典精神安定藥治療的好處是以犧牲許多副作用為代價的，許多患者經常抱怨感覺“被吸毒”或昏昏欲睡，無法集中註意力。 他們缺乏動力，情緒反應遲鈍：他們行動遲緩，身體僵硬。 一些患者抱怨“感覺自己像個殭屍”。 （第 493 頁）
The benefits of treatment with classical neuroleptics are, however, obtained at the expense of a number of side effects, and many patients frequently complain of feeling “drugged” or drowsy and of being unable to concentrate; they lack motivation and are emotionally unresponsive: they also appear slow-moving and physically rigid. Some patients have complained of “feeling like a zombie.” (p. 493)
The zombie effect is the ultimate manifestation of medication spellbinding as a central aspect of the brain-disabling effects of psychiatric drugs.
在研討會上，沃爾夫岡·施特勞斯（如 Lader，1993 年所引用）描述了一種相關的精神安定藥引起的認知障礙綜合徵，其特徵是“失語、思維障礙、情緒退縮、難以用意志指導思維、矛盾心理、思維剝奪和創造力降低”。 第 495-496 頁）。 注意到早期研究試圖證明神經安定藥的認知功能得到改善，施特勞斯觀察到更嚴格的研究證實了有害影響。
At the symposium, Wolfgang Straus (as cited in Lader, 1993) described a related neuroleptic-induced dyscognitive syndrome characterized by “aphasia, thought disturbances, emotional withdrawal, difficulties in directing thought by will, ambivalence, thought deprivation, and reduced creativity” (pp. 495–496). Noting that early studies tried to demonstrate improved cognitive functioning on neuroleptics, Straus observed that more rigorous studies confirmed a detrimental effect.
非典型抗精神病藥（第 37 頁）
Atypical Neuroleptics (p. 37)
第 1 章提供了一些研究實例，證實了利培酮（最常用的非典型抗精神病藥之一）的腦功能障礙原理。
不管機制如何，所有的神經阻滯劑都會產生類似腦葉切除術的冷漠或失活。 這是迄今為止為控制標記為精神分裂症或急性躁狂症患者而開發的所有藥物的主要作用。 如果藥物不能產生失活效果，它們將無法用於控制非常困難或精神錯亂的個體。 我們會發現這些藥物是強效的多巴胺阻滯劑，會產生由其他精神抑製藥引起的所有更嚴重的中樞神經系統損傷。
Chapter 1 provided examples of research studies confirming the brain-disabling principles in regard to risperidone, one of the most commonly used atypical antipsychotics.
Regardless of the mechanism, all neuroleptics produce lobotomy-like indifference or deactivation. This is the primary effect of all drugs thus far developed for the control of patients labeled schizophrenic or acutely manic. If the medications failed to produce a deactivation effect, they would not be useful for the control of very difficult or disturbed individuals. We shall find that these drugs are potent dopamine blockers, producing all of the more severe central nervous system impairments caused by other neuroleptics.
抗精神病藥物的社會控制（第 37 頁）
SOCIAL CONTROL WITH ANTIPSYCHOTIC DRUGS (p. 37)
如果一種藥物具有足夠的滅活作用和引人入勝的能力，那麼它可以在任何權威機構想要施加控制的情況下用於人類和動物。 因此，抗精神病藥物被用於各種專製或極權機構。
If a drug is sufficiently deactivating and spellbinding, it can be used on humans and animals alike under any circumstances where an authority desires to impose control. Thus the antipsychotic drugs are used in every kind of authoritarian or totalitarian institution.
壓制療養院囚犯（第 37 頁）
Suppression of Nursing Home Inmates (p. 37)
在社會控制和行為抑制是重中之重以及藥物可以取代人類服務的每個機構中，神經安定藥都常規使用（詳見 Breggin，1983b）。 儘管 Haldol 和 Mellaril 已在很大程度上被 Zyprexa 和 Risperdal 等新藥取代，但其意圖仍然相同——行為控制。 幾十年來，使用抗精神病藥壓制養老院的老年囚犯一直是全國性的醜聞（Hughes 等，1979；Rogers，1971）。 一項針對田納西州療養院居民的研究發現，44% 的人正在服用藥物（研究總結於 Bishop，1989 年）。 1989 年馬薩諸塞州的一項研究（Avorn 等，1989）發現 39% 的患者正在接受抗精神病藥。 根據該報告，“在大多數情況下，處方都是在遙遠的過去寫的，並且會自動補充。”
Neuroleptics are routinely used in every institution in which social control and behavioral suppression are a top priority and in which drugs can replace human services (see Breggin, 1983b, for details). Although Haldol and Mellaril have been largely displaced by newer drugs such as Zyprexa and Risperdal, the intent remains the same—behavioral control. For decades, the suppression of elderly nursing home inmates with neuroleptics has been a national scandal (Hughes et al., 1979; Rogers, 1971). A study of nursing home residents in Tennessee found that 44% were being given the drugs (studies summarized in Bishop, 1989). A 1989 Massachusetts study (Avorn et al., 1989) found that 39% of patients were receiving neuroleptics. According to the report, “in most cases, the prescriptions had been written in the remote past and were refilled automatically.”
多年來，當公共醜聞並沒有顯著改善療養院時（Kolata，1991），國會通過了限制療養院使用約束和藥物的法規。 這些法規於 1991 年生效，但執行往往參差不齊，因此並不成功（Spiegel，1991）。 然而，在實際應用時，新法規減少了在療養院環境中使用抗精神病藥（Semla 等，1994）。
When public scandal did not substantially improve nursing homes over the years (Kolata, 1991), Congress passed regulations limiting the use of restraints and medications in nursing homes. These statutes went into effect in 1991, too often with spotty enforcement and therefore incomplete success (Spiegel, 1991). However, when actually applied, the new regulations have reduced the use of neuroleptics in nursing home settings (Semla et al., 1994).
二十年前，人們越來越意識到為老年患者開具抗精神病藥的不當和有害性（“Antipsychotic Drug Therapy”，1988；Gomez 等人，1990；Sherman，1987）。 使用安定藥來控制老年人的行為比對年輕患者更容易產生毒性，並且它不能替代所需的人類服務。 Sherman (1987) 質疑製藥公司將 Haldol 和 Navane 等神經安定藥的廣告刊登在以老年醫學實踐為導向的期刊上的做法。
Two decades ago, there was a growing awareness of the inappropriateness and harmfulness of prescribing neuroleptics to elderly patients (“Antipsychotic Drug Therapy,” 1988; Gomez et al., 1990; Sherman, 1987). The use of neuroleptics for the behavioral control of the elderly produces toxicity even more readily than in younger patients, and it cannot substitute for needed human services. Sherman (1987) called into question the pharmaceutical company practice of placing advertisements for neuroleptics like Haldol and Navane in journals with a geriatric-practice orientation.
不幸的是，儘管 FDA 要求這些藥物的標籤在頂部顯示帶有粗體標題的黑框警告，但製藥公司現在已經成功地說服醫療保健提供者，新的精神安定藥對老年人比舊藥物更安全 , “老年癡呆症相關精神病患者的死亡率增加。” 由於不明原因的猝死、中風、心髒病發作和肺炎，Risperdal、Zyprexa 和 Geodon 等非典型藥物會導致老年癡呆症患者的死亡率增加。 這些藥物還更頻繁地引起心律失常以及本章前面描述的代謝綜合徵，所有這些都特別威脅著老年人的生命。
Unfortunately, the drug companies have now succeeded in convincing health care providers that the newer neuroleptics are safer for the elderly than the older drugs, even though the FDA requires the labels for these drugs to display a black box warning at the top with the bold heading, “Increased Mortality in Elderly Patients with Dementia-Related Psychoses.” The atypicals such as Risperdal, Zyprexa, and Geodon cause an increased death rate in elderly patients with dementia as a result of unexplained sudden death, stroke, heart attack, and pneumonia. These drugs also more frequently cause cardiac arrhythmias as well as the metabolic syndrome described earlier in the chapter, all of which especially threaten the lives of the elderly.
在各種環境中停用人和動物（第 38 頁）
Deactivating People and Animals in Varied Settings (p. 38)
1983 年，在《精神病藥物：對大腦的危害》一書中，我花了相當多的時間通過指出其對各種不同人群的影響來確認神經阻滯劑治療的大腦功能障礙原理。 我還討論了文獻中的其他確認來源。 本節中引用舊引文的材料在我早期的書中有更詳細的介紹。
In 1983, in Psychiatric Drugs: Hazards to the Brain, I devoted considerable time to confirming the brain-disabling principle of neuroleptic treatment by pointing to its effects on a variety of diverse populations. I also discussed other confirmatory sources in the literature. The material in this section that draws on older citations is presented at greater length in my earlier book.
精神安定藥產生的失活綜合症得到證實，它們在州立精神病院用於控制患者，無論其診斷如何，並在前蘇聯的精神病監獄中用於控制持不同政見者（Block et al., 1977;“Excerpts From Statement, ” 1976 年；爐邊，1979 年；“‘瘋人院’洗腦”，1976 年；Podrabinek，1979 年）。 它們已在監獄中用於壓制難纏的囚犯（Booth，1993；Coleman，1974；Greenhouse，1979；Kaufman，1980；McDonald，1979；Mitford，1973；Oregon State Prisoner，1971；Prison Drug Bill，1977）。 被定罪的囚犯報告說，大腦麻木效應使他們無法在法庭上進行適當的辯護（Espinosa，1993；Ogilvie，1992；Pund，1993）。
The deactivation syndrome produced by neuroleptics is confirmed by their use in state mental hospitals for the control of patients regardless of their diagnoses and in psychoprisons in the former U.S.S.R. for the control of political dissidents (Block et al., 1977; “Excerpts From Statement,” 1976; Fireside, 1979; “ ‘Madhouse’ Brainwashing,” 1976; Podrabinek, 1979). They have been used in prisons for the suppression of difficult inmates (Booth, 1993; Coleman, 1974; Greenhouse, 1979; Kaufman, 1980; McDonald, 1979; Mitford, 1973; Oregon State Prisoner, 1971; Prison Drug Bill, 1977). Convicted prisoners have reported that the brain-numbing effects rendered them unable to make a proper defense in court (Espinosa, 1993; Ogilvie, 1992; Pund, 1993).
神經安定劑通常用於發育障礙機構以抑制兒童和成人的行為（Kuehnel 等人，1984 年；Plotkin 等人，1979 年）。 Kuehnel 和 Slama (1984) 警告說，神經安定劑會進一步損害發育障礙者的學習能力，並導致“鎮靜劑‘下雪’效應，這會降低客戶對學習線索的積極反應”（第 94 頁）。 許多批評性書籍都譴責在醫院和其他環境中使用抗精神病藥和其他藥物來壓制兒童（Armstrong，1993；Hughes 等，1979；Sharkey，1994；Wooden，1976）。 本書第 11 章還將討論對使用精神抑製藥的兒童的控制。
Neuroleptics have been commonly used in institutions for the developmentally disabled to suppress the behavior of children and adults (Kuehnel et al., 1984; Plotkin et al., 1979). Kuehnel and Slama (1984) warned that neuroleptics can further compromise the learning abilities of the developmentally disabled and cause “the sedative ‘snowed’ effect, which can reduce a client’s positive response to learning cues” (p. 94). Many critical books have decried the use of neuroleptics and other drugs in the suppression of children in hospitals and other settings (Armstrong, 1993; Hughes et al., 1979; Sharkey, 1994; Wooden, 1976). The control of children with neuroleptics will also be discussed in chapter 11 of this book.
在獸醫學中使用安定藥來控制野生和家養動物提供了另一個說明，說明了失活效應及其獨立於接受治療的個體的任何假定的精神疾病（布斯，1977 年；霍爾，1971 年；羅索夫，1974 年）。 Hartlage (1965) 發現，Thorazine 抑制了動物的情緒反應，“從而可能為該藥物在精神病學環境中的廣泛接受提供一些線索”（另見 Mirsky，1970；Slikker 等，1976）。 Jarvik (1970) 指出，神經安定藥在包括人類在內的所有動物物種中都會導致自發活動減少和情緒冷漠，但他仍然主張具有特定的抗精神病作用。
The use of neuroleptics in veterinary medicine to control wild and domestic animals provides another illustration of the deactivation effect and its independence from any presumed mental illness in the individual being treated (Booth, 1977; Hall, 1971; Rossoff, 1974). Hartlage (1965) found that Thorazine dampened the emotional responses of animals, “thereby perhaps providing some clue to the widespread acceptance of the drug as effective in psychiatric settings” (see also Mirsky, 1970; Slikker et al., 1976). Jarvik (1970) pointed out that the neuroleptics produce diminished spontaneous activity and emotional indifference in all animal species, including man, but he nonetheless argued for a specific antipsychotic effect.
毫不奇怪，對人類（包括正常人）的各種研究也顯示了心理功能的損害，包括記憶和學習（DiMascio 等人，1970；Fischman 等人，1976；Gillis，1975；Seppala 等人， 1976 年；Tecce 等人，1975 年）。
Not surprisingly, a variety of studies on human beings, including normals, has also shown impairment of mental functioning, including memory and learning (DiMascio et al., 1970; Fischman et al., 1976; Gillis, 1975; Seppala et al., 1976; Tecce et al., 1975).
許多前精神病患者和囚犯已經描述了精神安定藥對大腦和精神麻木的影響（Burstow 等，1988；Chamberlin，1978；Frank，1980；Grobe，1995；Hudson，1980；Millett，1990；Modrow，1992 ）。
Many former psychiatric patients and inmates have described the brain- and mind-numbing effects of the neuroleptics (Burstow et al., 1988; Chamberlin, 1978; Frank, 1980; Grobe, 1995; Hudson, 1980; Millett, 1990; Modrow, 1992).
我不是第一個建議精神抑製藥物具有劇毒的人。事實上，它在使用的最初幾十年被認為是常識（Hunter et al., 1964; Hunter et al., 1968）。為了支持鋰的使用，一些研究人員批評了神經安定藥的令人震驚的效果。例如，Fieve（引自 Shah，1973 年）說，神經安定藥“讓一個人昏迷”並把他們放在“精神上的直夾克”中。 Fieve (1989) 還提到了由神經安定藥產生的“殭屍樣外觀”（第 4 頁）。一份 NIMH (1970) 的小冊子將這些藥物與鋰進行了不利的比較，因為它們的效果是“將患者的整個思想包裹在一個麻木的繭中”。同樣，Prien 等人。 (1972) 發現“大多數服用氯丙嗪的患者行動遲緩或疲倦。” Wittrig 和 Coopwood (1970) 證實了受損的“主動性和計劃”（第 488 頁）會產生類似腦葉切除術的效果，他們稱之為化學緊身衣。 Robitscher (1980) 指出，患者經常感到“死亡或‘像殭屍’”（第 90 頁）。
I am not the first to suggest that neuroleptic medications are highly toxic. In fact, it was considered common knowledge in the first decades of their use (Hunter et al., 1964; Hunter et al., 1968). In support of the use of lithium, a number of investigators have criticized the neuroleptics for their stupefying effects. Fieve (cited in Shah, 1973), for example, said that neuroleptics “zonk a person out” and put them in a “mental straight jacket.” Fieve (1989) also referred to the “zombielike appearance” (p. 4) produced by neuroleptics. A NIMH (1970) brochure compared the drugs unfavorably to lithium because of their effect of “wrapping the patient’s entire mind in a cocoon of stupefaction.” Similarly, Prien et al. (1972) found that “most patients receiving chlorpromazine were sluggish or fatigued.” Wittrig and Coopwood (1970) confirmed the lobotomy-like effect of impaired “initiative and planning” (p. 488), which they called the chemical straightjacket. Robitscher (1980) noted that patients frequently feel “dead or ‘like a zombie’ ” (p. 90).
也許是為了應對越來越多的專業和公眾批評，精神科醫生變得更不願意發表對任何治療的批評或提及它們對大腦的影響。 如今，精神安定藥物總是被描述為具有特定的抗精神病作用，而不是麻木的、腦葉切除樣的失活作用。 用我的研究助理伊恩·戈達德（Ian Goddard）的話來說，“歷史和當代關於精神安定藥影響的評論之間的顯著差異清楚地表明，存在一種普遍否認的現象，這種否認在現代已經吞噬了這個行業”（2007 年，未發表）。
Perhaps in response to growing professional and public criticism, psychiatrists have become much more reluctant to publish criticism of any treatments or to mention their brain-disabling effects. Nowadays the neuroleptic drugs are always described as having a specific antipsychotic effect, rather than a numbing, lobotomy-like deactivation effect. In the words of my research assistant, Ian Goddard, “This remarkable difference between historic and contemporary commentary on the effects of neuroleptics clearly reveals the existence of an all-pervasive denial that has consumed the profession in modern times” (2007, unpublished).
大腦的獨特功能（第 40 頁）
THE UNIQUE FUNCTION OF THE BRAIN (p. 40)
一些將腦殘疾作為治療的支持者認為，少量毒性是有幫助的，而只有過度毒性是有害的。他們為降低一個或另一個器官功能以提高其有效性的藥物開創了醫學先例。 因此，為了預防心律失常，一些心臟藥物實際上會削弱心肌功能。 但是在處理大腦時，這個類比就不足了。 當心肌的力量減弱時，對人的思想或個性沒有任何實質性的影響——當然，除非患者出現心力衰竭。 但是，當大腦功能降低時，個人作為有情生命的能力會直接且成比例地降低。 他或她的思考、感覺、選擇和發起活動的能力變得越來越差，最終被迷住了。
Some proponents of brain disability as therapy assume that a little toxicity is helpful and that only excessive toxicity is harmful. They bring up precedents in medicine for drugs that reduce function of one organ or another to improve its effectiveness. Thus some cardiac medications actually weaken heart muscle function in the interest of preventing arrhythmias. But the analogy falls short when dealing with the brain. When the strength of the heart muscle is reduced, nothing substantial is done to the mind or personality of the person—unless, of course, the patient goes into heart failure. But when brain function is reduced, the individual’s capacities as a sentient being are directly and proportionally reduced. He or she becomes less able to think, feel, choose, and initiate activities—and ultimately spellbound.
除此之外，人們還必須研究醫療和精神干預的目的。 破壞一種心臟功能的醫療干預旨在改善整體心臟功能。 使大腦失能的精神干預旨在以降低整體心理功能為代價抑制某些思想、情緒或行為。 這樣一來，它就會使個人的自我意識和自決能力降低，變得更加無助和易於管理。 當他或她在現實中缺乏情緒意識或生命力時，他或她可能會表現出較少的情緒困擾。
Beyond this, one must also look at the purposes of medical and psychiatric interventions. The medical intervention that disrupts one kind of heart function is intended to improve overall heart function. The psychiatric intervention that disables the brain is aimed at suppressing certain thoughts, emotions, or behaviors at the cost of reducing overall mental function. In doing so, it renders the individual less self-aware and less self-determining, more helpless, and more manageable. The individual may appear to be less emotionally disturbed when he or she is, in reality, less emotionally aware or vital.
總之，與第 1 章中介紹的生物精神治療的大腦功能障礙原則一致，抗精神病藥物或抗精神病藥物會產生一種類似腦葉切除術的失活綜合徵，其特徵是情緒冷漠或冷漠、自發性降低和順從。 這是包括 Haldol、Risperdal、Zyprexa、Geodon 和 Seroquel 在內的所有抗精神病藥物的主要或“治療”影響。
In summary, consistent with the brain-disabling principles of biopsychiatric treatment presented in chapter 1, the neuroleptic or antipsychotic drugs produce a lobotomy-like deactivation syndrome characterized by emotional indifference or apathy, reduced spontaneity, and docility. This is the primary or “therapeutic” impact of all neuroleptic drugs including Haldol, Risperdal, Zyprexa, Geodon, and Seroquel.
這種臨床結果在絕大多數患者中是顯而易見的，其中一些患者已淪為殭屍狀態。最近涉及非典型抗精神病藥 Risperdal 和其他抗精神病藥的研究記錄了這一點。 對動物、正常人、持不同政見者和叛逆兒童的研究以及對精神病院、發育障礙機構、療養院和監獄的囚犯的研究也證實了這一點。給定有效的“治療”劑量，所有人類和動物都會在情緒上被抗精神病藥物扼殺和制服。
This clinical result is obvious in the great majority of patients, some of whom are reduced to a zombielike state. It is documented by recent research studies involving the atypical antipsychotic Risperdal and other neuroleptics. It is also confirmed by studies of animals, normal human beings, political dissenters, and rebellious children as well as by studies of the inmates of mental hospitals, institutions for the developmentally disabled, nursing homes, and prisons. Given an effective “therapeutic” dose, all human beings and animals alike are emotionally stifled and subdued by antipsychotic drugs.
該領域的先驅者在首次使用抗精神病藥物時就認識到並撰寫了有關腦葉切開術的作用，但近年來藥物倡導者宣傳了這些藥物具有特定的抗精神病或抗精神分裂症作用的錯誤印象。 實際上，這些劇毒化學製劑的壓倒性臨床效果是使患者和囚犯在情緒上更加平淡和冷漠，更加冷漠和溫順，以及更少的自主和自我導向。
Pioneers in the fi eld recognized and wrote about the lobotomy-like effects of the neuroleptic drugs when they first came into use, but in recent years drug advocates have promoted the false impression that these medications have a specific antipsychotic or antischizophrenic effect. In reality, the overriding clinical effect of these highly toxic chemical agents is to render patients and inmates more emotionally flat and indifferent, more apathetic and docile, and less autonomous and self-directed.
因此，這些患者和囚犯有時在情緒上的痛苦似乎不那麼明顯，而且他們幾乎總是更容易控制。 但這種效果與治療精神疾病無關。 相反，這些藥物使患者在情緒和神經上都失去了能力。
As a result, these patients and inmates sometimes seem less obviously in emotional pain, and they are almost always much more manageable. But the effect has nothing to do with treating a psychiatric disorder. Instead, the patients have been rendered emotionally and neurologically disabled by the drugs.
筆記 (p. 41)
1. 在明顯的疏忽中，該表沒有指出最初的抗精神病藥氯丙嗪 (Thorazine) 是一種有效的 D 受體阻滯劑。
2. 抗精神病藥或抗精神病藥清單見附錄。
NOTES
1. In an apparent oversight, the table fails to note that the original antipsychotic, chlorpromazine (Thorazine), is a potent D blocker.
2. A list of antipsychotic or neuroleptic drugs can be found in the appendix.