自從我第一次表達我的擔憂並回顧了這個主題（Breggin，1983b）以來，越來越多的證據表明，精神安定藥會對大腦的最高中心造成持續性損傷或功能障礙，包括腦萎縮。 我認為神經安定藥或抗精神病藥一般具有神經毒性和細胞毒性的概念在當時似乎很激進，但我們會發現它現在已被研究這些毒性作用的實驗室研究人員所接受。 在過去的幾年裡，世界各地的實驗室都將重點放在典型和非典型抗精神病藥如何導致神經元細胞死亡的機制上，但教科書和臨床醫生在很大程度上對這些重要發現視而不見。

演示神經致麻藥性腦損傷和細胞死亡(p. 85)
最近一項涉及靈長類動物的研究表明，在常規臨床暴露期間，較老的和非典型的精神安定藥都會縮小腦組織。 多爾夫-彼得森等人。 (2005) 來自匹茲堡大學精神病學系，對三組六隻獼猴進行了 17-27 個月的口服氟哌啶醇 (Haldol)、奧氮平 (Zyprexa) 或假治療。 Haldol 和 Zyprexa 的劑量產生的血漿濃度與人類臨床實踐中使用的濃度相似。 暴露後，研究人員發現兩個藥物組的腦重量減少了 8% 到 11%，但假手術組沒有。 “在所有主要的大腦區域（額葉、頂葉、顳葉、枕葉和小腦）都觀察到了大腦的萎縮，但在額葉和頂葉區域表現得最為強勁”（第 1649 頁）。 額葉區域是產生類似腦葉切除術的大腦功能障礙的最關鍵區域（第 1 章）。

作者總結道：“總而言之，我們發現猴子以模擬臨床使用的方式長期接觸氟哌啶醇或奧氮平與影響灰質和白質的腦容量顯著減少有關”（第 1659 頁）。 由同一研究小組（Konopaske 等人，2007 年）進行的一項後續研究基於相同的方案，旨在確定與臨床劑量 Haldol 和 Zyprexa 引起的腦萎縮相關的特定細胞損傷。 對頂葉區域灰質的檢查發現，灰質減少 14.6% 與神經膠質細胞減少 14.2% 相關。 神經元和內皮細胞的數量沒有變化，導致它們在收縮組織中的密度增加。
作者得出的結論是，他們的數據提出了一種可能性，即被診斷患有精神分裂症的患者的大腦變化可能至少部分歸因於抗精神病藥物。 這是由 NIH 和 Zyprexa 的製造商 Eli Lilly 贊助的研究人員提出的一個引人注目的建議。 正如本章將證實的那樣，事實上，毫無疑問，在被標記為精神分裂症的患者的大腦中看到的破壞性變化完全歸因於對他們施加的藥物。

就其本身而言，這些研究應該足以引起人們對將這些藥物施加於人類的擔憂。 該研究的贊助聯邦機構 NIH 沒有舉行新聞發布會來警告這些不祥的發現。 奧氮平的製造商禮來（Eli Lilly）沒有發出“親愛的醫療保健提供者”的信函，警告稱腦細胞死亡導致大腦廣泛萎縮。 儘管有這項研究和更早的驗證性動物研究（見本章進一步內容），但醫學界尚未對讓患者接受一類破壞大部分腦細胞的藥物——抗精神病藥——眨眼 並大幅縮小患者的大腦大小。

抗精神病藥可以通過多種機制損傷或破壞腦細胞。 它們不僅抑制多巴胺能神經元的總體功能，還會破壞神經元和全身其他細胞內的多種代謝功能。

幾十年來，眾所周知，這些藥物抑制線粒體中的大多數酶系統（Teller 等，1970），線粒體是細胞中許多最重要代謝過程的主要部位。 Inuwa 等人的研究。 (1994) 證明精神安定藥被人體細胞線粒體吸收，在那裡它們會干擾代謝過程並導致結構異常。 作者建議，“這種相互作用可能是導致細胞過早死亡的細胞病變”（第 1091 頁）。

最近的研究在研究安定藥對神經元過程細胞的毒性作用方面變得更加複雜。 Ethier 等人。 (2004) 發現氟哌啶醇會損害紋狀體神經肽基因的表達。 他們將大鼠的這種情況與僵直症的產生聯繫起來———一種身體運動的減慢——-從而對神經安定藥的大腦致殘作用進行了研究。 這些藥物破壞細胞過程並同時抑制自發運動。 患者自發性的整體降低與所謂的治療效果密切相關。

博內利(Bonelli, 2005年)等人。觀察到“目前尚未在體內研究精神藥物藥物對急性細胞死亡的影響，儘管一些體外實驗表明抗精神病藥物具有神經毒性。”組織轉谷氨酰胺酶 (tTG) 是細胞凋亡的標誌物，細胞凋亡是神經元死亡的一個階段。研究人員研究了暴露於經典和非典型抗精神病藥的患者脊髓液中這種細胞死亡標誌物的發生情況。一些患者患有阿爾茨海默病和其他神經系統疾病，而另一些則沒有：“發現抗精神病藥物對阿爾茨海默氏症和非阿爾茨海默氏症組的大腦 tTG 蛋白水平有顯著影響 (P < .01)脊髓液。”其他多種藥物，包括鎮靜劑和抗抑鬱藥，對“腦細胞死亡”沒有這種影響。作者總結說：“結果表明典型和非典型抗精神病藥物可能會導致腦細胞死亡。”女性的結果比男性更糟。

與 Bonelli 等人的生化發現一致，給予最新抗精神病藥的阿爾茨海默病患者的自傳記憶損失明顯大於未治療的患者 (Harrison & Therrien, 2007)。 簡而言之，抗精神病藥會加重阿爾茨海默氏症的癡呆症。

Bishnoi 等人試圖闡明安定藥誘導錐體外系反應的機制。 (2007) 長期給予大鼠氟哌啶醇 (1 mg/kg) 和氯丙嗪 (5 mg/kg)，導致口面部多動性運動隨時間增加。 他們發現大腦各個皮質和皮質下區域的去甲腎上腺素、多巴胺和血清素的細胞外水平相應地隨時間降低。

由於它們的神經毒性，抗精神病藥可能會加重任何腦部疾病。 對遭受創傷性腦損傷的大鼠進行的對照實驗表明，長期、高劑量的利培酮或氟哌啶醇是有害的，會導致持續的認知缺陷（Kline 等，2000）。

與我自己的臨床觀察一致，即安定藥會加重阿爾茨海默病和其他癡呆症，Bonelli 等人。 (2005) 警告說，患有阿爾茨海默病的人更容易受到神經安定藥誘導的細胞死亡的影響。 研究人員表示，“建議對老年患者使用第一代和第二代抗精神病藥進行限制。” 最後，他們發現“觀察到的腦細胞死亡增加與遲發性運動障礙（抗精神病藥物治療中最具威脅性的副作用）之間可能存在聯繫。

賈斯科格等人。 (2007) 研究了氟哌啶醇、氯氮平和喹硫平對許多所謂的細胞凋亡標誌物的影響，以研究這些藥物對細胞凋亡的影響。 從本質上講，他們檢查了抗精神病藥的神經毒性，特別是它們誘導細胞退化過程中典型的細胞死亡過程的能力。 他們發現，神經安定藥，無論是較老的還是非典型的，都會引起 caspase-3 的激活，caspase-3 是細胞凋亡的標誌物。 他們試圖向讀者保證“這種活動可能不會致命。”

賈斯科格等人。 (2007) 沒有找到試圖證明神經安定藥實際上可以保護細胞免受創傷的流行研究的證據（有關神經安定藥和情緒穩定劑的所謂保護作用，請參見第 8 章）。事實上，相反的證據繼續增加，證實抗精神病藥會殺死腦細胞。注意到氟哌啶醇會導致異常的運動行為，Kim 等人。 (2006) 試圖增加關於“它如何觸發神經元損傷”的知識。他們引用 Tseng 和 Lin-Shiau (2003) 的話說，“紋狀體中多巴胺 D2 受體的慢性阻斷會導致谷氨酸鹽的釋放持續增強，從而殺死紋狀體神經元。”使用小鼠的海馬神經元，Kim 等人。發現氟哌啶醇誘導鈣離子流入細胞，這使神經元更容易受到氧化應激的影響。抗精神病藥不能保護細胞免受壓力，它們會誘導毒性過程，使它們更容易受到壓力，有時會殺死它們。

抗精神病藥對全身細胞有毒。 臨床觀察表明非典型會導致糖尿病和體重增加（Jin et al., 2004），最近導致 FDA 在所有非典型精神病標籤（包裝插頁）中加入警告。 這導致了對潛在細胞毒性過程的研究探索。 韋斯特里等人。 (2007) 比較了兩種較老的抗精神病藥與非典型藥利培酮、氯氮平、奧氮平和喹硫平對培養細胞中葡萄糖代謝的影響。 所有藥物都乾擾了一些細胞內過程。 然而，只有非典型“能夠損害胰島素反應性葡萄糖轉運系統並損害脂肪細胞中的脂肪分解。 . . . SGAs [第二代抗精神病藥] 對脂肪細胞的這些影響可以部分解釋 SGAs 與體重增加和糖尿病的關係。”

抗精神病藥會增加陽光對人體皮膚的毒性，導致皮膚變色和其他不良皮膚反應。 研究人員注意到了這種稱為光毒性的現象，並著手研究其對裝有抗精神病藥氟奮乃靜、奮乃靜或硫利達嗪的細胞的影響（Bastianon 等人，2005 年）。 他們發現這些細胞暴露在光下會導致質膜和線粒體出現異常。
由於骨髓抑制，Clozaril 可能導致致命的白細胞粒細胞缺乏症。 該機制可能是對骨髓細胞的直接毒性作用。 經測試，安定藥氯丙嗪、奧氮平和喹硫平對骨髓細胞也有毒性（Pereira 等，2006）。

抗精神病藥可導致猝死，有時與心力衰竭有關。 貝爾哈尼等人。 （2006 年）證明，許多經典和非典型抗精神病藥在治療 3 個月的兔子中會產生心臟損傷和/或肥大。 例如，奧氮平（0.30 mg/kg/天）產生心室肥大。 病變符合中毒性心肌炎。 同樣，精神安定藥通常具有細胞毒性。

德懷爾(Dwyer)等人。 （2003 年）回顧了有關抗精神病藥物細胞毒性的文獻，並指出，“舊的吩噻嗪抗精神病藥物的細胞毒性特性是眾所周知的。” 他們引用的研究證實，這些藥物“抑制多種細胞系的增殖並改變細胞形態”。 他們著手通過研究葡萄糖代謝的影響來比較和評估新型非典型藥物的細胞毒性作用。 他們證實，抗精神病藥通過抑制細胞對葡萄糖的利用產生了一些毒性作用。 雖然一般來說，非典型的毒性較小，但結果並不一致，但都表現出一定的毒性。 他們描述了複雜性：

利培酮是一種相當有效的葡萄糖轉運抑製劑，但[在他們的測試中]對細胞毒性不大，而奧氮平是一種適度的葡萄糖轉運抑製劑，實際上刺激了神經元細胞的增殖。 氟哌啶醇對[實驗細胞]有毒，但它不影響葡萄糖轉運。 另一方面，這種藥物抑制線粒體功能（能量代謝），這可能解釋了它的毒性。

研究人員還指出，與其他細胞不同，神經元細胞完全依賴葡萄糖代謝，這使得它們特別容易受到抗精神病藥物抑制葡萄糖代謝的影響。 然而，由於抗精神病藥物會產生多種毒性作用，他們得出結論：“綜合來看，各種數據表明，抗精神病藥物的細胞毒性可能是由於對許多獨立途徑的影響的總和，這些途徑反過來會損害細胞活力”（p . 37).

儘管研究人員沒有討論這一點，但葡萄糖利用率的降低會導致由抗精神病藥引起的額葉代謝率降低和活動減退，從而導致或促成其大腦致殘、類似腦葉切除術的效果。 他們成為一廂情願的犧牲品，認為奧氮平刺激的神經細胞異常增殖可能具有治療作用。

讀者將在主要的精神病學和精神藥理學教科書中發現很少或根本沒有關於這些有充分記錄的精神安定藥誘導的神經毒性和細胞毒性過程的信息。

PET 掃描 (p. 90)

在過去的二十年中，正電子發射斷層掃描 (PET) 掃描已被用於測量大腦各個部位的代謝率和血流量。該儀器可以檢測不一定表現為大體病理的功能障礙。它還可以測量沒有病理起源的功能變化。當一個人注意時，額葉活動會增加。當同一個人看圖片時，大腦的視覺中心就會被激活。第 1 章分析了三項涉及利培酮作用的 PET 掃描研究（Lane 等人，2004；Liddle 等人，2000；Ngan 等人，2002）。這些研究共同證明了大腦功能障礙的概念：首先，利培酮會導致額葉和顳葉的全面功能障礙（新陳代謝抑制）；其次，這種效應發生在正常志願者和被標記為精神分裂症的患者身上，因此對精神分裂症沒有特異性；第三，這種故障與所謂的改善有關，即減少有關症狀的交流。抑制大腦中的新陳代謝是一種神經毒性作用。

從最早的研究開始，精神分裂症患者的額葉和額葉皮質活動減退的發現在某種程度上是一致的（Buchsbaum 等人，1982；Farkas 等人，1984；Wolkin 等人，1988， 正如 Andreasen, 1988; Wolkin et al., 1985) 所評論的那樣。 在大多數研究中，患者在 PET 掃描之前有很長的精神抑制治療史，並且當時暫時停用了藥物。 然而，暫時停止抗精神病藥物治療並不會逆轉其對額葉的長期持續抑製作用。
PET 掃描已被用於研究大腦的特定部分，其中已知安定藥通過阻斷多巴胺神經遞質系統（包括基底神經節）產生功能障礙。 各種研究表明，接受抗精神病藥治療的患者的基底神經節出現異常（Farde 等，1988）。 然而，也有許多負面的 PET 研究（參見 Buchsbaum 等人，1992 年，以及 Andreasen 等人，1992 年的冗長匯總表；另見 Andreasen，1988 年）。

一項涉及未服藥患者的 PET 研究未發現額葉活動減退（Sheppard 等，1983）。 另一位未服藥患者的額葉代謝增加（Cleghorn 等，1989）。 未服藥患者的額葉沒有表現出活動減退證實了這種影響，當發現時，可能是由抗精神病藥物引起的。 作為一個例外，Buchsbaum 等人。 （1992 年）在診斷為精神分裂症的從未服藥的患者中發現了低額症狀。 然而，結果並不明確：“低額效應是適度敏感的，而不是強烈的特異性。”

一些 PET 研究測量了從未接觸過抗精神病藥的被標記為精神分裂症的患者的腦血流量。 在要求受試者執行旨在激活額葉的任務時進行 PET 測量。 安德烈森等人。 （1992 年）發現“僅在陰性症狀得分高的患者中減少激活。 這些結果表明，低額與陰性症狀有關，而不是精神抑制治療或疾病慢性的長期影響。”

Andreasen 等人的結論有一個明顯的缺陷。 “精神分裂症”的負面症狀包括冷漠、冷漠、缺乏情感、缺乏意志力或意志力、缺乏語言交流和社交退縮。 陰性症狀的高分意味著患者不能或不願意配合項目的要求來執行所要求的測試，因此在本應引發額葉活動的任務上投入的精力較少。 還要注意，所有這些症狀都可能由抗精神病藥物引起（第 1 章和第 2 章），這表明這些患者可能服用了特別大量的藥物，導致他們的額葉活動受到抑制。

總體而言，無論是否診斷為精神分裂症，在任何個體的大腦中發現能量使用的細微差異都可能有心理根源。 例如，眾所周知，不同的意識狀態會影響大腦不同部位的電波的幅度和頻率。 例如，視覺和聽覺活動反映在大腦不同區域的電活動增強中。 生物反饋實驗表明，人們可以有意識地控制腦電波活動的某些方面。

然而，在大多數情況下，被診斷患有精神分裂症的患者額葉活動減退的發現是由抗精神病藥引起的腦功能障礙和損傷所致。 PET 掃描顯示服藥和先前服藥患者的額葉活動減退證實了生物精神病治療的大腦功能障礙原則。

核磁共振 (p. 92)
在她對神經影像學研究的回顧中，Jackson (2005) 評論了結果的不一致。 共同的發現是，對暴露於安定藥的患者的研究揭示了大腦中各種各樣的解剖異常。 作為朗等人。 (2004) 指出，“已知抗精神病藥物會改變人類和動物基底神經節的結構和新陳代謝。”

同時，大量證據表明，抗精神病藥會導致紋狀體（尾狀核、殼核和蒼白球）增大（體積增加；Lang 等人的研究結果和綜述，2004）。 多巴胺能神經在該區域占主導地位，並且擴大可能代表多巴胺能係統內響應於神經阻滯劑的增殖。 另一方面，安定藥會導致額葉區域的腦組織收縮，同時腦室空間的體積會補償性增加。 這可能是由於腦細胞的破壞。
近年來，磁共振成像 (MRI) 已取代 CT 掃描來研究大腦形態。 利伯曼等人。 (2005b) 評估了被診斷為精神分裂症並接受氟哌啶醇或奧氮平治療的首發患者的腦容量變化。 接受氟哌啶醇治療的患者“灰質體積顯著減少，而接受奧氮平治療的患者則沒有”。 作者認為氟哌啶醇“對大腦形態的影響可能是由於氟哌啶醇相關的毒性”。 他們引用了三項研究表明氟哌啶醇可以“誘導氧化應激和興奮性神經毒性”。 當然，這是唯一合理的結論，因為安定藥對腦細胞有毒。 此外，他們觀察到尾狀核的大小增加，他們承認“已知這是由於常規藥物的治療效果導致紋狀體神經元的超微結構變化”（第 368 頁）。

Magnetic resonance imaging (MRI) has been replacing CT scans in recent years for studying brain morphology. Lieberman et al. (2005b) assessed brain volume changes in first-episode patients diagnosed with schizophrenia and treated with haloperidol or olanzapine. The patients treated with haloperidol “exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not.” The authors suggested that the haloperidol “effects on brain morphology could be due to haloperidol-associated toxicity.” They cited three studies showing that haloperidol can “induce oxidative stress and excitatory neurotoxicity.” That, of course, is the only reasonable conclusion, given that neuroleptics are toxic to brain cells. In addition, they observed an increase in the size of the caudate, which they acknowledge is “known to be due to treatment effects of conventional drugs causing ultrastructural changes in striatal neurons” (p. 368).

然而，利伯曼等人。 （2005b）華夫餅，表明“奧氮平的更大治療效果”使結果無效。 該研究的第二作者 Gary Tollefson 一直是奧氮平製造商 Eli Lilly 的長期顧問和工作人員（Breggin 等人，2004 年以及文章末尾的作者隸屬關係）。 另一位作者 Mauricio Tohen 也是禮來的員工，該項目獲得了禮來基金會的部分資助。

However, Lieberman et al. (2005b) waffle, suggesting that the “greater therapeutic effects of olanzapine” threw off the results. The second author of the study, Gary Tollefson, has been a longtime consultant and then staff member of Eli Lilly, the manufacturer of olanzapine (Breggin et al., 2004 and author affiliations at the end of the article). Another author, Mauricio Tohen, is also a Lilly employee, and the project received partial funding from the Lilly Foundation.

文章摘要中的摘要也具有誤導性。 奧氮平確實在一定程度上減少了額葉的體積，但相對較少。 此外，與氟哌啶醇相比，奧氮平的劑量相對溫和。 奧氮平的劑量範圍（5-20 毫克）與氟哌啶醇（2-20 毫克）相似，但毫克對毫克來說，氟哌啶醇更有效，因此有毒。 奧氮平的推薦初始劑量為 10-15 毫克/天，而氟哌啶醇的初始推薦劑量是 1-6 毫克/天的一小部分（Drug Facts and Compares, 2007）。 因此，氟哌啶醇的比較劑量要大得多，這說明了為什麼它會對額葉造成更大的傷害。 這是製藥公司在試圖證明他們的藥物比競爭對手的藥物毒性更低時常用的技巧：為您的藥物使用相對較低且因此毒性較小的劑量。

The summary in the abstract of the article is also misleading. Olanzapine did cause some degree of reduction in the volume of the frontal lobes, but it was relatively less. In addition, the doses of olanzapine were relatively mild compared to those for haloperidol. The range of olanzapine doses (5–20 mg) was similar to that of haloperidol (2–20 mg), but milligram for milligram, haloperidol is much more potent and hence toxic. The recommended initial dose of olanzapine is 10–15 mg/day, and for haloperidol, the initial recommended dose is a fraction of that amount at 1–6 mg/day ( Drug Facts and Comparisons, 2007). The comparative doses of haloperidol were thus much larger, indicating why it was causing more damage to the frontal lobes. This is a common trick used by drug companies when trying to show that their drug is less toxic than a competitor’s drug: utilize a comparatively lower and hence less toxic dose for your drug.

霍拉姆等人。 （2006 年）發現，與正常志願者相比，常規抗精神病藥導致丘腦體積呈劑量依賴性增加。 當患者從較舊的抗精神病藥物轉換為奧氮平時，丘腦體積恢復正常。 但是，沒有提供奧氮平的劑量。 作者總結說，“抗精神病藥物可能導致精神分裂症中報導的廣泛的丘腦體積”（p. 2007）。 換句話說，是藥物而不是疾病導致了大腦結構異常。 當然，這證實了精神抑製作用的大腦功能障礙原理。

Khorram et al. (2006) found that conventional antipsychotics caused a dose-dependent increase in the volume of the thalamus compared to normal volunteers. The thalamic volumes returned to normal when the patients were switched from the older antipsychotic drugs to olanzapine. However, the doses of olanzapine are not provided. The authors conclude, “Antipsychotic medication could contribute to the wide range of thalamic volumes reported in schizophrenia” (p. 2007). In other words, the drugs and not the disorder are causing the brain structure abnormalities. This, of course, confirms the brain-disabling principles of neuroleptic effects.

CT 掃描和神經心理學相關性 (p. 93)

CT SCANS AND NEUROPSYCHOLOGICAL CORRELATIONS

許多較早的研究涉及對精神病患者進行計算機軸向斷層掃描 (CT) 掃描，其中大多數但並非全部被診斷為精神分裂症。 他們發現側腦室擴大，有時腦溝擴大，表明大腦萎縮或萎縮。 幾乎所有這些研究都涉及大量接受抗精神病藥治療的患者。

Many older studies involved computerized axial tomography (CT) scans of psychiatric patients, most but not all of whom were diagnosed schizophrenic. They have found enlarged lateral ventricles and sometimes enlarged sulci, indicating shrinkage or atrophy of the brain. Nearly all these studies involved patients heavily treated with neuroleptics.

許多 CT 掃描研究發現，在這些接受抗精神病藥物治療的患者中，萎縮與持續性認知缺陷或明顯癡呆之間存在相關性（DeMeyer 等人，1984；Famuyiwa 等人，1979；Golden 等人，1980；Johnstone 等人） 等人，1976 年；勞森等人，1988 年）。 其中一些研究使用了 Nebraska 和 Halstead-Reitan 電池，它們被認為是檢測腦損傷和功能障礙最敏感的電池之一。

A number of the CT scan studies have found a correlation between atrophy and persistent cognitive deficits or frank dementia in these neuroleptic-treated patients (DeMeyer et al., 1984; Famuyiwa et al., 1979; Golden et al., 1980; Johnstone et al., 1976; Lawson et al., 1988). Some of these studies used the Nebraska and Halstead–Reitan batteries, considered among the most sensitive for detecting brain damage and dysfunction.

雖然一些研究聲稱藥物不會導致觀察到的大腦異常，但他們沒有提供證實這一觀點的證據（例如，Johnstone 等人，1976；Johnstone 等人，1978；Lawson 等人，1988； Shelton 等人，1988；Weinberger 等人，1980；Weinberger 等人，1979）。

While some of the studies claimed that drugs could not have caused the observed brain abnormalities, they did not provide evidence that confirmed this viewpoint (e.g., Johnstone et al., 1976; Johnstone et al., 1978; Lawson et al., 1988; Shelton et al., 1988; Weinberger et al., 1980; Weinberger et al., 1979).

兩項對診斷為精神分裂症的相對年輕和相對未經治療的患者進行評估的研究發現腦室擴大，這是腦萎縮的標誌（Schulz 等，1983；Weinberger 等，1982；在 Breggin，1990 中進行了詳細回顧）。 然而，涉及的患者數量非常少，其他研究尚未證實他們的發現（Benes 等人，1982；Iacono 等人，1988；Jernigan 等人，1982；Tanaka 等人，1981）。

Two studies that evaluated relatively young and relatively untreated patients diagnosed with schizophrenia found enlarged ventricles, a marker for brain atrophy (Schulz et al., 1983; Weinberger et al., 1982; reviewed in detail in Breggin, 1990). However, very small numbers of patients were involved, and other studies have not confirmed their findings (Benes et al., 1982; Iacono et al., 1988; Jernigan et al., 1982; Tanaka et al., 1981).

將遲發性運動障礙 (TD) 與腦損傷和癡呆相關聯（第 94 頁）

Correlating Tardive Dyskinesias (TD) With Brain Damage and Dementia (p. 94)

令人驚訝的是，很少有研究試圖將腦部掃描結果與遲發性運動障礙 (TD) 的存在聯繫起來。 Bartels 和 Themelis (1983) 發現 TD 患者的基底神經節存在異常，但總體而言，結果喜憂參半且不確定（Besson 等人，1987；Goetz 等人，1986；Jeste 等人，1980；Koshino 等人） 等人，1986 年）。 然而，正如第 4 章關於抗精神病藥惡性綜合徵 (NMS) 所述，對抗精神病藥物有這些更極端反應的患者通常表現出嚴重的腦損傷（Zarrouf 和 Bhanot，2007 年）。

Surprisingly few studies have attempted to correlate brain scan findings with the presence of tardive dyskinesias (TD). Bartels and Themelis (1983) found abnormalities in the basal ganglia of TD patients, but overall, the results have been mixed and inconclusive (Besson et al., 1987; Goetz et al., 1986; Jeste et al., 1980; Koshino et al., 1986). However, as noted in chapter 4 in regard to neuroleptic malignant syndrome (NMS), patients with these more extreme reactions to antipsychotic drugs often show gross brain damage (Zarrouf and Bhanot, 2007).

大腦研究數據摘要（第 94 頁）

Summary of Brain Study Data (p. 94)

來自 PET、MRI 和 CT 掃描的越來越多的放射學證據證實，在診斷為精神分裂症的接受抗精神病藥物治療的患者中存在慢性腦功能障礙（PET 掃描）和腦萎縮（MRI 和 CT 掃描）。 它也證實了大腦殘疾的概念。

Mounting radiological evidence from PET, MRI, and CT scans confirms the presence of chronic brain dysfunction (PET scans) and brain atrophy (MRI and CT scans) in neuroleptic-treated patients diagnosed with schizophrenia. It also confirms the brain-disabling concept.

到 1988 年，Kelso 等人。 估計相關 CT 掃描研究的總數超過 90 項，其中大部分顯示損傷。 一些研究表明終生服用精神安定藥的總量（DeMeyer 等人，1984 年；Lyon 等人，1981 年）。 許多研究人員試圖將這些發現歸因於精神分裂症，但幾乎沒有理由這樣做（見隨後的討論）。

By 1988, Kelso et al. estimated the total number of relevant CT scan studies to be over 90, most of which show damage. Some studies implicate the total lifetime amount of neuroleptic intake (DeMeyer et al., 1984; Lyon et al., 1981). A number of researchers try to attribute the findings to schizophrenia, but there is little justification for this (see subsequent discussion).

基於腦部掃描的遲發性癡呆率（第 94 頁）

RATES OF TARDIVE DEMENTIA BASED ON BRAIN SCANS (p. 94)

研究表明，被診斷患有精神分裂症的藥物治療患者在 CT 掃描中表現出萎縮的百分比從 0% 到超過 50% 不等。 如果治療是漫長而密集的，如 Suddath 等人。 (1990)，大多數患者可能表現出腦萎縮。 報告的比率很大，通常在 10% 到 40% 的範圍內。 得出類似的結論，Andreasen (1988) 回顧了文獻，發現 6% 到 40% 的範圍。 Andreasen 指出，隨著疾病的嚴重程度和病程的增加，報告的發病率也更高。 然而，“疾病”的嚴重程度和持續時間也與抗精神病藥治療的強度和持續時間相關。

Studies indicate that the percentage of drug-treated patients diagnosed with schizophrenia who demonstrate atrophy on CT scans varies from 0% to over 50%. If treatment has been lengthy and intensive, as in Suddath et al. (1990), most patients may show brain atrophy. Reported rates are substantial, typically in a range of 10% to 40%. Coming to a similar conclusion, Andreasen (1988) reviewed the literature and found a range of 6% to 40%. Andreasen noted that higher rates were reported with increasing severity and length of illness. However, severity and length of “illness” would also correlate with intensity and duration of treatment with neuroleptics.

臨床證據 (p. 95)

CLINICAL EVIDENCE

來自幾個不同臨床來源的證據證實，精神安定藥會永久性地損害心理功能。

Evidence from several different clinical sources confirms that the neuroleptics can permanently impair mental functioning.

TD 與認知功能障礙之間的早期相關性（第 95 頁）

Early Correlations Between TD and Cognitive Dysfunction(p. 95)

癡呆這一術語將被定義為一種基於器質性的多種認知缺陷的綜合症，包括記憶障礙以及其他大腦功能障礙，如情緒不穩定、人格改變或抽象思維、判斷和其他高級皮層或執行功能的障礙。 見美國精神病學協會，2000）。 本章重點關注與長期接觸抗精神病藥相關的逐漸演變的持續性腦損傷和功能障礙。

The term dementia will be defined as a syndrome of organically based multiple cognitive deficits, including memory impairment as well as other brain dysfunctions, such as emotional lability, personality change, or impairments in abstract thinking, judgment, and other higher cortical or executive functions (see American Psychiatric Association, 2000). The chapter focuses on gradually evolving persistent brain damage and dysfunction associated with chronic exposure to neuroleptics.

較早的一篇綜述 (Breggin, 1983b) 披露，許多 TD 患者也患有嚴重的認知功能障礙（例如，Edwards，1970；Hunter 等，1964；Ivnik，1979；Rosenbaum，1979）。 從圖表和腳註中挑選出來，因為大多數研究將這種相關性歸咎於文章中的晦澀之處。 其他研究在沒有證據的情況下得出結論，腦損傷一定早於 TD。 然而，隨後的多項研究證實了我最初的觀察結果，遲發性運動障礙與認知功能之間的相關性現在已經確立。 （見後續部分）。

An earlier review (Breggin, 1983b) disclosed that many patients with TD are also suffering from severe cognitive dysfunction (e.g., Edwards, 1970; Hunter et al., 1964; Ivnik, 1979; Rosenbaum, 1979). Often the data had to be culled from charts and footnotes because most of the studies relegated this correlation to obscurity within the article. Other studies concluded, without evidence, that the brain damage must have predated the TD. However, multiple subsequent studies have confirmed my initial observations, and the correlation between tardive dyskinesia and cognitive function is now well established. (See subsequent sections).

遲發性精神障礙和遲發性癡呆（第 95 頁）

Tardive Dysmentia and Tardive Dementia (p.95)

許多臨床研究現已證實存在與使用抗精神病藥相關的持續性認知缺陷和癡呆症。 然而，在某種程度上，研究人員已經失去了一遍又一遍地證明抗精神病藥會導致認知缺陷的熱情，而精神病學教科書根本不想提及它（例如，Hales 等，2003）。 這讓人想起休克治療對腦損傷影響的研究歷史（第 9 章）。 當反復的動物研究表明電休克療法會導致腦損傷，包括分散的小出血和細胞死亡時，研究停止了，教科書忽略或否認了它的存在。

Many clinical studies have now confirmed the existence of persistent cognitive deficits and dementia in association with neuroleptic use. However, to some extent, researchers have lost their enthusiasm for demonstrating over and over again that neuroleptics cause cognitive deficits, and textbooks of psychiatry simply do not want to mention it (e.g., Hales et al., 2003). This is reminiscent of the history of research into the brain-damaging effects of shock treatment (chapter 9). When repeated animal studies showed that electroconvulsive therapy caused brain damage, including scattered small hemorrhages and cell death, the research stopped, and textbooks ignored or denied its existence.

一項對住院藥物治療患者的臨床研究發現，許多人患有典型的慢性器質性腦綜合症的精神惡化，研究人員將其稱為精神障礙（Wilson 等人，1983 年）。遲發性精神障礙包括“情緒不穩定、說話大聲和[不恰當地靠近]考官”。它可能是輕躁狂癡呆的一種變體。（^1）Wilson 等人研究中的精神異常。 (1983) 與異常不自主運動量表上測量的 TD 症狀呈正相關。此外，抗精神病藥治療的時間長短與癡呆症的三個指標相關：情緒不穩定、說話大聲和欣快。作者說：“我們的假設是，隨著時間的推移，在精神分裂症患者中觀察到的某些行為變化代表了遲發性運動障礙的行為等價物，我們將其稱為遲發性精神障礙”（第 188 頁）。文獻中的傾向，也許是為了尋找委婉說法，一直使用術語“遲發性癡呆”，即使描述的是一種成熟的癡呆綜合症。

A clinical study of hospitalized drug-treated patients found many suffering from mental deterioration typical of a chronic organic brain syndrome that the researchers labeled dysmentia (Wilson et al., 1983). Tardive dysmentia consists of “unstable mood, loud speech, and [inappropriately close] approach to the examiner.” It is probably a variant of hypomanic dementia.(^1) The mental abnormalities in the study by Wilson et al. (1983) correlated positively with TD symptoms measured on the Abnormal Involuntary Movement Scale. In addition, length of neuroleptic treatment correlated with three measures of dementia: unstable mood, loud speech, and euphoria. The authors stated, “It is our hypothesis that certain of the behavioral changes observed in schizophrenic patients over time represent a behavioral equivalent of tardive dyskinesia, which we will call tardive dysmentia” (p. 188). The tendency in the literature, perhaps in search of a euphemism, has been to use the term tardive dysmentia even when a full-blown dementing syndrome is described.

各種研究證實了遲發性精神障礙的存在（dementia；Goldberg，1985；Jones，1985；Mukherjee，1984；Mukherjee 等人，1985；Myslobodsky，1986）。 Myslobodsky (1993) 將遲發性精神障礙的特徵總結為“偶爾過度的情緒反應、對環境刺激的反應增強以及對異常不自主運動的漠不關心或意識降低”。 他回顧了一項研究，該研究表明，被診斷為患有 TD 的精神分裂症患者的攻擊性和緊張程度得分明顯高於沒有 TD 的類似患者。 他指出，其中一些患者患有典型的額葉體症。 他還警告說，常規的神經心理學測試可能會漏掉與 TD 相關的額葉綜合症。(^2)

A variety of studies confirmed the existence of tardive dysmentia (dementia; Goldberg, 1985; Jones, 1985; Mukherjee, 1984; Mukherjee et al., 1985; Myslobodsky, 1986). Myslobodsky (1993) summarized the triad of features of tardive dysmentia as “occasional excessive emotional reactivity, enhanced responsiveness to environmental stimuli, and indifferent or reduced awareness of abnormal involuntary movements.” He reviewed a study indicating that patients diagnosed with schizophrenia with TD score significantly higher on measures of aggression and tension than similar patients without TD. He pointed out that some of these patients suffer from typical frontal lobe signs. He also warned that routine neuropsychological testing can miss the frontal lobe syndrome associated with TD.(^2)

除了威爾遜等人。 （1983 年），其他幾項研究報告了 TD 症狀與全身性精神功能障礙之間的關聯（Baribeau 等人，1993；DeWolfe 等人，1988；Itil 等人，1981；Spohn 等人，1993；Struve 等人。 , 1983 年；Waddington 等人，1986a&b；Wolf 等人，1982 年；許多人在 Breggin，1993 年進行了審查）。 在消除精神分裂症作為致病因素後，Waddington 和 Youssef（1988 年）還發現，與沒有這種疾病的患者相比，接受抗精神病藥物治療的雙相 TD 患者的認知缺陷增加。

In addition to Wilson et al. (1983), several other studies reported an association between TD symptoms and generalized mental dysfunction (Baribeau et al., 1993; DeWolfe et al., 1988; Itil et al., 1981; Spohn et al., 1993; Struve et al., 1983; Waddington et al., 1986a&b; Wolf et al., 1982; many reviewed in Breggin, 1993). After eliminating schizophrenia as a causative factor, Waddington and Youssef (1988) also found increased cognitive deficits in neuroleptic-treated bipolar patients with TD in comparison to those without the disorder.

韋德等人。 (1987) 指出亨廷頓氏病和帕金森氏病為 TD 提供了相關模型，包括認知障礙的發展（參見 Koshino 等人，1986 年；Breggin，1993 年的類似討論）。 他們研究了 54 名被診斷為患有 TD 的躁狂症或精神分裂症的患者，並得出結論，TD 是更大的“慢性精神安定藥誘導的神經毒性過程”的一種表現（Wade 等，1987，p.395）。

Wade et al. (1987) pointed out that Huntington’s and Parkinson’s diseases provide a related model for TD, including the development of cognitive impairments (see Koshino et al., 1986; Breggin, 1993, for similar discussions). They studied 54 patients who were diagnosed with mania or schizophrenia with TD and concluded that TD is one expression of a larger “chronic neuroleptic-induced neurotoxic process” (Wade et al., 1987, p. 395).

保爾森等人。 (1994) 回顧了文獻，發現“據報導，TD 通常與認知障礙有關。” 克拉本丹等人。 (2000) 發現口面 TD 與認知障礙之間存在特殊的相關性，尤其是可能由與口面 TD 相關的“額葉皮質下障礙”引起的記憶延遲。 很明顯，TD 不僅是一種運動障礙，而且會影響一系列認知和情緒功能。

Paulsen et al. (1994) reviewed the literature and found that “TD was generally reported to be associated with cognitive impairment.” Krabbendam et al. (2000) found a particular correlation between orofacial TD and cognitive impairment, especially delayed memory that may be caused by a “frontal subcortical disturbance” related to orofacial TD. It is apparent that TD is not merely a motor disorder but afflicts a range of cognitive and emotional functions.

帕爾默等人。 (1999) 關注錐體外系症狀 (EPS) 而不是 TD，發現 EPS 的嚴重程度與神經心理缺陷的嚴重程度相關，尤其是在學習和運動技能領域。 克勞斯等人。 (1999) 在自評量表上發現 EPS 和認知缺陷之間存在類似的相關性。 他們認為這些缺陷足以導致洞察力和日常生活技能的潛在困難。

Palmer et al. (1999) focused on extrapyramidal symptoms (EPS) rather than TD and found that severity of EPS correlated with the severity of neuropsychological deficits, especially in the areas of learning and motor skills. Krausz et al. (1999) found a similar correlation between EPS and cognitive deficits on a self-rating scale. They believed the deficits were sufficient to cause potential difficulty with insight and everyday life skills.

Gualtieri 和 Barnhill (1988) 指出，“在幾乎所有解決該問題的臨床調查中，都發現 TD 患者與非 TD 患者相比，患癡呆症的機率更大”（第 149 頁）。 他們認為癡呆是由 TD 引起的基底神經節損傷引起的（見後續討論）。(^3) Gualtieri (2002)，該領域最有經驗的研究人員之一，繼續指出 TD 與沒有 TD 的類似患者相比，患者有更多的“癡呆跡象”（第 401 頁）。

Gualtieri and Barnhill (1988) pointed out, “In virtually every clinical survey that has addressed the question, it is found that TD patients, compared to non-TD patients, have more in the way of dementia” (p. 149). They believed that the dementia results from damage to the basal ganglia caused by the TD (see subsequent discussion).(^3) Gualtieri (2002), one of the most experienced researchers in the fi eld, has continued to make the point that TD patients have more “signs of dementia” (p. 401) than similar patients who do not have TD.

由於 TD 的發病率如此之高（見第 4 章），影響了大部分接受抗精神病藥物治療的患者，其與認知功能障礙和癡呆症的關係尤其不祥。 這些數據本身就提供了足夠的證據來得出結論，精神安定藥經常且不可逆轉地損害心理功能。 再次有充分的理由謹慎對待向成人開具這些有毒物質並禁止將其提供給兒童和青少年。

Since the rates of TD are so high (see chapter 4), affecting a large proportion of neuroleptic-treated patients, its association with cognitive dysfunction and dementia is especially ominous. These data by themselves provide sufficient evidence to conclude that neuroleptics frequently and irreversibly impair mental function. Once again there is ample reason to be cautious about prescribing these toxic agents to adults and to prohibit giving them to children and youth.

神經安定藥引起的廣泛認知功能障礙的偶然發現（第 97 頁）

A Serendipitous Finding of Neuroleptic-Induced Generalized Cognitive Dysfunction (p. 97)

一個多地點的國家研究項目評估了由多種藥物濫用引起的腦功能障礙，包括街頭毒品（更詳細的分析，參見 Breggin，1983b）。使用 Halstead-Reitan 神經心理學電池，該研究出人意料地揭示了被診斷患有精神分裂症的患者的全身性腦功能障礙與終生精神藥物消耗之間的顯著相關性（Grant 等，1978a&c）。超過四分之一接受精神抑制藥治療的患者有持續性腦功能障礙。與精神分裂症的診斷相比，慢性腦功能障礙更多地與終生服用安定藥有關：“神經心理異常與更多的抗精神病藥物使用有關”（Grant 等人，1978c，p.1069）。事實上，被診斷患有精神分裂症的患者濫用街頭毒品而不是服用精神安定藥表明精神分裂症的診斷與腦功能障礙增加之間沒有相關性。沒有一名患者接觸過精神抑制藥超過 5 年。

A multisite national research project evaluated brain dysfunction caused by polydrug abuse, including street drugs (for a more detailed analysis, see Breggin, 1983b). Using the Halstead–Reitan Neuropsychological Battery, the study unexpectedly uncovered a significant correlation between generalized brain dysfunction and total lifetime psychiatric drug consumption in patients diagnosed with schizophrenia (Grant et al., 1978a&c). More than one-fourth of the neuroleptic-treated patients had persistent brain dysfunction. The chronic brain dysfunction was related more to lifetime neuroleptic intake than to the diagnosis of schizophrenia: “Neuropsychological abnormality was associated with greater antipsychotic drug experience” (Grant et al., 1978c, p. 1069). Indeed, patients diagnosed with schizophrenia who abused street drugs rather than taking neuroleptics showed no correlation between the diagnosis of schizophrenia and increased brain dysfunction. None of the patients had been exposed to neuroleptics for more than 5 years.

在一次專業會議上發表的論文未發表版本中（Grant 等，1978a），作者強調了 TD 和認知缺陷之間的聯繫，並在他們的結論句中警告說，“很明顯，抗精神病藥物必須繼續 仔細檢查它們是否有可能導致一般性腦功能障礙”（第 31 頁）。 發表在《普通精神病學檔案》(Grant et al., 1978c) 上的版本警告了與使用精神安定藥相關的長期認知缺陷的可能性，但語言的威脅性要小一些。 《美國精神病學雜誌》版本（Grant 等人，1978b）消除了精神安定藥引起的慢性腦功能障礙的危險。 強調了與精神分裂症的誤導性相關性。 前藥編輯使風險從所謂的科學文章中消失了。

In an unpublished version of the paper presented at a professional meeting (Grant et al., 1978a), the authors underscored the connection between TD and cognitive deficits and warned in their concluding sentence,“It is also clear that the antipsychotic drugs must continue to be scruti-nized for the possibility that their extensive consumption might cause general cerebral dysfunction” (p. 31). The version published in the Archives of General Psychiatry (Grant et al., 1978c) warned of the possibility of long-term cognitive deficits associated with neuroleptic use, but in somewhat less threatening language. The danger of neuroleptic-induced chronic brain dysfunction was expurgated from the American Journal of Psychiatry version (Grant et al., 1978b). The misleading correlation with schizophrenia was highlighted. Prodrug editing made the risk disappear from the supposedly scientific article.

安定藥引起的兒童精神和行為惡化（第 98 頁）

Neuroleptic-Induced Mental and Behavioral Deterioration in Children (p. 98)

Gualtieri 及其同事的報告（Gualtieri，2002 年；Gualtieri 等人，1988 年；Gualtieri 等人，1984 年；Gualtieri 等人，1986 年）表明，許多被收容的兒童和年輕人在接受治療後會經歷一段持續惡化的精神症狀期。 從抗精神病藥中撤出，通常對他們的損害超過治療前的原始症狀。 這發生在尚未診斷出精神分裂症的發育障礙患者身上。 研究人員將戒斷引起的問題歸因於藥物引起的癡呆過程。 如果保持不用藥，一些患者會穩定或改善，但另一些患者似乎因藥物而永久惡化。 他們需要增加藥物來控製藥物引起的症狀。

Reports by Gualtieri and his colleagues (Gualtieri, 2002; Gualtieri et al., 1988; Gualtieri et al., 1984; Gualtieri et al., 1986) indicated that many institutionalized children and young adults go through a persistent period of worsening psychiatric symptoms after withdrawal from neuroleptics, typically impairing them more than their original symptoms prior to treatment. This occurred in developmentally disabled patients in whom schizophrenia had not been diagnosed. The researchers attributed the withdrawal-emergent problems to a drug-induced dementing process. Some patients stabilized or improved if kept medication-free, but others seemed permanently worsened by the medications. They required increased medication to control their drug-induced symptoms.

Denial of Symptoms in TD Patients As a Symptom of Cognitive Dysfunction (p. 98)

TD 患者否認或失認症的臨床報告也證實他們患有認知功能障礙，在更嚴重的情況下，會出現癡呆症。 失認症涉及否認神經損傷後功能受損或喪失（第 1 章）。 我的經驗與 Fisher (1989) 的經驗一致，他說失認症“可能符合腦功能障礙的一般規則之一”（第 128 頁）。 因此，TD 患者存在失認症傾向於證實這些患者存在全身性腦功能障礙。 如第 1 章所述，失認症是更廣泛的中毒失認症或藥物迷惑概念的一個方面。 精神安定藥的引人入勝的作用是由它們直接的毒性作用以及它們對大腦造成的不可逆轉的損害引起的。

Clinical reports of denial or anosognosia among TD patients also confirm that they are suffering cognitive dysfunction and, in more severe cases, a dementing process. Anosognosia involves denial of impaired or lost function following neurological injury (chapter 1). My experience coincides with that of Fisher (1989), who stated that anosognosia “may qualify as one of the general rules of cerebral dysfunction” (p. 128). Thus the presence of anosognosia in TD patients tends to confirm the existence of generalized cerebral dysfunction in these patients. Anosognosia, as described in chapter 1, is an aspect of the broader concept of intoxication anosognosia or medication spellbinding. The spellbinding effect of neuroleptics is caused by their direct toxic effects and also by the irreversible damage that they inflict upon the brain.

多份出版物證實，大多數 TD 患者不會抱怨他們的症狀，甚至在面對這些症狀時會拒絕承認自己的存在（Alexopoulos，1979；Breggin，1983b，1993；Chard 等人，引自 Myslobodsky，1993；DeVeaugh- Geiss，1979；Smith 等人，1979；Wojcik 等人，1980）。

Multiple publications confirm that most TD patients do not complain about their symptoms and will even refuse to admit their existence when confronted with them (Alexopoulos, 1979; Breggin, 1983b, 1993; Chard et al., as cited in Myslobodsky, 1993; DeVeaugh-Geiss, 1979; Smith et al., 1979; Wojcik et al., 1980).

患有 TD 的患者不僅對他們的症狀表現出漠不關心，他們有時還會胡編亂造。 史密斯等人。 (1979) 引用了幾項研究，表明 TD 患者通常拒絕承認他們的症狀。 他們觀察到，

Patients with TD not only display indifference toward their symptoms, they sometimes confabulate about them. Smith et al. (1979) cited several studies showing that TD patients typically refuse to recognize their symptoms. They observed,

我們確信許多患者知道他們的症狀但不願意報告，因此在項目結束時，我們開始在檢查完成時詢問患者是否注意到其他患者有任何異常運動。 一些患者詳細描述了其他患者的遲發性運動障礙症狀。 儘管可以想像這些患者可能不知道自己的舌頭或嘴巴的運動，但很難看出他們怎麼可能觀察不到自己的手、腳或腿的運動。

We were so convinced that many patients were aware of their symptoms but unwilling to report them that toward the end of the project we started to ask patients at the completion of the examination if they noticed any abnormal movements in other patients. Several of the patients described the symptoms of tardive dyskinesia in other patients in great detail. Although it is conceivable that these patients might have been unaware of their own tongue or mouth movements, it is difficult to see how they could not have observed their own hand, feet, or leg movements.

DeVeaugh-Geiss (1979) 證實了 TD 患者的症狀和腦葉切開樣冷漠的否認。 儘管反复詢問，

DeVeaugh-Geiss (1979) confirmed denial of symptoms as well as lobotomy-like indifference in TD patients. Despite repeated inquiries,

這些 [15 名 TD] 患者中有 7 名一直並反复否認他們有異常或不自主運動，儘管事實上他們中的大多數人的症狀嚴重到足以導致言語、行走或普通運動運動的協調困難，例如 那些用於吃飯或穿衣的。
Seven of these [fifteen TD] patients consistently and repeatedly denied that they had abnormal or involuntary movements, despite the fact that most of them had symptoms that were severe enough to cause some difficulty with speech, ambulation, or coordination of ordinary motor movements such as those used in eating or dressing.

Wojcik 等人。 (1980) 發現 44% 的 TD 患者否認他們的異常運動意識。 Joyce Kobayashi（在“Patient May Not Be Cognizant”中引用，1982 年）描述了從布朗克斯退伍軍人管理局醫療中心的四個病房中選出的一半以上的 TD 患者對他們的症狀缺乏認識或擔憂。

Wojcik et al. (1980) found that 44% of patients with TD denied awareness of their abnormal movements. Joyce Kobayashi (as cited in “Patient May Not Be Cognizant,” 1982) described the lack of awareness or concern about their symptoms found in more than half the TD patients selected from four wards at the Bronx Veterans Administration Medical Center.

Myslobodsky 等人。 (1985) 發現 88% 的 TD 患者“對他們的不自主運動表現出完全不關心或失認”（第 156 頁）。 該研究還發現了這些患者認知缺陷的其他跡象。 Myslobodsky (1986) 報導了 95% 的 TD 患者“情緒冷漠或對異常運動的坦率的失認”。 他認為，最可能的原因是“與癡呆症相關的某種形式的認知能力下降，可能是由於多巴胺能迴路中的某些抗精神病藥引起的缺陷”（第 4 頁）。 1993 年，Myslobodsky 指出，即使患者仍然能夠對其他醫療問題和症狀提出投訴，他們也會遭受 TD 的否認。 他當時假設“TD患者失去了他們‘意識路線圖’的運動部分。”

Myslobodsky et al. (1985) found that 88% of the TD patients “showed complete lack of concern or anosognosia with regard to their involuntary movement” (p. 156). The study also found other indications for cognitive deficits in these patients. Myslobodsky (1986) reported “emotional indifference or frank anosognosia of abnormal movements” in 95% of TD patients. He theorized that the most probable cause was “some form of cognitive decline associated with dementia disorder, probably owing to some neuroleptic-induced deficiency within the dopaminergic circuitry” (p. 4). In 1993, Myslobodsky pointed out that patients suffer from denial of TD even while they remain able to voice complaints about their other medical problems and symptoms. He postulated at that time that “TD patients lose the motor part of their ‘road map of consciousness.’ ”

這些對 TD 患者否認的研究有力地證實了 TD 與認知功能障礙之間的關聯。 如前所述，原因可能是雙重的：藥物本身的迷人作用，當患者仍在服用它們時，以及藥物引起的腦損傷的持續作用。

These studies of denial in TD patients strongly confirm the association between TD and cognitive dysfunction. As mentioned earlier, the cause is probably twofold: the spellbinding effect of the drugs themselves, when the patients are still taking them, and the persistent effect of the brain damage caused by the drugs.

永久性腦葉切除術或停用（第 100 頁）

Permanent Lobotomy or Deactivation (p. 100)

第 2 章描述並記錄了抗精神病藥的主要腦葉切除或失活作用。 如此多的 TD 病例表現出的失認或否認可能反映了一種永久性的失活現像以及更具體的中毒失認（藥物迷惑）。

Chapter 2 described and documented the primary lobotomizing or deactivating effect of the neuroleptics. The anosognosia or denial exhibited by so many TD cases probably reflects a permanent deactivation phenomenon as well as a more specific intoxication anosognosia (medication spellbinding).

Bleuler (1978) 提出，長期接觸抗精神病藥會產生一種不可逆的額葉綜合徵，表現為冷漠和冷漠。 這種綜合症似乎是多巴胺能神經元永久性功能障礙的必然結果，而這種永久性功能障礙通常是由安定藥治療引起的。 其中一些神經元（起源於腹側被蓋）投射到邊緣系統和額葉。 其他（從黑質）投射到紋狀體，在那裡它們還與邊緣系統以及網狀激活系統相互連接（Alheid 等，1990；另見 Ethier 等，2004；Seeman，1995）。 大腦中任何這些區域的損傷都會導致大腦和思維失活（第 1 章）。

Bleuler (1978) suggested that long-term exposure to neuroleptics can produce an irreversible frontal lobe syndrome with apathy and indifference. The syndrome would seem an inevitable consequence of the permanent dysfunction of dopaminergic neurons that frequently results from neuroleptic treatment. Some of these neurons (originating in the ventral tegmentum) project to the limbic system and frontal lobes. Others (from the substantia nigra) project to the striatum, where they also interconnect with the limbic system as well as with the reticular activating system (Alheid et al., 1990; see also Ethier et al., 2004; Seeman, 1995). Injury in any of these regions of the brain tends to lead to deactivation of the brain and mind (chapter 1).

神經阻滯劑治療患者的遲發性精神病（第 100 頁）

Tardive Psychosis in Neuroleptic-Treated Patients (p. 100)

第 3 章記錄了抗精神病藥可導致急性抑鬱症和精神病。 本章記錄了兒童遲發性精神障礙和遲發性癡呆以及遲發性行為異常的存在。 還有進一步的證據表明，精神安定藥還可以產生不可逆的精神分裂樣精神病，分別稱為超敏性精神病、遲發性精神病和反跳性精神病。

Chapter 3 documented that the neuroleptics can produce acute depression and psychosis. This chapter has documented the existence of tardive dysmentia and tardive dementia as well as tardive behavioral abnormalities in children. There is further evidence that the neuroleptics can also produce irreversible, schizophrenic-like psychoses, variously called supersensitivity psychosis, tardive psychosis, and rebound psychosis.

當 Chouinard 和 Jones 在加拿大精神病學協會年會上首次宣布他們發現遲發性或超敏性精神病時（見 Jancin，1979 年），聽眾中的一位精神病學家抗議，

When Chouinard and Jones first announced their discovery of tardive or supersensitivity psychosis at the annual meeting of the Canadian Psychiatric Association (see Jancin, 1979), one psychiatrist in the audience protested,
我讓我的病人服用抗精神病藥物，因為他們有精神病。 現在你是說控制他們精神分裂症的同一種藥物也會導致精神病，除此之外，該藥物會導致三分之一的遲發性運動障礙。 這是霍布森的選擇。 無論哪種方式，我的患者最終都會失敗。

I put my patients on neuroleptic drugs because they’re psychotic. Now you’re saying that the same drug that controls their schizophrenia also causes a psychosis and that on top of that the drug causes tardive dyskinesia one third of the time. It’s a Hobson’s choice. My patients are going to lose in the end either way.

其中一位小組成員 Barry D. Jones 警告說：“一些似乎需要終生使用精神安定藥的患者實際上可能因為這種療法而這樣做。”

One of the panelists, Barry D. Jones, warned, “Some patients who seem to require lifelong neuroleptics may actually do so because of this therapy.”

在已發表的版本中（Chouinard 等，1980），作者提出不可逆的超敏性精神病是由邊緣系統中被阻斷的多巴胺受體的反跳性過度活躍引起的。 他們將超敏性精神病的機制與 TD 的機制進行了比較。 遲發性精神病可能是導致 TD 運動現象的相同過程的心理表現。

In the published version (Chouinard et al., 1980), the authors suggested that the irreversible supersensitivity psychosis results from rebound hyperactivity of the blockaded dopamine receptors in the limbic system. They compared the mechanism of supersensitivity psychosis to that of TD. Tardive psychosis may be a mental manifestation of the same processes that cause the motor phenomena of TD.

Chouinard 和 Jones (1980) 指出，當患者服用藥物時，TD 和超敏性精神病都會被掩蓋或隱藏。 他們進一步指出，持續使用這些藥物往往會使這兩種疾病惡化。 接受神經安定藥治療的患者通常會出現遲發性精神病，比他們原來的精神疾病更嚴重（Chouinard 等人，1980；Chouinard 等人，1982；Chouinard 等人，1978；Csernansky 等人，1982；Hunt 等人 ., 1988; Mayerhoff et al., 1992; 另見 Jancin, 1979 的新聞報導; “超敏性精神病”, 1983)。 可悲的是，患者可能需要終生服藥來治療可能具有更短且更良性的自然病程的疾病。

Chouinard and Jones (1980) noted that both the TD and the supersensitivity psychosis are masked, or hidden, when the patient is taking drugs. They further stated that continuous use of the drugs tends to worsen both diseases. Neuroleptic-treated patients have often developed tardive psychoses that became more severe than their original psychiatric disorders (Chouinard et al., 1980; Chouinard et al., 1982; Chouinard et al., 1978; Csernansky et al., 1982; Hunt et al., 1988; Mayerhoff et al., 1992; see also news reports by Jancin, 1979; “Supersensitivity Psychosis,” 1983). Tragically, patients can require lifetime medication for a disorder that could have had a much shorter and more benign natural history.

儘管 Chouinard 和 Jones (1980) 發現患病率為 30% 至 40%，但 Hunt 等人。 （1988 年）回顧了 265 名患者的圖表，僅發現了 12 名可能且沒有明確的遲發性精神病病例。 柯克帕特里克等人。 (1992) 對遲發性精神病的存在進行了批判性的審視。 研究通常無法檢測到最明顯的藥物不良反應，導致如此多的藥物進入市場而沒有發現其最嚴重的副作用。 這麼多研究人員記錄了遲發性精神病，現在應該證實它的存在。

Although Chouinard and Jones (1980) found a prevalence of 30% to 40%, Hunt et al. (1988) reviewed the charts of 265 patients and located only12 probable and no definite cases of tardive psychosis. Kirkpatrick et al. (1992) cast a critical eye on the existence of tardive psychosis. Research commonly fails to detect even the most obvious adverse drug effects, resulting in so many drugs reaching the market without their most serious side effects being detected. That so many researchers have documented tardive psychosis should, by now, confirm its existence.

Psychiatry Avoids Facing Tardive Psychosis (p. 101)

自從我在《精神病藥物：對大腦的危害》(1983b) 以及本書 1997 年版中對該主題進行了長時間的回顧以來，關於遲發性精神病的文獻已經變得越來越少。 在這一領域的初步研究爆發之後，就像關於認知障礙和癡呆的研究一樣，人們的興趣已經放緩。 毫不奇怪，精神藥物複合體不鼓勵破壞其產品的研究。

Since my lengthy review of the subject in Psychiatric Drugs: Hazards to the Brain (1983b), and then in the 1997 edition of this book, the literature on tardive psychosis has become sparser. After an initial burst of research in this arena, much like in research concerning cognitive disorders and dementia, there has been a slowing down of interest. Not surprisingly, the psychopharmaceutical complex discourages research that undermines its products.

The American Psychiatric Publishing Textbook of Clinical Psychiatry 的 2003 年版在討論神經安定藥的不良反應時未提及遲發性精神病或超敏性精神病，包括在“遲發性障礙”部分（Hales 等人，2003 年）。 也沒有討論與精神抑製藥，特別是與 TD 相關的認知缺陷的許多研究。 遲發性精神病的唯一提及發生在對情緒障礙的討論中，並引用了 1991-1993 年的三項研究。 1993 年的研究指出了紋狀體膽鹼能神經元死亡的一種可能的生物學機制，這是由長期接觸抗精神病藥引起的（Miller 等，1993）。

The 2003 edition of The American Psychiatric Publishing Textbook of Clinical Psychiatry makes no mention of tardive psychosis or supersensitivity psychosis in the discussion of adverse neuroleptic effects, including in the section “Tardive Disorders” (Hales et al., 2003). Nor is there any discussion of the many studies on cognitive deficits associated with neuroleptics and in particular with TD. The only mention of tardive psychosis occurs within a discussion of mood disorders with citations to three studies spanning 1991–1993. The 1993 study points to a possible biological mechanism in the death of striatal cholinergic neurons, caused by prolonged exposure to neuroleptics (Miller et al., 1993).

就好像這個行業已經發現這個概念是無法忍受的——長時間服用所謂的抗精神病藥物會導致比原來的疾病更嚴重的持續性精神病——所以它選擇忽略它。 這與我們發現所謂的抗抑鬱藥即使在短期內也會導致抑鬱和自殺（第 6 章和第 7 章）的阻力相似。

It is as if the profession has found the concept intolerable—that taking so-called antipsychotic drugs for prolonged periods of time causes a persistent psychosis worse than the original disorder—so it has chosen to ignore it. It is similar to the resistance we will find to admitting that so-called antidepressants, even in the short run, cause depression and suicidality (chapters 6 and 7).

儘管如此，一些研究仍在不斷湧現，人們繼續表達擔憂。 洛爾卡等人。 （2001 年）描述了奧氮平突然停藥後的超敏性精神病病例。 盧等人。 (2002) 報告了兩例老年患者在停用甲氧氯普胺 (Reglan) 後出現幻覺和妄想。

Nonetheless, some studies continue to crop up, and concerns continue to be expressed. Llorca et al. (2001) described a case of supersensitivity psychosis following abrupt olanzapine withdrawal. Lu et al. (2002) reported two cases of older patients who developed hallucinations and delusions following withdrawal from metoclopramide (Reglan).

斯坦尼拉等人。 (1997) 描述了三例因氯氮平戒斷而出現精神病症狀的譫妄病例（另見 Adams 等人，1991，有關氯氮平戒斷精神病的早期報告）。 他們認為氯氮平比典型的抗精神病藥物產生更嚴重的戒斷症狀。 在一項為期 3 年的喹硫平開放標籤研究中，Margolese 等人。 (2004) 將 23 名男性患者從經典抗精神病藥和利培酮換成喹硫平：“在使用喹硫平至少三個月後復發的 7 名患者中有 6 名符合超敏性精神病的標準。” 這是一個非常高的比率，再次引發了關於非典型患者是否更容易導致遲發性精神病的問題。

Stanilla et al. (1997) described three cases of delirium with psychotic symptoms due to clozapine withdrawal (see also Adams et al., 1991, for an early report of clozapine withdrawal psychosis). They believed that clozapine produces more severe withdrawal symptoms than typical antipsychotic agents. In a 3-year open label study of quetiapine, Margolese et al. (2004) switched 23 male patients from classical antipsychotics and risperidone to quetiapine: “Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met the criteria for supersensitivity psychosis.” This is a very high rate, again raising questions about whether atypicals may be more prone to cause tardive psychosis.

英國精神病學家 Moncrieff (2006b) 回顧了文獻，發現特別有力的證據表明氯氮平會導致戒斷性精神病。 她觀察到一些報告的病例發生在沒有精神病史的人身上，並得出結論：“這些影響需要進一步的緊急研究。” Moncrieff (2006a) 在另一篇討論患者停止精神科藥物治療為何如此困難的文章中警告說，“這些影響的影響包括許多關於維持治療的研究可能存在缺陷，以及精神疾病的反復發作可能 有時是醫源性的。” 她指出，研究表明，20% 至 40% 的嚴重精神病患者“可以毫無困難地停止長期治療”，並敦促考慮謹慎管理精神安定藥的戒斷。

British psychiatrist Moncrieff (2006b) reviewed the literature and found especially strong evidence that clozapine causes withdrawal psychoses. She observed that some reported cases occurred in people without a psychiatric history and concluded, “These effects require further urgent research.” In another article discussing why it is so difficult for patients to stop psychiatric medication, Moncrieff (2006a) warned, “The implications of these effects include the possibility that much of the research on maintenance treatment is flawed and that the recurrent nature of psychiatric conditions may sometimes be iatrogenic.” She noted studies indicating that 20% to 40% of people with severe psychotic disorders “can stop long-term treatment without difficulty” and urged consideration for the careful management of neuroleptic withdrawal.

遲發性靜坐不能和認知缺陷（第 103 頁）

Tardive Akathisia and Cognitive Deficits (p. 103)

Gualtieri (1993) 觀察到遲發性靜坐不能患者的焦慮和情緒緊張是該疾病的主要情緒和認知成分。 在回顧了功能性神經解剖學後，Gualtieri 總結道，

Gualtieri (1993) observed that the anxiety and emotional tension suffered by tardive akathisia patients are primary emotional and cognitive components of the disease. After reviewing the functional neuroanatomy, Gualtieri concluded,

因此，人們有權推測，情感不穩定和智力障礙可能是基底節水平神經病理學的結果。 . . . TDAK [遲發性靜坐不能] 是這種效應的一種表現。 可能還有其他人。

One is entitled to surmise, therefore, that affective instability and intellectual impairment may be the consequence of neuropathology at the level of the basal ganglia. . . . TDAK [tardive akathisia] is one manifestation of that effect. There are probably others.

換言之，遲發性靜坐不能綜合徵的存在表明，精神安定藥可以對個體的精神生活產生不可逆轉的損害。

In other words, the existence of the syndrome of tardive akathisia demonstrates that the neuroleptics can produce irreversible damage to the mental life of the individual.

人類和動物屍檢研究（第 103 頁）

HUMAN AND ANIMAL AUTOPSY STUDIES (p. 103)

動物屍檢數據提供了強有力的證據，表明精神安定藥經常導致腦損傷。 人體屍檢研究太少且相互矛盾，無法得出明確的結論。 對它們的興趣再次下降。

Animal autopsy data provide strong evidence that the neuroleptics frequently cause brain damage. Human autopsy studies are too few and contradictory to lead to a definite conclusion. Once again, interest in them has declined.

抗精神病藥引起的腦損傷的動物屍檢研究（第 103 頁）

Animal Autopsy Studies of Neuroleptic-Induced Brain Damage (p. 103)

在本章前面，我總結了 Dorph-Petersen 等人的發現。 （2005 年），臨床劑量的氟哌啶醇和奧氮平在猴子中導致腦組織顯著收縮，細胞死亡通過大腦，但在額葉和頂葉最為明顯。 多項早期對照動物研究表明，長期，有時是短期的精神抑制治療會導致腦損傷。 結構損傷的證據，包括基底神經節中的細胞退化和死亡，在長期服用安定藥後尤其一致（Coln，1975；Jeste 等，1992；Mackiewicz 等，1964；Nielsen 等，1978；Pakkenberg 等人，1973 年；波波娃，1967 年；羅馬森科等人，1969 年；審查於布雷金，1983b）。 負面的研究要少得多（Fog et al., 1976; Gerlach, 1975）。

Earlier in the chapter I summarized the findings of Dorph-Petersen et al. (2005) that clinical doses of haloperidol and olanzapine in monkeys produced marked shrinkage of the brain tissue with cell death through the brain, but most markedly in the frontal and parietal lobes. Multiple earlier controlled animal studies indicate that long-term, and sometimes short-term, neuroleptic treatment cause brain damage. Evidence of structural damage, including cell degeneration and death in the basal ganglia, is especially consistent after chronic administration of neuroleptics (Coln, 1975; Jeste et al., 1992; Mackiewicz et al., 1964; Nielsen et al., 1978; Pakkenberg et al., 1973; Popova, 1967; Romasenko et al., 1969; reviewed in Breggin, 1983b). Far fewer studies have been negative (Fog et al., 1976; Gerlach, 1975).

在服用 0.5-5 mg/kg 的“相對低”劑量的氯丙嗪後，Popova (1967) 發現大鼠大腦中的結構發生了變化，包括許多區域的“神經細胞體腫脹、色解和空泡化”（第 87 頁）， 包括感覺運動皮層、中腦、下丘腦、丘腦和網狀結構。 1992 年，Jeste 等人。 回顧了文獻並發表了將大鼠暴露於氟奮乃靜癸酸酯（5 mg/kg，肌肉注射）每 2 週持續 4、8 或 12 個月的結果。 在犧牲後通過計算機圖像分析系統測量紋狀體中大神經元的密度。 該團隊發現經過 8 個月的治療後密度降低。

After one “comparatively low” dose of chlorpromazine, 0.5–5 mg/kg, Popova (1967) found structural changes in rat brains, including “swelling, chromatolysis and vacuolization of the nerve cell bodies” (p. 87) in many regions, including the sensory-motor cortex, midbrain, hypothalamus, thalamus, and reticular formation. In 1992, Jeste et al. reviewed the literature and published the results of exposing rats to fluphenazine decanoate (5 mg/kg, intramuscular) every 2 weeks for 4, 8, or 12 months. The density of large neurons in the striatum was measured after sacrifice by a computerized image analysis system. This team found a reduced density by 8 months of treatment.

大多數動物研究報告在相對短暫地暴露於抗精神病藥後會出現不可逆的神經元損傷，包括細胞死亡。 非常重要的是，對神經安定劑暴露時間較長的動物研究——1 年（Pakkenberg 等人，1973 年）、8 個月（Jeste 等人，1992 年）和 36 週（尼爾森等人，1978 年）——表明 預期基底神經節的神經元退化。

Most animal studies report irreversible neuronal damage, including cell death, after relatively brief exposure to neuroleptics. Of great importance, animal studies with longer durations of exposure to neuroleptics—1 year (Pakkenberg et al., 1973), 8 months (Jeste et al., 1992), and 36 weeks (Nielsen et al., 1978)—show the expected neuronal deterioration in the basal ganglia.

動物研究提供了明確且顯然無可爭辯的證據，表明抗精神病藥通常會導致不可逆轉的腦損傷。 這與本章前面回顧的最近的研究一致，這些研究證明了較舊和較新的非典型神經安定劑如何對動物的活細胞產生劇毒。

Animal research provides definitive and apparently incontrovertible evidence that neuroleptics often cause irreversible brain damage. This is consistent with more recent studies reviewed earlier in the chapter that demonstrate how both older and newer atypical neuroleptics are highly toxic to living cells in animals.

抗精神病藥引起的腦損傷的人體屍檢證據（第 104 頁）

Human Autopsy Evidence for Neuroleptic-Induced Brain Damage (p. 104)

令人驚訝的是，很少有人體屍檢報告檢查慢性精神病治療的效果。 Bracha 和 Kleinman (1986)、Brown 等人回顧了較早的研究。 （1986 年），傑斯特等人。 （1986 年）和 Rupniak 等人。 （1983 年）。 雖然有些不確定，但屍檢證據確實表明神經安定劑會損害基底神經節，這是一個對 TD 和遲發性癡呆產生潛在關鍵的區域。 但總體而言，文獻很少、相互矛盾，而且沒有定論。 Arai 等人的研究。 （1987 年），布朗等人。 （1986 年），克里斯滕森等人。 （1970），福雷斯特等人。 (1963)、Gross 和 Kaltenback (1968)、Hunter 等人。 (1968)、Jellinger (1977)、Roizin 等人。 （1959 年）和 Wildi 等人。 Breggin (1990) 對 (1967) 進行了更詳細的回顧。

There are surprisingly few human autopsy reports examining the effects of chronic neuroleptic therapy. Older studies have been reviewed by Bracha and Kleinman (1986), Brown et al. (1986), Jeste et al. (1986), and Rupniak et al. (1983). Although somewhat inconclusive, autopsy evidence does suggest that the neuroleptics can damage the basal ganglia, an area potentially critical in the production of both TD and tardive dementia. But the literature, overall, is scant, contradictory, and not conclusive. The studies of Arai et al. (1987), Brown et al. (1986), Christensen et al. (1970), Forrest et al. (1963), Gross and Kaltenback (1968), Hunter et al. (1968), Jellinger (1977), Roizin et al. (1959), and Wildi et al. (1967) are reviewed in more detail in Breggin (1990).

嗜睡性腦炎的教訓 (^4) (p. 104)

LESSONS OF LETHARGIC ENCEPHALITIS(^4) (p. 104)

第 3 章提到了抗精神病藥物惡性綜合徵與病毒性疾病、昏睡性腦炎（encephalitis lethargica 或 von Economo 病）的急性發作之間的相似性。 類似的情況表明，精神安定藥在其主要影響中會產生受控的化學性腦炎，當其失控時，會變成精神抑制藥惡性綜合徵，與暴發性病毒性腦炎無法區分（Breggin，1993）。

Chapter 3 mentioned the similarity between neuroleptic malignant syndrome and an acute episode of the viral disorder, lethargic encephalitis (encephalitis lethargica, or von Economo’s disease). The parallel suggests that the neuroleptics, in their primary impact, produce a controlled chemical encephalitis, which, when out of control, becomes neuroleptic malignant syndrome, indistinguishable from a fulminating viral encephalitis (Breggin, 1993).

正如第一次世界大戰期間和之後的報導（Breggin，1993），還有許多其他方式可以使神經安定藥物的效果與昏睡性腦炎的效果非常相似。 精神安定藥和病毒性疾病都會產生精神冷漠和冷漠。 在 1970 年的回顧展中，丹尼克爾觀察到，
There are many other ways in which neuroleptic drug effects closely mimic those of lethargic encephalitis, as reported during and after World War I (Breggin, 1993). Both the neuroleptics and the viral disease produce mental apathy and indifference. In a 1970 retrospective, Deniker observed,

結果發現，精神安定藥可以通過實驗重現幾乎所有昏睡性腦炎的症狀。 事實上，新藥有可能引起真正的腦炎流行。

It was found that neuroleptics could experimentally reproduce almost all symptoms of lethargic encephalitis. In fact, it would be possible to cause true encephalitis epidemics with the new drugs.

昏睡性腦炎和安定藥毒性之間的相似性在幾個方面是顯著的。 兩組患者最初都表現出冷漠或不感興趣，隨後出現各種運動障礙。 延遲一段時間後，兩組的運動障礙有時會成為永久性的。 許多昏昏欲睡的腦炎患者似乎康復了，但幾年後又復發成破壞性的神經系統疾病。 雖然帕金森樣障礙是與昏睡性腦炎相關的最常見的遲發性或遲發性運動障礙，但其他與藥物誘發的 TD 更相似的運動障礙也已知會發生。

The parallel between lethargic encephalitis and neuroleptic toxicity is remarkable in several respects. Both groups of patients initially display apathy or disinterest, followed by the onset of various dyskinesias. After a delay, the dyskinesias sometimes become permanent in both groups. Many lethargic encephalitis patients seemed to recover, only to relapse into devastating neurological disorders years later. While a Parkinson-like disorder was the most common tardive, or delayed, motor disorder associated with lethargic encephalitis, other dyskinesias more similar to drug-induced TD were also known to develop.

在明顯康復後，許多腦炎患者後來發展為嚴重的精神病和癡呆症（Abrahamson，1935；Matheson Commission，1939）。 因此，完成嗜睡性腦炎和安定藥作用之間的平行關係等待發現，除了 TD，遲發性精神病和遲發性癡呆可能會隨著暴露於安定藥而發生。

After an apparent recovery, many of the encephalitis victims later went on to develop severe psychoses and dementia (Abrahamson, 1935; Matheson Commission, 1939). Thus the completion of the parallel between lethargic encephalitis and neuroleptic effects awaited the discovery that in addition to TD, tardive psychosis and tardive dementia could follow the exposure to neuroleptics.

藥物作用和病毒性腦病作用之間的相似性發出了一個警告，即類似的機制——因此也有類似的不良後果——是可能的。 抗精神病藥問世僅幾年後，Paulson (1959) 在他寫道：

The parallel between the medication effects and the viral encephalopathic effects sounded a warning that similar mechanisms—and hence similar adverse outcomes—were possible. Only a few years after the advent of the neuroleptics, Paulson (1959) raised this concern when he wrote,

腦炎的後遺症包括許多肌肉、精神和自主反應； 吩噻嗪類藥物引起的大部分神經系統並發症都在腦炎後帕金森症的範圍內。 （第 800 頁）

The sequelae of encephalitis include many muscular, psychic and autonomic responses; and most of the neurologic complications from the phenothiazines are within the range of post-encephalitic Parkinsonism. (p. 800)

其他研究人員還注意到安定藥毒性和昏睡性腦炎之間的比較（Brill，1959；Hunter 等，1964）。 Brill (1959) 記錄了昏睡性腦炎中受打擊最嚴重的區域是基底神經節和黑質的細胞，這些區域在產生 TD 時受精神抑製藥物影響最大（參見 Breggin，1993，進一步討論了 解剖路徑）。 基底神經節、網狀激活系統、邊緣系統和大腦皮層之間存在多種相互聯繫，涉及運動和心理功能（例如，Adams 等人，1989；Alheid 等人，1990；Brodal，1969）。 由於相互聯繫，神經安定藥引起的基底神經節損傷如果足夠嚴重，預計會產生持續的認知缺陷和癡呆。

Other investigators also noticed comparisons between neuroleptic toxicity and lethargic encephalitis (Brill, 1959; Hunter et al., 1964). Brill (1959) documented that the hardest hit areas in lethargic encephalitis are the cells of the basal ganglia and the substantia nigra, the areas most affected by the neuroleptic medications in the production of TD (see Breggin, 1993, for a further discussion of the anatomic pathways). There are multiple interconnections between the basal ganglia, reticular activating system, limbic system, and cerebral cortex, involving both motor and mental functions (e.g., Adams et al., 1989; Alheid et al., 1990; Brodal, 1969). As a result of the interconnections, neuroleptic-induced damage to the basal ganglia, if severe enough, would be expected to produce persistent cognitive deficits and dementia.

精神退化與基底神經節和黑質疾病的關聯導致了皮層下癡呆的概念（Huber 等，1985），即由於基底神經節和周圍結構受損而引起的癡呆。 皮層下癡呆患者往往更加抑鬱和冷漠，沒有太多證據表明對高級皮層功能有嚴重損害。 基底神經節的皮層下損傷是大腦功能障礙之一，它使接受抗精神病藥物治療的患者更加溫順，對他人的麻煩也更少。 由於較高的皮層功能受到的損害不那麼明顯，因此觀察者可以放心，患者並沒有受到嚴重傷害，而實際上他們的整體能量水平和生活質量因皮層下功能的損害而受到損害。

The association of mental deterioration with diseases of the basal ganglia and substantia nigra led to the concept of subcortical dementia (Huber et al., 1985), that is, dementia arising from damage to the basal ganglia and surrounding structures. Patients with subcortical dementia tend to be more depressed and apathetic, without as much evidence of gross impairment to higher cortical functions. Subcortical damage to the basal ganglia is one of the brain-disabling mechanisms that make neuroleptic-treated patients more docile and less troublesome to others. Because higher cortical functions are less obviously damaged, observers can reassure themselves that the patients are not being grossly harmed, when in fact their overall energy level and quality of life are impaired by damage to subcortical functions.

Marsden (1976) 觀察到，“如果長期的精神安定治療可以引起紋狀體多巴胺受體作用的明顯永久性變化，那麼我們必須假設同樣的情況也可能發生在中腦邊緣皮質多巴胺受體中”（p. 1079），即 ，大腦的最高中心。 Marsden 和 Obeso (1994) 指出了基底神經節和額葉之間複雜的相互聯繫，以及它們在高級心理功能中的可能作用。

Marsden (1976) observed, “If long-term neuroleptic therapy can cause an apparently permanent change in striatal dopamine-receptor action, then one must assume that the same can occur in the mesolimbic cortical dopamine receptors” (p. 1079), that is, the highest centers of the brain. Marsden and Obeso (1994) pointed out the complex interconnections between the basal ganglia and the frontal lobes and their possible role in higher mental functioning.

動物研究證實，多巴胺受體的超敏反應在中腦邊緣和大腦皮質區域發展，就像在紋狀體中一樣（Chiodo 等人，1983 年；White 等人，1983 年），並且在終止精神安定藥後它可能會變成慢性 治療（Jenner 等人，1983 年；Rupniak 等人，1983 年）。 雖然 TD 難以在動物中繁殖，但 Gunne 和 Haggstrom (1985) 能夠在猴子和大鼠中產生急性和不可逆轉的運動障礙。 對於持續性運動障礙，他們發現了基底神經節和相關區域（黑質、內側蒼白球和丘腦底核）發生不可逆生化變化的證據。

Animal research confirmed that supersensitivity of dopamine receptors develops in the mesolimbic and cerebral cortical areas, much as it does in the striatum (Chiodo et al., 1983; White et al., 1983), and that it can become chronic after termination of neuroleptic treatment (Jenner et al., 1983; Rupniak et al., 1983). While TD is diffi cult to reproduce in animals, Gunne and Haggstrom (1985) were able to create both acute and irreversible dyskinesias in monkeys and rats. With persistent dyskinesias, they found evidence of irreversible biochemical changes in the basal ganglia and related areas (substantia nigra, medial globus pallidus, and nucleus subthalamicus).

許多研究人員評論了神經安定劑誘導的中腦邊緣和皮質多巴胺系統抑制與臨床產生遲鈍或冷漠之間的關係（Lehman，1975；White 等，1983）。 這些生物系統的不可逆變化導致了許多永久性認知功能障礙的發現。

Many researchers remarked on the relationship between neuroleptic-induced inhibition in the mesolimbic and cortical dopamine system and the clinical production of blunting or apathy (Lehman, 1975; White et al., 1983). Irreversible changes to these biological systems account for many findings of permanent cognitive dysfunction.

Gualtieri 和 Barnhill (1988) 證實了這些觀察結果：

Gualtieri and Barnhill (1988) confirmed these observations:

持續的 TD 可能是不可逆轉的紋狀體損傷的結果。 但是紋狀體不僅僅負責運動控制。 它是一個複雜的器官，會影響廣泛的複雜人類行為。 已知沒有一種影響紋狀體組織的疾病只會產生運動後果； 帕金森病和亨廷頓病只是兩個例子。 （第 150 頁）

Persistent TD is probably the consequence of irreversible striatal damage. But the corpus striatum is responsible for more than motor control; it is a complex organ that influences a wide range of complex human behaviors. No disease that afflicts striatal tissue is known to have only motor consequences; Parkinson’s disease and Huntington’s disease are only two examples. (p. 150)

可悲的是，精神病學堅持將抗精神病藥或精神安定藥作為“精神病”、“精神分裂症”和“躁狂症”的特定治療方法，而實際上這些藥物會導致嚴重的腦損傷和功能障礙，有效地使大腦和精神失能，使個體更溫順，對自己的需要或痛苦相對漠不關心。 精神安定藥的使用在很大程度上是為了方便醫生和看護人員，但犧牲了患者的健康。

It is tragic that psychiatry persists in promoting the antipsychotic or neuroleptic drugs as specific treatments for “psychosis,” “schizophrenia,” and “mania,” when in fact the drugs cause severe brain damage and dysfunction, effectively disabling the brain and mind, rendering individuals more docile as well as relatively indifferent to their own needs or suffering. The use of the neuroleptics is, to a great extent, a convenience for physicians and caretakers at the expense of the patients’ well-being.

精神分裂症會導致癡呆嗎？ （第 107 頁）
CAN SCHIZOPHRENIA CAUSE DEMENTIA? (p. 107)

有一個非常有說服力的理由相信 CT 掃描發現的萎縮不是精神分裂症的產物。 與 CT 或 MRI 腦部掃描相比，直接屍檢病理檢查更準確、更明確地評估腦萎縮。 實際病理，如果存在的話，可以通過直接觀察和顯微鏡分析更容易地識別和準確測量。

There is a very cogent reason to believe that the atrophy found on CT scans cannot be the product of schizophrenia. Brain atrophy is far more accurately and definitively evaluated by a direct postmortem pathological examination than on a CT or MRI brain scan. The actual pathology, if it exists, can more easily be identified and accurately measured by direct observation and microscopic analyses.

CT掃描和MRI掃描捕獲人眼範圍內的圖像。 例如，MRI 掃描檢查大約 1-3 毫米厚的大腦切片（Innis 等，1995）。 那是一到三根鉛筆芯的寬度。 此外，圖像僅限於黑白。 最好的 MRI 分辨率才開始接近屍檢時肉眼所能看到的（Innis 等，1995）。

The CT scan and the MRI scan capture images in the range of the human eye. The MRI scan, for example, examines a slice of brain approximately 1–3 mm thick (Innis et al., 1995). That is the width of one to three pencil leads. Furthermore, the images are limited to black and white. The best MRI resolution only begins to approximate what can be seen with the naked eye on autopsy (Innis et al., 1995).

屍檢也可以獲得組織切片，用光學顯微鏡或電子顯微鏡檢查。 此外，在對大腦進行大體檢查時，屍檢實際上可以對大腦進行稱重和測量，並在顯微鏡下檢查細胞密度，而不是估計 MRI 圖片中的組織損失。 因此，許多腦部疾病，如阿爾茨海默病，需要屍檢而不是 MRI 或 CT 掃描才能做出明確診斷（Caine 等，1995）。

An autopsy can also obtain tissue slices for examination with a light microscope or an electron microscope. Furthermore, on gross examination of the brain, instead of estimating tissue loss from MRI pictures, an autopsy can actually weigh and measure the brain and examine cell density under the microscope. As a result, many diseases of the brain, such as Alzheimer’s, require an autopsy rather than an MRI or CT scan to make the definitive diagnosis (Caine et al., 1995).

儘管屍檢和顯微病理學研究的敏感性、有用性和相關性無限地提高，儘管在使用抗精神病藥之前對數千名被診斷患有精神分裂症的患者進行了數百項此類研究，但尚未發現腦萎縮或任何其他病理學的一致發現（例如，Bleuler，1978 年；Nicholi，1978 年；Noyes 等人，1958 年）。 Arieti (1959) 得出結論，尋找精神分裂症神經病理學的希望“仍未實現”（第 488 頁）。 Weinberger 和 Kleinman (1986) 估計，到 1950 年，超過 250 項研究聲稱發現了精神分裂症的嚴重病理缺陷，“這些聲明中的絕大多數要么從未被複製、不可複制，要么被證明是人工製品。”事實證明，這項任務非常令人沮喪，以至於“這項工作在 1950 年代停滯不前”（第 52 頁）。當遲發性運動障礙特別工作組（美國精神病學協會，1980b）簡要提及神經安定藥治療患者腦萎縮的最初 CT 掃描結果時，它評論說：“這一觀察結果非常令人驚訝，因為它與早期的神經病學不一致。慢性精神分裂症的評估；它需要進一步的批判性評估”（第 59 頁）。

Despite the infinitely greater sensitivity, usefulness, and relevance of autopsy examinations and microscopic pathology studies, no consistent finding of brain atrophy or any other pathology has been made despite hundreds of these studies performed on thousands of patients diagnosed with schizophrenia prior to the use of neuroleptics (e.g., Bleuler, 1978; Nicholi, 1978; Noyes et al., 1958). Arieti (1959) concluded that hopes for finding a neuropathology of schizophrenia “have remained unfulfilled” (p. 488). Weinberger and Kleinman (1986) estimated that by 1950, more than 250 studies had claimed to find a gross pathological defect in schizophrenia, and “the overwhelming majority of these claims were either never replicated, unreplicable, or shown to be artifacts.” The task proved so frustrating that “the effort stalled in the 1950s” (p. 52). When the Task Force on Tardive Dyskinesia (American Psychiatric Association, 1980b) made a brief reference to the initial CT scan findings of brain atrophy in neuroleptic-treated patients, it remarked, “This observation is quite surprising as it is not consistent with earlier neurologic evaluations of chronic schizophrenics; it requires further critical evaluation” (p. 59).

此外，在使用安定藥之前，臨床上並沒有一致的癡呆綜合徵可以與所謂的精神分裂症相關聯。 換句話說，在精神安定治療出現之前，對標記為精神分裂症的患者的臨床檢查始終未能發現任何看起來像阿爾茨海默氏症或亨廷頓舞蹈症等腦部疾病的東西。 這就是為什麼精神分裂症被稱為功能性而非器質性疾病的原因，以及為什麼精神分裂症的診斷實際上需要首先排除潛在的器質性疾病。 精神分裂症是一種排除性診斷——這意味著在做出診斷之前已經排除了真正的疾病。

Furthermore, prior to the neuroleptics, there was no consistent dementia syndrome that could be clinically identified in association with so-called schizophrenia. In other words, until the advent of neuroleptic treatment, clinical examination of patients labeled schizophrenic had always failed to reveal anything that looks like a brain disease such as Alzheimer’s or Huntington’s chorea. That is why schizophrenia became known as a functional, rather than an organic, disorder and why a diagnosis of schizophrenia in fact requires first ruling out an underlying organic disorder. Schizophrenia is a diagnosis of exclusion—meaning that real diseases have been ruled out before making the diagnosis.

同時，正如本章和前幾章所記錄的，抗精神病藥確實在被標記為精神分裂症的患者中產生了可識別的身體或器質性疾病。 具有諷刺意味的是，精神病學創造了它一直試圖找到的東西——被診斷患有精神分裂症的人的大腦出現了問題。 發現它後，精神病學傾向於否認現實，或者再次聲稱問題必須來自患者先前存在的精神分裂症。 儘管有大量證據證明這些相同的藥物對動物的大腦也有毒，但還是提出了這一說法。

Meanwhile, as this chapter and earlier chapters document, the neuroleptics have indeed produced identifiable physical or organic disorders in patients labeled schizophrenic. Ironically, psychiatry has created what it always sought to find—something wrong with the brains of people diagnosed with schizophrenia. Having found it, psychiatry tends to deny the reality or to claim, once again, that the problem must emanate from the patients’ preexisting schizophrenia. This claim is made despite a mountain of evidence proving that these same drugs are also toxic to the brains of animals.

回答這個問題，被診斷患有精神分裂症的患者是否有腦萎縮、腦室擴張、神經功能缺損或癡呆？ Lidz (1981) 觀察到，“100 年來，研究人員報告了精神分裂症的神經病理學或生理病理學原因。 問題是沒有重複這樣的發現。 如果患者患有癡呆症，則診斷不是精神分裂症”（第 854 頁）。 Lidz 建議考慮藥物和休克治療對大腦的影響。

In reply to the question, Do patients diagnosed with schizophrenia have cerebral atrophy, dilated ventricles, neurological deficits, or dementia? Lidz (1981) observed, “For 100 years investigators have reported a neuropathological or physiopathological cause of schizophrenia. The trouble is that no such findings have been replicated. If the patient suffers from dementia, the diagnosis is not schizophrenia” (p. 854). Lidz recommended taking into account the impact of medications and shock treatment on the brain.

總之，在藥物時代之前未能在屍檢中獲得一致的腦病理學結果強烈表明，最近在腦部掃描中發現的萎縮不是所謂的精神分裂症的結果，而是對這些人的大腦的一些新威脅的結果。 患者。 新的威脅是廣泛使用已知會導致腦部疾病的抗精神病藥物，包括 TD、抗精神病藥物惡性綜合徵和遲發性癡呆。

In summary, the failure to obtain consistent findings of cerebral pathology on postmortem examination prior to the drug era strongly indicates that more recent findings of atrophy on brain scans are the result not of so-called schizophrenia but of some new threat to the brains of these patients. The new threat is the widespread use of the neuroleptic drugs that are already known to cause brain diseases, including TD, neuroleptic malignant syndrome, and tardive dementia.

Manfred Bleuler (1978) 多年前回顧了其他懷疑精神分裂症患者的腦部疾病惡化的原因。首先，除非由有毒物質引起，然後將其去除，否則以腦萎縮和癡呆為特徵的器質性疾病通常是進行性的。然而，Bleuler 和其他人充分證明了許多被診斷患有精神分裂症的患者會隨著時間的推移而改善。多年來，多達三分之一或二分之一的個體表現出顯著復甦。它們往往不會表現出通常與進行性神經功能喪失相關的身體惡化跡象，例如過早衰老、虛弱、癲癇發作或神經系統體徵和症狀。他們死於折磨正常人的相同疾病。 Bleuler 數十年來跟踪了 208 名患者，發現他們中的大多數人“儘管年事已高(in spite of advanced age)”（第 450 頁），總體上仍然保持著良好的健康狀況。當然，如今，神經安定藥的廣泛使用對那些不幸經歷數月甚至數年暴露於這些有毒物質的人來說，除了“普遍健康(generally good health)”之外，什麼都沒有。

Other reasons to doubt that patients with schizophrenia have a deteriorating brain disorder were reviewed years ago by Manfred Bleuler (1978). First, unless caused by a toxic agent, which is then removed, organic disorders characterized by brain atrophy and dementia are usually progressive. Yet it is well documented by Bleuler and others that many patients diagnosed with schizophrenia improve over time; up to one-third or one-half show significant recovery over the years. They do not tend to show the physical signs of deterioration usually associated with progressive neurological losses, such as premature aging, infirmity, seizures, or neurological signs and symptoms. They die of the same diseases that afflict normal people. In following 208 patients for decades, Bleuler found that most of them remained in generally good health, “in spite of advanced age” (p. 450). Nowadays, of course, the widespread use of neuroleptics results in anything but “generally good health” for those unfortunate enough to experience months and years of exposure to these toxic agents.

其次，癡呆症一旦發展，就很少會自發消失，如果有的話。 然而，即使在藥物問世之前，也有很多例子表明患者會突然自發地好轉多年或終生。 此外，許多患者時好時壞，時而清晰，時而極度不理性（參見 Bleuler，1924；Bleuler，1978）。 這些較早的觀察結果與我自己的臨床經驗完全一致。 在不使用藥物的情況下，我通常能夠幫助患者從幻覺、妄想和其他症狀中恢復過來，這些症狀會讓他們被診斷為精神分裂症並接受大多數精神科醫生的終生藥物治療。 也不是只有我一個人發現這種所謂的生物障礙通常可以通過社會心理干預來逆轉（第 16 章）。

Second, a dementing disorder, once it has progressed, would rarely, if ever, clear up spontaneously. Yet there are many examples, even before the advent of medications, of patients abruptly and spontaneously improving for years at a time or for a lifetime. In addition, many patients wax and wane, showing great clarity at one moment and extreme irrationality at another (see Bleuler, 1924; Bleuler, 1978). These older observations are entirely consistent with my own clinical experience. Without using drugs, I am often able to help patients recover from hallucinations, delusions, and other symptoms that would have earned them a diagnosis of schizophrenia and a lifetime of drug treatment from most psychiatrists. Nor am I alone in finding that this supposed biological disorder can often be reversed by psychosocial interventions (chapter 16).

作為對這些患者沒有患有不可逆的大腦生理障礙的另一個確認，有時緊急情況會暫時使看似慢性和無行為能力的患者進入敏銳的意識和理性行為的狀態。 作為一名住院醫師，我是一名被診斷為偏執型精神分裂症患者的住院醫生。 她拒絕讓我進行例行體檢，作為她進入精神病房的一部分，直到我從她的呼吸中註意到她有肺炎的跡象。 當我實際上告訴她，“你真的病了； 我需要檢查你，”她停止了不理智的行為，讓我聽她的肺，證實了我對肺炎的懷疑。 考試結束後，她又恢復了以前幾乎緊張的行為。

As another confirmation that these patients do not suffer from an irreversible physical disorder of the brain, sometimes an emergency will temporarily arouse a seemingly chronic and incapacitated patient into a state of acute awareness and rational behavior. As a resident, I was the admitting doctor for a patient diagnosed paranoid schizophrenic. She refused to let me perform a routine physical examination as a part of her admission to the psychiatric ward, until I noticed from her breathing that she had signs of pneumonia. When I told her, in effect, “You’re really sick; I need to examine you,” she stopped behaving irrationally and allowed me to listen to her lungs, confirming my suspicion of pneumonia. When the exam was over, she reverted to her previous nearly catatonic behavior.

第三，被診斷患有精神分裂症的患者不會出現癡呆症早期階段的典型症狀，例如短期記憶功能障礙。 它們通常很容易與阿爾茨海默病、多發性梗塞性癡呆以及與帕金森病、亨廷頓舞蹈病或多發性硬化症相關的癡呆症患者區分開來。

Third, patients diagnosed with schizophrenia do not suffer from the typical signs of the earlier stages of a dementing disorder such as short-term memory dysfunction. They are usually easy to distinguish, for example, from victims of Alzheimer’s disease, multi-infarct dementia, and the dementias associated with Parkinson’s disease, Huntington’s chorea, or multiple sclerosis.

第四，被診斷患有精神分裂症的患者的智力功能非但沒有惡化，反而變得被誤導或心理上不合理。正如我在《有毒精神病學》中所描述的，被診斷患有精神分裂症的患者經常用不尋常而復雜的隱喻來處理關於愛、生命或上帝的意義的心理和精神衝突。他們經常對自己假定的邪惡或崇高本性的概念表現出極大的熱情。很多時候，在正常的心理生活中只會出現一兩個特定的錯誤想法（妄想）。這些錯覺將得到智力活力和高度的精神敏銳度的保護，這表明整體大腦功能本身是正常的，而且通常高於平均水平。除非接觸過精神抑制藥，否則被診斷患有精神分裂症的患者智商不會受損，也不會出現神經心理缺陷的跡象。出於這個原因，旨在發現器質性腦缺陷的神經心理學測試對診斷所謂的精神分裂症沒有用，除非排除其他“真正的”疾病，如癡呆症。

Fourth, instead of deteriorating, the intellectual functions in patients diagnosed with schizophrenia become misdirected or psychologically irrational. As I describe in Toxic Psychiatry, patients diagnosed with schizophrenia often speak in unusual and complex metaphors dealing with psychological and spiritual conflicts over the meaning of love, life, or God. Often they display enormous passion around the concept of their own presumed evil or exalted nature. Quite frequently, only one or two specific false ideas (delusions) will appear in an otherwise normal mental life. These delusions will be defended with intellectual vigor and a high degree of mental acuity, indicating that overall brain function itself is normal and often above average. Unless there has been exposure to neuroleptics, the patient diagnosed with schizophrenia will have an unimpaired IQ and no signs of neuropsychological deficits. For this reason, neuropsychological testing aimed at discovering organic brain deficits are of no use in diagnosing so-called schizophrenia, except to rule out other “real” diseases such as dementia.

總之，幾乎沒有理由相信腦萎縮和癡呆症的發現是由所謂的精神分裂症引起的，而有壓倒性的證據表明抗精神病藥治療。

In summary, there is little or no reason to believe that findings of brain atrophy and dementia are caused by so-called schizophrenia, while there is overwhelming evidence to indict neuroleptic therapy.

與此同時，“什麼是精神分裂症？”的問題。 仍然很複雜，而且基本上沒有答案。 與現在流行的生物學理論相反，許多研究人員發現診斷幾乎沒有科學有效性或沒有科學有效性，而其他人則認為它反映了可追溯到兒童早期的深刻心理障礙。 這不是深入討論這個問題的地方。 無論我們如何看待精神分裂症的診斷，被貼上標籤的人都應該受到保護，免受精神抑制藥的侵害，這類藥物如果不是針對手無寸鐵、被污名化的精神病患者，可能會從市場上撤下。

Meanwhile, the question “What is schizophrenia?” remains complicated and largely unanswered. In contrast to the biological theories now in vogue, many researchers have found that diagnosis holds little or no scientific validity, while others believe it reflects profound psychological disturbances reaching back into early childhood. This is not the place to discuss this question in any depth. However we view the diagnosis of schizophrenia, people given the label deserve to be protected from neuroleptics, a class of drugs that would probably be taken off the market if they weren’t aimed at defenseless, stigmatized mental patients.

對神經麻痺性癡呆的精神病學否認（第 110 頁）

PSYCHIATRIC DENIAL OF NEUROLEPTIC-INDUCED DEMENTIA (p. 110)

精神病學花了 20 年時間才將 TD 認定為一種醫源性疾病，儘管它影響了一半或更多的住院患者（Gelman，1984）。 如第 4 章所述，對充分處理 TD 的抵制仍在繼續（Breggin，1983b；Brown 等人，1986；Cohen 等人，1990；Wolf 等人，1987）。 由於損害仍然更具災難性，因此人們更不願意承認遲發性癡呆和腦萎縮是可以預料的。 此外，忽視認知缺陷和癡呆比忽視運動障礙更容易，也更容易將精神症狀錯誤地歸因於患者的精神疾病。

It took psychiatry 20 years to recognize TD as an iatrogenic illness, even as it afflicted half or more of hospitalized patients (Gelman, 1984). As noted in chapter 4, resistance to dealing adequately with TD continues (Breggin, 1983b; Brown et al., 1986; Cohen et al., 1990; Wolf et al., 1987). An even greater reluctance to recognize tardive dementia and brain atrophy was to be anticipated since the damage is still more catastrophic. Furthermore, it is easier to overlook cognitive deficits and dementia than to ignore dyskinesias, and easier as well to mistakenly attribute the mental symptoms to the patient’s psychiatric disorder.

治療急性錐體外系副作用的藥物（第 111 頁）

DRUGS TO TREAT ACUTE EXTRAPYRAMIDAL SIDE EFFECTS (p. 111)

多種藥物用於控制精神安定藥引起的急性錐體外系效應，例如震顫、強直、靜坐不能和肌張力障礙。 大多數這些藥物抑制膽鹼能神經系統。 它們包括苯托品 (Cogentin)、比哌立登 (Akineton)、丙環利定 (Kemadrin) 和苯海索 (Artane)。 這些藥物會產生多種抗膽鹼能副作用，包括青光眼、嚴重便秘、腸梗阻和無法排空膀胱。 由於許多精神安定藥也產生抗膽鹼能作用，因此當它們合用時，這些不良反應的可能性會增加。

A variety of drugs are used to control neuroleptic-induced acute extrapyramidal effects such as tremors, rigidity, akathisia, and dystonia. Most of these agents suppress the cholinergic nervous system. They include benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and trihexyphenidyl (Artane). These agents produce multiple anticholinergic side effects, including glaucoma, severe constipation, ileus, and the inability to empty the bladder. Since many of the neuroleptics also produce anticholinergic effects, the likelihood of these adverse reactions is increased when they are combined.

從大腦功能障礙的角度來看，抗膽鹼能藥物會導致精神錯亂、器質性腦綜合徵和精神病。 很少有人注意到它們對記憶和學習的不利影響，這可能會干擾日常生活、康復或學校（Marcus et al., 1988; McEvoy, 1987）。 此外，人們擔心使用這些藥物會增加 TD 的風險（APA，1992）。

From the brain-disabling viewpoint, anticholinergic drugs can cause confusion, organic brain syndromes, and psychoses. Far too little attention has been paid to their adverse effects on memory and learning, which can interfere with everyday living, rehabilitation, or school (Marcus et al., 1988; McEvoy, 1987). Furthermore, there is concern that the use of these drugs increases the risk of TD (APA, 1992).

退出藥劑問題和知情同意（第 111 頁）

WITHDRAWAL PROBLEMS AND INFORMED CONSENT (p. 111)

如第 4 章所述，與精神安定藥戒斷相關的困難使我提出了它們可能導致依賴的問題（Breggin，1989a，1989b）。 與此同時，臨床醫生越來越意識到將患者從抗精神病藥物中移除的困難，部分原因是遲發性精神病。 停藥還會產生短暫或持續的運動障礙、煩躁不安和自主神經失衡，導致噁心和體重減輕。 此外，隨著精神抑制霧的解除，潛在的認知缺陷對患者和其他觀察者來說變得更加明顯。 如前所述，具有顯著抗膽鹼能作用的抗精神病藥可引起嚴重的流感樣綜合徵。

As described in chapter 4, the difficulties associated with neuroleptic withdrawal have led me to raise the issue of their potential to cause dependence (Breggin, 1989a, 1989b). Meanwhile, clinicians have become increasingly aware of the difficulty of removing patients from neuroleptics, partly because of tardive psychosis. Withdrawal from the drugs can also produce transient or persistent dyskinesias, dysphoria, and autonomic imbalances, resulting in nausea and weight loss. In addition, underlying cognitive deficits become more apparent to the patient and other observers as the neuroleptic fog is lifted. As previously described, neuroleptics possessing marked anticholinergic effects can cause a severe flulike syndrome.

由於抗精神病藥非常具有吸引力，因此在戒斷期間或更可能在戒斷後，個體將不得不面對在藥物影響下數月和數年未被注意到的各種持續或永久性的藥物不良反應。許多前精神病患者感到被給他們服用這些藥物的醫生背叛了，有時違背了他們的意願，而且幾乎總是沒有充分告知他們風險。我是否過分暗示患者及其家人幾乎從未通過處方醫生完全了解與神經安定藥相關的風險？我不相信我在誇大其詞。多年審查其他醫生的病歷和治療歷史以及他們在法律案件中的宣誓證詞的經驗證實了一個常識性結論，即開藥的醫生不能完全告知患者與精神抑制藥相關的風險，因為除了最自我的人之外，沒有人– 破壞性患者會故意服用此類有毒藥物。醫生必須隱藏與這些藥物相關的大量風險，以便讓他們的患者服用它們。從這個意義上說，知情同意在很大程度上是一種虛假的抗精神病藥物管理。
Since neuroleptics are extremely spellbinding, during or more likely after withdrawal the individual will have to face a variety of persistent or permanent adverse drug effects that went unnoticed during months and years under the influence of the drugs. Many former psychiatric patients feel betrayed by the doctors who inflicted these drugs on them, sometimes against their expressed will, and almost always without fully informing them about the risks. Am I going too far in suggesting that patients and their families are almost never fully informed by prescribing physicians about the risks associated with neuroleptics? I don’t believe that I am exaggerating. Years of experience reviewing the medical records and treatment histories of other doctors, as well as their sworn depositions in legal cases, have confirmed the common sense conclusion that prescribing physicians cannot fully inform patients about the risks associated with neuroleptics because no one except the most self-destructive patient would knowingly take such toxic drugs. Doctors have to hide the mountain of risks associated with these drugs in order to get their patients to take them. In this sense, informed consent is largely a sham in regard to antipsychotic drug administration.

第 15 章描述瞭如何戒除精神科藥物。

Chapter 15 describes how to withdraw from psychiatric drugs.

結論

CONCLUSION

精神抑制藥物，包括較新的非典型藥物，對腦細胞具有劇毒。 它們導致整個大腦的細胞死亡和組織收縮，特別是損害基底神經節中的多巴胺神經元。 因此，它們會產生多種潛在的不可逆運動異常，包括 TD、遲發性肌張力障礙、遲發性靜坐不能、遲發性癡呆和遲發性精神病，以及潛在致命的抗精神病藥惡性綜合徵。 它們經常引起帕金森綜合症，同時伴有精神和運動過程的遲緩。 長期治療經常會產生不可逆轉的精神功能障礙，如認知缺陷、癡呆、精神狀況惡化和精神病。

The neuroleptic drugs, including the newer atypicals, are highly toxic to brain cells. They cause cell death and tissue shrinkage throughout the brain and especially impair dopamine neurons in the basal ganglia. As a result, they produce a variety of potentially irreversible motor abnormalities in the form of TD, tardive dystonia, tardive akathisia, tardive dementia, and tardive psychosis, as well as the potentially lethal neuroleptic malignant syndrome. They frequently cause a parkinsonian syndrome with retardation of both mental and motor processes. Long-term treatment frequently produces irreversible mental dysfunction in the form of cognitive deficits, dementia, a worsening mental condition, and psychosis.

關於明顯或明顯腦損傷發生率的最一致信息是通過動物研究產生的，這些研究證明了細胞內的毒性機制以及細胞死亡和腦萎縮。 動物研究結果通過測量腦萎縮的腦部掃描在人類身上得到證實。 我們可以估計在接受抗精神病藥物治療的患者中的患病率為 10% 至 40%。 在老年患者和更強烈的長期治療後，它可能超過 50%。 毫不奇怪，這些數字與 TD 的數字有些相似，後者撞擊大腦的相同解剖區域，並且可以在 40% 至 50% 或更多的相對年輕的長期接受精神抑制藥物治療的患者中找到。

The most consistent information on the prevalence of marked or obvious brain damage has been generated by animal studies that demonstrate the mechanisms of toxicity within the cells as well as cell death and brain shrinkage. The animal research findings are confirmed in humans by brain scans measuring brain atrophy. We can estimate a prevalence of 10% to 40% among neuroleptic-treated patients. It probably exceeds 50% in older patients and after more intense, long-term treatment. Not surprisingly, these figures are somewhat parallel to those for TD, which strikes the same anatomical region of the brain, and can be found in 40% to 50% or more of relatively young long-term neuroleptic-treated patients.

此外，許多危及生命的不良反應已經出現在新的非典型反應的最前沿，例如高血壓； 心血管疾病，包括老年人中風； 肥胖; 血清膽固醇升高； 血糖升高; 糖尿病; 和胰腺炎。 最後，有令人信服的新證據將抗精神病藥的使用與過早死亡聯繫起來。

In addition, numerous life-threatening adverse reactions have come to the forefront with the newer atypicals, such as hypertension; cardiovascular disease, including stroke in the elderly; obesity; elevated serum cholesterol; elevated blood sugar; diabetes; and pancreatitis. Finally, there is compelling new evidence linking neuroleptic use to premature death.

如前幾章所述，Haldol、Zyprexa、Risperdal、Seroquel、Abilify 和 Geodon 等抗精神病藥的“抗精神病”作用是神話般的。 所有的精神安定藥，包括所謂的非典型藥物或第二代藥物，都會產生類似腦葉切除術的功能障礙，降低個體的情緒反應能力和意志力，並導致冷漠和冷漠（第 2 章）。 與第 1 章中描述的生物精神治療的大腦功能障礙原則一致，這些影響使患者更易於管理，對其他人的麻煩更少，並且更少意識到或無法對自己的需求和痛苦做出反應。 實際上，假定的治療需要對患者施加一種毒性疾病過程，該過程與稱為嗜睡性腦炎的病毒性疾病非常相似，這種疾病會影響大腦的相同區域並引起冷漠和冷漠，以及 EPS。

As described in earlier chapters, the “antipsychotic” effect of neuroleptics such as Haldol, Zyprexa, Risperdal, Seroquel, Abilify, and Geodon is mythical. All of the neuroleptics, including the so-called atypicals or second-generation drugs, produce a lobotomy-like disability of the brain, reducing the individual’s emotional responsiveness and willpower, and causing apathy and indifference (chapter 2). Consistent with the brain-disabling principles of biopsychiatric treatment described in chapter 1, these effects render the patient more manageable, less troublesome to others, and less aware or able to respond to his or her own needs and suffering. The supposed treatment in reality entails the infliction of a toxic disease process upon the patient remarkably similar to the viral disorder called lethargic encephalitis that afflicts the same regions of the brain and also caused apathy and indifference, as well as EPS.

所有的精神安定藥都具有很強的藥物吸引力（第 1 章），使用戶無法感知對他或她的大腦、思想和身體造成的損害。 正因為如此，精神安定藥很容易造成醫源性否認和無助，在這種情況下，醫生利用藥物引起的腦損傷和功能障礙來製造一個更溫順、更少麻煩的病人。

All of the neuroleptics are profoundly medication spellbinding (chapter 1), rendering the user unable to perceive the damage being done to his or her brain, mind, and body. Because of this, the neuroleptics readily lend themselves to the creation of iatrogenic denial and helplessness, in which the doctor uses drug-induced brain damage and dysfunction to produce a more docile, less troublesome patient.

自 1950 年代中期以來，全球數以億計的患者開出抗精神病藥物，導致醫源性腦損傷的流行、廣泛的疾病和受害者死亡率的增加。 正如第 4 章結尾所建議的那樣，倫理和科學的精神病學將致力於終止使用這些劇毒藥物。 相反，在 FDA 的支持下，有組織的精神病學和製藥公司繼續成功地推動擴大這些藥物的使用，甚至在兒童和青少年的治療中。

Since the mid-1950s, neuroleptic drugs have been prescribed to hundreds of millions of patients worldwide, producing an epidemic of iatrogenic brain damage, a broad spectrum of diseases, and an increased death rate among its victims. As suggested at the conclusion of chapter 4, an ethical and scientific psychiatry would devote itself to ending the use of these highly toxic agents. Instead, organized psychiatry and the pharmaceutical companies, supported by the FDA, continue to push successfully for an expanded use of these drugs, even in the treatment of children and youth.

筆記

1. 額葉損傷和功能障礙可能導致欣快和冷漠（Bradley 等，1991）。

2. 真正需要的是能夠證明在腦葉切除術 (Tow, 1955) 和新形式的心理外科手術 (Hansen et al., 1982) 後發生微妙但具有破壞性的心理變化的研究，包括不同程度的以下情況：無法自發產生或寫自傳觀察；洞察力、判斷力和自我反省能力受損；創造力、幻想生活和想像力減少；喪失自主權和自決權，相應地需要加強對任務的指導和監督；減少抽象推理，增加具體思維；膚淺的影響；社會不敏感和缺乏同理心；無法關心和愛；以及整體的冷漠和冷漠。在臨床有效劑量下，安定藥幾乎立即產生某種程度的所有這些作用。足以“控制”精神病或躁狂症的劑量會在很大程度上導致所有這些腦葉切開術樣效應。在較小程度上，所有精神科藥物都傾向於產生部分或全部這些影響，特別是在長期使用時，尤其是冷漠和冷漠。然而，藥物處方者和倡導者幾乎從未注意到、記錄或評估這些影響。

3. Gualtieri 和 Barnhill (1988) 宣稱“該領域開明的從業者認為精神安定治療是一種特殊的干預措施”（第 137 頁），需要有充分的理由。

4. 這個主題讓我著迷，以至於我用整篇文章來討論它（Breggin，1993）。

NOTES

1. Euphoria as well as apathy can result from frontal lobe damage and dysfunction (Bradley et al., 1991).

2. What is really needed is the kind of research that demonstrated subtle yet devastating psychological changes after lobotomy (Tow, 1955) and newer forms of psychosurgery (Hansen et al., 1982), including varying degrees of the following: inability to spontaneously generate or to write autobiographical observations; impaired insight, judgment, and self-reflection; reduced creativity, fantasy life, and imagination; loss of autonomy and self-determination with a corresponding need for increased direction and supervision in tasks; reduced abstract reasoning and increased concrete thinking; shallow affect; social insensitivity and lack of empathy; the inability to care and to love; and overall apathy and indifference. In clinically effective doses, neuroleptics produce some degree of all of these effects almost immediately. Doses sufficient to “control” psychosis or mania cause all of these lobotomy-like effects to a significant degree. To a lesser degree, all psychiatric drugs tend to produce some or all of these effects, particularly in long-term use and especially apathy and indifference. However, medication prescribers and advocates almost never notice, record, or evaluate these effects.

3. Gualtieri and Barnhill (1988) declared that “neuroleptic treatment is considered by enlightened practitioners in the fi eld to be an extraordinary intervention” (p. 137) requiring serious justification.

4. This subject fascinated me sufficiently for me to devote an entire article to it (Breggin, 1993).