CHAPTER 4 第 4 章

由抗精神病藥引起的嚴重和潛在不可逆的神經系統綜合症（遲發性運動障礙和抗精神病藥惡性綜合症）p. 56

Severe and Potentially Irreversible Neurological Syndromes (Tardive Dyskinesia and Neuroleptic Malignant Syndrome) Caused by Neuroleptics

本章重點關注由抗精神病藥引起的兩種眾所周知的神經系統疾病——遲發性運動障礙 (TD) 和抗精神病藥惡性綜合症 (NMS)——重點關注它們的頻率及其對個體身心生活的破壞性影響。 它還討論了安定藥戒斷綜合症。 下一章將探討主要影響心理功能的不可逆轉的大腦損傷，包括遲發性精神病和遲發性癡呆。 然而，作為安定藥神經毒性的產物，所有這些藥物引起的異常在臨床和神經學上都是相互關聯的。 第 5 章將研究導致或促成這些藥物不良反應的這些藥物的神經毒性作用。

This chapter focuses on two well-known neurological disorders caused by the neuroleptics—tardive dyskinesia (TD) and neuroleptic malignant syndrome (NMS)—with emphasis on their frequency and their destructive impact on the physical and emotional life of the individual. It also discusses neuroleptic withdrawal syndrome. The next chapter will explore irreversible damage to the brain that primarily affects mental functioning, including tardive psychosis and tardive dementia. However, as products of neuroleptic neurotoxicity, all these drug-induced abnormalities are clinically and neurologically interrelated. Chapter 5 will examine the neurotoxic effects of these medications that cause or contribute to these adverse drug effects.

所謂的抗精神病藥的臨床效果，即它們的化學性腦葉切除作用，主要是由於多巴胺能神經的阻滯，尤其是腹側紋狀體中的 D2 受體，以及它們與邊緣系統和額葉的連接（第 1 章和第 2 章） . 然而，背側紋狀體中相同 D2 受體的阻斷是錐體外系反應的可能原因，包括 TD（Ethier 等，2004；Seeman，1995）。 因此，如第 1 章所述，所謂的治療效果與一些最嚴重的副作用密不可分。

The so-called clinical effect of neuroleptics, their chemical lobotomizing impact, is primarily caused by the blockade of dopaminergic nerves, especially the D2 receptors, in the ventral striatum, with their connections to the limbic system and frontal lobes (chapters 1 and 2). However, blockade of the same D2 receptors in the dorsal striatum is the probable cause of extrapyramidal reactions, including TD (Ethier et al., 2004; Seeman, 1995). Hence, as described in chapter 1, the so-called therapeutic effect is inextricably entwined with some of the worst adverse effects.

遲發性運動障礙 (TD) p.57

TARDIVE DYSKINESIA (TD) p.57

TD的臨床表現

Clinical Manifestations of TD

TD 通常始於面部不受控制的運動，包括眼睛（眨眼或眼瞼痙攣）、舌頭、嘴唇、嘴巴和臉頰，但它幾乎可以從任何肌肉群開始。 最常見的早期症狀是舌頭顫抖或捲曲。 舌頭突出和咀嚼動作也很常見，並且可能變得嚴重到傷害牙齒並損害咀嚼和吞嚥。 手和腳、手臂和腿、頸部、背部和軀幹都可能受累。

TD often begins with uncontrolled movements of the face, including the eyes (blinking or blepharospasm), tongue, lips, mouth, and cheeks, but it can start with almost any group of muscles. The most common early sign is a quivering or curling of the tongue. Tongue protrusions and chewing movements are also common and can become serious enough to harm teeth and impair chewing and swallowing. The hands and feet, arms and legs, neck, back, and torso can be involved.

顯示的運動變化很大，包括快速抽搐運動（舞蹈症）或較慢的扭轉運動（手足徐動症）、抽搐、痙攣和震顫。 人的步態可能會嚴重受損。 更微妙的功能可能會受到影響並且很容易被忽視：呼吸（涉及橫膈膜）、吞嚥（涉及咽部和食道肌肉組織以及舌頭）、嘔吐反射和言語（Yassa 等，1985）。

The movements displayed are highly variable and include rapid jerking movements ( chorea) or slower twisting movements ( athetosis), tics, spasms, and tremors. The person’s gait can be badly impaired. More subtle functions can be affected and are easily overlooked: respiration (involving the diaphragm), swallowing (involving the pharyngeal and esophageal musculature as well as the tongue), the gag reflex, and speech (Yassa et al., 1985).

這些動作通常在睡眠期間消失，儘管我看到過例外情況。 它們有時會被意志力部分壓制，經常因焦慮或疲倦而變得更糟，並且可能會不時變化（見後續討論）。

The movements usually disappear during sleep, although I have seen exceptions. They sometimes can be partially suppressed by willpower, frequently are made worse by anxiety or tiredness, and can vary from time to time (see subsequent discussions).

許多 TD 病例似乎相對較輕，通常僅限於舌頭、嘴巴、下巴、面部或眼瞼的運動。 儘管如此，它們經常令人不快，而且常常令人尷尬。 已知患者會自殺（Yassa 等，1985）。

Many cases of TD appear to be relatively mild, often limited to movements of the tongue, mouth, jaw, face, or eyelids. Nonetheless, they are frequently disfi guring and often embarrassing. Patients have been known to commit suicide (Yassa et al., 1985).

異常運動有時會變得完全喪失能力。 Turner (1971) 描述了不能進食並且必須拔掉牙齒以促進食物進入口腔的患者。 他還描述了一些患者無法將鞋子放在腳上，因為他們在坐著進行持續的洗腳活動時會磨損它們。 我評估了一些 TD 完全致殘的案例，包括頸部或身體位置的大量扭曲、搖擺和搖擺、肩膀聳肩、骨盆的旋轉或推力運動以及呼吸障礙，例如 如周期性快速呼吸、不規則呼吸和咕嚕聲。

The abnormal movements can sometimes become totally disabling. Turner (1971) described patients who cannot eat and must have their teeth removed to facilitate the entry of food into their mouths. He also described patients who cannot keep shoes on their feet because they wear them out while sitting with the constant foot-shuffling activity. I have evaluated a number of cases in which the TD was wholly disabling, including massive distortions of the position of the neck or body, rocking and swaying, shoulder shrugging, and rotary or thrusting movements of the pelvis as well as disturbances of respiration, such as periodic rapid breathing, irregular breathing, and grunting.

具有諷刺意味的是，由於看似怪異的面部和身體動作，這種疾病使患者看起來非常瘋狂。 可悲的是，這常常導致患者更積極地接受抗精神病藥治療，最終使他們的 TD 惡化。

Ironically, the disease makes the patient look very crazy because of the seemingly bizarre facial and bodily movements. Tragically, this has often led to patients being treated more vigorously with neuroleptics, ultimately worsening their TD.

與其他神經系統疾病一樣，患者可能會試圖通過在非自願運動中添加自願運動來掩飾這些疾病。 例如，為了掩蓋手臂不斷移動的傾向，患者可能會在面部和頭髮周圍進行修飾動作。 這會使人看起來好像患有心理強迫症而不是神經系統疾病。 或者，患者可能將他或她的雙臂抱在一起以控制動作，使他或她看起來好像是在試圖在心理上控制自己。

As in other neurological disorders, the patient may attempt to hide the disorder by adding voluntary movements to the involuntary ones to disguise them. For example, to cover up a tendency to move the arms continually, the patient may make grooming movements around the face and hair. This can make it seem as if the individual suffers from a psychological compulsion instead of a neurological disorder. Or the patient may clasp his or her arms together to control the movements, making it seem as if he or she is trying to psychologically hold onto himself.

TD Rates (p. 57)

正如以下部分將記錄的，接受抗精神病藥物治療的患者的 TD 發生率是天文數字。 否則，健康成人每年接觸抗精神病藥物的累積率會達到 3% 至 8%。 老年人（55 歲以上）以每年藥物暴露的累積率超過 20% 的速度發展 TD。 兒童也處於高風險之中。

As the following section will document, rates for TD among patients treated with antipsychotic drugs are astronomical. Otherwise healthy adults develop TD at the cumulative rate of 3% to 8% per year of exposure to neuroleptics. The elderly (over age 55) develop TD at a cumulative rate that can exceed 20% per year of drug exposure. Children are at high risk as well.

1980 年，APA 在其工作組報告中對醫源性疾病進行了詳細分析：遲發性運動障礙。 工作組明確表示，TD 是一種嚴重的、通常不可逆的、基本上無法治療的、高度流行的疾病，由抗精神病藥治療引起。 工作組估計常規治療（數月至 2 年）中 TD 的患病率至少為 10% 至 20%，超過最小疾病。 對於長期接觸精神安定藥，超過最小疾病的比率至少為 40%。

In 1980 the APA produced a detailed analysis of the iatrogenic disease in its Task Force Report: Tardive Dyskinesia. The task force made it clear that TD is a serious, usually irreversible, largely untreatable, and highly prevalent disease resulting from therapy with neuroleptics. The task force estimated the prevalence rate for TD in routine treatment (several months to 2 years) as at least 10% to 20% for more than minimal disease. For long-term exposure to neuroleptics, the rate was at least 40% for more than minimal disease.

即使在 1980 年特別工作組報告和大量證實性證據發表之後，一些以生物學為導向的精神病學家，例如 Nancy Andreasen (1984)，在《破碎的大腦：精神病學中的生物革命》中，繼續誤導公眾認為 TD 是“ 不常見”（第 210 頁）並且發生在“少數患者”（第 211 頁）中。

Even after the publication of the 1980 task force report and a mountain of confirmatory evidence, some biologically oriented psychiatrists, such as Nancy Andreasen (1984), in The Broken Brain: The Biological Revolution in Psychiatry, continued to misinform the public that TD is “infrequent” (p. 210) and occurs in “a few patients” (p. 211).

最近的 APA (1992) 工作組報告引用了每年 5% 的速度，在治療的前幾年累積。 Jeste 和 Caligiuri (1993) 估計年輕人的年發病率為 4% 至 5%。 根據這兩項估計，12% 至 15% 的患者會在接觸抗精神病藥物的前 3 年內發展為 TD。 實際上，利率可能更高。

A more recent APA (1992) task force report cited a rate of 5% per year, cumulative over the first several years of treatment. Jeste and Caligiuri (1993) estimated the annual incidence rate among young adults at 4% to 5%. According to these two estimates, 12% to 15% of patients will develop TD within the first 3 years of exposure to antipsychotic drugs. In reality, the rates are probably even higher.

在耶魯大學的一個前瞻性項目中，Glazer 等人。 (1993) 報告了對 362 名門診精神病患者的長期評估，這些患者在基線時沒有 TD，並且一直在使用抗精神病藥。 對於開始使用抗精神病藥物的患者，根據他們的數據預測，在接觸 5 年後，TD 的風險將達到 31.8%——每年略高於 6%。 10年後風險為49.4%，15年後為56.7%，20年後為64.7%，25年後為68.4%。

In a prospective project emanating from Yale, Glazer et al. (1993) reported a long-term evaluation of 362 outpatient psychiatric patients who were free of TD at baseline and who were being maintained on neuroleptics. For patients who are starting neuroleptics, according to projections from their data, the risk of TD will be 31.8% after 5 years of exposure—a rate of slightly over 6% per year. The risk is 49.4% after 10 years, 56.7% after 15 years, 64.7% after 20 years, and 68.4% after 25 years.

喬伊納德等人。 (1986) 跟踪了一組 136 名已經接受抗精神病藥但尚未出現 TD 的人。 5 年多來，35%（每年 7%）患上了這種疾病。

Chouinard et al. (1986) followed a group of 136 persons who had already been receiving neuroleptics but had not yet manifested TD. Over 5 years, 35%—a rate of 7% per year—developed the disorder.

美國精神病學協會是一個保守的組織，傾向於對精神病治療進行自我保護。 儘管如此，APA 的精神疾病診斷和統計手冊的兩個最新版本（1994 年，2000 年）發現，長期患者（意味著幾年或更長時間）的 TD 患病率為 20% 至 30%。 “年輕人”的估計率為每年 3% 至 5%。

The American Psychiatric Association is a conservative organization that tends to be self-protective of psychiatric treatments. Nonetheless, the two most recent editions of the APA’s Diagnostic and Statistical Manual of Mental Disorders (1994, 2000) fi nd a prevalence of 20% to 30% for TD in long-term patients (meaning a few years or more). The estimated rate for “younger individuals” is 3% to 5% per year.

總體而言，在相對年輕和健康的患者中，在治療的最初幾年中，接觸抗精神病藥物時感染 TD 的累積風險為每年 4% 至 7%。 大約三分之一的患者將在治療的前 5 年內發展為這種基本上不可逆的疾病。 這對患者來說是一個天文數字的風險，應該成為所有精神衛生專業人員、他們的患者和他們的患者家屬意識的一部分。 此外，我們會發現 TD 帶來了不可逆轉的認知功能障礙和癡呆的額外風險（第 5 章）。

Overall, in relatively young and healthy patients, the cumulative risk of contracting TD when exposed to neuroleptics ranges from 4% to 7% per year during the first several years of treatment. Approximately one-third of the patients will develop this largely irreversible disorder within the first 5 years of treatment. This represents an astronomical risk for patients and should become part of the awareness of all mental health professionals, their patients, and their patients’ families. Furthermore, we shall fi nd that TD brings with it the additional risk of irreversible cognitive dysfunction and dementia (chapter 5).

有證據表明 TD 的比率在 1990 年代有所增加。 這可能是由於傾向於使用對錐體外系具有更大毒性作用的藥物，例如 Haldol 和 Prolixin（參見 Jeste 等，1981）。 這些藥物還採用長效肌肉注射製劑，不允許患者通過服用比處方藥更少的藥片來獨立降低自己的劑量。 長效形式的新型抗精神病藥（如 Zyprexa(金普薩, 奧氮平)）的開發可能會延續這一趨勢。

There is evidence that rates for TD increased in the 1990s. It may have been caused by the tendency to use drugs with seemingly more toxic effects on the extrapyramidal system such as Haldol and Prolixin (see Jeste et al., 1981). These drugs also come in long-acting intramuscular preparations that do not permit patients to independently lower their own dosages by taking fewer pills than prescribed. The development of long-acting forms of newer neuroleptics, such as Zyprexa, is likely to continue this trend.

TD 在不到 3-6 個月的治療中發展是不尋常的。 然而，正如 Tepper 和 Haas (1979) 和其他人 (例如，Hollister, 1976) 所指出的，TD 即使在低劑量、短期治療中也會發生。 DeVeaugh-Geiss (1979) 看到病例在幾週內出現。 我評估了幾例在治療約 3 個月時出現的 TD 病例。 一名患者在最近接觸 1 個月後出現 TD，幾年前有 2 個月的既往接觸史。 我還看到在服用幾劑 Compazine 或 Reglan 以控制噁心後出現病例，例如，在幾個月內服用 3-5 劑。 在老年人中，許多病例可能在幾週內出現（見後續討論）。

It is unusual for TD to develop in less than 3–6 months of treatment. However, as Tepper and Haas (1979) and others (e.g., Hollister, 1976) noted, TD can develop even in low-dose, short-term treatment. DeVeaugh-Geiss (1979) saw cases develop in a matter of weeks. I have evaluated several cases of TD that developed at around 3 months of treatment. One patient developed TD after 1 month of recent exposure, with a history of 2 months’ prior exposure several years earlier. I have also seen cases develop after a few doses of Compazine or Reglan for the control of nausea, for example, 3–5 doses given over a several month period. In the elderly, many cases may develop within a few weeks (see subsequent discussions).

非典型抗精神病藥導致成人TD (p. 58)

Atypical Neuroleptics Cause TD in Adults (p. 58)

所有的精神安定藥（見附錄）都可引起 TD，包括非典型的精神安定藥，如氯氮平（Weller 等，1993）、奧氮平（Herran，1999）和利培酮（Addington 等，1995；Buzan，1996；Kumar 等人，2000 年；Kwon，2004 年）。 阿立哌唑（Abilify）被認為是較安全的非典型藥物之一，但已有遲發性運動障礙的報導（Maytal 等人，2006；Oommen 等人，2006）。 鑑於除氯氮平外的非典型藥物都是強效多巴胺 (D2) 阻滯劑（第 2 章和第 3 章），因此預期它們在與較老的精神安定藥等劑量給藥時會產生顯著較少量的 TD 是不合理的 .

All the neuroleptics (see the appendix) can cause TD, including the atypical neuroleptics such as clozapine (Weller et al., 1993), olanzapine (Herran, 1999), and risperidone (Addington et al., 1995; Buzan, 1996; Kumar et al., 2000; Kwon, 2004). Aripiprazole (Abilify) has been considered one of the safer atypicals, but there are already reports of tardive dyskinesia (Maytal et al., 2006; Oommen et al., 2006). Given that the atypicals, with the exception of clozapine, are all potent dopamine (D2 ) blockers (chapters 2 and 3), it is irrational to anticipate that they will produce a significantly lesser amount of TD when given at equivalent doses to the older neuroleptics.

如前所述，在暴露於老年精神安定藥和幾種非典型藥物的成年人中進行干預效果的臨床抗精神病藥物試驗（Nasrallah，2007），在產生錐體外系效應、運動障礙、 或靜坐不能。

As already noted, in the clinical antipsychotic trials of intervention effectiveness among adults exposed to older neuroleptics and several atypicals (Nasrallah, 2007), no difference was found between the older antipsychotic drugs and the newer ones in regard to producing extrapyramidal effects, movement disorders, or akathisia.

一種稱為兔子綜合徵的 TD 變體的特徵是沿著嘴的垂直軸進行精細、快速、有節奏的運動。 最近的一項審查發現 11 例與非典型相關的病例，主要是利培酮（Dell’Osso 等，2007）。 所有 FDA 批准的非典型抗精神病藥標籤都帶有與舊抗精神病藥相同的警告等級。

One variant of TD called rabbit syndrome is characterized by fi ne, rapid, rhythmic movements along the vertical axis of the mouth. A recent review found 11 cases associated with atypicals, mostly risperidone (Dell’Osso et al., 2007). All of the FDA-approved atypical neuroleptic labels carry the same class warning as the older neuroleptics.

1997 年美國精神病學雜誌發表了一項誤導醫學界的關鍵研究，比較了奧氮平和氟哌啶醇的 TD 率。 精神科醫生似乎忽略了前兩位作者，加里·托勒夫森和查爾斯·比斯利，他們是奧氮平製造商禮來公司的長期僱員，並且以參與為公司產品辯護而聞名，一直追溯到 百憂解爭議的早期階段（Breggin 等，1994a）。
A key study in misleading the medical profession was published by the American Journal of Psychiatry in 1997, comparing TD rates on olanzapine and on haloperidol. It seemed lost on psychiatrists that the first two authors, Gary Tollefson and Charles Beasley, were longtime employees of Eli Lilly, the manufacturer of olanzapine, and well known for stepping into the fray in defense of the company’s products, going all the way back to early days of the Prozac controversies (Breggin et al., 1994a).

該研究旨在表明奧氮平在幾個月內的 TD 發生率較低。 但三個因素值得注意。 在最後一次就診時，2.3% 的奧氮平患者表現出治療中出現的 TD。 但平均曝光時間不到一年。 如果計算奧氮平的實際 TD 年發生率，大約為 3%，這在經典精神安定藥的發生率範圍內（3% 至 8%）。

The study purported to show that olanzazpine had a lower rate of TD over a several-month period. But three factors were noteworthy. At the last visit, 2.3% of the olanzapine patients displayed treatment-emergent TD. But the average exposure time was less than a year. If the actual annual rate of TD on olanzapine were calculated, it would be approximately 3%, which is within the range of rates for classic neuroleptics (3% to 8%).

此外，在對他們進行評估時，患者繼續服用奧氮平，與所有精神安定藥一樣，奧氮平可以抑制 TD 症狀的出現，同時導致或惡化潛在疾病（見下一節）。 因此，確定 TD 準確率的唯一方法是在最終評估之前將患者從違規藥物中撤出。 在這項研究中，如果患者在最終 TD 評估前停止使用奧氮平，TD 的實際發生率將遠高於每年 3%。

Furthermore, at the times they were being evaluated, the patients continued to take the olanzapine, which, like all neuroleptics, suppresses the appearance of TD symptoms while at the same time causing or worsening the underlying disorder (see subsequent section). Therefore, the only way to determine an accurate rate of TD is to withdraw the patients from the offending drug before the final evaluation. In this study, the actual rate of TD would have been much higher than 3% per year if the patients had been withdrawn from the olanzapine before the final TD evaluation.

最後，與氟哌啶醇相比，奧氮平的劑量相對較低，這是一種使一種藥物看起來比另一種更安全的老把戲。 奧氮平的推薦起始劑量為 5-10 毫克，目標是在幾天內達到 10 毫克。 氟哌啶醇的推薦起始劑量為 1-6 毫克/天（Drug Facts and Compares, 2007）。 患者被給予最多 20 毫克的任何一種藥物，就好像它們的強度相當。

Finally, the dose of olanzapine was relatively low compared to haloperidol, an old trick for making one drug look safer than another. The recommended starting dose of olanzapine is 5–10 mg with the aim of achieving 10 mg within several days. The recommended starting dose of haloperidol is 1–6 mg/day ( Drug Facts and Comparisons, 2007). The patients were given up to 20 mg of either drug as if they were of comparable strength milligram for milligram.

一般的醫生沒有時間也沒有興趣深入分析我評估過 Tollefson 等人的研究。 報告。 醫生通常不會注意到或掌握主要作者是製藥公司員工以發表科學研究為幌子鞭打他們的產品。 醫生不太可能知道這些特定作者專門解決潛在的促銷問題，因為它們在專業人士或公眾中出現。 結果，這項研究使許多醫生相信 Zyprexa 比它更安全。

The average physician does not have the time or inclination to analyze a study in the depth with which I have evaluated the Tollefson et al. report. Often physicians will not notice or grasp that the main authors are drug company employees flogging their product under the guise of publishing a scientific study. Physicians are not likely to know that these particular authors specialize in fixing potential promotional problems as they surface among professionals or with the public. As a result, this study convinced many physicians that Zyprexa is safer than it is.

截至 2006 年 5 月，兩位知識淵博的 TD 專家 Daniel Tarsy 和 Ross Baldessarini 得出的結論是，尚未明確確定非典型 TD 的風險低於使用經典精神安定藥的風險，並且患者應該使用非典型藥物治療 關於精神抑制治療的通常注意事項。

As of May 2006, two of the more knowledgeable TD experts, Daniel Tarsy and Ross Baldessarini, concluded that the risk of TD with atypicals had not been clearly established to be less than that with the classic neuroleptics and that patients should be treated with atypicals with the usual caution concerning neuroleptic treatment.

非典型抗精神病藥導致兒童 TD (p.60)

Atypical Neuroleptics Cause TD in Children

1983 年，在撰寫本書的最早版本時，我成為第一個得出結論並強調兒童是TD 是的主要風險人。 儘管有太多的精神科醫生繼續將兒童的風險降到最低，但人們的意識卻在增強。 在 2003 年版的臨床精神病學美國精神病學出版教科書中，現在處於非典型抗精神病藥時代，Cozza 等人。 解釋說，

In 1983, while writing the earliest edition of this book, I became one of the first to conclude and to emphasize that TD is a major risk in children. While too many psychiatrists have continued to minimize the risk to children, awareness has grown. In the 2003 edition of The American Psychiatric Publishing Textbook of Clinical Psychiatry, now in the era of the atypical antipsychotics, Cozza et al. explained,

遲發性或戒斷性運動障礙，有些是短暫的，但有些是不可逆的，見於 8%–51% 的抗精神病藥物治療的兒童和青少年，因此在隨意使用這些藥物時要謹慎。 兒童和青少年在短至 5 個月的治療後出現遲發性運動障礙，即使在持續服藥期間也可能出現。 在接受利培酮治療的青少年中報告了遲發性運動障礙病例，這表明非典型抗精神病藥也可能導致這種嚴重的不良反應。(p. 1422)

Tardive or withdrawal dyskinesias, some transient but others irreversible, seen in 8%–51% of antipsychotic-treated children and adolescents, mandate caution regarding casual use of these drugs. Tardive dyskinesia has been documented in children and adolescents after as brief a period of treatment as 5 months and may appear even during periods of constant medication dose. Cases of tardive dyskinesia have been reported in youths treated with risperidone, indicating that atypical antipsychotics may also cause this serious adverse reaction.(p. 1422)

為了進一步檢查非典型抗精神病藥導致兒童 TD 的風險，Wonodi 和馬里蘭精神病學研究中心的一個團隊（2007 年）對 118 名服用抗精神病藥（主要是非典型抗精神病藥）至少 6 個月的兒童進行了隨訪。 作為這些藥物不合理過度處方的一個標誌，只有 19% 的服用抗精神病藥物的兒童曾出現過精神病症狀。

To further examine the risk of atypical neuroleptics causing TD in children, Wonodi and a team from the Maryland Psychiatric Research Center (2007) followed up 118 children who had been taking neuroleptics, mostly atypicals, for at least 6 months. As a sign of the irrational overprescription of these drugs, only 19% of the children on antipsychotic drugs had ever displayed psychotic symptoms.

11 名 (9%) 的兒童發展為 TD，而匹配的對照組為 0% (p = .003)。 非裔美國兒童的 TD 率特別高（15%）。 鑑於接觸時間相對較短，這些比率非常高，應該會阻止任何嘗試給兒童服用非典型或非典型抗精神病藥的嘗試。

Eleven (9%) of the children developed TD, compared to 0% in a matched control group ( p = .003). The TD rate was particularly high among African American children (15%). Given the relatively short period of exposure, these rates are astronomically high and should discourage any attempts to give neuroleptics, atypical or not, to children.

TD的歷史 (p. 61)

History of TD

在開發出第一種精神安定藥後的幾年內，很明顯許多患者並未從藥物引起的神經系統疾病中恢復過來，即使在藥物治療終止後也是如此。 報告發表於 1950 年代後期，Delay 和 Deniker (1968) 將他們對不可逆轉的神經系統綜合症的認識追溯到 1959 年。到 1968 年，他們能夠對包括頰舌、軀乾和可變舞蹈動作在內的幾種類型進行生動的回顧。1964 年，Faurbye 等人。 （1964 年）將該疾病命名為遲發性運動障礙。

Within a few years after the development of the first neuroleptic, it became obvious that many patients were not recovering from their drug-induced neurological disorders, even after termination of the drug treatment. Reports were made in the late 1950s, and Delay and Deniker (1968) date their awareness of irreversible neurological syndromes to 1959. By 1968, they were able to provide a vivid review of several varieties, including buccolingual, truncal, and variable choreic movements.In 1964, Faurbye et al. (1964) named the disorder tardive dyskinesia.

彷彿受制於一個思想，精神病學作為一個職業二十年來拒絕對這種潛在的悲劇給予任何官方承認。 然後，在氯丙嗪最初湧入北美的州立精神病院近 20 年後，Crane（1973 年）將其作為個人討伐，以獲得該行業對該問題的認可。 同年，美國神經精神藥理學會/食品和藥物管理局工作組（1973 年）在一份特別報告中描述了該綜合症。 1973 年之後，該行業的每個人都應該警惕神經安定藥引起的 TD 的危險，但是太多的精神科醫生繼續表現得好像風險太無關緊要而不會影響他們的治療決定。

As if governed by one mind, psychiatry as a profession for two decades refused to give any official recognition to this potential tragedy. Then, nearly two decades after chlorpromazine initially flooded the state mental hospitals of North America, Crane (1973) made it a personal crusade to gain the profession’s recognition of the problem. In the same year, the American College of Neuropsychopharmacology/Food and Drug Administration Task Force (1973) described the syndrome in a special report. Following 1973, everyone in the profession should have been alerted to the dangers of neuroleptic-induced TD, but too many psychiatrists have continued to act as if the risk is too inconsequential to affect their treatment decisions.

1980 年，美國精神病學協會 (APA, 1980b) 發表了一份關於 TD 的工作組報告。 1985 年，FDA 採取了不同尋常的步驟，為與所有抗精神病藥標籤和廣告相關的類別警告設定了明確措辭的要求（“Neuroleptics”，1985 年）。 FDA 重新審查精神安定藥標籤的決定很大程度上是由於 1983 年本書第一版《精神病藥物：對大腦的危害》的出版，以及我為提醒國家和行業注意危險而開展的全國性運動 TD，包括一份特別的丹拉瑟報告，突出了我的書和我的擔憂。 同年，APA 採取了前所未有的舉措，就 TD 對其全體成員的危險發出了警告信（有關 FDA 作用的進一步討論，請參見第 13 章）。

In 1980, the American Psychiatric Association (APA, 1980b) published a task force report on TD. In 1985, the FDA took the unusual step of setting specifically worded requirements for a class warning in association with all neuroleptic labeling and advertising (“Neuroleptics,” 1985). The FDA’s decision to reexamine the labeling for neuroleptics was driven in large part by the 1983 publication of the first edition of this book, Psychiatric Drugs: Hazards to the Brain, and the national campaign I conducted to alert the nation and the profession to the dangers of TD, including a special Dan Rather report that highlighted my book and my concerns. In a wholly unprecedented move, in the same year, the APA sent out a warning letter about the dangers of TD to its entire membership (see chapter 13 for further discussion of the FDA’s role).

通過持續的精神抑制治療掩蓋 TD 的症狀 (p.61)

Masking the Symptoms of TD With Continued Neuroleptic Treatment

TD 的症狀自相矛盾地被引起它們的藥物所掩蓋或抑制，因此在患者從治療中移除之前，疾病症狀不會完全出現。 出於這個原因，除了在盡可能短的時間內使用盡可能小的劑量外，只要有可能，患者應該定期從他們的精神安定藥中取出，即使只是短期的，以確定他們是否正在發展 TD。 從精神抑製藥中永久移除是一件更困難的事情，通常需要數月的逐漸退出大腦才能適應無藥物環境。 在作者看來，使用安定藥的最佳方法是永遠不要使用它們（第 16 章）。

The symptoms of TD are paradoxically masked or suppressed by the drugs that cause them so that the disease symptoms do not fully appear until the patient has been removed from the treatment. For this reason, in addition to using the smallest possible dose for the shortest possible time, whenever possible, patients should periodically be removed from their neuroleptics, if only for a short period, to determine if they are developing TD. Permanent removal from the neuroleptics is a more difficult matter, often requiring many months of gradual withdrawal for the brain to adjust to the drug-free environment. The best approach to neuroleptics, in this author’s opinion, is never to use them (chapter 16).

由於抗精神病藥抑制 TD 症狀，一些醫生提倡將其用於治療 TD。 Harold Klawans 討論了試圖用病原體控製或治療 TD 的危險。 他斷言（在 Goetz et al., 1980 之後的討論中），“用抗精神病藥本身治療遲發性運動障礙顯然是用假定的致病藥物治療，應該避免。” 他稱使用安定藥治療遲發性運動障礙是短視的，並得出結論認為該療法“有助於加重其發病機制”。 不幸的是，Klawans 本人在同一篇文章中也很容易推薦利血平作為治療 TD 的有用藥物，因為它也具有安定作用並可能導致該疾病。

Because the neuroleptics suppress TD symptoms, some physicians have advocated their use for the treatment of TD. Harold Klawans has discussed the danger of trying to control or treat TD with the causative agent. He asserts (in the discussion following Goetz et al., 1980), “Treatment of tardive dyskinesia with neuroleptics themselves is clearly treatment with the presumed offending agent and should be avoided.” He calls it short-sighted to use the neuroleptics in the treatment of tardive dyskinesia and concludes that the therapy “serves to aggravate its patho-genesis.” Unhappily, Klawans himself, in the same article, too readily recommends reserpine as a helpful agent in the treatment of TD, because it also has neuroleptic effects and can cause the disorder.

儘管我有嚴重的保留意見，但我看到的 TD 病例是如此致殘，以至於唯一的辦法是使用抗精神病藥進行治療。 但是對於這些情況，必須牢記兩點。 首先，在每種情況下，病例都變得如此嚴重，因為醫生在 TD 首次出現時未能檢測到它，並在它本應終止的很長時間後繼續進行精神抑制治療。 在我研究過的幾乎所有最致殘的案例中，情況都是如此。 其次，有關個人遭受苦難，完全無法在 TD 下發揮作用。 他們和他們的家人被警告了 TD 惡化的危險，然後做出明智的決定繼續使用違規藥物，因為 TD 讓患者的生活難以忍受。 相比之下，大多數發生嚴重 TD 病例的患者並未被警告風險。

Despite my serious reservations, I have seen cases of TD that were so disabling that the only recourse was treatment with a neuroleptic. But two points must be borne in mind about these cases. First, in each instance, the case became so severe because physicians failed to detect the TD when it first appeared and continued neuroleptic treatment long after it should have been terminated. This has been true in nearly all the most disabling cases I have examined. Second, the individuals in question were overcome with suffering and rendered wholly unable to function by the TD. They and their families were warned about the danger of worsening the TD and then made informed decisions to continue the offending agent because the TD was making life unbearable for the patient. By contrast, most patients who develop severe cases of TD have not been warned about the risk.

通常用於改善藥物性帕金森症症狀的抗膽鹼能藥物也可能加重 TD 的症狀（Yassa 等，1992）。 它們包括苯托品 (Cogentin)、比哌立登 (Akineton) 和苯海索 (Artane, Tremin)。 眾所周知，這些藥物會加重亨廷頓舞蹈病的類似症狀（Hunter 等，1968；Klawans，1973）。 目前，這些藥物在 TD 發展或惡化中的作用是有爭議的和不確定的，但在給服用抗精神病藥物的患者時需要謹慎。 這些藥物通常用於治療急性錐體外系症狀，可能被錯誤地用於治療 TD。

The anticholinergic drugs typically used to ameliorate the symptoms of drug-induced parkinsonism also may aggravate the symptoms of TD (Yassa et al., 1992). They include benztropine (Cogentin), biperiden (Akineton), and trihexyphenidyl (Artane, Tremin). These agents are known to worsen similar symptoms in Huntington’s chorea (Hunter et al., 1968; Klawans, 1973). At present, the role of these drugs in the development or exacerbation of TD is controversial and undetermined, but caution is required in giving them to patients on neuroleptics. These agents are often used to treat acute extrapyramidal symptoms and may be mistakenly prescribed for TD.

錐體外系症狀作為未來 TD 的預測指標

Extrapyramidal Symptoms As Predictors of Future TD (p. 62)

抗精神病藥會在絕大多數患者中產生各種急性、暫時性的神經系統疾病，稱為錐體外系症狀 (EPS)。 如第 3 章所述，藥物性帕金森症是最常見的一種，可能在一定程度上發生在絕大多數暴露於有效劑量抗精神病藥的患者身上； 靜坐不能也很常見。 肌張力障礙通常以頸部和肩部肌肉痙攣為特徵，不太常見，但可能會非常疼痛和致殘。

The neuroleptics produce a variety of acute, temporary neurological disorders referred to as extrapyramidal symptoms (EPS) in the great majority of patients. As described in chapter 3, drug-induced parkinsonism is one of the most common, probably occurring to some degree in the vast majority of patients exposed to effective doses of neuroleptics; akathisia is also very common. Dystonia, often characterized by cramping of the muscles of the neck and shoulders, is less common but can be extremely painful and disabling.

這些急性 EPS 反應通常類似於 TD，事實上，肌張力障礙和靜坐不能成為遲發性（持續性）疾病。 所有這些，包括帕金森症，都是由於對基底神經節中的多巴胺能神經遞質系統的安定作用造成的。

These acute EPS reactions often resemble TD, and indeed, the dystonias and akathisia can become tardive (persistent) disorders. All of them, including parkinsonism, result from neuroleptic effects on the dopaminergic neurotransmitter system in the basal ganglia.

我已經註意到非典型神經安定藥會導致 EPS，並且研究表明較低的比率有時使用較低的等效劑量。 台灣的一個研究小組試圖通過檢查服用 14 種不同抗精神病藥中的一種或多種的患者同時開具抗帕金森藥物的比率來確定 EPS 的比較頻率（Yang 等人，2007 年）。 他們發現，服用非典型藥物的患者服用抗帕金森藥物的頻率較低，但存在相當大的重疊。 喹硫平的共同處方率最低（27%），而利培酮的處方率最高（66.5%）。 Mellaril 低於 (61%) 利培酮，而洛沙平最高 (96%)。 然而，一個混雜因素是醫生傾向於開具抗帕金森藥物作為預防措施，如果他們認為該藥物可能導致 EPS，則更容易開出這些藥物。

I have already noted that the atypical neuroleptics can cause EPS and that studies indicating lower rates have sometimes used lower equivalent doses. A Taiwanese research team tried to determine the comparative frequency of EPS by examining the rates at which patients taking one or more of 14 different neuroleptics were coprescribed anti-Parkinson drugs (Yang et al., 2007). They found a tendency for the anti-Parkinson drugs to be prescribed less frequently to patients taking atypicals, but there was considerable overlap. Quetiapine had the lowest coprescrib-ing rate (27%), but risperidone had one of the highest (66.5%). Mellaril was lower (61%) than risperidone, and loxapine was the highest (96%). A confounding factor, however, is the tendency for doctors to prescribe anti-Parkinson drugs as a prophylaxis and to prescribe them more readily if they consider the drug likely to cause EPS.

問題自然出現，急性 EPS 會增加 TD 的風險嗎？ 如果急性 EPS 確實預測未來 TD 的增加，那麼 EPS 的出現表明終止藥物的需求增加。 這些問題多年來一直在爭論，但最近的研究給出了迄今為止最明智的答案。 2006 年，歐洲精神分裂症門診健康結果 (SOHO) 研究對 9,298 名患者進行了一項前瞻性隨訪研究，發現基線 EPS 與後期 TD 之間存在統計學上顯著的相關性。 根據 Tenback 等人的說法。 (2006)，“大約一半出現遲發性運動障礙的患者有早期的錐體外系症狀。” 他們得出的結論是“藥物治療方案。 . . 增加錐體外系症狀可能導致遲發性運動障礙的風險增加。”

The question naturally arises, Do acute EPS increase the risk of TD? If acute EPS do predict an increase in future TD, then the emergence of EPS indicates an increased need to terminate the medication. These questions have been debated over the years, but recent research gives the best-informed answer to date. In 2006 a prospective follow-up study of 9,298 patients by the European Schizophrenia Outpatient Health Outcomes (SOHO) Study found a statistically significant correlation between baseline EPS and later TD. According to Tenback et al. (2006), “about half of the patients who developed tardive dyskinesia had earlier extrapyramidal symptoms.” They concluded that “drug regimens . . . that increase extrapyramidal symptoms are likely to result in increased risk of tardive dyskinesia.”

老年人和其他弱勢群體 (p. 63)
The Elderly and Other Vulnerable Populations

一般來說，老年人更容易出現藥物不良反應（Nolan 等，1988）。老年人和患有癡呆症的人在接觸抗精神病藥時極有可能出現許多不同的不良反應。最近對美國一家醫療保險公司的行政數據進行的一項研究檢查了 959 例至少 45 歲的患者，這些患者被診斷患有癡呆症，並已對至少一種處方藥提出索賠，並且已註冊3 年（Kolanowski 等人，2006 年）。他們發現，29% 的社區居民接受了抗精神病藥物治療，其中女性比例不成比例。非典型是最常用的處方。即使在對多種藥物、年齡和性別進行控制後，使用經典或非典型抗精神病藥治療的組發生不良事件的風險增加，包括譫妄、抑鬱、髖部骨折、跌倒和暈厥。結合研究顯示心血管問題和死亡率以及代謝綜合徵的發生率增加，抗精神病藥應禁用於老年人。

Medication adverse effects in general are more likely to develop in the elderly (Nolan et al., 1988). People who are elderly and people suffering from dementia are at extreme risk for many different adverse effects when exposed to neuroleptics. A recent study of administrative data from a health care insurer in the United States examined 959 cases of patients at least 45 years old who had been diagnosed with dementia, who had made a claim for at least one prescription drug, and who had been enrolled for 3 years (Kolanowski et al., 2006). They found that 29% of this community-dwelling population had been dispensed antipsychotic treatment, with a disproportionate number being female. The atypicals were the most commonly prescribed. Even when controlled for polypharmacy, age, and sex, the group treated with neuroleptics, either classic or atypical, had an increased risk of adverse events, including delirium, depression, hip fracture, falls, and syncope. Combined with research showing increased rates of cardiovascular problems and death as well as the metabolic syndrome, neuroleptics should be contraindicated in the elderly.

老年人的脆弱性在 TD 方面最為明顯。 精神疾病診斷和統計手冊的兩個最新版本 (APA, 1994, 2000) 提供了總結老年人風險程度的共識聲明，並指出“在平均 1 年累積接觸抗精神病藥物後，患病率數據報告高達 50%，發病率為 25%–30%。”這令人難以置信，值得轉述：超過四分之一的老年人會在接觸的第一年內患上 TD！

The vulnerability of the elderly is nowhere more apparent than in regard to TD. The two most recent editions of the Diagnostic and Statistical Manual of Mental Disorders (APA, 1994, 2000) provide a consensus statement that sums up the degree of risk in the elderly, noting “prevalence figures reported up to 50% and an incidence of 25%–30% after an average of 1 year’s cumulative exposure to neuroleptic medication.” This is so hard to believe that it is worth paraphrasing: More than one-quarter of the elderly will develop TD within the first year of exposure!

除了年齡，先前的腦損傷可能會增加 TD 的風險（Breggin，1983b；Chouinard 等，1979；McKeith 等，1992）。 Cohen 和 Cohen (1993) 發現 TD 與先前的器質性腦疾病之間存在相關性。

In addition to age, prior brain damage probably increases the risk of TD (Breggin, 1983b; Chouinard et al., 1979; McKeith et al., 1992). Cohen and Cohen (1993) found a correlation between TD and prior organic brain disorder.

亞薩等人。 (1988) 發現 41% 的老年患者在 24 個月內發展為 TD，並且沒有人完全康復。由老年患者組成的非藥物治療對照組在 2 年內均未出現自發性運動障礙。亞薩等人。 (1988) 在平均年齡為 60 歲的門診人群中發現 45% 的 TD。亞薩等人。 (1992) 發現 35.4% 的患者在平均暴露 20.7 個月後發展為 TD。薩爾茨等人。 （1991 年）發現，在老年人累積抗精神病藥物治療 43 週後，TD 的發生率為 31%。既往接受過電擊治療的患者的發病率較高。有早期帕金森症狀的患者發展為 TD 的速度更快。非常重要的是，在這個老年人群中，服用抗精神病藥的平均累積時間非常短，僅為 22.7 週。 一名患者在 2 週時出現 TD。
Yassa et al. (1988) found that 41% of elderly patients developed TD over a period of only 24 months and that none fully recovered. None of the non-drug-treated controls made up of elderly patients developed spontaneous dyskinesias during the 2 years. Yassa et al. (1988) found TD in 45% of an outpatient clinic population with a mean age of 60. Yassa et al. (1992) found that 35.4% of patients developed TD after a mean exposure of 20.7 months. Saltz et al. (1991) found that the incidence of TD was 31% following 43 weeks of cumulative neuroleptic treatment in the elderly. The incidence was higher among patients who had previous electroshock treatment. Patients with early signs of parkinsonism developed TD at a faster rate. Of great importance, in this older population, the mean cumulative time while taking neuroleptics was very brief, a mere 22.7 weeks. One patient developed TD at 2 weeks.

傑斯特等人。 (1993) 在一項正在進行的前瞻性研究中發現，26% 的中老年患者在 12 個月後發展為 TD。回顧有關精神安定藥戒斷的文獻，作者發現“幾乎 60% 的精神安定藥戒斷患者在平均 6 個月內沒有復發。”他們得出的結論是：“如果在進行充分監測和跟進的情況下仔細進行，那麼從選定的老年精神分裂症患者群體中停止使用抗精神病藥物似乎是可行的。”他們還在他們自己的患者組（包括年輕和年長患者）中進行了為期 2 週的短暫安慰劑替代戒斷試驗，發現它相對良性：沒有人復發或需要重新使用抗精神病藥。他們總結說：“鑑於老年患者患 TD 的風險增加，似乎有必要在這一人群中進行抗精神病藥物戒斷試驗。” 我要補充一點，所有年齡段的人都是如此：盡可能多地戒掉這些藥物。

Jeste et al. (1993), in an ongoing prospective study, found that 26% of middle-aged and elderly patients developed TD after 12 months. Reviewing the literature on neuroleptic withdrawal, the authors found “that almost 60 percent of the patients withdrawn from neuroleptics did not relapse over a mean period of 6 months.” They concluded, “It seems feasible to discontinue neuroleptic medication from a select population of older schizophrenic patients, if it is done carefully with adequate monitoring and follow up.” They also experimented with brief 2-week placebo-substituted withdrawal in their own group of patients, both younger and older patients, and found it relatively benign: None relapsed or required resumption of neuroleptics. They concluded, “Given the heightened risk of TD in older patients, it seems that a trial of neuroleptic withdrawal is warranted in this population.” I would add that the same is true for all ages: Take as many as possible off these drugs.

傑斯特等人。 (1993) 強調，“神經安定藥引起的 TD 的潛在嚴重性需要獲得患者或監護人對治療的充分知情同意。”他們建議定期更新同意並引用其他來源來確認他們的立場。

Jeste et al. (1993) emphasized, “The potential seriousness of neuroleptic-induced TD warrants obtaining competent, informed consent to treatment from patients or guardians.” They recommended that consent be periodically renewed and cited other sources to confirm their position.

沃爾納等人。 （1998 年）研究了一組 55 歲及以上未使用過神經安定劑的患者，在開始使用安定劑之前對他們進行基線評估，並每隔 3 個月進行一次隨訪。使用了相對低劑量的常規抗精神病藥：“在累積抗精神病藥物治療 1、2 和 3 年後，TD 的發生率為 25%、34% 和 53%。”再一次，發生率高得驚人：“TD 的更大風險與[電休克治療] 治療史、更高的平均每日和累積抗精神病藥劑量以及治療早期出現錐體外系體徵有關。”

Woerner et al. (1998) studied a group of neuroleptic-naïve patients aged 55 and above, evaluated them at baseline before the start of neuroleptics, and followed up at 3-month intervals. Relatively low doses of conventional neuroleptics were used: “The rates of TD were 25%, 34%, and 53% after 1, 2, and 3 years of cumulative antipsychotic treatment.” Once again, the rates were astronomically high: “A greater risk of TD was associated with history of [electroconvulsive therapy] treatment, higher mean daily and cumulative antipsychotic doses, and presence of extrapyramidal signs early in treatment.”

Jeste et al. (1999) concluded, “The risk of tardive dyskinesia in older outpatients is high, even with relatively short treatment with low doses of conventional neuroleptics.”

儘管關於老年人非典型藥物誘發 TD 發生率的研究似乎很少（如果有的話），但它們無疑也會很高。 與此同時，與老年人非典型藥物相關的其他風險——包括認知障礙、抗精神病藥惡性綜合徵、EPS、中風、猝死、高血壓、糖尿病、胰腺炎、肥胖和膽固醇升高——提供了充分的理由從不服用這些藥物 對老年人。 同樣，在理性和倫理醫學中，精神安定藥在治療老年人時是禁忌的。

Although there appear to be few, if any, studies of the rates of TD induced by atypical drugs in the elderly, they, too, will undoubtedly be high. In the meanwhile, the other risks associated with atypical drugs in the elderly—including cognitive impairment, neuroleptic malignant syndrome, EPS, stroke, sudden death, hypertension, diabetes, pancreatitis, obesity, and elevated cholesterol—provide ample reason never to give these drugs to older people. Again, in rational and ethical medicine, the neuroleptics would be contraindicated—forbidden—in the treatment of the elderly.

終止後復發、惡化和延遲發作 (p. 65)

Relapse, Exacerbation, and Delayed Onset Aft er Termination

TD 通常會在一天的過程中以及在數週或數月的過程中起起伏伏。 特別是在老年人中，部分緩解和復發都很常見（Lacro 等，1994）。

TD typically waxes and wanes, both in the course of a day and in the course of weeks or months. Especially in the elderly, both partial remissions and relapses are common (Lacro et al., 1994).

與許多神經系統疾病一樣，TD 的表現在壓力期間會惡化，並且可以通過鎮靜來稍微平靜（Jeste 等，1993）。 以我的臨床經驗，並經文獻證實，對身心的焦慮、疲憊和其他一般壓力會暫時加劇症狀，而放鬆（如果可能）可以暫時減輕症狀。

As in many neurological disorders, the manifestations of TD can worsen during stress and can be somewhat calmed with sedation (Jeste et al., 1993). In my clinical experience, and as confirmed by the literature, anxiety, exhaustion, and other general stresses to the mind and body can temporarily exacerbate the symptoms, while relaxation, when possible, can temporarily reduce them.

通過極大的努力，患者有時可以在短時間內抑制他們的一些症狀。 正如本書前面提到的，他們還可以將自己的動作整合到看起來更自然的動作中，例如修飾或微笑，以掩飾它們。 我諮詢過的一位患者會通過試圖微笑來隱藏她不自覺的面部表情。 不幸的是，結果是讓她在不經意的觀察者看來更加陌生。 TD 有時會因壓力而起起落落的事實，或者患者用意志力部分抑制它的能力，都不應該誤導觀察者相信它是心理或情緒的起源。 醫生常常以這些錯誤的理由忽視、否認或忽視 TD 的早期跡象。

With great effort, patients can sometimes suppress some of their symptoms for a short time. As mentioned earlier in the book, they can also integrate their movements into more natural-looking actions, such as grooming or smiling, to disguise them. One patient with whom I consulted would hide her involuntary facial grimaces by trying to smile. Unfortunately, the effect was to make her look even stranger to the casual observer. Neither the fact that TD waxes and wanes, sometimes in response to stress, nor the patient’s ability to partially suppress it with an exertion of will should mislead observers into believing that it is psychological or emotional in origin. Too often, the early signs of TD are overlooked, denied, or dismissed by physicians on these mistaken grounds.

有時，我看到一些病例在治療終止幾個月或更長時間後才變得明顯。 克里斯滕森等人。 (1970) 記錄了相當大比例的 TD 病例可能在停止治療後的數月甚至數年內才出現。 他們認為，這些症狀是由藥物造成的損害和衰老過程之間的相互作用引起的。 如果這是真的，那麼當我們觀察到老齡人口中 TD 的演變時，一個悲慘的現實可能會發展。

I have, on occasion, seen cases that did not become apparent until several months or more after termination of treatment. Christensen et al. (1970) have documented that a significant percentage of TD cases may not show up at all until many months or even several years after discontinuation of the treatment. They believe that the symptoms are brought on by the interaction between the damage caused by the drugs and by the aging process. If this is true, then a tragic reality may develop as we observe the evolution of TD in aging populations.

可逆性是罕見的 (p. 66)

Reversibility Is Rare

在絕大多數情況下，TD是不可逆的，沒有有效的治療方法。 一份報告指出，在持續 TD 患者中，隨訪 5 年，82% 的患者總體上沒有顯著變化，11% 改善，7% 惡化（Bergen 等，1989）。

In the vast majority of cases, TD is irreversible, and there is no effective treatment. One report indicated that among patients with persistent TD, followed for a period of 5 years, 82% showed no overall significant change, 11% improved, and 7% became worse (Bergen et al., 1989).

另一項研究跟踪了 49 例門診 TD 病例，在停藥後平均 40 週（範圍 1-59 個月）（Glazer 等，1990）。 許多患者在停用抗精神病藥後的第一年內表現出明顯的運動改善，但只有 2% 的患者表現出完全和持續的恢復。 作者總結說：“這項研究的一個主要發現是，在長期治療的患者中，停藥後完全逆轉 TD 是罕見的。”

Another study followed 49 outpatient TD cases for a mean of 40 weeks (range 1–59 months) after discontinuation of medication (Glazer et al., 1990). Many patients showed noticeable improvement in their movements within the first year after stopping neuroleptics, but only 2% showed complete and persistent recovery. The authors concluded, “A major finding of this study is that complete reversal of TD following neuroleptic discontinuation in chronically treated patients was rare.”

隨著越來越多的兒童接受抗精神病藥物治療，在過去的幾年裡，我評估了數十個青少年 TD 病例。 Risperdal 和 Zyprexa 等非典型藥物通常會導致兒童 TD。 但是，根據我的經驗，康復率似乎比成年人要好，而且我已經看到一些案例完全解決了。 儘管如此，就其頻率、致殘和毀容影響、相關的認知缺陷以及患病兒童的絕對數量而言，TD 仍然是兒童的一種災難性疾病。

With the increasing number of children receiving neuroleptics, in the last few years, I have evaluated several dozen cases of TD in youngsters. Atypicals like Risperdal and Zyprexa commonly cause TD in children. However, the rate of recovery in my experience seems better than in regard to adults, and I have seen a few cases completely resolve. Nonetheless, TD remains a catastrophic disorder in children in terms of its frequency, its incapacitating and disfiguring effects, its associated cognitive deficits, and the sheer number of children afflicted.

醫生和患者否認 TD（第 67 頁）

Physician and Patient Denial of TD (p. 67)

可以理解的是，面對治療的破壞性影響，醫生會感到痛苦。 很多時候，他們也很難面對其他醫生對患者造成的傷害。 此外，醫生可能會通過不承認或記錄明顯的 TD 症狀而有意識地尋求保護自己或他們的同事免受批評或醫療事故訴訟。 我看過許多醫院和門診記錄，其中明顯的、嚴重的 TD 病例要么未被識別，要么未被記錄，有時由幾位醫生接連出現。 例如，護士的記錄可能清楚地表明患者在不斷運動，但醫生的身體檢查或進展記錄並不會顯示出疾病的跡象。 即使是正式出院總結也可能無法記錄在整個住院或臨床治療期間一直表現出疾病的患者的 TD。 即使在住院期間進行了 TD 診斷並且可以在圖表中找到該診斷，也可能不會將診斷放入出院摘要中，即使警告未來的醫生關於患者的狀況至關重要以避免 進一步接觸抗精神病藥。 這種對顯而易見的否認反映在行業本身，在承認或強調問題的嚴重性方面非常疏忽（有關否認歷史的分析，請參見 Breggin，1983b；Brown 等人，1986；Cohen 等人） 等人，1990 年；沃爾夫等人，1987 年）。

Physicians understandably find it painful to face the damaging effects of their treatments. Too often, it is difficult for them to confront the damage done to patients by other physicians as well. In addition, physicians may consciously seek to protect themselves or their colleagues from criticism or malpractice lawsuits by failing to acknowledge or to record obvious symptoms of TD. I have seen many hospital and outpatient records in which obvious, severe cases of TD have gone either unrecognized or undocumented, sometimes by several physicians in succession. For example, the nurse’s notes may make clear that the patient is in constant motion, yet the doctor’s physical examination or progress notes will give no indication of the disorder. Even official discharge summaries may fail to record TD in patients who have been demonstrating the disorder throughout the period of hospital or clinic treatment. Even when the TD diagnosis has been made during the hospitalization and can be found buried inside the chart, the diagnosis may not be put in the discharge summary, even though it is critical for future physicians to be warned about the patient’s condition in order to avoid further exposure to neuroleptics. This denial of the obvious is mirrored within the profession itself, which has been very remiss in recognizing or emphasizing the seriousness of the problem (for an analysis of this history of denial, see Breggin, 1983b; Brown et al., 1986; Cohen et al., 1990; Wolf et al., 1987).

精神科醫生有時會指責患者誇大他們的 TD。 實際上，大多數患者傾向於否認其 TD 的存在或嚴重性。 正如第 5 章中詳細討論的那樣，患者的否認部分是由抗精神病藥引起的腦葉切除效應引起的，部分是由與 TD 腦損傷相關的否認引起的。 患者無法識別 TD 症狀反映了服藥時藥物的引人入勝作用以及生物疾病本身的持續引人入勝作用。

Psychiatrists sometimes accuse patients of exaggerating their TD. In reality, most patients tend to deny the existence or severity of their TD. As discussed in detail in chapter 5, patient denial is caused in part by neuroleptic-induced lobotomy effects and in part by denial associated with TD brain damage. Patient nonrecognition of TD symptoms is a re-flection of the spellbinding effects of the drug when being taken and the continued spellbinding effect of the biological disorder itself.

醫生和患者對 TD 的相互否認是醫源性無助和否認的一個方面——在精神病學中使用腦損傷治療來強制患者否認他或她最初的個人問題以及醫源性腦功能障礙和損傷。 第1章）。
The mutual denial of TD by physician and patient is an aspect of iatrogenic helplessness and denial—the use of brain-disabling treatments in psychiatry to enforce the patient’s denial of both his or her original personal problems as well as the iatrogenic brain dysfunction and damage (chapter 1).

流行病的規模（第 67 頁）

The Size of the Epidemic (p. 67)

TD病例總數很難確定。 Van Putten（引用於 Lund，1989 年）估計美國有 400,000–1,000,000 人。 我自己早先的估計更高，有幾百萬（Breggin，1983b）。 毫不誇張地說，TD 是一種廣泛流行的流行病，可能是歷史上最嚴重的醫學災難。

It is difficult to determine the total number of TD cases. Van Putten (as cited in Lund, 1989) estimated 400,000–1,000,000 in the United States. My own earlier estimate is higher, ranging in the several millions (Breggin, 1983b). It is no exaggeration to call TD a widespread epidemic and possibly the worst medically induced catastrophe in history.

遲發性肌張力障礙 (p. 68)

TARDIVE DYSTONIA

TD 至少有兩種相對常見的變體：遲發性肌張力障礙和遲發性靜坐不能。 根據伯克等人的說法。 （1982 年），遲發性肌張力障礙涉及“持續的不自主扭轉運動，通常緩慢，可能影響四肢、軀幹、頸部或面部”（第 1335 頁）。 到目前為止，面部和頸部是身體最常受影響的部位。 頸部嚴重畸形（斜頸）會導致極度疼痛和殘疾。 我見過幾個影響眼眶肌肉的病例（眼瞼痙攣），導致個體視力受損，需要注射肉毒桿菌（Botox）來麻痺肌肉。 我還看到呼吸和腹部肌肉以痛苦和虛弱的方式受到影響。

There are at least two relatively common variants of TD: tardive dystonia and tardive akathisia. According to Burke et al. (1982), tardive dystonia involves “sustained involuntary twisting movements, generally slow, which may affect the limbs, trunk, neck, or face” (p. 1335). The face and neck are by far the most frequently affected areas of the body. Severe deformities of the neck ( torticollis) can cause extreme pain and disability. I have seen several cases affecting the orbital muscles of the eyes ( blepharospasm) to the degree that the individual’s vision was impaired, requiring botulinum (Botox) injections to paralyze the muscles. I have also seen respiratory and abdominal muscles affected in a painful and debilitating manner.

遲發性肌張力障礙可產生痙攣樣疼痛性痙攣，暫時阻止個體進行正常活動。 有時痙攣是如此持續，以至於個體在很大程度上已經殘疾。 可能會發生關節和骨骼系統的損傷，包括骨折（Burke 等，1988）。 疼痛和肌肉緊張以及補償痙攣的努力可能會讓人筋疲力盡和士氣低落。

Tardive dystonia can produce cramplike, painful spasms that temporarily prevent the individual from carrying out normal activities. Sometimes the spasms are so continuous that the individual is largely disabled. Damage to the joint and skeleton system, including fractures, can occur (Burke et al., 1988). The pain and muscle tension as well as the effort to compensate for the spasms can be exhausting and demoralizing.

扭轉（扭轉運動，通常涉及頸部）可能會因嘗試書寫或行走等活動而惡化。 有時可以通過特定的動作來緩解它們，例如觸摸下巴以緩解斜頸或觸摸額頭以緩解眼瞼痙攣。

The torsions (twisting movements, often involving the neck) can be worsened by activity such as attempts to write or walk. Sometimes they can be relieved by particular movements such as touching the chin to relieve torticollis or touching the brow to relieve blepharospasm.

正如 Burke 和 Kang (1988) 所指出的，遲發性肌張力障礙可能被錯誤地認為是歇斯底里或其他一些心理問題的表現：“在這方面，重要的是要認識到肌張力障礙，像許多其他神經系統疾病一樣，可以暫時受到以下因素的影響。 建議、安慰劑或鎮靜劑（例如，在阿莫巴比妥訪談期間），並且此類操作不能排除真正的肌張力障礙。” 此外，像許多其他神經系統疾病一樣，它有時可以通過極端的意志力得到部分控制。

As Burke and Kang (1988) pointed out, tardive dystonia can be mistakenly dismissed as a manifestation of hysteria or some other psychological problem: “In this regard it is important to realize that dystonia, like many other neurological disorders, can be influenced transiently by suggestion, placebo, or sedation (e.g., during an amobarbital interview) and such maneuvers cannot exclude a true dystonia.” Also, like many other neurological disorders, it can sometimes be partially controlled by extreme exertions of will.

遲發性肌張力障礙會使一個人顯得缺乏同情心或怪異，尤其是對於不知情的觀察者，他們將面部表情或頸部扭曲等同於瘋狂。 與所有藥物引起的運動障礙一樣，個體可能會試圖通過額外的運動來掩蓋這種疾病，使這種疾病看起來是自願的，因此不是精神疾病的產物。 結果可能會讓觀察者非常困惑甚至痛苦。 我讀過幾份醫療記錄，其中護士記錄了他們對所謂粗魯的病人的抱怨，這些病人似乎伸出舌頭或對著他們做鬼臉。 患者有未確診的 TD。 護士在臨床判斷上的錯誤延誤了對疾病的識別和迅速終止致病藥物。

Tardive dystonia can make an individual appear unsympathetic or bizarre, especially to the uninformed observer, who equates the facial grimaces or neck distortions with being crazy. As in all the drug-induced dyskinesias, the individual may try to cover up the disorder with additional movements that make the disorder seem voluntary and therefore not a product of mental illness. The result can be very confusing and even distressing to the observer. I have read several medical records in which nurses recorded their complaints about supposedly rude patients who seemingly stuck out their tongues or made faces at them. The patients had undiagnosed TD. The nurses’ errors in clinical judgment delayed recognition of the disorder and speedy termination of the causative drugs.

在 1988 年對遲發性肌張力障礙的回顧中，Burke 和 Kang 發現 21 份報告描述了 131 名患者（有關評論，另見 Greenberg 等，1985；Kane 等，1992）。 正如已經強調的那樣，因為所有非典型精神安定藥都是強效的多巴胺阻滯劑（氯氮平除外），所以應該假設它們都可能導致 TD 和遲發性肌張力障礙。病例報告證實，利培酮（Vercueil 等，1999；Narendran 等，2000）和奧氮平（Gunal 等，2001；Dunayevich 等，1999）可引起遲發性肌張力障礙。

In a 1988 review of tardive dystonia, Burke and Kang found 21 reports describing 131 patients (for reviews, see also Greenberg et al., 1985; Kane et al., 1992). As already emphasized, because all the atypical neuroleptics are potent dopamine blockers (except clozapine), it should have been assumed that all of them could cause TD and tardive dystonia. Case reports confirm that risperidone (Vercueil et al., 1999; Narendran et al., 2000) and olanzapine (Gunal et al., 2001; Dunayevich et al., 1999) can cause tardive dystonia.

遲發性肌張力障礙是一種特別痛苦、致殘和頑固的疾病，通常需要注射肉毒桿菌毒素，甚至需要手術切除肌肉以緩解痙攣。 在 Kiriakakis 等人對 107 名患者的回顧中。 （1998 年），只有 14% 的患者在平均 5.2 年的發病和停藥後的 2.6 年（範圍為 1 個月至 9 年）內得到緩解。 根據 Kiriakakis 等人的說法。 （1988 年），“停用抗精神病藥將緩解的機會增加了四倍。” 使用抗精神病藥 10 年或更短時間的患者緩解的機會增加了 5 倍。 因此，與一般 TD 一樣，必須限制長期接觸抗精神病藥，並在出現遲發性肌張力障礙的最早跡象時停止使用。

Tardive dystonia is a particularly painful, disabling, and intractable disease often requiring injections of Botox or even surgical excision of muscle to relieve the spasms. In a review of 107 patients by Kiriakakis et al. (1998), only 14% had a remission over a mean of 5.2 years from onset and 2.6 years after discontinuation of neuroleptics (range 1 month to 9 years). According to Kiriakakis et al. (1988), “discontinuation of neuroleptics increased the chances of remission fourfold.” Patients with 10 years or less exposure to neuroleptics had a 5 times greater chance of remission. Therefore, as in regard to TD in general, it is imperative to limit long-term exposure to neuroleptics and to stop them at the earliest sign of tardive dystonia.

基里亞卡基斯等人。 (1988) 證實了我的經驗，頸部疼痛可能是頸部肌張力障礙的前兆。 一些患者還會經歷“預示著他們遲發性肌張力障礙的奇怪軀體感覺”。 最常見的表現是眼瞼痙攣（伴有或不伴有口下頜肌張力障礙）或斜頸。 不太常見的初始症狀包括導致吞嚥困難的咽肌張力障礙和導致嚴重障礙的口下頜肌張力障礙。 其他患者出現四肢或軀幹肌張力障礙。 五人有“非常奇怪”的步態障礙。 肌張力障礙通常逐步進展，涉及身體的其他部位。 30% 的患者還患有 TD，22% 患有靜坐不能，27% 患有帕金森症，9% 患有先前的急性肌張力障礙反應。

Kiriakakis et al. (1988) confirmed my experience that neck pain can be a precursor to cervical dystonia. Some patients also experience “odd somatic sensations heralding their tardive dystonia.” The most common presentations were blepharospasm (with or without oromandibular dystonia) or torticollis. Less common initial symptoms included pharyngeal dystonia, causing dysphagia, and oromandibular dystonia, causing severe disturbance. Other patients experienced dystonia of the limbs or trunk. Five had “very bizarre” disturbances of gait. The dystonia often progressed stepwise, involving additional parts of the body. Thirty percent of the patients also had TD, 22% had akathisia, 27% had parkinsonism, and 9% had a prior acute dystonic reaction.

基里亞卡基斯等人。 (1988) 得出結論，“遲發性肌張力障礙可以在暴露於 [神經安定藥] 後 4 天到 23 年之間的任何時間發生，並且沒有‘安全’期。” 它可以獨立於他們的精神病診斷而折磨任何人，精神分裂症患者僅佔報告的 TD 病例的一半。 從各種研究中，他們估計在接受抗精神病藥物治療的患者中的患病率為 2.8%。

Kiriakakis et al. (1988) concluded, “Tardive dystonia can develop at any time between 4 days and 23 years after exposure to [neuroleptics] and there is no ‘safe’ period.” It can afflict anyone independently of their psychiatric diagnosis, and patients with schizophrenia have accounted for only half of reported TD cases. From assorted studies, they estimate the prevalence at 2.8% among neuroleptic-treated patients.

在我的臨床和法醫實踐中，我諮詢並評估了許多遲發性肌張力障礙病例，主要涉及面部、頸部和肩部，但有時也涉及軀幹。 我看到不成比例的肌張力障礙病例，可能是因為他們患有相當大的疼痛和殘疾，因此更有可能尋求臨床諮詢或聘請我作為醫療事故或產品責任案件的醫學專家。

In my clinical and forensic practice, I have consulted with and evaluated many cases of tardive dystonia, mostly involving the face, neck, and shoulders, but sometimes the torso. I see a disproportionate number of dystonia cases, probably because they suffer from considerable pain and disability and are therefore more likely to seek a clinical consultation or to hire me as a medical expert in a malpractice or product liability case.

根據我的臨床經驗，在精神抑制治療期間出現永久性肌張力障礙的患者有時會被誤診為特發性（原因不明）肌張力障礙。 有人認為，與普通人群中來源不明的肌張力障礙相比，抗精神病藥引起的肌張力障礙是罕見的。 然而，反過來也是如此。 弗里德曼等人。 (1987) 發現在長期住院患者中遲發性肌張力障礙的患病率為 1.5%，但正如他們所指出的，整個美國人口的患病率僅為 0.000003%（每 100,000 人中有 0.3%）。 當持續性肌張力障礙與使用安定藥有關時，以 500,000 比 1 的比例，診斷為遲發性肌張力障礙而不是特發性肌張力障礙的機率是壓倒性的。

In my clinical experience, patients who develop permanent dystonias during neuroleptic therapy are sometimes misdiagnosed with idiopathic (of unknown origin) dystonia. The argument is made that neuroleptic-induced dystonia is rare compared to dystonia of unknown origin in the general population. However, the reverse is true. Friedman et al. (1987) found a prevalence rate of tardive dystonia of 1.5% among chronically hospitalized patients, but as they pointed out, the rate in the U.S. population as a whole is a mere 0.000003% (0.3 per 100,000). When a persistent dystonia appears in association with neuroleptic exposure, by 500,000 to 1, the odds are overwhelming in favor of a diagnosis of tardive dystonia, rather than idiopathic dystonia.

遲發性靜坐不能 (p. 70)

TARDIVE AKATHISIA

遲發性靜坐不能是一種內心緊張或焦慮的感覺，會驅使個體進行不安的活動，例如踱步（詳見第 3 章），儘管有時它可能很少或沒有表現出多動症。我能夠在文獻中找到的關於遲發性靜坐不能的第一份報告是由 Walter Kruse 於 1960 年發表的。他描述了 3 例肌肉不安，這些病例在停止使用經典的抗精神病藥氟奮乃靜和三氟丙嗪治療後持續至少 3 個月。 “靜坐不能綜合徵。 . .包括無法靜坐，整天在地板上踱步，手臂和肩膀動作不穩。”再一次，Delay 和 Deniker (1968) 也是第一批註意到這種疾病的臨床醫生之一。在討論“停藥後持續存在的綜合徵”時，他們提到了“多動症”。早在 1977 年，辛普森就更明確地將 TD 與不可逆轉的靜坐不能聯繫起來。 Gualtieri 和 Sovner (1989) 回顧了遲發性靜坐不能的主題，引用了在接受抗精神病藥物治療的患者中患病率為 13% 至 18% 的研究，並稱其為“一個重大的公共衛生問題”。

Tardive akathisia involves a feeling of inner tension or anxiety that drives the individual into restless activity, such as pacing (see chapter 3 for details), although on occasion, it can occur with little or no display of hyperactivity. The first report of tardive akathisia that I was able to locate in the literature was published by Walter Kruse in 1960. He described three cases of muscular restlessness that persisted at least 3 months after discontinuation of treatment with the classic neuroleptics fluphenazine and triflupromazine. The “akathisia syndrome . . . consisted of inability to sit still, pacing the floor all day, jerky movements of arms and shoulders.” Once again, Delay and Deniker (1968) were also among the first clinicians to notice the disorder. In discussing “syndromes persisting after cessation of medication,” they mentioned “hyperkinetic” ones. As early as 1977, Simpson more definitively made an association between TD and irreversible akathisia. Gualtieri and Sovner (1989) reviewed the subject of tardive akathisia, cited studies with prevalence rates of 13% to 18% among neuroleptic-treated patients, and called it “a significant public health issue.”

不應減少與急性和持續性靜坐不能相關的痛苦。 想想 Van Putten (1974) 對輕度、暫時性靜坐不能或運動過度的描述：“患者感覺‘神經緊張’、‘內心不安’、‘緊張’、‘緊張’、‘緊張’、‘不舒服’、‘不耐煩’。 . . . 主觀的不適感可能伴隨著不安的姿勢變化。”

The anguish associated with both acute and persistent akathisia should not be minimized. Consider Van Putten’s (1974) description of a mild, temporary akathisia or hyperkinesia: “Patient feels ‘all nerved up,’ ‘squirmy inside,’ ‘uptight,’ ‘nervous,’ ‘tense,’ ‘uncomfortable,’ ‘impatient.’ . . . Subjective feeling of ill-being may be accompanied by restless changes in posture.”

很少關注與運動障礙相關的精神障礙的一個原因是傾向於將精神因素歸咎於由嚴重和潛在不可逆的神經系統綜合症 71 患者造成的先前存在的情緒問題。 事實上，將明顯的運動障礙歸咎於所謂的精神疾病是司空見慣的，通常會導致治療增加，症狀惡化，直到精神安定藥引起的不動，掩蓋了整個過程。

One reason that so little attention has been given to the mental disruption associated with the dyskinesias is the tendency to blame the mental component on preexisting emotional problems attributed to the Severe and Potentially Irreversible Neurological Syndromes 71 patient. Indeed, it has been commonplace to blame the obvious motor disturbances on the so-called mental illness, often resulting in increased treatment, and a worsening of the symptoms, until neuroleptic-induced immobility sets in, masking the entire process.

無需多想就能理解一個終生患有相對輕微的遲發性靜坐不能的患者的痛苦。 我曾見過這種情況，以前被誤認為是嚴重的焦慮或激動的抑鬱症。 第 3 章回顧了表明急性靜坐不能使患者陷入精神病、暴力和/或自殺的研究。 考慮到數以百萬計的患者遭受這種折磨，這個問題具有流行病的程度。

It takes no great imagination to grasp the suffering of a patient condemned to even a relatively mild tardive akathisia for a lifetime. I have seen cases of this kind that were previously mistaken for severe anxiety or agitated depression. Chapter 3 reviewed research indicating that acute akathisia can drive a patient into psychosis and to violence and/or suicide. Considering the millions of patients subjected to this torment, the problem takes on epidemic proportions.

遲發性靜坐不能是微妙的。 一位 60 多歲的女士因為看似奇怪的感覺向我諮詢，其他醫生將其歸咎於她的抑鬱症和妄想或幻覺。 她有一種“電”的感覺，在她的全身周期性地爆發。 儘管她安靜地坐在辦公室裡，但她說她感到坐立不安，不得不四處走動。

Tardive akathisia can be subtle. A woman in her mid-60s consulted me because of seemingly bizarre feelings that other doctors attributed to her depression and to delusions or hallucinations. She had a feeling of“electricity” going in periodic bursts throughout her body. Although she sat quietly in the office, she spoke of feeling fidgety and driven to move about.

她的醫院和診所圖表顯示，2 年前，她接受了大約 6 個月的抗精神病藥治療。 她所描述的感覺是在她服藥時首次被注意到的。 我得出的結論是，她可能患有遲發性靜坐不能，這是一種微妙的情況，不會迫使她四處走動。 然而，由於她沒有表現出這種疾病的外部跡象，其他醫生不願做出診斷。 病人感到“分心”甚至自殺，但經過我的診斷，她感到有些欣慰。 終於，一位醫生認真地對待她，誠實地與她交談。

她的醫院和診所圖表顯示，2 年前，她接受了大約 6 個月的抗精神病藥治療。 她所描述的感覺是在她服藥時首先注意到的。 我得出的結論是，她可能患有遲發性靜坐不能，這是一種微妙的情況，不會迫使她四處走動。 然而，由於她沒有表現出這種疾病的外部跡象，其他醫生不願做出診斷。 病人感到“分心(driven to distraction)”甚至自殺，但經過我的診斷，她感到有些欣慰。 終於，一位醫生認真地對待她，誠實地與她交談。

Her hospital and clinic charts disclosed that 2 years earlier, she had been treated for approximately 6 months with neuroleptics. The sensation she was describing had first been noted while she was taking the medication. I concluded that she probably had tardive akathisia, a subtle case that did not force her to move about. However, because she did not show external signs of the disorder, other physicians were reluctant to make the diagnosis. The patient felt “driven to distraction” and even to suicide, but after my diagnosis, she felt somewhat relieved. At last, a physician was taking her seriously and talking honestly to her.

1993 年，Gualtieri 寫道，然而，就臨床治療和公共衛生而言，TDAK [遲發性靜坐不能] 是事實，而不是問題。 它是神經阻滯劑治療的一種更嚴重的副作用，如 TD 和神經阻滯劑惡性綜合徵。 總而言之，他們將精神安定治療定義為一種必要的邪惡，一種應該小心謹慎地進行的治療，並保留給沒有其他追索權的患者。

In 1993, Gualtieri wrote, In terms of clinical treatment and the public health, however, TDAK [tardive akathisia] is a fact, not a question. It is one more serious side effect of neuroleptic treatment, like TD and the Neuroleptic Malignant Syndrome. Taken together, they defi ne neuroleptic treatment as a necessary evil, a treatment that should be administered with care and caution, and reserved for patients who have no other recourse.

我同意 Gualtieri 的所有觀點，除了這種邪惡的“必要性”。 在不使用這些劇毒藥物的情況下治療兒童和成人是完全可能的，甚至是更可取的（第 16 章）。

I agree with Gualtieri about everything, except for the “necessity” of this evil. It is entirely possible and even preferable to treat children and adults without resort to these highly toxic agents (chapter 16).

遲發性疾病的並發症 (p. 71)

COMPLICATIONS OF TARDIVE DISORDERS

TD 是一種複雜的疾病，具有精神和情感影響，而醫療保健提供者經常忽視這種影響。 作為醫源性疾病患者的最後救命醫生和代表受傷患者的醫學專家，我經常面臨評估各種遲發性疾病對患者及其家人造成的整體損害的任務， 包括經典的 TD、遲發性肌張力障礙和遲發性靜坐不能。

TD is a complex disorder with mental and emotional effects that are often overlooked by health care providers. In my professional capacity as a doctor of last resort for patients with iatrogenic disorders, and as a medical expert on behalf of injured patients, I often am confronted with the task of evaluating the overall damage to patients and their families by the various tardive disorders, including classic TD, tardive dystonia, and tardive akathisia.

身體疲憊 (p. 72)

Physical Exhaustion

疲勞到筋疲力盡的程度幾乎總是伴隨著任何嚴重程度的遲發性疾病。 患者經常因這些動作、隱藏它們的努力以及與進行日常活動相關的難度增加而筋疲力盡。 對大腦本身的主要影響也可能產生疲勞。 儘管這些疾病往往會在睡眠中消失，但它們會使入睡變得困難，從而加劇疲勞。

Fatigue to the point of exhaustion almost always accompanies tardive disorders of any severity. Patients often become exhausted by the movements, by the effort to hide them, and by increased difficulty associated with carrying out daily activities. The primary impact on the brain itself may also produce fatigue. Although the disorders tend to disappear in sleep, they can make it difficult to fall asleep, adding to the exhaustion.

不得不應對與遲發性靜坐不能（內心折磨）和遲發性肌張力障礙（肌肉痙攣）相關的身體疼痛也會使人疲憊不堪。

Having to contend with the physical pain associated with tardive akathisia (inner torment) and with tardive dystonia (muscle spasms) can also wear a person down.

由於疲勞以及任何運動障礙，患者通常無法繼續工作。 許多人放棄了娛樂活動，例如騎自行車、散步和游泳。 結果，他們體重增加，感覺遲鈍。

Because of the fatigue, as well as any motor disabilities, patients are often unable to continue working. Many give up recreational activities such as bike riding, walking, and swimming. As a result, they gain weight and feel sluggish.

心理痛苦 (p. 72)

Psychological Suffering

因為 TD 經常讓患者看起來很奇怪，甚至奇怪，他們會感到羞恥和羞辱，通常會導致自尊心降低和社交退縮。 即使是影響面部表情的看似輕微的運動障礙，也足以讓人感到羞辱，以至於想要待在家里遠離人群。 同樣，使一個人“說話有趣”的言語異常會導致避免交流。

Because TD often makes the sufferers look odd or even bizarre, they experience shame and humiliation, typically leading to lowered self-esteem and social withdrawal. Even a seemingly mild dyskinesia that affects facial expression can be sufficiently humiliating to cause a person to want to stay at home and away from people. Similarly, a speech abnormality that makes a person “talk funny” can lead to the avoidance of communicating.

肌張力障礙帶來的持續疼痛或靜坐不能帶來的內心折磨會驅使一個人走向自殺的絕望。 與疾病相關的身體殘疾也會讓患者感到非常沮喪。

在 Rosenbaum (1979) 的 Mayo Clinic 臨床報告中，發現抑鬱症與 TD 密切相關。 Rosenbaum 說：“我們系列中的幾乎所有患者都有伴隨遲發性運動障礙發作的抑鬱症狀，”他引用了其他研究證實了他的觀察。

The experience of constant pain from dystonia or inner torture from akathisia can drive a person to suicidal despair. The physical disabilities associated with disorders can also become very depressing to patients.
In a clinical report from the Mayo Clinic by Rosenbaum (1979), depression was found to be closely linked to TD. Rosenbaum stated, “Almost all patients in our series had depressive symptoms accompanying the onset of tardive dyskinesia,” and he cited other studies confirming his observation.

TD患者經常感到被開藥的醫生或未能發現疾病或沒有告訴患者的醫生背叛。 太頻繁了，也許是出於對同事的自我保護立場，連續的幾位精神病學家或神經學家無法告知患者或家屬明顯的醫源性疾病。 這種對真相的忽視會讓患者覺得他們不能信任精神科醫生。

TD patients often feel very betrayed by the doctors who prescribed the medication or who failed to detect the disorder or to tell the patients about it. Too frequently, perhaps in a self-protective stance toward their colleagues, several psychiatrists or neurologists in a row will fail to inform the patient or family about the obvious iatrogenic disorder. This neglect of the truth can leave patients feeling that they cannot trust psychiatrists.

第 5 章將研究幾乎總是在藥物誘發的遲發性障礙患者身上發現的精神功能障礙。總體而言，即使是輕微或最小程度的遲發性障礙最終也會嚴重損害個人的生活質量。

Chapter 5 will look at impairments to mental functioning that are almost always found in patients with drug-induced tardive disorders.Overall, even a slight or minimal degree of tardive disorder can end up seriously impairing an individual’s quality of life.

神經麻痺性戒斷症狀 (p. 73)

NEUROLEPTIC WITHDRAWAL SYMPTOMS

戒斷經常導致精神狀態惡化，包括緊張和焦慮。 產生強效抗膽鹼能作用的藥物，如 Thorazine 和 Mellaril，可引起與流感相似的膽鹼能反彈，包括情緒不安、失眠、噁心和嘔吐、腹瀉、厭食和體重減輕以及肌肉疼痛。

Withdrawal frequently causes a worsening mental state, including tension and anxiety. Drugs that produce potent anticholinergic effects, such as Thorazine and Mellaril, can cause cholinergic rebound that mimics the flu, including emotional upset, insomnia, nausea and vomiting, diarrhea, anorexia and weight loss, and muscle aches.

戒斷症狀通常包括運動障礙效應的暫時惡化，既痛苦又可怕。 如第 5 章所述，停用抗精神病藥通常會產生一定程度的情緒痛苦和乾擾，比個人在開始服藥前所經歷的任何事情都要嚴重。 在成人中，這通常表現為精神病症狀，比開始服藥前經歷的任何症狀都要嚴重。 在兒童中，它可能導致非常不安的行為。

Withdrawal symptoms often include a temporary worsening of dyskinetic effects, both painful and frightening. As documented in chapter 5, withdrawal from neuroleptics commonly produces a level of emotional suffering and disturbance more severe than anything the individual experienced prior to starting the medication. In adults, this frequently manifests as psychotic symptoms worse than anything experienced prior to starting on the medication. In children, it can result in very disturbed behavior.

非典型或較新的精神安定藥並非沒有戒斷症狀。 在我的一個案例中，一名年輕女性在退出 Zyprexa 時變得極度疲勞、抑鬱和自殺。 在從 Zyprexa、Risperdal 和 Abilify 撤出期間，我看到了嚴重的運動障礙症狀。 吸毒時，她就像殭屍一樣。 撤軍經過了幾個月的仔細監督。 氯氮平可能具有特別顯著的戒斷綜合徵，其特徵是精神病惡化、憤怒或辱罵性語言、多動、激動和不安、運動障礙、精神錯亂以及攻擊性或自殺行為（“氯氮平Clozapine”，1994）。 第 5 章將討論各種抗精神病藥戒斷症狀，包括遲發性精神病。

The atypical or newer neuroleptics are not free of withdrawal symptoms. In one of my cases, a young woman became extremely fatigued, depressed, and suicidal when withdrawing from Zyprexa. I have seen severe dyskinetic symptoms during withdrawal from Zyprexa, Risperdal, and Abilify. While on the drug, she was zombielike. Withdrawal took careful supervision over several months. Clozapine may have an especially marked withdrawal syndrome characterized by a worsening psychosis, angry or abusive language, hyperactivity, agitation and restlessness, dyskinesia, confusion, and aggressive or suicidal behavior (“Clozapine,”1994). Chapter 5 will discuss a variety of neuroleptic withdrawal symptoms, including tardive psychosis.

第 15 章討論瞭如何戒除精神藥物。
How to withdraw from psychiatric drugs is discussed in chapter 15.

抗精神病藥會上癮嗎？ (p. 73)

Are Neuroleptics Addictive?

雖然尚未證明對這些物質的經典成癮，但抗精神病藥物會導致嚴重的戒斷症狀，使患者無法停止服用。 出於這個原因，我很久以前就建議將這些藥物視為上癮（Breggin，1989a，1989b）。 我相信我之前的觀察需要修改。 更準確地說，精神安定藥以戒斷反應的形式產生依賴，阻止患者停止服用，但它們不會引起通常與依賴和較早成癮相關的強迫性尋求藥物行為。 相反，人們經常發現抗精神病藥令人不快、痛苦或使人衰弱，但無法忍受戒斷過程。

While classic addiction to these substances has not been demonstrated, the antipsychotic drugs can cause severe withdrawal symptoms, making it impossible for patients to stop taking them. For this reason, I long ago suggested viewing these drugs as addictive (Breggin, 1989a, 1989b). I believe that my earlier observations need modification. It is more accurate to say that neuroleptics create dependence in the form of withdrawal reactions that prevent patients from stopping them, but they do not cause the compulsive drug-seeking behavior commonly associated with dependence and with the older term addiction. Instead, individuals often find neuroleptics unpleasant, painful, or debilitating but cannot endure the withdrawal process.

為了澄清，有必要討論術語依賴和成癮。 幾代人以來，成癮一詞一直被用來描述藥物的影響，例如酒精、興奮劑和苯二氮卓類藥物，這些藥物會導致生理耐受、身體戒斷症狀，以及在極端情況下導致有害的身體、心理的強迫性吸毒。 、社會和經濟後果。 成癮是一個在治療成癮者的專業社區以及非專業社區中繼續使用的術語。 然而，DSM 委員會通過一票投票決定用 DSM-III (APA, 1980a) 中的依賴一詞取代成癮一詞，部分是為了消除一些污名。 結果造成了巨大的混亂（O’Brien et al., 2006）。

For clarification, it is necessary to discuss the terms dependence and addiction. For generations, the term addiction had been used to describe the effects of drugs, such as alcohol, stimulants, and benzodiazepines, that cause physiological tolerance, physical withdrawal symptoms, and, in the extreme, compulsive drug taking that results in harmful physical, psychological, social, and economic consequences. Addiction is a term that continues to be used in the professional community that treats addicts as well as in the lay community. However, by one vote, a DSM committee voted to replace the term addiction with the term dependence in the DSM–III (APA, 1980a), in part to remove some of the stigma. The result has been enormous confusion (O’Brien et al., 2006).

許多人在數月或數年內接觸過 SSRI 抗抑鬱藥和精神安定藥等精神科藥物後發現他們無法輕易戒除，但他們不會像典型的癮君子那樣強迫性地尋求藥物。 同樣，接受疼痛治療的人通常會依賴阿片類藥物，而不必尋求不斷增加的劑量。

Many people exposed for months or years to psychiatric drugs such as the SSRI antidepressants and the neuroleptics find that they cannot easily withdraw from them, but they do not, like the classic addict, compulsively pursue drug seeking. Similarly, people treated for pain often become dependent on the opiates without necessarily seeking ever-increasing doses.

為了清楚起見，我建議使用“依賴”一詞來描述主要的藥物影響，例如耐受性和戒斷症狀，而將“成癮”一詞保留用於涉及強迫、升級、尋求藥物行為的情況。 簡而言之，抗抑鬱藥、精神安定藥和一些情緒穩定劑會導致依賴而不導致成癮； 興奮劑、苯二氮卓類鎮靜劑和相關的安眠藥會導致依賴和成癮。

For clarity, I propose using the term dependence to describe primary drug effects, such as tolerance and withdrawal symptoms, while reserving the term addiction for cases that involve compulsive, escalating, drug-seeking behavior. In short, antidepressants, neuroleptics, and some mood stabilizers cause dependence without causing addiction; stimulants, benzodiazepine tranquilizers, and related sleeping medications can cause both dependence and addiction.

由於戒斷症狀，通常需要以非常緩慢的速度減少精神抑制藥物。 有時退出似乎變得不可能。 我在第 15 章描述了安全戒除精神科藥物的原則。

Because of the withdrawal symptoms, it is often necessary to reduce neuroleptic drugs at a very slow rate. Sometimes withdrawal seems to become impossible. I describe the principles of safely withdrawing from psychiatric drugs in chapter 15.

其他不良反應 (p. 74)

OTHER ADVERSE REACTIONS

精神抑製藥可產生多種其他中樞神經系統功能障礙症狀，包括腦電圖 (EEG) 異常、癲癇發作頻率增加、呼吸抑制和體溫控制障礙 (Davis, 1980; Davis et al., 1975) . 內分泌失調，尤其是女性，也可能源於中樞神經系統（Davis，1980）。 有一些證據表明自主神經功能障礙可能變得不可逆（遲發性自主神經障礙）。

The neuroleptics can produce a variety of other symptoms of central nervous system dysfunction, including abnormal electroencephalogram (EEG) findings, an increased frequency of seizures, respiratory depression, and disturbances of body temperature control (Davis, 1980; Davis et al., 1975). Endocrine disorders, especially in females, may also be of central nervous system origin (Davis, 1980). There is some evidence that autonomic dysfunction can become irreversible ( tardive autonomic disorders).

神經麻痺性惡性綜合徵

NEUROLEPTIC MALIGNANT SYNDROME (p. 75)

這種毀滅性的疾病看似如此奇怪、出人意料、莫名其妙，以至於多年來的醫生都不敢相信自己的眼睛。 在將藥物引入北美七年後，Leo Hollister (1961) 在《新英格蘭醫學雜誌》上回顧了它們的副作用。 在兩個不同的地方，他提到了可能是 NMS 的綜合徵。 他描述了一種“奇怪的”張力障礙綜合徵，它可能“與癔症、破傷風、腦炎或其他急性神經系統疾病相混淆； 可能會發生罕見的死亡事件。” 後來，他提到，“歸因於這些藥物對中樞神經系統影響的其他臨床綜合徵類似於急性腦炎、重症肌無力、延髓麻痺或假性麻痺。”

This devastating disorder was seemingly so bizarre, unexpected, and in-explicable that physicians for years literally refused to believe their eyes. Seven years after the introduction of the drugs into North America, Leo Hollister (1961) reviewed their side effects in the New England Journal of Medicine. In two separate places, he referred to syndromes that probably were NMS. He described a “bizarre” dystonic syndrome that can be “confused with hysteria, tetanus, encephalitis or other acute nervous-system disorders; a rare fatality may occur.” Later, he mentioned, “Other clinical syndromes attributed to central nervous-system effects of these drugs have resembled acute encephalitis, myasthenia gravis, bulbar palsy or pseudotabes.”

儘管早在 1968 年，Delay 和 Deniker 就在一份英文出版物中發現了 NMS，但醫生們仍然不願意承認這種綜合徵。 Delay 和 Deniker 宣稱它是由抗精神病藥引起的，特別是包括氟哌啶醇 (Haldol) 和氟奮乃靜 (Prolixin)，儘管我們現在知道任何抗精神病藥都可能導致 NMS，包括較新的藥物，如 Zyprexa 和 Risperdal。 臨床醫生還發現長效可注射精神安定藥的危險性增加，這可能是因為患者無法秘密減少服用量。

Although NMS was identified in an English-language publication by Delay and Deniker as early as 1968, physicians continued to be reluctant to recognize the syndrome. Delay and Deniker declared that it was caused by the neuroleptics, specifically including haloperidol (Haldol) and fluphenazine (Prolixin), although we now know that any neuroleptic can cause NMS, including the newer ones such as Zyprexa and Risperdal. Clinicians have also found an increased danger with long-acting injectable neuroleptics, probably because patients are unable to secretly cut back on the amount they are taking.

Delay 和 Deniker (1968) 已經能夠識別 NMS 的許多組成部分，包括蒼白、體溫過高、伴有運動障礙和昏迷的嚴重精神運動綜合徵，或伴有各種運動障礙的高滲性。 他們警告說，在第一次懷疑時，“必須立即徹底停藥。 ” 他們已經意識到死亡人數。 該綜合徵於 1968 年以英文命名並最終確定是最引人注目的，因為製藥公司未能給予正式承認，直到近 20 年後被 FDA 強制這樣做（進一步討論見第 13 章）。

Delay and Deniker (1968) were already able to identify many of the components of NMS, including pallor, hyperthermia, a severe psychomotor syndrome with akinesia and stupor, or hypertonicity with varying dyskinesias. They warn that at the first suspicion, “one must stop medication immediately and completely. ” They were already aware of fatalities. That the syndrome was named and definitively identified in English in 1968 is most remarkable in light of the failure of drug companies to give it formal recognition until compelled to do so by the FDA almost 20 years later (see chapter 13 for further discussion).

NMS 的特徵是“嚴重運動障礙或運動不能、體溫升高、心動過速、血壓波動、出汗、呼吸困難、吞嚥困難和尿失禁等症狀”（Coons 等，1982）。 DSM-IV-TR 建立了嚴重肌肉僵硬和體溫升高的標準，加上 10 種相關特徵中的另外 2 種，包括出汗、吞嚥問題、震顫、失禁、意識水平從混亂到昏迷的變化、緘默、心率加快、不穩定 血壓、白細胞計數升高或肌肉損傷的實驗室證據（例如，血清肌酸磷酸激酶或 CPK 水平升高）。

NMS is characterized by “such symptoms as severe dyskinesia or akinesia, temperature elevation, tachycardia, blood pressure fluctuations, diaphoresis, dyspnea, dysphagia, and urinary incontinence” (Coons et al., 1982). The DSM–IV–TR establishes criteria of severe muscle rigidity and elevated temperature plus 2 more of 10 associated features, including sweating, swallowing problems, tremor, incontinence, changes in level of consciousness from confusion to coma, mutism, elevated heart rate, unstable blood pressure, elevated white count, or laboratory evidence of muscle injury (e.g., elevated serum level of creatine phosphokinase, or CPK).

在我的臨床和法醫經驗中，剛性對於建立 NMS 的標準過於狹窄。 相反，臨床醫生應尋找異常運動的任何急性、嚴重增加，包括與 TD 和遲發性肌張力障礙相關的任何一種或幾種運動。 與我的經驗一致，在回顧了 20 名患者的 NMS 發作後，Rosebush 和 Stewart (1989) 發現大多數病例符合以下一系列症狀：譫妄； 發高燒並出汗； 不穩定的心血管體徵； 呼吸頻率升高； 以及一系列運動障礙，包括震顫、僵硬、肌張力障礙和舞蹈症。 患者在急性病期間很少說話，後來報告說他們發現自己無法表達自己的焦慮和厄運感。

In my clinical and forensic experience, rigidity is too narrow a criterion for establishing NMS. Instead, the clinician should look for any acute, severe increase in abnormal movements, including any one or several of the movements associated with TD and tardive dystonia. Consistent with my experience, after reviewing episodes of NMS in 20 patients, Rosebush and Stewart (1989) found that most cases fi t the following cluster of symptoms: delirium; a high fever with diaphoresis; unstable cardiovascular signs; an elevated respiratory rate; and an array of dyskinesias, including tremors, rigidity, dystonia, and chorea. Patients spoke little during the acute illness and later reported that they had found themselves unable to express their anxiety and feelings of doom.

幾乎所有患者在發生 NMS 前不久都情緒激動，這向 Rosebush 和 Stewart (1989) 表明他們正在經歷靜坐不能。 在所有病例中，白細胞計數均升高，脫水很常見，實驗室測試顯示廣泛的酶異常，包括肌肉分解的跡象，例如 CPK 升高。

Almost all patients were agitated shortly before developing NMS, suggesting to Rosebush and Stewart (1989) that they were undergoing akathisia. White blood cell counts were elevated in all cases, dehydration was common, and lab tests showed a broad spectrum of enzymatic abnormalities, including indications of muscle breakdown such as an elevated CPK.

如果不被識別，就像經常發生的那樣，NMS 在超過 20% 的情況下可能是致命的。 該綜合徵經常使倖存的患者出現永久性運動障礙和癡呆（見第 5 章）。
If unrecognized, as too often happens, NMS can be fatal in more than 20% of cases. The syndrome frequently leaves the surviving patient with permanent dyskinesias and dementia (see chapter 5).

大多數病例在治療的最初幾週內發生（甚至在 45 分鐘內），但有些病例在數月或數年或增加劑量後發生（Gratz 等，1992）。

Most cases develop within the first few weeks of treatment (even within 45 minutes), but some develop after months or years or after increased dosage (Gratz et al., 1992).

對 NMS 發生率的估計差異很大，但研究表明它們非常高。 教皇等人。 (1986) 調查了 500 名在 1 年內入住大型精神病醫院的患者，發現率為 1.4%。 患者的累積率會高得多。 作者評論說，“神經阻滯劑惡性綜合徵可能比以前認為的更常見，並且可能被漏診。”

Estimates for rates of NMS vary widely, but studies indicate that they are very high. Pope et al. (1986) surveyed 500 patients admitted during a 1-year period to a large psychiatric hospital and found a rate of 1.4%. The cumulative rate for patients would be much higher. The authors remarked, “Neuroleptic malignant syndrome may be more common than previously thought and may be underdiagnosed.”

Addonizio 等人。 (1986) 對 82 名男性住院患者的圖表進行了回顧性審查，發現診斷為 NMS 的患病率更高，為 2.4%。 同樣，重複住院或多年治療的累積率會高得多。 雖然它有時被稱為“罕見”，但 NMS 應該被描述為常見或頻繁（FDA 標準為 1/100）。

Addonizio et al. (1986) carried out a retrospective review of 82 charts of male inpatients and found an even higher prevalence of 2.4% for diagnosed NMS. Again, the cumulative rate over repeated hospitalizations or years of treatment would be much higher. Although it is sometimes called “rare,” NMS should be described as common or frequent (1/100 is common by FDA standards).

NMS 的發病率，以及其潛在的嚴重性和致死性，使其對接受抗精神病藥物的患者構成極大風險。 這種規模的風險可能會導致普通醫學中的大多數藥物從市場上撤出。

The rates for NMS, as well as its potential severity and lethality, make it an extreme risk for patients receiving antipsychotic drugs. A risk of this size would probably result in most drugs in general medicine being removed from the market.

作為一名醫學專家，我曾回顧過幾位醫生一次未能做出正確診斷的病例，從我的回顧性分析來看，這似乎是一個明顯的 NMS 病例。 未能停止使用精神抑製藥並進行適當的治療會導致嚴重的永久性損傷或死亡。 認為 NMS 很少見的錯誤想法可能會導致這些判斷錯誤。 在我的幾個法醫案例中，將任何奇怪的事情歸因於患者的精神疾病的傾向在醫生未能做出正確診斷的過程中起到了明顯的作用。

As a medical expert, I have reviewed cases in which several physicians at a time missed making the correct diagnosis in what seemed, from my retrospective analysis, like an obvious case of NMS. The failure to stop the neuroleptic and to institute proper treatment resulted in severe, permanent impairments, or death. The mistaken idea that NMS is rare may contribute to these errors in judgment. In several of my forensic cases, the tendency to attribute anything strange to the patient’s mental illness played an obvious role in physician failure to make the proper diagnosis.

急性 NMS 幾乎無法將其與急性、嚴重的腦炎發作區分開來，尤其是昏睡性腦炎（也稱為 von Economo 病），除了最近接受過精神抑制治療的事實。 我之前曾詳細比較過安定藥毒性和昏睡性腦炎（Breggin，1983b，1993；另見第 5 章）。

There is little or nothing about acute NMS to distinguish it from an acute, severe episode of encephalitis, especially lethargic encephalitis (also called von Economo’s disease), except for the fact of recent exposure to neuroleptic therapy. I have previously compared neuroleptic toxicity and lethargic encephalitis in detail (Breggin, 1983b, 1993; see also chapter 5).

儘管 Rosebush 和 Stewart (1989) 提供的數據不足以得出確切的相似性，但他們的 NMS 患者也遭受了與昏睡性腦炎患者相似的慢性損傷。 在 20 名患者中，14 名繼續出現“出院時錐體外系症狀或生命體徵和肌酶輕度異常”（第 721 頁），但我們不知道這 14 名患者中有多少人特別有持續的錐體外系體徵。 與昏睡性腦炎驚人的相似之處是，三名患者表現出持續的帕金森症狀，直到他們失去隨訪。 一名在 NMS 之前患有輕度認知障礙的患者，其癡呆症持續惡化。

Although Rosebush and Stewart (1989) provided insufficient data to draw exact parallels, their NMS patients also suffered chronic impairments similar to those reported in lethargic encephalitis patients. Of the 20 patients, 14 continued to have “extrapyramidal symptoms or mild abnormalities of vitals signs and muscle enzymes at the time of discharge” (p. 721), but we are not told how many of the 14 specifically had persistent extrapyramidal signs. In a striking parallel with lethargic encephalitis, three patients displayed persistent parkinsonism symptoms until they were lost to follow-up. One patient, who had mild cognitive impairment prior to NMS, developed a persistent worsening of her dementia.

DSM-IV-TR 表明，

The DSM–IV–TR indicated,

抗精神病藥惡性綜合徵的基本特徵是使用抗精神病藥物的個體出現嚴重的肌肉僵硬和體溫升高。 這伴有以下兩種（或多種）症狀：出汗、吞嚥困難、震顫、大小便失禁、意識水平從混亂到昏迷的變化、緘默、心動過速、血壓升高或不穩定、白細胞增多和肌肉的實驗室證據 損傷（例如，肌酸磷酸激酶 [CPK] 升高。(^1)

The essential feature of Neuroleptic Malignant Syndrome is the development of severe muscle rigidity and elevated temperature in an individual using neuroleptic medication. This is accompanied by two (or more) of the following symptoms: diaphoresis, dysphagia, tremor, incontinence, changes in level of consciousness ranging from confusion to coma, mutism, tachycardia, elevated or labile blood pressure, leukocytosis, and laboratory evidence of muscle injury (e.g., elevated creatine phosphokinase [CPK].(^1)

在我的臨床和法醫經驗中，對肌肉僵硬的強調過於狹隘。 NMS 可伴有任何類型的嚴重錐體外系反應。 尤其是在 NMS 早期，患者可以表現出任何一種由安定藥引起的異常運動，包括舞蹈手足徐動樣運動、肌張力障礙和運動不能。 有些病例看起來很像嚴重的 TD，而且患者通常會留下持續的 TD 症狀。

In my clinical and forensic experience, the emphasis on muscle rigidity is much too narrow. NMS can be accompanied by any kind of severe extrapyramidal reaction. Especially early in NMS, patients can display any of the wide array of neuroleptic-induced abnormal movements, including choreoathetoid movements, dystonia, and akinesia. Some cases look very much like severe TD, and often, the patients are left with persistent symptoms of TD.

NMS 已與非典型抗精神病藥氯氮平（Anderson 等人，1991；Dasgupta 等人，1991）和利培酮（Dave，1995；Mahendra，1995；Raitasuo 等人，1994；Singer 等人，1995）一起報導。

NMS has been reported with the atypical neuroleptics clozapine (Anderson et al., 1991; Dasgupta et al., 1991) and risperidone (Dave, 1995; Mahendra, 1995; Raitasuo et al., 1994; Singer et al., 1995).

2007 年，Zarrouf 和 Bhanot 發表了最廣泛的最新綜述，並確定了 88 篇與六種非典型精神抑製藥相關的 NMS 報告：奧氮平、氯氮平、利培酮、齊拉西酮、喹硫平和阿立哌唑。 作為對那些在 NMS 進入緩解期後隨便恢復使用精神安定藥的醫生的警告，20 例患者顯示了先前 NMS 的“明確病史”，這表明患者的首例 NMS 在再次接觸神經安定藥時易患另一例。 奧氮平（Zyprexa）被吹捧為相對沒有 NMS 的風險，但作者找到了 36 例。
In 2007 Zarrouf and Bhanot published the most extensive recent review and identified 88 reports of NMS associated with six atypical neuroleptics: olanzapine, clozapine, risperidone, ziprasidone, quetiapine, and aripiprazole. As a warning to those doctors who cavalierly resume neuroleptics once the NMS has gone into remission, 20 cases showed a “clear history” of prior NMS, indicating that a patient’s fi rst case of NMS predisposes toward another when reexposed to neuroleptics. Olanzapine (Zyprexa) has been touted as being relatively free of the risk of NMS, but the authors located 36 cases.

Zarrouf 和 Bhanot (2007) 證實 NMS 經常以遲發性運動障礙的各種表現形式導致不可逆的腦損傷； 共濟失調和平衡問題； 軀乾和四肢的異常運動； 言語異常； 和猛烈的、單方面的運動爆發（偏頭痛）。 NMS 還使患者患有多種認知障礙，包括難以理解命令、注意力問題和持續性健忘症。 屍檢研究顯示“小腦退化、浦肯野細胞和顆粒細胞減少以及齒狀核中的神經膠質增生”（第 93 頁）。

Zarrouf and Bhanot (2007) confirmed that NMS often leads to irreversible brain damage in the form of various manifestations of tardive dyskinesia; ataxia and balance problems; abnormal movements of the trunk and limbs; speech abnormalities; and violent, unilateral outbursts of movement (hemiballismus). NMS also left patients suffering from multiple cognitive disabilities including difficulties comprehending commands, attention problems, and persistent amnesia. Postmortem studies revealed “cerebellar degeneration, reduction of the Purkinje and granule cells, and gliosis in the dentate nucleus” (p. 93).

Zarrouf 和 Bhanot 正確地發現“沒有確鑿的證據表明哪種抗精神病藥物可以降低患者復發 NMS 的風險”（第 94 頁）。 NMS 是與所有抗精神病藥（包括較新的非典型藥）相關的一種更具破壞性的風險！

Zarrouf and Bhanot correctly find that “no conclusive evidence indicates which antipsychotic might lower a patient’s risk of recurrent NMS”(p. 94). NMS is one more devastating risk associated with all neuroleptics, including the newer atypicals!

研究表明，典型和非典型抗精神病藥物會增加神經元對細胞死亡的脆弱性，甚至會殺死腦細胞，並且已經患有阿爾茨海默氏症等腦部疾病的患者的風險會增加（第 5 章）。 與此一致，Sechi 等人。 （2000 年）報導了一例患有路易體的家族性癡呆患者暴露於低劑量利培酮後的 NMS 病例。

Research indicates that typical and atypical neuroleptic drugs increase the vulnerability of neurons to cell death and even kill brain cells and that the risk increases in patients already suffering from brain disorders such as Alzheimer’s (chapter 5). Consistent with this, Sechi et al. (2000) reported on a case of NMS following exposure of a patient with familial dementia with Lewy bodies to low doses of risperidone.

神經麻痺性神經綜合徵的生物學基礎 (p. 78)

BIOLOGICAL BASIS OF NEUROLEPTIC-INDUCED NEUROLOGICAL SYNDROMES

藥物誘發的帕金森症顯然部分但不是全部由基底神經節，特別是紋狀體區域或紋狀體（尾狀核和殼核）中的多巴胺受體的阻滯發展，產生運動遲緩、僵硬和其他症狀。 黑質色素神經元的損傷和退化起關鍵作用。 這些神經元終止於紋狀體，當正常運作時，它們釋放多巴胺作用於紋狀體多巴胺受體。

Drug-induced parkinsonism apparently develops in part, but not wholly, from blockade of dopamine receptors in the basal ganglia, specifically the striatal region or striatum (the caudate and putamen), producing motor retardation, rigidity, and other symptoms. Damage and degeneration in the pigmented neurons of the substantia nigra play a key role. These neurons terminate in the striatum, where, when functioning normally, they release dopamine to act on striatal dopamine receptors.

TD 是一種更延遲的反應，可能部分基於在連續阻斷後這些相同的紋狀體多巴胺受體中反應性超敏反應或過度活躍的發展（參見 APA，1980b；Fann 等人，1980；Klawans，1973；和本卷的第 5 章）。當藥物減少或消除時，多巴胺受體的這種超敏感性變得最明顯，從而終止阻斷。過度活躍、未受阻的受體會產生 TD 症狀。 毫無疑問，必須對這兩種藥物引起的疾病的神經病理學有更多的了解，這可能涉及多種神經遞質系統異常。然而，如果醫療保健提供者停止向患者開這些藥物，問題實際上就會消失。

TD is a more delayed reaction, probably based in part on the development of reactive supersensitivity or hyperactivity in these same striatal dopamine receptors following continuous blockade (see APA, 1980b; Fann et al., 1980; Klawans, 1973; and chapter 5 in this volume). This supersensitivity of the dopamine receptors becomes most obvious when the drug is reduced or eliminated, terminating the blockade. The overactive, unblocked receptors produce the TD symptoms. Undoubtedly, a great deal more must be learned about the neuropathology of both these drug-induced diseases, which probably involve multiple neurotransmitter system abnormalities. However, if health care providers were to stop prescribing these drugs to patients, the problem would virtually disappear.

最近的研究表明，TD 可能是多巴胺和膽鹼能係統之間複雜相互作用的結果，當多巴胺能係統的抑製或平衡作用被抗精神病藥阻斷時，膽鹼能係統變得更加活躍。 此外，精神安定藥通過破壞許多獨立的生化途徑直接對神經元有毒（第 5 章）。

More recent studies have indicated that TD may be the result of complex interactions between dopamine and the cholinergic system, which becomes more active when the suppressive or balancing effect of the dopaminergic system is blocked by the neuroleptics. In addition, the neuroleptics are directly toxic to neurons by means of disrupting a number of separate biochemical pathways (chapter 5).

兒童和精神病患者 (p. 79)

CHILDREN AND NEUROLEPTICS

近年來，不道德的醫生一直在推動增加對兒童的抗精神病藥物處方。 主要的理由是兒童雙相情感障礙的診斷，完全是基於假設某些常見的兒童行為，如憤怒和激動，是成人雙相情感障礙的前兆。 這些藥物倡導者在很大程度上忽略了與給兒童服用抗精神病藥相關的多種嚴重風險，包括遲發性運動障礙（見前面的討論）、腦細胞損傷和腦萎縮（第 5 章）、肥胖和糖尿病。 這些藥物倡導者也沒有考慮過將正在發育的大腦浸泡在毒素中所帶來的難以衡量的風險。

In recent years, unscrupulous physicians have been pushing for the increased prescribing of neuroleptic drugs to children. The main justification has been the diagnosis of bipolar disorder in children, a complete sham based on nothing more than the assumption that certain common childhood behaviors, such as anger and agitation, are precursors to adult bipolar disorder. These drug advocates have largely ignored the manifold serious risks associated with giving neuroleptics to children, including tardive dyskinesia (see previous discussion), brain cell damage and brain shrinkage (chapter 5), obesity, and diabetes. Nor have these drug advocates considered the difficult-to-measure risks associated with bathing the growing brain in toxins.

在 2006 年 12 月發表在《美國精神病學雜誌》上的題為“獲得：兒科患者和非典型抗精神病藥的使用”的社論中，托賓說：

In an editorial titled “Gaining: Pediatric Patients and Use of Atypical Antipsychotics,” published in the American Journal of Psychiatry in December 2006, Tobin stated:

最近對兒科總體使用的研究表明，在四個州醫療補助計劃中，非典型抗精神病藥物的處方增加了 6 到 20 倍，在全國范圍內，包括抗精神病藥物處方在內的兒科就診人數增加了 6 倍，其中超過 90% 是非典型抗精神病藥的處方。

Recent studies of overall pediatric use have shown a 6- to 20-fold increase in prescription of atypical antipsychotics in four state Medicaid-programs and, nationally, a sixfold increase in pediatric visits that included prescriptions of antipsychotic medication, more than 90% of which were prescriptions for atypical antipsychotics.

托賓聲稱給兒童開抗精神病藥物有一些很好的理由，但警告說這些藥物會導致體重過度增加和 II 型糖尿病。 在表達了這種擔憂之後，社論是否建議減少給兒童開非典型抗精神病藥物？ 否。社論是否建議在兒童和青少年開始出現藥物引起的體重增加跡象時停止服藥？ 不會。社論建議繼續使用抗精神病藥，同時添加用於治療 II 型糖尿病的高度實驗性且具有潛在危險的藥物二甲雙胍（Klein 等，2006）。 由於決心為成千上萬的兒童開出抗精神病藥物，精神病學對美國青年的身體健康造成了重大的公共衛生威脅。

Tobin claims that there are some good justifications for prescribing antipsychotic drugs to children but warns about the drugs causing excessive weight gain and type II diabetes. After showing this concern, does the editorial recommend cutting back on prescribing atypical antipsychotic drugs to children? No. Does the editorial recommend stopping the drug when children and adolescents begin to show signs of drug-induced weight gain? No. The editorial recommends continuing the neuroleptic while adding the highly experimental and potentially dangerous drug metformin (Klein et al., 2006), which is used for treating type II diabetes. As a result of its determination to prescribe neuroleptic drugs to tens of thousands of children, psychiatry has created a major public health threat to the physical health of America’s youth.

表現出與躁狂發作或雙相情感障礙一致的躁狂症狀的兒童也有所增加。 在 1989 年百憂解問世之前，我從未見過有真正躁狂症狀的孩子。 從那以後，我看到越來越多的人。 為什麼？ 我所見過的每一例兒童雙相情感障礙或躁狂症都是由藥物不良反應引起的，通常是對新的抗抑鬱藥如百憂解或帕西爾，在少數情況下是對利他林和阿得拉爾等興奮劑。 在任何情況下，違規的醫療保健提供者都沒有承認這種疾病是由他們的處方藥引起的。他們最多只是告訴父母，這種藥物暴露了一種先前存在的雙相情感障礙，而這種說法完全缺乏科學依據。

There has also been an increase in children displaying maniclike symptoms consistent with a manic episode or bipolar disorder. Prior to the advent of Prozac in 1989, I never saw a child with genuine manic symptoms. Since then, I have seen an increasing number. Why? Every single case of childhood bipolar disorder or mania that I have seen has resulted from an adverse drug reaction, usually to the newer antidepressants such as Prozac or Paxil, and on fewer occasions, to stimulants like Ritalin and Adderall. In no case have the offending health care providers admitted that the disorder was caused by their prescribed medications. At the most, they told parents that the drug had unmasked a preexisting bipolar disorder, a claim wholly lacking in scientific foundation.

由於 Zyprexa、Risperdal 和 Geodon 等藥物對兒童的處方增加，我看到年輕人中的 TD 病例越來越多。 我親自評估了十幾個涉及 Risperdal 的案例，以及由 Zyprexa 和 Geodon 引起的額外案例，我在 Medication Madness（印刷中）中詳細描述了其中幾個案例。

As a result of the increased prescription of drugs like Zyprexa, Risperdal, and Geodon to children, I am seeing an increasing number of TD cases in young people. I have personally evaluated well over a dozen cases involving Risperdal and an additional number caused by Zyprexa and Geodon, several of which I describe in detail in Medication Madness (in press).

根據我的經驗，TD 在兒童中的發生率並不低於成人，而且可能更嚴重，通常涉及軀幹並導致步態困難（參見 Breggin，1983b 的評論）。 如前所述，兒童似乎比成人更有彈性，我看到有幾個病例顯著改善，少數病例在停藥後病情緩解。 有時逐漸改善需要幾個月的時間，使孩子長期殘疾。

In my experience, TD is no less frequent in children than in adults, and it can be more severe, often involving the torso and causing difficulties with gait (see Breggin, 1983b, for a review). As already mentioned, children seem more resilient than adults, and I have seen several cases that have improved dramatically and a limited few that have gone into remission after withdrawal of the drug. Sometimes the gradual improvement has required many months, subjecting the child to a lengthy disability.

TD 的污名化後果對兒童的破壞性甚至比對成人的更大。 我評估了一個 10 歲的孩子，該孩子從 Risperdal 引起的嚴重病例中基本康復，只留下她的眼部肌肉偶爾出現異常，導致她的眼睛短暫地在她的頭部內捲起，露出白色。 想像一下，當她對男孩產生興趣，並通過她自己或通過羞辱的經歷意識到，小男孩看著一個小女孩的眼睛在她腦海裡翻滾時會感到不舒服。

The stigmatizing consequences of TD are even more devastating to children than to adults. I evaluated one 10-year-old child who largely recovered from a severe case caused by Risperdal, leaving her only with an occasional abnormality of her eye muscles that caused her eyes to briefly roll up inside her head, showing the whites. Imagine how she is going to feel when she develops an interest in boys and realizes, on her own or through humiliating experiences, that little boys will not feel comfortable watching a little girl’s eyes roll up inside her head.

用抗精神病藥治療兒童抽動穢語(p.80)

Treating Childhood Tourette’s With Neuroleptics

當今兒童治療中最悲慘的情況之一是使用抗精神病藥來控制妥瑞氏症。 抽動穢語包括抽動和自發的、不恰當的發聲，例如罵人的話。 雖然已經提出了生物起源的說法，但沒有一個被證明。 另一方面，有非常充分的證據表明，抗精神病藥經常在患有更多致殘性抽動、痙攣和其他異常運動的兒童中產生 TD。

One of the most tragic situations in the treatment of children today involves the use of neuroleptics for the control of Tourette’s disorder. Tourette’s involves a combination of tics and spontaneous, inappropriate vocalizations, such as curse words. While claims have been made for a biological origin, none has been demonstrated. On the other hand, it is extremely well documented that neuroleptics frequently produce TD in children with far more disabling tics, spasms, and other abnormal movements.

神經安定劑對診斷出患有圖雷特氏症的兒童的破壞性影響往往未被認識到。 Dulcan (1994) 報告說，在停用抗精神病藥後，妥瑞氏症的症狀可能會惡化幾個月。 Bruun (1988) 回顧了 208 個案例。 她發現 34 人患有以“器質性情感綜合徵”形式出現的藥物引起的煩躁不安，9 人因藥物引起的抽動穢語惡化，5 人因攻擊性和敵意，3 人因“迷霧狀態”，2 人因 “坦率的精神運動性癲癇發作。” 一些孩子忍受了藥物引起的靜坐不能，這使他們的情緒和神經狀況惡化。 作者還注意到戒斷性運動障礙的出現。 其中三名兒童出現了 TD 症狀，作者報告稱，這些症狀在數週或數月內得到緩解。

The devastating effects of neuroleptics in children diagnosed with Tourette’s often go unrecognized. Dulcan (1994) reported that the symptoms of Tourette’s can be exacerbated for several months following withdrawal from neuroleptics. Bruun (1988) reviewed 208 cases. She found that 34 suffered from drug-induced dysphoria that appeared in the form of an “organic affective syndrome,” 9 from a drug-induced worsening of their Tourette’s, 5 from aggression and hostility, 3 from “fog states,” and 2 from “frank psychomotor seizures.” A number of the children endured drug-induced akathisia, which worsened their emotional and neurological condition. The author also noted the appearance of withdrawal dyskinesias. Three of the children developed symptoms of TD, which, the author reported, resolved over a period of weeks or months.

我評估了幾名兒童和年輕人，他們在治療妥瑞氏症後出現了嚴重的遲發性運動障礙。 其中一名 20 歲男子曾接受利培酮治療，最終從妥瑞氏症中康復。 然而，他因藥物引起的嚴重異常舌頭運動和下巴痙攣需要接受肉毒桿菌毒素治療，而且他可能永遠無法完全康復。 患有妥瑞氏症的他能夠過上幸福的生活，而且基本上沒有受到任何損害。 但 TD 嚴重損害了他的學校、職業和社交生活。

I have evaluated several children and young adults who developed severe cases of tardive dyskinesia following neuroleptic treatment for Tourette’s. One, a 20-year-old man who had been treated with Risperdal, eventually recovered from Tourette’s. However, his drug-induced severe abnormal tongue movements and jaw spasms have required treatment with Botox, and he may never fully recover from them. He had been able to live a happy and largely unimpaired life with Tourette’s; but the TD has severely impaired his school, occupational, and social life.

就其風險：收益比而言，使用抗精神病藥治療圖雷特氏症不符合合理的醫療標準。

The use of neuroleptics for the treatment of Tourette’s does not meet a reasonable medical standard in terms of its risk:benefit ratio.

食品藥品監督管理局為兒童打開 TD 和 NMS 閘門 (p. 81)

The Food and Drug Administration Opens the TD and NMS Floodgates for Children

2006 年 10 月 6 日，FDA 宣布批准 Risperdal 用於治療自閉症兒童的“極度煩躁”。 Risperdal 可以減少這種所謂的極端易怒（憤怒和發脾氣）的唯一方法是停用額葉、邊緣系統和網狀激活系統，從而導致情緒遲鈍的化學腦葉切除術。 由於 Risperdal 是一種有效的多巴胺阻滯劑，它具有這種能力。

On October 6, 2006, the FDA announced its approval of Risperdal for the treatment of “extreme irritability” in autistic children. The only way Risperdal can reduce this so-called extreme irritability (anger and temper tantrums) is by deactivating the frontal lobes, limbic system, and reticular activating system, causing a chemical lobotomy with emotional blunting. Since Risperdal is a potent dopamine blocker, it has this capacity.

主要影響將是進一步損害自閉症兒童本已有限的關心他人和與他人交往的能力。 利培酮會使兒童更加自閉。 在許多情況下，它還會通過引起躁動和靜坐不能而加劇孩子所謂的易怒。 但是在讓孩子變得更加機器人化的過程中，會讓一些看起來不那麼麻煩。

A primary effect will be the further impairment of the autistic child’s already limited ability to care about and relate to other people. Risperdal will make children more autistic. In many cases, it will also worsen the child’s so-called irritability by causing agitation and akathisia. But in the process of making children more robotic, it will make some seem less troublesome.

最糟糕的是，FDA 對該藥物治療自閉症兒童極度易怒的有限批准將進一步鼓勵這種破壞性藥物在大量有行為問題的兒童中的廣泛、超說明書使用。 Risperdal 已經經常在沒有科學依據的情況下向廣泛的兒童開出標籤外的處方，通常是為了抑制不良行為。 FDA 的行動將極大地鼓勵這種藥物的濫用，最終在兒童中引發新一波 TD、遲發性癡呆和遲發性精神病。

Worst of all, the FDA’s limited approval of the drug for treating extreme irritability in autistic children will further encourage the widespread, off-label use of this devastating drug in large numbers of children with behavior problems. Risperdal is already frequently prescribed off label with no scientific justification to a wide range of children, usually with the aim of suppressing unwanted behaviors. The FDA’s action will greatly encourage this abusive use of the drug, ultimately causing a new wave of TD, tardive dementia, and tardive psychosis among children.

在我寫下關於利培酮治療兒童越來越廣泛使用的這些擔憂之後，FDA（2007d，8 月 22 日）在宣布這一消息時採取了更加魯莽的步驟：

After I had written these concerns about the increasingly widespread use of Risperdal for treating children, the FDA (2007d, August 22) took an even more reckless step when it made this announcement:

美國食品和藥物管理局今天批准利培酮（利培酮）用於治療 13 至 17 歲青少年的精神分裂症，以及用於 10 至 17 歲兒童和青少年躁狂或混合型雙相 I 障礙的短期治療。 這是 FDA 首次批准一種非典型抗精神病藥物來治療這些年齡組的任何一種疾病。

The U.S. Food and Drug Administration today approved Risperdal (risperidone) for the treatment of schizophrenia in adolescents, ages 13 to 17, and for the short-term treatment of manic or mixed episodes of bipolar I disorder in children and adolescents ages 10 to 17. This is the first FDA approval of an atypical antipsychotic drug to treat either disorder in these age groups.

Risperdal 具有阻斷多巴胺 D2 受體的強大能力，是所有所謂的非典型藥物中最不“非典型”的藥物。 我評估過的大多數兒童 TD 病例都是由 Risperdal 引起的。 正如您在第 2 至第 5 章中所讀到的“抗精神病”藥物的毀滅性毒性，請記住，美國的藥物監管機構已經通過向其兒童釋放最嚴重的醫源性疾病之一來攻擊他們。

Risperdal, with its potent capacity to block dopamine D2 receptors, is the least “atypical” of all the so-called atypicals. Most of the cases of TD in children that I have evaluated have been caused by Risperdal. As you read in chapters 2–5 about the devastating toxicity of the “antipsychotic” drugs, keep in mind that America’s drug watchdog agency has turned on its children by unleashing one of the worst iatrogenic disorders upon them.

快死 (p. 82)

HURRYING DEATH

在精神抑製藥物出現之前，人們觀察到被診斷患有精神分裂症的患者壽命正常，除非受到國家精神病院的暴力和不健康環境的影響（Breggin，1991c）。 自從精神安定藥問世以來，西方世界幾乎所有被診斷患有精神分裂症的患者最終都受到精神抑製藥誘發的各種神經系統疾病的折磨，以及許多其他嚴重疾病的風險，如中風、心臟病、肥胖症和 糖尿病。
Until the advent of neuroleptic drugs, it was observed that patients diagnosed with schizophrenia lived normal life spans, unless subjected to the violent and unhealthy environments of state mental hospitals (Breggin, 1991c). Since the advent of neuroleptics, almost every patient in the Western world diagnosed with schizophrenia ends up being afflicted with a variety of neurological disorders induced by neuroleptics as well as the risk of many other serious disorders, such as stroke, heart disease, obesity, and diabetes.

2006 年，Joukamaa 及其同事在英國精神病學雜誌上對 7,217 名年齡在 30 歲及以上的芬蘭人的代表性人口樣本中被診斷患有精神分裂症的患者的死亡率進行了調查。 使用了包括既往醫療記錄在內的全面健康和精神檢查，並對患者進行了 17 年的隨訪。 當時，99 人中有 39 人死亡。 精神分裂症患者與其他患者之間的相對死亡風險為 2.84（95% 置信區間 [CI] 2.06-3.90）。 據作者稱，“基線調查時使用的抗精神病藥的數量顯示出與死亡率的分級關係。” 作者總結說，仍然不願意面對現實，“迫切需要確定精神分裂症的高死亡率是歸因於疾病本身還是抗精神病藥物。”

In 2006 Joukamaa and colleagues, in the British Journal of Psychiatry, examined the mortality rates for patients diagnosed with schizophrenia in a representative population sample of 7,217 Finns age 30 and over. A comprehensive health and psychiatric examination, including previous medical records, was utilized, and the patients were followed up for 17 years. At that time, 39 of 99 individuals had died. The relative mortality risk between those with schizophrenia and others was 2.84 (95% confidence interval [CI] 2.06–3.90). According to the authors, “the number of neuroleptics used at the time of the baseline survey showed a graded relation to mortality.” Still short of willing to face the reality, the authors concluded, “There is an urgent need to ascertain whether the high mortality in schizophrenia is attributable to the disorder itself or the antipsychotic medication.”

毫無疑問，致死劑是精神分裂症還是精神抑製藥。沒有已知的身體疾病，甚至沒有任何異常的實驗室測試與精神分裂症的診斷相關，而抗精神病藥物具有細胞毒性，會導致許多大腦和身體的身體疾病，從糖尿病和肝臟疾病到無法解釋的猝死。它們還會產生冷漠和冷漠作為主要影響，大大降低了個人對心髒病、中風和其他需要立即治療的疾病的早期症狀做出反應的能力。 2005 年 4 月，FDA (2005b) 發布了一項公共衛生諮詢，在安慰劑對照臨床試驗中，使用非典型抗精神病藥物治療老年癡呆症患者與死亡風險增加有關。 2005 年 6 月，加拿大衛生部發出了類似的警告。提供數據的試驗涉及利培酮、奧氮平、喹硫平和阿立哌唑。與安慰劑相比，死亡率大約高出 1.6 至 1.7 倍。

There cannot be any question whether the lethal agent is schizophrenia or the neuroleptics. There are no known physical disorders, not even any abnormal lab tests, associated with the diagnosis of schizophrenia, whereas the neuroleptic drugs are cytotoxic and cause numerous physical disorders of the brain and body from diabetes and liver disease to unexplained sudden death. They also produce apathy and indifference as their primary effect, greatly reducing the capacity of an individual to respond to the early onset signs of heart disease, stroke, and other illnesses that require immediate treatment. In April 2005, the FDA (2005b) issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk of death in placebo-controlled clinical trials. In June 2005, Health Canada issued a similar warning. The trials that provided the data involved risperidone, olanzapine, quetiapine, and aripiprazole. Mortality was approximately 1.6 to 1.7 times higher when compared to placebo.

2007 年，吉爾等人。 研究了加拿大安大略省老年癡呆症患者 5 年期間抗精神病藥物的使用和死亡率（另見 Medline Plus，2007 年）。 共確定了 27,259 對匹配對。 比較了非典型抗精神病藥物暴露與無抗精神病藥物暴露以及非典型抗精神病藥物暴露與常規抗精神病藥物暴露之間的比較。 患者在社區或長期護理中。 在最初分配抗精神病藥物後的 30、60、120 和 180 天評估死亡風險。 在包括 180 天在內的所有評估時間內，較老的和非典型的精神安定藥都與死亡風險增加相關，增加了 1.31-1.55 倍。 在所有時間點，常規抗精神病藥物的風險都高於非典型藥物。 作者得出結論，

In 2007, Gill et al. examined antipsychotic use and mortality in older adults with dementia in Ontario, Canada, over a 5-year period (see also Medline Plus, 2007). A total 27,259 matched pairs were identified. Comparisons were made between atypical neuroleptic exposure and no antipsychotic drug exposure and between atypical neuroleptic drug exposure and conventional antipsychotic drug exposure. Patients were in community or in long-term care. The risk of death was assessed at 30, 60, 120, and 180 days after the initial dispensing of the antipsychotic drug. Both the older and the atypical neuroleptics were associated with an increased risk of death at all assessment times, including 180 days, by a factor of 1.31–1.55 times. Conventional antipsychotics had a greater risk than atypicals at all points in time. The authors concluded,

我們的研究提供了進一步的證據，表明使用非典型抗精神病藥與老年癡呆症患者的道德有小幅但顯著的提高有關。 此外，與抗精神病藥相關的死亡風險在使用 1 個月後就很明顯，並且可能持續 6 個月。
Our study provides further evidence that use of atypical antipsychotics is associated with a small but significant increase in morality among older patients with dementia. In addition, the risk of death associated with antipsychotics is apparent after as little as 1 month of use and may persist for six months.

結論

CONCLUSION (p. 84)

神經安定藥的廣泛使用在世界範圍內引發了神經系統疾病的流行。 即使 TD 是這些藥物造成的唯一不可逆轉的殘疾，這也將是歷史上最嚴重的醫學災難之一。 實際上，抗精神病藥物還會降低生活質量，導致多種嚴重且可能致命的身體疾病，並縮短壽命。

The widespread use of neuroleptics has unleashed an epidemic of neurological disease on the world. Even if TD were the only irreversible disability produced by these drugs, this would be among the worst medically induced disasters in history. In reality, the antipsychotic drugs also reduce the quality of life, cause multiple severe and potentially lethal physical disorders, and shorten the life span.

Meltzer (1995) 敦促嘗試將長期患者從抗精神病藥中移除，並試圖證明其可行性。 Gualtieri (1993)，警告極端危險，建議將精神安定藥視為一種必要的邪惡和最後的治療手段。 我認為該行業應盡一切可能避免開具抗精神病藥物。 同時，應停止 FDA 推動向兒童和青少年開具這些藥物的升級。

Meltzer (1995) urged that attempts be made to remove long-term patients from neuroleptics and tried to demonstrate its feasibility. Gualtieri (1993), warning about the extreme dangers, suggested that neuroleptics be viewed as a necessary evil and a therapy of last resort. I believe that the profession should make every possible effort to avoid prescribing antipsychotic drugs. Meanwhile, the FDA-driven escalation in prescribing these drugs to children and adolescents should be stopped.

作為向更符合倫理的精神病學邁出的一步，應禁止在兒童治療中使用任何抗精神病藥。 從長遠來看，如果精神病學完全放棄使用抗精神病藥，它會發現心理社會方法的風險要小得多，而且真正有效得多。 第 16 章將研究其中一些更好的選擇。

As a step toward a more ethical psychiatry, the use of any neuroleptics in the treatment of children should be prohibited. In the long run, if psychiatry entirely gave up the use of neuroleptics, it would find that psychosocial approaches are much less risky and much more genuinely effective. Chapter 16 will examine some of these better alternatives.

筆記

1. 肌紅蛋白尿應列入此清單。

NOTE

1. Myoglobinuria should be added to this list.