# **第8章_用於雙極情感障礙的鋰和其他藥物(第193頁)**
CHAPTER 8
Lithium and Other Drugs for Bipolar Disorder (p. 193)

用於治療躁狂發作或雙相情感障礙的鋰最初是作為針對特定精神疾病的特定生化治療的最終示例向公眾和心理健康專業推廣的。 為了支持這一說法，據說鋰對患者或正常志願者都沒有任何大腦功能障礙。 這種對鋰的看法直接挑戰了藥物迷幻的概念和精神科治療的腦殘原則。 儘管現在已經將許多新藥添加到情緒穩定劑武器庫中，但鋰仍然是原型。
Lithium for the treatment of manic episodes or bipolar disorder was originally promoted to the public and to the mental health profession as the ultimate example of a specific biochemical treatment for a specific psychiatric disorder. To bolster this claim, it was said that lithium lacks any brain-disabling effects on either patients or normal volunteers. This view of lithium directly challenges the concept of medication spellbinding and brain-disabling principle of psychiatric treatment. Although a number of new drugs have now been added to the mood stabilizer armamentarium, lithium remains the prototype.

對MANIA的鋰特異性聲明（第 193 頁）
CLAIMS OF LITHIUM SPECIFICITY FOR MANIA (p. 193)

1970 年，美國國家心理健康研究所 (NIMH) 出版的一本供公眾使用的小冊子聲稱，鋰“不會對情緒和行為產生不良影響”，並且“只有症狀被濾掉，而其他人格不受影響 。” NIMH 報告的結論是“該藥物在精神藥物中是獨一無二的，因為它很少對情緒和智力功能產生任何不良影響。” 它將這種物質稱為“針對精神疾病的第一種特定化學療法”。
In 1970, a booklet published by the National Institute of Mental Health (NIMH) and intended for public consumption claimed that lithium produces “no unwanted effects on mood and behavior” and “only the symptoms are leached out while the rest of the personality remains unaffected.” The NIMH report concludes that “the drug is unique among psychopharmaceuticals in that it rarely produces any undesirable effects on emotional and intellectual functioning.” It calls the substance “the first specific chemical treatment for a mental disease.”

五年後，美國精神病學協會 (APA, 1975) 發表了“鋰療法的現狀：APA 工作組的報告”。 作者在沒有引用證據的情況下表示，“工作組得出的結論是，鋰是一種比精神抑製藥更具體的抗躁狂劑，其治療效果是通過獨特的藥理作用而不是非特異性鎮靜作用實現的。”
Five years later, the American Psychiatric Association (APA, 1975) published “The Current Status of Lithium Therapy: Report of the APA Task Force.” Without citing evidence, the authors stated, “The task force has concluded that lithium is a more specific anti-manic agent than neuroleptics and that its therapeutic results are achieved in a unique pharmacologic effect rather than nonspecific calming action.”

Ronald Fieve 成為鋰的主要倡導者之一。 在他的《Moodswing》（1989 年）一書中，他說：“我在精神病學中還沒有發現另一種治療方法能像鋰一樣快速、如此具體、如此持久地治療復發性躁狂和抑鬱情緒狀態”（第 4 頁）。 他將這種非凡的治療效果描述為沒有明顯的副作用。 相反，證據將表明鋰的影響既不快速也不特異，也不是永久性的。 鋰也不是相對沒有副作用的。 它是精神科武器庫中較為失活、致殘的藥物之一。
Ronald Fieve became one of the leading advocates of lithium. In his book Moodswing (1989), he stated, “I have not found another treatment in psychiatry that works so quickly, so specifically, and so permanently as lithium for recurrent manic and depressive mood states” (p. 4). He describes this extraordinary therapeutic effect as occurring with no discernible adverse effects. The evidence will reveal that instead that lithium is neither quick nor specific nor permanent in its impact. Nor is lithium relatively free of adverse effects. It is one of the more deactivating, disabling drugs in the psychiatric armamentarium.

對動物、嬰兒、患者和志願者的腦殘影響 (p. 194)
BRAIN-DISABLING EFFECTS ON ANIMALS, INFANTS, PATIENTS, AND VOLUNTEERS

Subduing Effects on Animals

Cade (1949) 在對豚鼠進行實驗時偶然發現了鋰的潛在治療價值，並立即決定嘗試將其用於人類。 用他自己的話說，這是他做出的演繹飛躍：
Cade (1949) discovered the potential therapeutic value of lithium accidentally while experimenting with guinea pigs and immediately decided to try administering it to human beings. In his own words, here is the deductive leap he made:

一個值得注意的結果是，在大約兩個小時的潛伏期後，這些動物雖然完全清醒，但在一到兩個小時內變得極度昏昏欲睡，對刺激沒有反應，然後再次變得正常活躍和膽小。
從豚鼠的嗜睡到精神病患者的興奮似乎還有很長的路要走，但隨著這些調查的開始，試圖證明躁狂患者尿液中可能排泄出一些毒素，這些想法的關聯是可以解釋的。
A noteworthy result was that after a latent period of about two hours the animals, although fully conscious, became extremely lethargic and unresponsive to stimuli for one to two hours before once again becoming normally active and timid.
It may seem a long distance from lethargy in guinea pigs to the excitement of psychotics, but as these investigations had commenced in an attempt to demonstrate some possibly excreted toxin in the urine of manic patients, the association of ideas is explicable.

凱德從使動物產生毒性嗜睡到“治療”人類的飛躍表明他直觀地認識到失活在精神病治療中的核心作用。 正如 Schou (1957, 1968, 1976) 的評論所指出的，在人類廣泛使用鋰之前，沒有對靈長類動物行為進行大規模研究。 Schou 對鋰如何影響小鼠和大鼠的總結中可能指出了其中一個原因。
Cade’s leap from producing a toxic lethargy in animals to “treating” human beings shows his intuitive recognition of the central role of deactivation in psychiatric treatment. As reviews by Schou (1957, 1968, 1976) indicated, no large studies on primate behavior were conducted before the widespread use of lithium in humans. One reason for this may be indicated in Schou’s summary of how lithium affected mice and rats.

在 1957 年的一篇評論中，他指出，“某種冷漠和反應遲緩是實驗動物的常見症狀。” 或者，正如他在後來的評論中所說（Schou，1976），“自發的探索活動減少了”。
In a 1957 review, he noted, “A certain apathy and slowness of reaction have been frequent symptoms in the experimental animals.” Or, as he remarked in a later review (Schou, 1976), there is “decreased spontaneous and exploratory activity.”

這種對“自發性和探索性活動”的抑制，以及對其他意志和活力表達的抑制，是大多數生物精神病學治療的標誌，並幫助激發了我的失活概念和精神病藥物的大腦致殘原則。 在腦葉切開術的研究以及對精神抑製藥物的早期和最直接的早期研究中，主要或基本作用被確定為冷漠的產生。 在抗抑鬱藥文獻中，關於這些藥物如何在長期使用中產生冷漠，這種相同的效果正在獲得認可。 興奮劑倡導者未能認識到利他林、Adderall 和其他用於控制兒童行為的藥物的這些相同效果； 但科學文獻將證實，它們的主要影響是破壞自發性，對自主產生的、想像的、創造性的和社會活動失去興趣。
This suppression of “spontaneous and exploratory activity,” as well as the suppression of other expressions of volition and vitality, are the hallmarks of most biopsychiatric treatments and helped to inspire my concept of deactivation and the brain-disabling principles of psychiatric drugs. In studies of lobotomy and in the early and most forthright early studies of neuroleptic drugs, the primary or essential effect was identified as the production of indifference. In the antidepressant literature, this same effect is gaining recognition in regard to how these drugs produce apathy in long-term use. Stimulant advocates have failed to recognize these same effects in regard to Ritalin, Adderall, and other drugs used for the control of behavior in children; but the scientific literature will confirm that their primary effect is the crushing of spontaneity with a loss of interest in autonomously generated, imaginative, creative, and social activities.

鋰在與人類相同的血清濃度下對大鼠有毒（Schou，1976）。 在 Smith 和 Smith (1973) 的一項大鼠研究中，鋰在低治療範圍內給藥僅 1 週。 作者總結說：“鋰最一致的作用是減少大鼠的自主活動。”
Lithium is toxic in rats at the same serum concentrations as in humans (Schou, 1976). In a rat study by Smith and Smith (1973), lithium was administered in the low therapeutic range for a period of only 1 week. The authors summarized, “The most consistent effect of lithium was to decrease the voluntary activity of the rats.”

對動物普遍行為抑制的一致發現破壞了鋰是治療躁狂症的特殊靈丹妙藥的說法。 抑制自願或自發活動可能是對所有腦殘治療對動物和人類的主要影響的最簡潔描述。
The consistent finding of generalized behavioral suppression in animals undermines the claim that lithium is a specific magic bullet for mania. Suppression of voluntary or spontaneous activity is perhaps the most concise description of the primary impact of all brain-disabling therapies on animals and humans alike.

抑制對正常嬰兒的影響（第 195 頁）
如果一種藥物能製服人類胎兒或嬰兒，那麼它的作用很可能不是特定的精神疾病所特有的。 鋰在子宮內自由穿過胎盤屏障，可以通過母乳（Ananth，1978）。 鋰對血清水平相對較低的嬰兒產生嗜睡和肌張力減退（肌肉功能喪失）的影響已得到充分證明（Rane 等人，1978 年；Strothers 等人，1973 年）。 Hollister (1976) 指出鋰會導致“嗜睡、發紺、吸吮不良和莫羅反射”。 嬰兒嗜睡描述了主要的大腦功能障礙。 與動物研究一樣，關於新生兒和哺乳嬰兒的臨床報告表明，鋰會抑制甚至使中樞神經系統失能。
Subduing Effects on Normal Infants (p. 195)
If a drug subdues the human fetus or infant, it is likely that its effect is not specific for a particular psychiatric disorder. Lithium freely crosses the placental barrier in utero and can be passed through breast milk (Ananth, 1978). The effects of lithium in producing lethargy and hypotonia (loss of muscle function) in babies at relatively low serum levels has been thoroughly documented (Rane et al., 1978; Strothers et al., 1973). Hollister (1976) noted that lithium causes “lethargy, cyanosis, poor suck and Moro refl exes.” Lethargy in an infant describes the primary brain-disabling effect. As in animal studies, clinical reports concerning newborn and nursing babies demonstrate that lithium suppresses, and even disables, the central nervous system.

對正常志願者的致殘作用（第 196 頁）
Disabling Effects on Normal Volunteers (p. 196)

因為他們認為鋰對躁狂症具有特定的疾病，所以該藥物的倡導者最初聲稱它對正常人幾乎沒有影響（Dempsey 等，1977；Hollister，1976）。 就連通常是藥物效應敏銳觀察者的 van Putten (1975a) 也表示，“鋰預防不會影響正常的心理功能，也不會剝奪患者正常的人類悲傷或興奮。”
Because they considered lithium to be disease-specific for mania, advocates of the drug initially claimed that it had little or no effect on normal individuals (Dempsey et al., 1977; Hollister, 1976). Even van Putten (1975a), usually a keen observer of drug effects, stated that “lithium prophylaxis does not affect normal mental functioning or deprive a patient of normal human sorrow or elation.”

聲稱鋰對正常志願者沒有影響的說法通常基於 Schou 等人的一項研究。 （1968 年），他說：“最引人注目的觀察似乎是鋰對正常心理功能的影響是多麼小：在預防劑量中根本沒有，而在較高的治療劑量中只是適度。”
Claims that lithium has no effect on normal volunteers are often based on a study by Schou et al. (1968), who stated: “The most striking observation seems to be how little lithium affects normal mental functions: in prophylactic dosage not at all and in higher therapeutic dosage only moderately.”

然而，Schou 等人 (1968) 自己的數據並不支持這種觀點。
確實，當以低劑量給予藥物僅 1 週時，研究人員發現六名志願者沒有受到影響。 然而，作者也在治療範圍（1.0 mEq/L）內給自己服用鋰，持續 1-3 週。 現在成為實驗對象的作者們經歷了常見的初始軀體副作用，包括“短暫的噁心、腹瀉、手部輕微震顫等”。 此外，他們還受到了束縛效應的影響：“所有受試者的肌肉無力或沉重感都很明顯。 他們必須克服對起身和移動的一定阻力，並且感覺需要腦力才能完成任何體力任務。”
However, Schou et al.’s (1968) own data do not support this view.
It is true that the researchers found no impact in six volunteers when the drug was given at low doses for only 1 week. However, the authors also administered lithium to themselves within the therapeutic range (1.0 mEq/L) for 1–3 weeks. The authors, who now became the subjects of the experiment, experienced the common initial somatic side effects, including “transient nausea, diarrhea, slight tremor of the hands, etc.” In addition, they suffered from a straitjacketing effect: “A feeling of muscular weakness or heaviness was prominent in all the subjects. They had to overcome a certain resistance against rising and moving and also had a feeling that mental effort was needed to undertake any physical task.”

最顯著的影響是主觀的。 請記住，Schou 等人。 (1968) 試圖證實鋰對正常心理功能的影響很小，當時他們描述了以下對自己的影響：
The most remarkable effects were subjective. Keep in mind that Schou et al. (1968) are trying to substantiate how little effect lithium has on normal mental function when they described the following effects on themselves:

總體而言，心理影響是微妙且不明確的。情緒水平沒有一致的變化，但有時會注意到易怒或情緒不穩定。可能對日常的景象和聲音過敏。在其他情況下，對環境刺激的反應減弱；這是其中一個受到家人歡迎的案例（“爸爸比平時輕鬆多了”），而另外兩個受試者的家人則抱怨他們太沉悶了。主觀體驗主要是一種冷漠和輕微的全身不適。這導致了一定的被動性。受試者經常有一種與環境相距甚遠的感覺，就好像被玻璃牆隔開一樣。被治療改變的主觀感覺與客觀行為變化不成比例地強烈。受試者可以參與討論和社交活動，但發現很難理解和整合情境中的多個元素。例如，其中一名受試者指出，雖然他在國際象棋等只有兩名參與者的遊戲中具有不變的能力，但他在四名參與者的橋牌方面不太擅長。智力主動性減弱，有一種注意力和記憶能力下降的感覺；但思維過程不受影響，受試者可以邏輯思考並產生想法。對時間的評估經常受到損害；很難確定某個事件是最近發生的還是前一段時間發生的。
Psychological effects were, on the whole, subtle and ill defined. There was no consistent change of the mood level, but irritability or emotional lability could at times be noted. There might be hypersensitivity to everyday sights and sounds. On other occasions responsiveness to environmental stimuli was diminished; this was in one of the cases welcomed by the family (“Dad is much easier and nicer than usual”), while the families of the two other subjects complained about their being so dull. The subjective experience was primarily one of indifference and slight general malaise. This led to a certain passivity. The subjects often had a feeling of being at a distance from their environment, as if separated from it by a glass wall. The subjective feeling of having been altered by the treatment was disproportionately strong in relation to objective behavioral changes. The subjects could engage in discussions and social activities but found it difficult to comprehend and integrate more than a few elements of a situation. One of the subjects noted, for example, that whereas he had unaltered ability in a game such as chess with only two participants, he was less good at bridge with its four players. Intellectual initiative was diminished, and there was a feeling of lowered ability to concentrate and memorize; but thought processes were unaffected, and the subjects could think logically and produce ideas. The assessment of time was often impaired; it was difficult to decide whether an event had taken place recently or some time ago.

提到“對環境刺激的反應性”減弱、“智力主動性”減弱、“冷漠和輕微的全身不適”和“某種被動”明確描述了鋰的失活、大腦功能障礙（第 1 章）。 使用的語言與用於描述腦葉切除效果的語言相同。
References to diminished “responsiveness to environmental stimuli,” diminished “intellectual initiative,” “indifference and a slight general malaise,” and “a certain passivity” definitively describe the deactivating, brain-disabling effects of lithium (chapter 1). The language used is identical to that used to describe lobotomy effects.

也許最有趣的是，作者在寫關於他們自己的文章時，似乎對藥物著迷。 也就是說，即使他們報告了藥物，他們也沒有意識到藥物對他們的心智能力造成了多大的傷害。 他們以他們的研究為基礎，廣泛宣傳鋰對正常志願者的影響很小或沒有影響。 他們的研究發表在如此晦澀難懂的外語期刊上，甚至在國家醫學圖書館都沒有，因此其他研究人員和專業人士不得不依賴他們對結果的聲明。(^1)
Most interesting, perhaps, the authors, in writing about themselves, seem medication spellbound. That is, they fail to recognize how much harm the drugs are doing to their mental capacities, even as they report them. They used their study as the basis for their widely publicized claim that lithium has little or no effect on normal volunteers. Their study was published in such an obscure foreign-language journal that it was not even available in the National Library of Medicine, and therefore other researchers and professionals had to rely upon their claims concerning their results.(^1)

作者的一個孩子認為他因停用而得到改善，這證實了大腦功能障礙的原理。 至少從這個孩子的角度來看，讓她的父親變得屈服和孤僻是一種解脫。
That one of the author’s children thought he was improved by deactivation confirms the brain-disabling principles. At least from this child’s viewpoint, it was a relief to have her father become subdued and withdrawn.

Small 等人。 (1972) 以更系統的方式檢查了鋰對 11 名正常志願者的心理影響。 三人的反應如此嚴重，以至於“有客觀跡象表明工作和學習成績受損”。 第四個人在服用鋰的第十天出現了“嚴重、劇烈的毒性譫妄”。 第五名志願者在第一周因“嚴重的肌肉無力、精神錯亂和抑鬱”而退出研究，作者認為，在沒有證據的情況下，這“更有可能”與心理因素有關，而不是與藥物有關。
Small et al. (1972) examined the mental effects of lithium on 11 normal volunteers in a more systematic fashion. Three had such serious reactions that there were “objective indications of impairment in work and school performance.” A fourth developed a “severe, precipitous toxic delirium on the tenth day of taking lithium.” A fifth volunteer dropped out of the study in the first week with “severe muscle weakness, confusion, and depression,” which, the authors argue, without evidence, was “more likely” related to psychological factors than to the drug.

林諾拉(Linnoila)等人。 (1974) 專注於模擬汽車駕駛中的行為反應，發現鋰引起的反應和反應時間以及判斷力受損。
Linnoila et al. (1974) focused on behavioral reactions in simulated automobile driving and found lithium-induced impairment in response and reaction times, and in judgment.

賈德(Judd)等人。 (1977a&b) 還研究了正常志願者在 2 週內對鋰（平均，0.9 mEq/L）的反應。 在一項研究中（Judd 等人，1977 年），他們報告了鋰對 23 名受試者的情緒和性格的影響。 他們對他們的發現表示驚訝，其中包括志願者的“幸福感”下降和“大量自發的抱怨”。 作者毫不含糊地描述了他們的結果：
Judd et al. (1977a&b) also studied the reactions of normal volunteers to lithium (mean, 0.9 mEq/L) over a 2-week period. In one study (Judd et al., 1977) they reported the effects of lithium on mood and personality in 23 subjects. They expressed surprise at their findings, which included a decreased “sense of well-being” among their volunteers and a “large number of spontaneous complaints.” The authors described their results in no uncertain terms:

這些主觀變化不是情緒升高，而是情緒降低。 一般來說，這些感覺基調的改變是煩躁的，其特徵是疲倦、嗜睡、消極和抑鬱的感覺。 此外，激動、焦慮、緊張和不安的感覺與碳酸鋰的維持有關。 還有一些證據表明，受試者表示他們不想處理與人類環境互動的需求。 最後，有一致的自我報告無法集中註意力、精神錯亂、感覺頭昏眼花和頭腦清醒。
These subjective changes are not mood elevating, but rather mood lowering. In general, these feeling-tone alterations are dysphoric and characterized by lassitude, lethargy, and feelings of negativism and depression. In addition, feelings of agitation, anxiety, tension, and restlessness are related to lithium carbonate maintenance. There is also some evidence that subjects indicated they did not want to have to deal with the demands of interacting with their human environments. Finally, there are consistent self-reports of inability to concentrate, mental confusion, feeling muddleheaded, and a loss of clear-headedness.

雖然不像 Schou 等人自我描述的鋰效應那樣風景如畫，但大腦致殘效應的印像是相似的。 1979 年，賈德總結了 42 名健康年輕男性的研究結果。 他得出的結論是，鋰會產生“各種人格功能的普遍遲鈍和遲鈍”和“普遍的主觀不安”。 與大腦致殘原則一致，他將鋰的治療效果歸因於認知過程的普遍減慢。
Although not as picturesque as Schou et al.’s self-described lithium effects, the impression of brain-disabling effects is similar. In 1979, Judd summarized the results of studies with 42 healthy young men. He concluded that lithium produces a “general dulling and blunting of various personality functions” and a “generalized subjective dysphoria.” Consistent with the brain-disabling principles, he attributed the therapeutic effect of lithium to a general slowing of cognitive processes.

Judd 研究的一個特別有趣的方面證實，訓練有素的獨立觀察者不太可能報告藥物的不良反應，即使這些不良反應對於服用藥物的人和與服用藥物的人有個人關係的人來說都是顯而易見的（Judd 等，1977a ):
An especially interesting aspect of Judd’s research confirms that trained independent observers are not likely to report adverse drug effects, even when they are apparent to those who administered the drug and to those personally associated with the persons receiving the drug (Judd et al., 1977a):

有趣的是，在實驗情況下，訓練有素的獨立觀察者無法察覺碳酸鋰對正常受試者的影響。 我們最初推測，這些變化雖然對經歷它們的個人來說意義重大，但即使是訓練有素的觀察者也不容易察覺。 與此相反的是，“重要的他人”，一個與受試者有更廣泛的人際交往經驗的人，能夠識別受試者在碳酸鋰維持期間行為和情緒的變化。 此外，他們的觀察結果與從受試者自身的自評數據中獲得的質變完全一致。 因此，碳酸鋰引起的這些變化不僅是主觀體驗的，而且對於熟悉每個受試者的正常行為範圍的獨立觀察者來說也是顯而易見的。
It was of interest to find that the effects of lithium carbonate in normal subjects were not perceptible to trained independent observers in the experimental situation. We initially speculated that these changes, although profound to the individual experiencing them, were not such that they were easily discernible, even to trained observers. In contrast to this was the fact that the “significant other,” an individual who had a much more extensive interpersonal experience with the subject, was able to identify alterations in behavior and mood during the time the subjects were being maintained on lithium carbonate. Further, their observations were completely consistent with qualitative changes obtained from the self-rating data from the subjects themselves. Thus, these changes due to lithium carbonate are not just subjectively experienced, but are apparent to independent observers who are well acquainted with the normal range of behavior of each of the subjects.

受試者的個人同事最常注意到的不利影響包括“嗜睡程度增加，努力工作和清晰思考的能力降低”（Judd，1979）。 報告受試者這些變化的群體包括“朋友、室友、女朋友等”。 沒有描述“訓練有素的獨立觀察員”的背景，但推測他們是心理健康專業人士。
The adverse effects most frequently noted by personal associates of the subjects included “increased levels of drowsiness and lowered ability to work hard and to think clearly” (Judd, 1979). The group who reported these changes in the subjects consisted of “friends, roommates, girlfriends, etc.” The background of the “trained independent observers” is not described, but presumably they are mental health professionals.

令人驚訝的是，受過訓練的觀察者“無法檢測到鋰引起的受試者的任何行為變化”，而這些變化對個人同事來說是顯而易見的，並且可以在測試中進行測量。 Judd (1979) 將他們的失敗歸因於對正常環境中的受試者缺乏熟悉。 但本書中的各種發現證實，未能觀察到藥物不良反應是藥物文獻中絕大多數研究報告和評論文章的特徵。 這是醫生在醫源性否認中的一部分：傾向於否認精神病治療對大腦的影響（第 1 章）。
It is striking that the trained observers were “unable to detect any behavioral changes in the subjects induced by lithium” when they were apparent to personal associates and could be measured on testing. Judd (1979) attributed their failure to a lack of familiarity with the subjects in their normal surroundings. But various findings in this book confirm that this failure to observe adverse drug effects is characteristic of the vast majority of research reports and review articles in the drug literature. It is the doctor’s part in iatrogenic denial: the tendency to deny the brain-disabling effects of psychiatric treatments (chapter 1).

研究繼續證明鋰對正常受試者的不利影響（Glue 等人，1987；Kroph 等人，1979；Muller-Oerlinghausen 等人，1977；Weingartner 等人，1985）。 Schatzberg 和 Cole (1991) 適當地警告說，應該認真對待患者對精神功能障礙的主觀體驗：
Studies have continued to demonstrate adverse effects of lithium on normal subjects (Glue et al., 1987; Kroph et al., 1979; Muller-Oerlinghausen et al., 1977; Weingartner et al., 1985). Schatzberg and Cole (1991) appropriately warned that the patient’s subjective experience of mental dysfunction should be taken seriously:

一些服用鋰鹽的患者抱怨思維遲緩和健忘，並且在測試中發現記憶缺陷。 儘管此類患者經常被懷疑或指責“使用”此類症狀來避免必要的鋰治療，但我們的印像是，這些抱怨通常是真實的，並構成降低劑量或嘗試另一種療法的基礎。 （第 159 頁）
Some patients on lithium complain of slowed mentation and forgetfulness and, on testing, a memory deficit has been found. Although such patients are often suspected or accused of “using” such symptoms to avoid necessary lithium therapy, our impression is that these complaints are often real and constitute a basis for lowering the dosage or trying another therapy. (p. 159)

Jefferson (1993) 總結了鋰的失活作用，
Jefferson (1993) summed up the deactivating effect of lithium,

鋰的神經系統不良反應包括反應性降低、缺乏自發性、智力不足、記憶問題、注意力不集中、煩躁不安。 其中一些作用可能與鋰在減輕輕躁狂症方面的治療作用有關。 然而，在存在這些症狀的情況下，必須考慮甲狀腺功能減退、高鈣血症引起的虛弱和疲勞以及突破性抑鬱症。
Neurologic adverse effects of lithium include reduced reactivity, lack of spontaneity, intellectual insufficiency, memory problems, difficulty in concentration, dysphoria. Some of these effects may be related to the therapeutic action of lithium in reducing hypomania. However, hypothyroidism, weakness and fatigue due to hypercalcemia, and breakthrough depression must be considered in the presence of these symptoms.

鋰引起的甲狀腺疾病很常見，需要在整個治療過程中不斷關注。 鋰引起的甲狀腺功能減退會產生抑鬱和其他精神功能障礙，極大地混淆和復雜化患者的臨床表現。
The production of thyroid disorders by lithium is common and requires constant concern throughout the treatment. Lithium-induced hypothyroidism can produce depression and other mental dysfunction, greatly confusing and complicating the patient’s clinical picture.

Judd 等人回顧了有關精神科藥物對正常受試者認知影響的文獻。 (1987) 發現如下：
In a review of the literature concerning the impact of psychiatric drugs on cognition in normal subjects, Judd et al. (1987) found the following:

總之，鋰通常會導致認知減慢的主觀感覺以及學習、集中和記憶能力的下降。 此外，對照研究一致描述了各種認知測試（包括記憶測試）的小但一致的性能下降。 現有數據表明，性能下降可能繼發於中央信息處理速度的下降。 （第 1468 頁）
In summary, lithium often induces subjective feelings of cognitive slowing together with decreased ability to learn, concentrate and memorize. In addition, controlled studies have consistently described small but consistent performance decrements on various cognitive tests, including memory tests. The available data suggest that the slowing of performance is likely to be secondary to a slowing in the rate of central information processing. (p. 1468)

對正常志願者的研究應該可以推翻鋰只影響疾病過程的說法。 它還應該結束關於鋰具有特定的抗躁狂作用，而不是普遍的大腦致殘、失活作用的說法。 這種效果有時可能會減少躁狂發作的發生，但它是通過降低整體大腦功能來實現的。 即使在減少躁狂發作頻率方面，它的功效也是值得懷疑的，並且會引起躁狂戒斷反應（見以下部分）。
Studies of normal volunteers should lay to rest the claim that lithium only affects a disease process. It should also put an end to the claim that lithium has a specific antimanic effect, rather than a generalized brain-disabling, deactivating effect. This effect may at times reduce the occurrence of manic episodes, but it does so by reducing overall brain function. Even in regard to reducing the frequency of manic episodes, its efficacy is doubtful and it causes manic withdrawal reactions (see following sections).

調低生命的刻度（第 200 頁）
Turning Down the Dial of Life (p. 200)

證實了大腦功能障礙的原理，鋰對精神病患者的抑製作用與對正常志願者的抑製作用相同。 談到成功使用鋰治療的個體，Dyson 和 Mendelson (1968) 觀察到以下幾點：
Confirming the brain-disabling principle, lithium has the same subduing effects on psychiatric patients as on normal volunteers. Speaking of individuals successfully treated with lithium, Dyson and Mendelson (1968) observed the following:

就好像他們的“生活強度”錶盤被調低了幾個檔次。 事情似乎並不那麼重要或迫切； 人們更願意接受日常生活的本來面目，而不是人們可能希望的樣子； 他們的配偶報告說他們的生活更加和平。
It is as if their “intensity of living” dial had been turned down a few notches. Things do not seem so very important or imperative; there is greater acceptance of everyday life as it is rather than as one might want it to be; and their spouses report a much more peaceful existence.

作為對精神治療的腦殘概念的證明，提及配偶關於更和平生活的報告讓人想起 Schou 等人 (1968) 的觀察，即當父親“對環境的反應能力”時，其中一個孩子更喜歡它。 刺激減少了。” 與神經阻滯劑失活和腦葉切除術的比較似乎很明顯。
As a demonstration of the brain-disabling concept of psychiatric treatment, the reference to the spouse’s report of a more peaceful existence is reminiscent of Schou et al.’s (1968) observation that one of the children preferred it when Dad’s “responsiveness to environmental stimuli was diminished.” The comparison to neuroleptic deactivation and to lobotomy again seems apparent.

根據 Dyson 和 Mendelson (1968) 的說法，即使在有效的維持治療中，生命的刻度仍然被調低。 他們引用了他們的一些病人：
According to Dyson and Mendelson (1968), even on effective maintenance therapy, the dial of life remains turned down. They quoted some of their patients:

“我只是不再像以前那樣對事情感到惱火和沮喪。” “曾經困擾我的事情似乎不再那麼重要了。” “我沒有任何精力，無法完成我曾經能夠做到的事情。”
“I just don’t get irritated and upset at things as I used to.” “Things that used to bother me don’t seem so important anymore.” “I don’t have any energy, can’t accomplish what I used to be able to.”

施拉根豪夫等人。 (1966) 發現“當第一次注意到改善時，患者抱怨內部感覺‘受到抑制’，這是一種主觀體驗，他們所有人都很難準確描述。” 患者感到“無法以他們想要的速度說話、思考或行動”。 再一次，鋰顯然嚴重損害了大腦和思維。
Schlagenhauf et al. (1966) found that “when improvement was first noted the patients complained of feeling internally ‘curbed,’ a subjective experience that all of them had considerable difficulty in describing very precisely.” The patients felt “unable to talk, think or move as fast as they would like.” Again, lithium is obviously and grossly disabling the brain and mind.

Demers 和 Davis (1971) 研究了配偶對接受鋰治療的患者的態度。 無意強調這一點，該研究明確表明，所有形式的生動表達或活力總體上都在減少：
Demers and Davis (1971) examined the attitudes of spouses toward patients treated with lithium. Without intending to emphasize the point, the study made clear that there is an overall reduction in all forms of lively expression or vitality:

鋰治療的一個明顯不利結果是熱情行為的減少，以及躁鬱症患者的性反應。 輕躁狂的快活、熱情和自發性通常被視為社交優勢； 躁鬱症患者和他們的配偶抱怨失去了這些有價值的屬性。 當被要求討論婚姻的性兼容性時，他們經常會說自從鋰治療開始以來情況更糟，因為鋰治療的配偶的性慾減少。
An apparent unfavorable result of lithium treatment was a reduction in enthusiastic behavior, as well as sexual responsiveness in the manic-depressive. Hypomanic joviality, enthusiasm, and spontaneity are often regarded as social pluses; and manic-depressives and their spouses complain about the loss of these valued attributes. When pressed to discuss the sexual compatibility of the marriage, frequently they will say it is worse since lithium treatment started, as the lithium-treated spouse has less libidinal strivings.

這段摘錄說明了大腦功能障礙原則，即治療成功的評估取決於觀察者對藥物引起的精神障礙的態度。 在這些情況下，配偶被描述為缺少伴侶的活力和性慾。 另一方面，醫生將這些有價值的屬性標記為“輕躁狂”，以證明他們的治療對大腦造成的損害是合理的。
This excerpt illustrates the brain-disabling principle that the evaluation of treatment success depends upon the observer’s attitude toward the drug-induced mental disability. In these instances, the spouses are described as missing their partners’ vitality and sexuality. On the other hand, the doctors label these valued attributes “hypomanic” in order to justify the brain-disabling effect of their treatments.

粉碎創造力（第 201 頁）
Crushing Creativity (p. 201)

紐約州精神病學研究所的 Ronald Fieve 在美國醫學協會年會上介紹戲劇製作人兼導演 Joshua Logan 時，在報紙和雜誌上引起了全國的關注（“New Old Treatment”，1973 年），Logan 在那裡發表了 鋰的見證。
Ronald Fieve, of the New York State Psychiatric Institute, achieved national attention (“New Old Treatment,” 1973) in newspapers and magazines when he presented theatrical producer–director Joshua Logan at the annual meeting of the American Medical Association, where Logan gave a testimonial for lithium.

各種治療方法的推薦信的整個問題是一個困難而復雜的問題。 例如，庸醫往往有狂熱的支持者。 Logan (1976) 在他的自傳中描述了他多年來與精神病治療的許多接觸，包括早期的精神病學公開推薦。 他對人們對電擊治療持批評態度表示驚訝，他認為這種治療非常“良性”。
The entire question of testimonials for various treatments is a difficult and complex one. Quack cures, for example, often have avid supporters. Logan (1976), in his autobiography, described his many contacts with psychiatric treatment over the years, including earlier public testimonials for psychiatry. He expressed surprise that people are critical of electroshock treatment, which he found to be very “benign.”

Logan 自己的精神病醫生 Fieve 與人合著了一篇文章（Polatin 等人，1971 年），描述了三個拒絕維持鋰的人（在作者看來，這種情況很少見），其中兩個人之所以這樣做，是因為它干擾了他們的創造力 作為暢銷書的作者：“這些患者報告說碳酸鋰抑制了創造力，以至於個人無法表達自己，動力減弱，沒有動力。”
Logan’s own psychiatrist, Fieve, coauthored an article (Polatin et al., 1971) describing three individuals (rare cases, in the authors’ opinion) who rejected maintenance lithium, two of whom did so specifically on the grounds that it interfered with their creativity as writers of bestsellers: ”These patients report that lithium carbonate inhibits creativity so that the individual is unable to express himself, drive is diminished, and there is no incentive.”

儘管他們聲稱鋰不會干擾創造力，但 Schou 和 Baastrup (1973) 描述了它的抑制、扁平化效果：
Despite their claim that lithium does not interfere with creativity, Schou and Baastrup (1973) described its inhibiting, flattening effect:

錯過的並不總是興高采烈。 一位殯葬業者的顧客將抑鬱的悲傷誤認為是同情，抱怨他在接受鋰治療時表現出冷漠。 另一位患者遺憾的是，在討論中他無法達到他認為必要的興奮程度：“醫生，我是一名共產黨員，我必須在討論時感到興奮。” 也有患者認為鋰治療使生活“平淡”、不那麼豐富多彩，“限制”了他們的活動，並阻止他們隨心所欲地進行。 在大多數情況下，當患者習慣了穩定的生活過程時，這些抱怨就會消失。
It is not always the elation that is missed. An undertaker’s customers, mistaking depressive sadness for compassion, complained about his appearance of indifference when he was in lithium treatment. Another patient regretted that in discussions he was unable to attain the level of excitement he considered necessary: “Doctor, I am a communist and I must get excited when I discuss.” There are also patients who feel that lithium treatment makes life “flat” and less colorful, “curbs” their activity, and prevents them from going as fast as they would like. In most cases these complaints disappear when the patients become used to the stable life course.

在大多數情況下，這些投訴是否真的消失了，從來沒有仔細調查過。 即使投訴變得不那麼頻繁，這也可能有許多不幸的原因，包括鋰的極其引人入勝的作用。 根據我的臨床經驗，長時間接觸任何精神藥物的兒童和成人會失去感知其情緒抑製作用的能力。 但鋰的引人入勝的效果特別強大
Whether these complaints do in fact disappear in most cases has never been carefully investigated. Even if the complaints become less frequent, there may be many unfortunate reasons for this, including the extremely spellbinding effect of lithium. In my clinical experience, children and adults exposed to any psychiatric drug for a lengthy period of time lose their ability to perceive their emotionally subduing effects; but the spellbinding effect of lithium is especially potent

Jefferson (1993) 和 Goodwin 和 Jamison (1990) 也證實了一些服用鋰的患者會喪失創造力。 但這並沒有阻止他們對這種藥物的宣傳。
Jefferson (1993) and Goodwin and Jamison (1990) also confirmed that loss of creativity is experienced by some patients on lithium; but it did not daunt their advocacy for the drug.

凱德(Cade)支持大腦功能障礙假說（第 202 頁）
Cade Supports the Brain-Disabling Hypothesis (p. 202)

首次發表關於在精神病患者中使用鋰的日期具有特別的諷刺意味：Cade 的文章發表於 1949 年，與 Corcoran 等人同年發表。 在美國醫學會雜誌上發表了“使用鹽替代品引起的鋰中毒”。
There is a particular irony in the date of the first publication on the use of lithium in mental patients: Cade’s article appeared in 1949, the same year that Corcoran et al. published “Lithium Poisoning From the Use of Salt Substitutes” in the Journal of the American Medical Association.

關於精神安定藥，我們發現使用它們的先驅者對其大腦致殘作用最為直接。 我們發現鋰也有同樣的現象。 Cade (1949) 指出，鋰在用於其他藥用目的時，會在各種患者中產生“實際的精神抑鬱”，而不僅僅是那些患有躁狂症或躁狂抑鬱症的患者。 這種藥物對他認為患有精神分裂症的人（早發性癡呆，在他的疾病學中）產生了所謂的鎮靜作用：
In regard to neuroleptics, we found that pioneers in their use were most straightforward about its brain-disabling effects. We find the same phenomenon with lithium. Cade (1949) indicated that lithium, when used for other medicinal purposes, produced “actual mental depression” in a variety of patients, not just those suffering from mania or manic depression. The drug enforced a so-called quieting effect on persons he considered schizophrenic (dementia praecox, in his nosology):

一個重要的特點是，他們三個人雖然沒有任何根本性的改善，但平時總是坐立不安，吵吵鬧鬧，罵罵咧咧。 . . 失去了興奮和不安，多年來第一次變得安靜和順從。
An important feature was that, although there was no fundamental improvement in any of them, three who were usually restless, noisy and shouting nonsensical abuse . . . lost their excitement and restlessness and became quiet and amenable for the first time in years.

Cade (1949) 更喜歡鋰而不是腦葉切除術來治療“躁動和精神病態的精神缺陷”，以“控制他們躁動不安的衝動和無法控制的脾氣”。
Cade (1949) preferred lithium to lobotomy on “restless and psychopathic mental defectives” in order “to control their restless impulses and ungovernable tempers.”

咒語和醫源性無助和否認（第 203 頁）
SPELLBINDING AND IATROGENIC HELPLESSNESS AND DENIAL (p. 203)

賈德先前引用的研究表明，專業人士完全看不到鋰引起的殘疾，這些殘疾對朋友來說是顯而易見的，並且可以通過心理測試檢測到。 由於藥物令人著迷，患者自己很難評估他們對鋰的精神狀態。 毒性通常會在數天或數週內緩慢上升，以至於他們的判斷力以幾乎難以察覺的漸進方式受損。事實上，不能依靠患者注意到他們何時變得嚴重中毒，即使症狀包括明顯的胃腸道紊亂、震顫 和精神功能紊亂。 必須仔細監測血液水平並仔細觀察患者，而不是依賴患者的感知。
The previously cited research by Judd demonstrates how professionals utterly fail to see lithium-induced disabilities that are obvious to friends and detectable with psychological testing. Due to medication spellbinding, patients themselves have difficulty evaluating their mental status on lithium. Toxicity often creeps up slowly over many days or weeks so that their judgment is impaired in an almost imperceptibly gradual manner. In fact, patients cannot be relied on to notice when they are becoming severely toxic, even though the symptoms include marked gastrointestinal disturbances, tremor, and disturbed mental functions. Instead of relying on the perceptions of patients, blood levels must be carefully monitored and the patients carefully watched.

為了與這種藥物的迷人效果保持一致，服用小劑量的正常志願者會出現反射損傷，但沒有意識到或承認這種損傷（Linnoila 等，1974）。 報告沒有副作用的鋰患者通常有非常明顯的震顫。 維持治療的患者未能注意到自己的神經系統缺陷清楚地表明，鋰的長期治療是藥物治療的魅力。
In keeping with this medication spellbinding effect, normal volunteers on small doses suffer impairments of their reflexes but do not realize or acknowledge the impairment (Linnoila et al., 1974). Lithium patients who report no side effects often have grossly obvious tremors. The failure of patients on maintenance therapy to notice their own neurologic defects clearly demonstrates that long-term treatment with lithium is medication spellbinding.

對中樞神經系統的毒性（第 203 頁）
TOXICITY TO THE CENTRAL NERVOUS SYSTEM (p. 203)

認知缺陷的產生
The Production of Cognitive Deficits

現在普遍認為鋰會損害智力功能。 例如，肖等人。 (1987) 發現鋰會損害記憶力和手部運動速度。 Frederick Goodwin 和 Kay Jamison (1990) 在 Manic-Depressive Illness 這本完全從生物精神病學角度撰寫的書中得出結論，鋰確實會導致嚴重的認知障礙。 他們總結了當時的大部分文獻並宣布，
It is now generally accepted that lithium can impair intellectual function. For example, Shaw et al. (1987) found impairments of memory and hand motor speed on lithium. In Manic-Depressive Illness, a book written wholly from a biopsychiatric perspective, Frederick Goodwin and Kay Jamison (1990) nonetheless concluded that lithium does cause serious cognitive impairments. They summarized much of the literature up to that time and declared,

由於該藥物的主要作用是通過中樞神經系統介導的，因此鋰會導致不同類型和嚴重程度的認知障礙也就不足為奇了。 事實上，記憶問題是患者最常報告的鋰治療的副作用之一。 雖然情感疾病本身會導致認知缺陷和對此類缺陷的抱怨，但重要的是要記住，鋰引起的智力功能損害並不少見，並且在許多患者中會導致不依從性。 創造力也會受到影響。 （第 706 頁）
Since the drug’s primary action is mediated through the central nervous system, it is not surprising that lithium can cause cognitive impairments of varying types and degrees of severity. Indeed, memory problems are among the side effects of lithium treatment that patients report most frequently. Although affective illness itself contributes both to cognitive deficits and complaints about such deficits, it is important to bear in mind that impairment of intellectual functioning caused by lithium is not uncommon and, in many patients, leads to noncompliance. Creativity can also be affected. (p. 706)

最近，Stip 等人。 (2000) 總結了關於鋰引起的記憶問題的文獻：“幾項研究表明，服用鋰的雙相情感障礙患者的短期記憶、長期記憶和精神運動速度存在認知障礙。” 他們的研究旨在在一項為期 3 週的雙盲研究中測試鋰對正常受試者的影響。 他們發現，與安慰劑組相比，接受鋰治療的志願者在回憶單詞方面存在長期記憶缺陷。
More recently, Stip et al. (2000) summarized the literature on lithium-induced memory problems: “Several studies have shown cognitive impairment in short-term memory, long-term memory and psychomotor speed in bipolar patients taking lithium.” Their study aimed at testing the effect of lithium in normal subjects in a double-blind, 3-week study. They found that lithium-treated volunteers had long-term memory deficits on recalling words compared to the placebo group.

急性器質性腦綜合徵（第 204 頁）
Acute Organic Brain Syndromes (p. 204)

考慮到鋰被大力宣傳為相對沒有壓倒性的精神影響，令人驚訝的是，在常規鋰治療期間，在藥物開始使用後不久就報告了多少中毒性譫妄病例（Johnson 等人，1968 年；Mayfi eld 等人， 1966；Prien 等人，1972；Shopsin 等人，1971；Strayhorn 等人，1977）。 普里恩等人。 （1972 年）發現，在他們高度活躍的類別中，幾乎三分之一的患者出現“嚴重”反應，其中包括一些被描述為“迷失方向、混亂、缺乏連續性思維和理解力下降”的毒性混亂。 鋰具有高度的神經毒性。
Considering how vigorously lithium is promoted as relatively free of overpowering mental effects, it is surprising how many cases of toxic delirium during routine lithium therapy were reported soon after the drug came into use (Johnson et al., 1968; Mayfi eld et al., 1966; Prien et al., 1972; Shopsin et al., 1971; Strayhorn et al., 1977). Prien et al. (1972) found that almost one-third of the patients in their highly active category suffered “severe” reactions, including several with toxic confusion described as “disorientation, confusion, lack of continuity of thought, and reduced comprehension.” Lithium is highly neurotoxic.

沉默：不可逆的鋰誘導神經毒性（第 204 頁）
SILENT: Irreversible Lithium-Induced Neurotoxicity (p. 204)

1987 年，Adityanjee 討論了所謂的鋰中毒，並做出了今天仍然正確的觀察：“儘管有相反的證據，但人們普遍缺乏對鋰治療不可逆轉和無法治療的並發症的認識。”
In 1987, Adityanjee discussed so-called lithium poisoning and made an observation that remains true today: “There is a general lack of awareness about irreversible and untreatable complications of lithium treatment despite evidence to the contrary.”

最初，人們認為，除極端情況外，鋰引起的神經毒性是可逆的。然而，最終很明顯，許多患者會出現不可逆的腦損傷和功能障礙，通常涉及小腦（Grignon 等，1996）。在過去的二十年裡，研究人員定義了一種不可逆的鋰效應神經毒性綜合徵 (SILENT)。 Adityanjee 等人。 (2005) 回顧了 1965 年至 2004 年關於鋰神經毒性病例的文獻，這些病例在停止治療後持續存在至少 2 個月的後遺症。他們發現了 90 例 SILENT，其中持續性小腦功能障礙是最常報告的持續性後遺症。這些慢性殘疾患者可能需要“步態共濟失調的身體康復、構音障礙的言語訓練以及癡呆和記憶障礙的認知訓練”（第 47 頁）。這組作者說，最可能的原因是“鋰在神經系統多個部位引起的脫髓鞘，包括小腦。”毫不奇怪，鋰中毒還會導致慢性神經心理變化，包括記憶力、注意力、執行控制功能和視覺空間缺陷（Brumm 等，1998）。
Originally, it was thought that, except in extreme cases, lithium-induced neurotoxicity was reversible. However, it eventually became apparent that many patients develop irreversible brain damage and dysfunction, often involving the cerebellum (Grignon et al., 1996). In the last two decades, researchers have defined a syndrome of irreversible lithium-effectuated neurotoxicity (SILENT). Adityanjee et al. (2005) reviewed the literature from 1965 to 2004 for cases of lithium neurotoxicity with the persistence of sequelae for at least 2 months after cessation of treatment. They found 90 cases of SILENT, with persistent cerebellar dysfunction as the most commonly reported persistent aftereffect. These chronically disabled patients may need “physical rehabilitation for gait ataxia, speech training for dysarthria, and cognitive training for dementia and memory impairments” (p. 47). The most likely cause, according to the authors, is “demyelination caused by lithium in multiple sites in the nervous system, including the cerebellum.” Not surprisingly, lithium toxicity can also cause chronic neuropsychological changes, including impaired memory, attention, executive control functions, and visuospatial deficits (Brumm et al., 1998).

在相對較低的血清劑量下會發生不可逆的神經毒性。 Lang 和 Davis (2002) 描述了“一名 44 歲男性的案例，他出現了兩個月的構音障礙、共濟失調和腿部無力病史，同時因雙相情感障礙而服用鋰鹽。” 他有明顯的小腦和錐體功能障礙。 他的血清鋰為 1.5 mmol/L，對於該患者來說是中度升高。 他的恢復只是部分的，主要是小腦性共濟失調。 作者警告說，在常規治療過程中會出現持續的神經毒性。
Irreversible neurotoxicity can occur at relatively low serum doses. Lang and Davis (2002) described “the case of a 44 year old man who presented with a two-month history of dysarthria, ataxia and leg weakness whilst on maintenance lithium for bipolar disorder.” He had significant cerebellar and pyramidal dysfunction. His serum lithium was 1.5 mmol/L, a moderate elevation for this patient. His recovery was only partial, leaving him mainly with cerebellar ataxia. The authors warned about the insidious onset of persistent neurotoxicity during routine treatment.

低劑量維持治療中的神經毒性作用（第 205 頁）
Neurotoxic Effects in Low-Dosage Maintenance Therapy (p. 205)

布蘭奇等人。 (1976) 發表了對長期鋰維持（6 個月至 7 年）患者的隨訪。 36 人中只有 10 人“沒有神經系統症狀”，即使使用了低維持劑量。 36 名患者中有 4 名出現“低嚴重程度”的帕金森症狀。
Branchey et al. (1976) published a follow-up of patients on long-term lithium maintenance (6 months to 7 years). Only 10 of 36 were “free of neurologic symptoms,” even with the low maintenance doses employed. Four of 36 patients had parkinsonian symptoms at a “low level of severity.”
常規鋰療法產生的異常腦電波（第 205 頁）
Abnormal Brain Waves Produced by Routine Lithium Therapy (p. 205)

從早期開始，腦電圖 (EEG) 就被發現對鋰療法有顯著的病理反應，證實了藥物的致醉作用 (Baldessarini, 1977; Corcoran et al., 1949; Mayfi eld et al., 1966; Peach, 1975 ；Schou，1957 年；Small 等人，1972 年）。 與大腦致殘原則一致，Mayfield 和 Brown (1966) 將 EEG 異常與治療的治療反應聯繫起來。 穆勒-歐林豪森等人。 (1977) 報告了患者和正常志願者的腦電波模式嚴重異常。 在停止鋰治療 7 天后的最後一次測試中，這些情況在志願者中持續存在。
From early on, the electroencephalogram (EEG) was found to demonstrate significant pathologic response to lithium therapy, confirming the intoxicating effect of the drug (Baldessarini, 1977; Corcoran et al., 1949; Mayfi eld et al., 1966; Peach, 1975; Schou, 1957; Small et al., 1972). Consistent with the brain-disabling principle, Mayfield and Brown (1966) correlated EEG abnormalities with the therapeutic response to treatment. Muller-Oerlinghausen et al. (1977) reported grossly abnormal brain wave patterns in patients and normal volunteers. These persisted in the volunteers at the final testing 7 days after the withdrawal of lithium therapy.

兩篇評論文章證實了鋰治療患者腦電波持續變化的報導（Friedman 等人，1977 年；Reisberg 等人，1979 年）。 Reisberg 和 Gershon (1979) 在完全沒有證據的情況下宣稱“有證據表明這些影響是良性的”。
Two review articles confirmed reports of persistent brain wave changes in patients treated with lithium (Friedman et al., 1977; Reisberg et al., 1979). Reisberg and Gershon (1979) declared, wholly without proof, that “the evidence is that these effects are benign.”

因為一些研究表明在認知測試期間被診斷患有雙相情感障礙的患者的功能成像發生了變化，Bell 等人。 (2005) 試圖區分藥物的影響。 他們使用功能性 MRI 對服用鋰或丙戊酸鹽的志願者進行了一項雙盲研究。 兩個藥物組均顯示血氧水平依賴性（BOLD）信號的幅度顯著降低。 作者將這些變化與許多鋰研究中測量的認知功能障礙聯繫起來。
Because some studies had shown changes in functional imaging in patients diagnosed with bipolar disorder during cognitive testing, Bell et al. (2005) sought to separate out the influence of medication. They conducted a double-blind study of volunteers taking lithium or valproate using functional MRI. Both medication groups showed a significant decrease in the magnitude of the blood-oxygen-level-dependent (BOLD) signal. The authors linked these changes to the cognitive dysfunction measured in many studies of lithium.
受損大腦的鋰破壞（第 206 頁）
Lithium Disruption of the Compromised Brain (p. 206)

與精神安定藥，尤其是氟哌啶醇合用時，出現有時不可逆的嚴重腦病綜合徵的可能性增加（Baldessarini，1978；Cohen 等，1974）。 有一個案例報告稱鋰與較新的精神安定藥利培酮結合會產生類似的反應（Swanson 等，1995）。
In combination with neuroleptics, especially haloperidol, there is an increased likelihood of severe encephalopathic syndromes that are sometimes irreversible (Baldessarini, 1978; Cohen et al., 1974). There is a case report of a similar reaction from combining lithium with the newer neuroleptic, risperidone (Swanson et al., 1995).

鋰與電擊結合使用會產生更嚴重的急性器質性腦綜合徵（Weiner 等，1980）。 Remick (1978) 和 Hoenig 和 Chaulk (1977) 報告了由這種組合引起的急性、嚴重譫妄的單個病例。 曼德爾等人。 (1980) 報導了另外兩個這種性質的案例。 1980 年，Small 等人。 回顧了 25 名在接受鋰治療時接受電擊的患者，發現這些患者有更嚴重的記憶喪失、更嚴重的精神錯亂和偶爾的神經功能障礙。 作者建議不要在接受鋰療法的患者中使用電休克療法 (ECT)。
Lithium administered in combination with electroshock produces more severe acute organic brain syndromes (Weiner et al., 1980). Remick (1978) and Hoenig and Chaulk (1977) reported single cases of an acute, severe delirium resulting from this combination. Mandel et al. (1980) reported on two more cases of this nature. In 1980, Small et al. reviewed 25 patients given electroshock while being treated with lithium and found that the patients had more severe memory loss, more severe confusion, and occasional neurologic dysfunctions. The authors recommended against the use of electroconvulsive therapy (ECT) in patients receiving lithium therapy.

關於對患有腦部疾病的個體進行鋰給藥的文獻很少，但表明腦部殘疾的預期增加，包括老年人（Baldessarini，1978 年）。
The literature concerning lithium administration to individuals with preexisting brain disease is sparse but indicates the expected increase in brain disability, including in the elderly (Baldessarini, 1978).

Beitman (1978) 描述了鋰治療導致遲發性運動障礙重新激活的案例； 遲發性運動障礙多年來一直處於靜止狀態。 Crews 和 Carpenter (1977) 還描述了鋰加重了先前存在的遲發性運動障礙的案例。
Beitman (1978) described a case of reactivation of tardive dyskinesia as a result of lithium therapy; the tardive dyskinesia had been quiescent for many years. Crews and Carpenter (1977) also described a case in which lithium aggravated a preexisting tardive dyskinesia.

腦損傷作為治療（第 206 頁）
BRAIN DAMAGE AS TREATMENT (p.206)
對神經元和其他細胞的一般毒性
General Toxicity to Neurons and Other Cells

Peach (1975) 從藥理學家而不是精神病學家的角度寫作：
Writing from the viewpoint of the pharmacologist, rather than the psychiatrist, Peach (1975) observed:

可以設想，鋰在細胞內環境中的積累會擾亂任何受單價陽離子（例如鈉或鉀）調節的事件。 這些可能的相互作用表明確定鋰離子精確作用機制的任務艱鉅。
The accumulation of lithium in the intracellular environment could be envisioned to perturb any event that is modulated by monovalent cations, e.g., sodium or potassium. These possible interactions signify the enormous magnitude of the task of determining precise mechanisms of action of the lithium ion.

鋰幾乎破壞了與神經傳遞以及許多其他重要功能有關的所有可測量的細胞活動。 此外，它在整個中樞神經系統中的分佈相當均勻，沒有已知的特定濃度區域。 它產生了什麼威爾遜等人。 （1975）稱為神經元活動的非選擇性減少。
Lithium disrupts almost every measurable cellular activity pertaining to nerve transmission as well as many other vital functions. In addition, its distribution is fairly uniform throughout the central nervous system, with no known areas of specific concentration. It produces what Wilson et al. (1975) called a nonselective diminution in neuronal activity.

即使沒有臨床數據支持，鋰的神經生理學也使針對特定疾病的特定生化治療的概念變得荒謬，並證實了大腦致殘效應。
The neurophysiology of lithium, even without supporting clinical data, renders absurd the notion of a specific biochemical treatment for a specific disease and confirms the brain-disabling effect.

由於其神經毒性影響，鋰似乎會增加服用抗精神病藥的患者發生遲發性運動障礙的風險（Ghadirian 等人，1996 年）。 與此一致，有報導稱服用鋰但未使用安定藥的患者出現錐體外系症狀，包括帕金森症（Lecamwasam 等人，1994 年）、舞蹈症（Podskalny 等人，1996 年）、遲發性帕金森症（Muthane 等人，2000 年） 、遲發性肌張力障礙 (Chakrabarti et al., 2002) 和遲發性運動障礙 (Meyer-Lindenberg et al., 1997)。 許多研究都發現了維持鋰存在錐體外系副作用（例如，Kane 等人，1978 年；Shopsin 等人，1975 年）。 Shopsin 和 Gershon (1975) 的患者，如 Branchey 等人的患者。 （1976 年），沒有抱怨他們的神經系統症狀，這表明進一步的精神障礙和深刻的藥物引人入勝的效果。
Because of its neurotoxic impact, lithium appears to increase the risk of tardive dyskinesia for patients taking neuroleptics (Ghadirian et al., 1996). Consistent with this, there have been reports of extrapyramidal symptoms in patients taking lithium without neuroleptic exposure, including parkinsonism (Lecamwasam et al., 1994), chorea (Podskalny et al., 1996), tardive parkinsonism (Muthane et al., 2000), tardive dystonia (Chakrabarti et al., 2002), and tardive dyskinesia (Meyer-Lindenberg et al., 1997). The existence of extrapyramidal side effects on maintenance lithium has been found in numerous studies (e.g., Kane et al., 1978; Shopsin et al., 1975). Shopsin and Gershon’s (1975) patients, like those of Branchey et al. (1976), did not complain about their neurologic symptoms, suggesting further mental impairment and a profound medication spellbinding effect.

鋰還會損害周圍神經系統的功能，降低運動神經傳導速度（Faravelli 等，1999）。 它會引起許多代謝不良反應，導致甲狀腺功能減退、甲狀腺功能亢進（罕見）、甲狀旁腺功能亢進和尿崩症（Livingston 等，2006）。
Lithium also impairs the function of the peripheral nervous system, reducing motor nerve conduction velocity (Faravelli et al., 1999). It causes many metabolic adverse effects, resulting in hypothyroidism, hyperthyroidism (rare), hyperparathyroidism, and diabetes insipidus (Livingston et al., 2006).

精神病學已經從否認鋰會導致腎臟損害到試圖忽略它。 威脅是非常真實的。 Lepkifker 等人。 （2004 年）回顧了 140 名接觸鋰至少 4 年的患者的文件，發現 20% 的患者出現了肌酐蠕變（腎功能不全的實驗室測試）和腎功能不全。 總的來說，鋰對細胞的毒性很大（Yao et al., 1999）。
Psychiatry has gone from denying that lithium causes kidney damage to trying to ignore it. The threat is very real. Lepkifker et al. (2004) reviewed the fi les of 140 patients exposed to lithium for at least 4 years and found that 20% developed creeping creatinine (a laboratory test for kidney malfunction) and renal insufficiency. Overall, lithium is very toxic to cells (Yao et al., 1999).

The “Protective” and Therapeutic Effects of Poisoning Brain Cells (p. 207)
越來越多的精神科藥物已被證明會導致腦細胞異常增殖。 這個過程是不正常的，首先是因為它是由藥物的毒性影響引起的； 第二，因為已知藥物會對腦細胞和身體的許多器官造成許多臨床上明顯的毒性作用； 第三是因為細胞的數量和形態異常。 然而，研究人員在情感和經濟上如此依賴精神藥物複合體，以至於許多人堅持將這些異常視為特定治療機制的證據。 Lagace 和 Eisch (2005) 回顧了情緒穩定劑的所謂神經保護作用，包括鋰、丙戊酸、卡馬西平和抗精神病藥。 研究了兩種不同的影響：由情緒穩定劑引起的神經保護和神經源性變化。
An increasing number of psychiatric drugs have been shown to cause abnormal proliferations of brain cells. The process is abnormal, first, because it is caused by the toxic impact of a drug; second, because the drugs are already known to cause many clinically obvious toxic effects on brain cells and many organs of the body; and third because the number and morphology of the cells are abnormal. Yet researchers are so dependent on the psychopharmaceutical complex, both emotionally and economically, that many persist in seeing these abnormalities as evidence of a specific therapeutic mechanism. Lagace and Eisch (2005) reviewed the so-called neuroprotective effects of mood-stabilizing agents, including lithium, valproic acid, carbamazepine, and neuroleptics. Two separate effects were studied: neuroprotective and neurogenic changes caused by mood stabilizers.

首先，這些藥物對細胞培養物發揮所謂的保護作用，防止細胞因某些創傷而死亡。例如，通過將大鼠固定在玻璃管中來對其施加壓力（Lim 等，2005）。這會導致腦細胞對電刺激的反應發生變化，正如在被斬首動物的死後大腦中所測量的那樣。如果在死後 1 小時，將動物的大腦切片浸泡在鋰中，則大腦不會因刺激而發生變化。令人難以置信的是，包括 Lagace 和 Eisch（2005 年）在內的研究人員在動物腦切片中發現的這一實驗室發現表明這種死後保護可能與這些藥物在活人中的臨床效果有關。別介意鋰，例如，對人體中樞神經系統和周圍神經系統有劇毒，對腦細胞是一種虛擬毒藥；儘管如此，培養皿中的這種怪癖可能表明這些藥物可以保護腦細胞。
First, these drugs exert a so-called protective effect on cell cultures, preventing cell death from occurring in response to certain trauma. For example, a rat is stressed by immobilizing it in a glass tube (Lim et al., 2005). This causes changes to take place in the responsiveness of brain cells to electrical stimulation, as measured in the decapitated animal’s postmortem brain. If 1 hour after death, slices of the animal’s brain are bathed in lithium, the brain changes in response to stimulation do not occur. Unbelievably, this laboratory finding in animal brain slices has been leaped on by researchers, including Lagace and Eisch (2005), as an indication that this postmortem protection may have something to do with the clinical effect of these drugs in living human beings. Never mind that lithium, for example, is extremely toxic to the human central nervous system and peripheral nervous system, a virtual poison to brain cells; this quirk in a Petri dish may nonetheless show that these drugs protect brain cells.

其次，這些藥物會產生異常的細胞生長。 研究人員稱這個過程為神經發生，就好像它是良性的。 但神經元外觀不正常。 根據 Lagace 和 Eisch (2005)，
Second, these drugs produce abnormal cell growth. The researchers call this process neurogenesis as if it were benign; but the neurons are not normal in appearance. According to Lagace and Eisch (2005),

一般來說，這些研究評估了神經元增殖、神經突[軸突]生長、再生和分化。 在感覺神經元中，鋰、丙戊酸和卡馬氮平具有增加錐體形成生長的共同作用，導致神經元的擴散和較短的神經元軸突。 . . . 最近，鋰已被證明可誘導 rap 海馬祖細胞的增殖和神經元分化。 . . . 與鋰一樣，丙戊酸治療已被證明在體外誘導神經發生，特別是誘導神經突生長、細胞重新出現和胚胎皮質細胞中成熟神經元的形成。
In general, these studies have assessed neuron proliferation, neurite [axonal] outgrowth, regeneration, and differentiation. In sensory neurons, lithium, valproic acid, and carbamazapine have a common effect of increasing growth of cone formation, leading to a spreading of the neuron and a shorter neuronal axon. . . . Recently, lithium has been shown to induce proliferation and neuronal differentiation of rap hippocampal progenitor cells. . . . Like lithium, valproic acid treatment has been shown to induce neurogenesis in vitro, specifically inducing neurite growth, cell reemergence, and the formation of mature neurons in embryonic cortical cells.

這些作者比其他作者更持懷疑態度。 他們不想完全飛躍到臨床治療效果。 但他們希望：“為了確定情緒穩定藥物的臨床療效是否取決於這些藥物的神經保護或神經源性特性，需要在將細胞培養和動物模型的發現與人體成像和病理學相關聯方面取得更大的進展。 ” 基於最脆弱的實驗基礎，為了促進更良性的效果，鋰的明顯的大腦功能障礙、情緒平緩作用被忽略了。
These authors are a little more skeptical than others; they do not want to make the complete leap to clinical, therapeutic effects. But they are hoping: “To determine if the clinical efficacy of mood-stabilizing drugs is dependent on the neuroprotective or neurogenic properties of these medications, greater strides need to be made in relating findings from cell culture and animal models to human imaging and pathology.” The obvious brain-disabling, mood-flattening effects of lithium are ignored in the interest of promoting a more benign effect based on the most flimsy experimental grounds.

陳(Chen)等人。 (2000) 給老鼠餵食鋰，達到與人類治療相當的血液水平，並發現海馬中的腦細胞增殖。 他們躍躍欲試地聲稱這種神經營養作用可能使鋰“用於其他神經精神疾病的長期治療”。 換句話說，刺激大腦製造異常的腦細胞，很可能對各種精神疾病都有好處。 這種完全無視鋰的明顯毒性作用的巨大飛躍，在文獻中已屢見不鮮。
Chen et al. (2000) gave lithium to rats in their chow, achieving blood levels comparable with human treatment, and found a proliferation of brain cells in the hippocampus. They made the leap to claim that this neurotrophic effect may make lithium “of use in long-term treatment of other neuropsychiatric disorders.” In other words, stimulating the brain to make abnormal brain cells is likely to be good for a variety of psychiatric disorders. This kind of giant leap, utterly ignoring the obvious toxic effects of lithium, has become common in the literature.

並非所有研究人員都如此迅速地假設任何藥物引起的腦細胞異常生長都會對人類有益。 原田等人。 （1996 年）著手“了解鋰的神經毒性機制”。 他們發現鋰會損害大鼠細胞中神經生長因子的功能。 在這樣做的過程中，它導致了鋰處理細胞中出現的一些異常，包括神經突生長減弱。
Not all researchers are so quick to assume that any drug-induced abnormal growth in brain cells will be beneficial to human beings. Harada et al. (1996) set out to “understand the mechanism underlying the neurotoxicity of lithium.” They found that lithium impaired the function of nerve growth factor in rat cells. In doing so, it caused some of the abnormalities seen in lithium treated cells, including attenuated neurite growth.

與此同時，這些研究人員並沒有想到鋰會導致明顯的記憶功能障礙，而海馬體在記憶過程中起著重要作用，這表明他們正在研究鋰是如何傷害大腦的，而不是它如何幫助大腦。事實上，有研究解決了鋰對生化過程的影響，這些生化過程特別影響了記憶和空間辨別等心理功能。 Banchaabouchi 等人。 (2004) 給大鼠鋰 4 週以達到典型的人類治療血清水平。這導致海馬體中與認知過程（Nurr 1）相關的生化因子受到抑制，並且還導致動物空間辨別力受損。 （Nurr 1 也在多巴胺細胞功能中發揮作用，並且可能在帕金森症的發展中起作用，Zetterstrom 等人，1997；Nurr 1 中鋰誘導的功能障礙可能與藥物引起多巴胺相關神經系統疾病的能力有關，例如帕金森症。）
Meanwhile, it does not occur to these researchers that lithium causes demonstrable memory dysfunction and that the hippocampus plays a major role in memory processes, suggesting instead that they were looking at how lithium harms the brain—and not how it might help it. Indeed, there is research that addresses the effect of lithium on biochemical processes that specifically affect mental functions such as memory and spatial discrimination. Banchaabouchi et al. (2004) gave rats lithium for 4 weeks to reach a typical human therapeutic serum level. This resulted in a suppression of a biochemical factor in the hippocampus associated with cognitive processes (Nurr 1) and also resulted in impairment of spatial discrimination in the animal. (Nurr 1 also plays a role in dopamine cell function and perhaps in the development of parkinsonism, Zetterstrom et al., 1997; lithium-induced dysfunction in Nurr 1 may be associated with the drug’s capacity to cause dopamine-related neurological disorders, such as parkinsonism.)

情緒穩定劑刺激異常細胞生長的發現與研究表明服用鋰和丙戊酸的雙相情感障礙患者在 MRI 上測量的海馬區域增加。 拜爾等人。 (2004) 發現海馬體大小的增加與鋰的使用相關。 他們還將其與神經發生的實驗室研究聯繫起來。
The finding of abnormal cell growth stimulated by mood stabilizers is consistent with research showing that bipolar patients taking lithium and valproic acid have increased hippocampal regions measured on MRI. Beyer et al. (2004) found that this increase in hippocampal size correlated with the use of lithium. They also related it to the laboratory studies of neurogenesis.

當然，文獻中有許多相互矛盾的發現，但很明顯，暴露於情緒穩定劑，尤其是鋰，會嚴重損害大腦的功能，在某些情況下甚至會導致細胞異常增殖，而在另一些情況下會導致細胞丟失（Blumberg 等人，2003）。 精神科學中的扭曲思維如此猖獗，以至於沒有一項研究將這些最近記錄的細胞生長和大腦大小異常視為引起恐慌的原因。 相反，它們被自動提升為利益的證據和希望的原因。
There are, of course, many contradictory findings in the literature, but it is apparent that exposure to mood stabilizers, especially lithium, profoundly impairs the function of the brain, even causing abnormal cell proliferation in some cases, and cell loss in others (Blumberg et al., 2003). The distorted thinking in the psychiatric sciences is so rampant that none of the studies view these recently documented abnormalities in cell growth and brain size as a cause for alarm. Instead, they are automatically promoted as evidence of benefit and cause for hope.

鋰在急性躁狂症中的相對無效性（第 210 頁）
THE RELATIVE INEFFECTIVENESS OF LITHIUM IN ACUTE MANIA (p. 210)

鋰特異性的神話在人們期望找到最多支持的領域被打破：正如其倡導者所描述的臨床使用。 早期，人們普遍認為，在停止急性躁狂症方面，安定藥而不是鋰最有效（Baldessarini，1978；Juhl 等，1977）。 即使隨著抗精神病藥-鋰聯合療法的發展，一些權威人士也提倡使用 ECT 來控制特別嚴重的病例（Hollister，1976 年）。
The myth of lithium specificity is shattered in exactly that arena in which one would expect to find the most support: clinical use as described by its advocates. Early on, it became generally accepted that the neuroleptics, not lithium, are most effective in stopping acute mania (Baldessarini, 1978; Juhl et al., 1977). Even with the development of combined neuroleptic–lithium therapy, some authorities advocate ECT, as well, for the control of especially severe cases (Hollister, 1976).

對精神抑製藥作為急性躁狂治療的臨床偏好是基於一項最全面的對照研究，該研究由 Prien 等人進行。 （1972）。 他們特別反駁了鋰對躁狂症或“潛在的躁狂症過程”有任何特異性的論點。 他們警告說，“不幸的是，這些觀察結果幾乎消失在大量對碳酸鋰療法的不合格認可中，這些認可淹沒了文獻。” 亞歷山大等人。 （1979 年）和 Growe 等人。 (1979) 還認為鋰對躁狂症沒有疾病特異性。
The clinical preference for the neuroleptics as the treatment for acute mania was based on the single most comprehensive, controlled study, which was conducted by Prien et al. (1972). They specifically contradicted the thesis that lithium has any specificity for mania or the “underlying manic process.” They cautioned that “unfortunately, these observations have been all but lost in the vast number of unqualified endorsements of lithium carbonate therapy that have deluged the literature.” Alexander et al. (1979) and Growe et al. (1979) also opined that lithium is not disease-specific for mania.

過去，關於使用鋰控制暴力的文章很多（Fieve，1989；Marini 等，1977；Micer 等，1974；Morrison 等，1973；Sheard 等， 1976 年，在 Breggin 中審查，1983b)。 雖然這些說法尚未得到證實，但他們再次關注將鋰用於各種目的的趨勢。
In the past, a great deal was written about the use of lithium for the control of violence (Fieve, 1989; Marini et al., 1977; Micer et al., 1974; Morrison et al., 1973; Sheard et al., 1976, reviewed in Breggin, 1983b). While these claims have not been confirmed, they focus once again on the tendency to use or advocate lithium for a variety of purposes.

鋰在預防躁狂發作方面的效果如何？
HOW EFFECTIVE IS LITHIUM IN PREVENTING THE RECURRENCE OF MANIC EPISODES?

鋰在精神病學領域和公眾中被大力推廣，作為一種預防躁狂症復發的方法，很少有從業者或消費者懷疑它的功效。 實際上，鋰在這方面的有效性仍然值得懷疑。 在鋰普及的高峰期，Prien 等人。 (1974) 回顧了文獻，發現研究表明在鋰預防性治療期間的 2 年內復發率高達 50%。 鋰確實減少了有不經常發作史的患者的躁狂發作次數。 但在過去躁狂發作率高的患者中，鋰鹽的效果並不比安慰劑好，並且該組中的所有患者最終都復發了。 如果鋰是一種針對疾病的治療方法，它肯定會比這表現得更好。
Lithium has been promoted so strongly within psychiatry and to the public as a method of preventing recurrences of mania that few practitioners or consumers doubt its efficacy. In reality, lithium’s effectiveness in this regard remains questionable. At the height of lithium’s popularity, Prien et al. (1974) reviewed the literature and found that studies showed a relapse rate as high as 50% over 2 years during lithium prophylactic treatment. Lithium did reduce the number of manic episodes in patients who had a history of infrequent attacks. But in patients with a high rate of past manic episodes, lithium did no better than placebo, and all patients in this group eventually relapsed. If lithium were a disease-specific treatment, it surely would have performed better than this.

持續的研究更加令人沮喪。 吉特林等人。 (1995) 對接受鋰治療的雙相情感障礙患者進行了一項前瞻性研究。 仔細監測患者的有效藥物治療。 儘管如此，73% 的患者在 5 年內再次出現躁狂症或抑鬱症。 在復發的人中，三分之二有多次發作。 即使在那些沒有完全復發的患者中，也有許多人遭受了嚴重的情緒困擾。 作者得出結論，“即使是積極的藥物維持治療也不能防止大量雙相情感障礙患者的相對較差的結果”（第 1635 頁）。
Continuing research has been even more discouraging. Gitlin et al. (1995) conducted a prospective study of patients treated with lithium for bipolar disorder. The patients were carefully monitored for effective drug treatment. Despite this, 73% of the patients relapsed into mania or depression within 5 years. Of those who relapsed, two-thirds had multiple episodes. Even among those patients who did not completely relapse, many suffered serious emotional difficulties. The authors concluded, “even aggressive pharmacological maintenance treatment does not prevent relatively poor outcome in a significant number of bipolar patients” (p. 1635).

鋰戒斷反應引起的躁狂和抑鬱（第 211 頁）
MANIA AND DEPRESSION AS LITHIUM WITHDRAWAL REACTIONS (p. 211)

儘管業內很少注意到這種現象，但我記得我自己的病人告訴我他們在鋰戒斷期間遭受的痛苦情緒反應。 現在有大量證據表明鋰戒斷引起的嚴重不良精神影響。
Although little notice was given of the phenomenon within the profession, I recall my own patients telling me about painful emotional reactions that they suffered during lithium withdrawal. The evidence is now substantial in regard to serious adverse psychiatric effects caused by lithium withdrawal.

蘇佩斯等人。 (1991) 分析了 14 項研究，發現停止使用鋰後躁狂症的複發率增加。 這些患者傾向於每年大約一次（平均 11.6 個月）進入躁狂症，在停止服藥後不到 2 個月（平均 1.7 個月）就出現了新的發作。 換句話說，與未接受治療的患者相比，停止使用鋰治療會產生更快的躁狂發作。
Suppes et al. (1991) analyzed 14 studies and found that the rate of relapse into mania increased following the discontinuation of lithium. The patients, who tended to cycle into mania about once a year (mean 11.6 months), developed a new episode less than 2 months (mean 1.7 months) after stopping their medication. In other words, discontinuation of treatment with lithium produced a much more rapid onset of mania than the untreated patients would have endured.

許多研究現已證實，從鋰中撤出會導致不良的精神反應。 卡瓦納等人。 （2004 年），在 7 年的隨訪中，發現鋰戒斷會導致躁狂和抑鬱。 他們總結說：“這些結果證實，鋰的急性停藥會導致較高的即刻復發率。” 然而，他們沒有發現這證明鋰的繼續存在是合理的。 相反，“結果並未因停藥而惡化。”
Numerous studies have now confirmed that withdrawal from lithium causes adverse psychiatric reactions. Cavanagh et al. (2004), in a 7-year follow-up, found that lithium withdrawal caused both mania and depression. They concluded, “These results confirm that acute discontinuation of lithium leads to a high immediate relapse rate.” However, they did not find that this justified the continuation of lithium. To the contrary, “outcome was not worsened by discontinuation.”

不幸的是，服用鋰後很快復發的患者很少（如果有的話）被告知他們的複發可能是由鋰戒斷引起的。 相反，他們被告知新的躁狂發作證明需要在他們的餘生中服藥。
Unfortunately, patients who relapse soon after taking lithium are rarely, if ever, told that their relapse was probably caused by lithium withdrawal. Instead, they are told that the new manic episode proves the need to take the medication for the rest of their lives.

許多精神科醫生建議被診斷為躁鬱症或躁狂症的患者必須服用鋰多年，甚至終生服用。 他們被告知不這樣做是不負責任的。 家庭和心理治療師被迫敦促或強迫患者服用鋰。 數據並未證實對這種藥物的強烈宣傳。
Many psychiatrists advise patients who are diagnosed bipolar or manic that they must take lithium for many years, or even for the rest of their lives. They are told that it is irresponsible for them not to do so. Families and psychotherapists are pressured to urge or coerce patients to take their lithium. The data do not confirm this strong advocacy for the drug.

基於大腦傾向於對抗大腦中的精神干擾的一般觀察，任何用於控制躁狂症的藥物都應被視為在戒斷期間有可能引起躁狂症。 例如，傑西等人。 （2004 年）描述了一個在卡馬西平戒斷期間出現反彈躁狂症的案例。
On the basis of the general observation that the brain tends to fight back against psychoactive interferences in the brain, any medication used to control mania should be viewed as having the potential to cause mania during withdrawal. For example, Jess et al. (2004) described a case of rebound mania during withdrawal from carbamazepine.

鋰退出的其他不良反應（第 212 頁）
OTHER ADVERSE REACTIONS TO LITHIUM WITHDRAWAL (p. 212)

Swartz 和 Jones (1994) 回顧了文獻並介紹了三個案例，這些案例涉及在常規治療期間血清水平升高的患者中突然停用鋰引起的嚴重且經常持續的不良反應。 其中一名患者嚴重癡呆。
Swartz and Jones (1994) reviewed the literature and presented three cases concerning severe and often persistent adverse reactions to the abrupt withdrawal of lithium in patients suffering from elevated serum levels during routine treatment. One of the patients became severely demented.

在對威斯康星大學鋰信息中心獲得的 50 例病例進行審查時，他們發現許多患者在突然停止使用鋰時會變得精神錯亂或嚴重惡化。 因鋰中毒而接受腎透析的患者通常精神惡化，鋰水平迅速下降。 50 名患者中有 30% 存在神經系統後遺症。 作者發現，從高鋰水平快速撤出患者有很大的神經毒性風險。
In their review of 50 cases obtained from the Lithium Information Center of the University of Wisconsin, they found that many patients became demented or otherwise deteriorated severely when abruptly withdrawn from lithium. Patients subjected to kidney dialysis for lithium toxicity often deteriorated mentally with a rapid drop in lithium levels. Neurologic sequelae persisted in 30% of the 50 patients. The authors found substantial neurotoxic risks in rapidly withdrawing patients from high lithium levels.

如果從高鋰水平快速戒斷會產生躁狂症並使神經系統反應失效，那麼從低鋰水平快速戒斷很可能會產生更微妙的不良反應。
If rapid withdrawal from high lithium levels can produce mania and disable neurologic reactions, then it is probable that rapid withdrawal from lower levels may produce more subtle adverse reactions.

飲用水中的鋰（第 212 頁）
LITHIUM IN YOUR DRINKING WATER (p. 212)

1970 年，道森等人。 試圖支持一個奇妙的論點：降雨量增加會稀釋水庫中的某些礦物質，包括鋰，從而在降雨量較少的地區、飲用水中鋰含量較高的地區以及以住院人數衡量的較低的精神疾病發病率之間產生相關性。 在 Psychiatric Drugs (1983b) 中，我檢查並揭穿了這項研究及其各種支持者（參見 Fieve，1989；“In Texas，”1971）。 研究人員建議在飲用水中加入鋰，就像飲用水被氟化一樣。 也許這是荒謬聲稱的邏輯延伸，即精神病治療可以糾正生化失衡而不會對大腦產生不利影響。
In 1970, Dawson et al. tried to support a fantastic thesis: Increased rainfall dilutes certain minerals in reservoirs, including lithium, producing a correlation between areas of lesser rainfall, higher lithium levels in drinking water, and a lower incidence of mental illness as measured by hospital admissions. In Psychiatric Drugs (1983b), I examined and debunked the study and its various supporters (see Fieve, 1989; “In Texas,” 1971). The researchers recommended putting lithium in the drinking water, much like drinking water has been fluoridated. Perhaps this is the logical extension of absurd claims that psychiatric treatments correct biochemical imbalances without adversely affecting the brain.

其他所謂的情緒穩定劑（第 213 頁）
OTHER SO-CALLED MOOD STABILIZERS (p. 213)

三種抗癲癇藥物現已被 FDA 批准作為情緒穩定劑，用於預防反復發作的躁狂症：雙丙戊酸鈉（Depakote）、緩釋卡馬西平（Equetro）和拉莫三嗪（Lamictal）。 這些藥物中有許多是給兒童開的，用於控制癲癇，並且越來越多地用於雙相情感障礙。 一個關鍵問題是它們對兒童發展的心理和情感功能的影響，但對該主題的研究很少（Loring，2005）。
Three antiepileptic drugs have now been FDA approved as mood stabilizers for the prevention of recurring episodes of mania: divalproex sodium (Depakote), extended-release carbamazepine (Equetro), and lamotrigine (Lamictal). Many of these drugs are prescribed to children for the control of epilepsy and, increasingly, for bipolar disorder. A critical question is their effect on the developing mental and emotional function of children, but there is little research on the subject (Loring, 2005).

丙戊酸（Depakene）、丙戊酸鈉（Depakene糖漿）和雙丙戊酸鈉（Depakote，其他兩種腸溶包衣組合）是一種已被 FDA 批准用於治療雙相情感障礙的抗癲癇藥物。 該藥物可能具有肝毒性，尤其是在兒童中。 從大腦功能障礙的角度來看，它會導致鎮靜、震顫和共濟失調。 更罕見的是，它會導致情緒和行為的不利變化，包括行為自動化、攻擊性和混亂。 可能會出現嗜睡或譫妄，尤其是與其他鎮靜劑合用時（Silver 等人，1994 年）。 “長期使用可能會導致認知功能的輕度損害”（Hyman 等，1995，第 127 頁）。 與鋰一樣，丙戊酸會導致很大一部分老年患者出現譫妄（Shulman 等，2005）。 它還會引起多種內分泌失調和代謝變化（Verrotti 等，2005）。 在臨床上，我已經看到這種藥物會導致抑鬱和敵意。
Valproic acid (Depakene), sodium valproate (Depakene syrup), and divalproex sodium (Depakote, enteric-coated combination of the other two) are forms of an antiepileptic agent that has been approved by the FDA for the treatment of bipolar disorder. The drug can be hepatotoxic, especially in children. From the brain-disabling perspective, it can cause sedation, tremor, and ataxia. More rarely, it can cause adverse changes in mood and behavior, including behavioral automatisms, aggression, and confusion. Somnolence or delirium can develop, especially when combined with other sedatives (Silver et al., 1994). There may be “mild impairment of cognitive function with chronic use” (Hyman et al., 1995, p. 127). Like lithium, valproic acid causes delirium in a significant percentage of older patients (Shulman et al., 2005). It also causes a variety of endocrine disorders and metabolic changes (Verrotti et al., 2005). Clinically, I have seen this drug cause depression and hostility.

對大腦和神經系統的影響尚不清楚，有許多研究表明丙戊酸會促進多種具有潛在危險的病毒（例如，Fan 等人，2005）。 丙戊酸和卡馬西平都會導致嬰兒主要先天性畸形發生率小幅增加（Wide 等，2004）。 已經報導了丙戊酸引起的急性和可能致命的胰腺炎（例如，Grauso-Eby 等，2003）。 肝功能衰竭也是一個已知問題。 已知丙戊酸會引起伴有腦病的高氨血症（例如，McCall 等人，2004）。 現在用作情緒穩定劑的所有抗癲癇藥物都可能發生嚴重甚至致命的皮膚病。 丙戊酸和其他情緒穩定劑的各種不良反應並不像醫生認為他們急於讓患者從鋰中切換的那樣良性。
Of as yet unknown consequence to the brain and nervous system, there are many studies indicating that valproic acid promotes a variety of potentially dangerous viruses (e.g., Fan et al., 2005). Both valproic acid and carbamazepine cause a small increase in the rate of major congenital malformations in infants (Wide et al., 2004). Acute and potentially fatal pancreatitis has been reported with valproic acid (e.g., Grauso-Eby et al., 2003). Liver failure is a known problem as well. Valproic acid is known to cause hyperammonemia with encephalopathy (e.g., McCall et al., 2004). Severe and even lethal skin disorders can occur with all of the antiseizure medications now used as mood stabilizers. The various adverse effects of valproic acid and other mood stabilizers are not nearly as benign as physicians believe in their eagerness to switch patients from lithium.

卡馬西平（Tegretol）與三環類抗抑鬱藥密切相關。 在神經醫學中，它的主要用途是作為部分複雜性癲癇發作的抗驚厥藥和治療抽動症（一種面部疼痛綜合徵）。 它會導致與較舊的抗抑鬱藥相似的大腦功能障礙，包括鎮靜、震顫、精神錯亂、抑鬱、精神病和記憶障礙（第 7 章）。 認知障礙更常見於同時使用抗精神病藥、先前存在的腦損傷和衰老（Hyman 等，1995）。 此外，它還構成潛在致命的粒細胞缺乏症或再生障礙性貧血的威脅。 卡馬西平可引起低鈉血症（低血清鈉），導致包括嗜睡、精神錯亂或敵意以及昏迷的綜合徵。
Carbamazepine (Tegretol) is closely related to the tricyclic antidepressants. In neurological medicine, its principal uses are as an anticonvulsant for partial complex seizures and in the management of tic douloureux, a facial pain syndrome. It causes similar brain-disabling effects to the older antidepressants, including sedation, tremor, confusion, depression, psychosis, and memory disturbances (chapter 7). Cognitive disturbances are more common with concomitant use of neuroleptics, with preexisting brain damage, and with aging (Hyman et al., 1995). In addition, it poses the threat of potentially lethal agranulocytosis or aplastic anemia. Carbamazepine can cause hyponatremia (low serum sodium), leading to a syndrome that includes lethargy, confusion or hostility, and stupor.

氯硝西泮 (Klonopin) 是一種苯二氮卓類鎮靜劑，已用於治療急性躁狂症和預防。 它具有與其他苯二氮卓類藥物相關的所有許多、有時是嚴重的問題，包括鎮靜、反彈和戒斷綜合徵、成癮和行為異常（第 12 章）。 抗精神病藥仍然是控制急性躁狂反應的主要藥物。
Clonazepam (Klonopin), a benzodiazepine tranquilizer, has been used to treat both acute mania and as prophylaxis. It has all the many, sometimes severe, problems associated with the other benzodiazepines, including sedation, rebound and withdrawal syndromes, addiction, and behavioral abnormalities (chapter 12). Neuroleptics remain the mainstay for controlling acute manic reactions.

維拉帕米（Calan 等）是一種鈣通道阻滯劑，用於治療心臟疾病，也被用作情緒調節劑。 它可以產生多種心血管副作用。
Verapamil (Calan and others) is a calcium channel blocker used for the treatment of cardiac disorders that has also been used off-label as a mood leveler. It can produce a variety of cardiovascular side effects.

可樂定，一種抗高血壓藥物，也被用於治療躁狂症。 突然停藥可產生反彈性高血壓危象。 符合大腦致殘原則，它會產生多種精神症狀，包括鎮靜、生動的夢或噩夢、失眠、煩躁、焦慮和抑鬱。 更罕見的是，它會引起幻覺。 不幸的是，這種藥物在兒童中被用作所謂的情緒穩定劑太常用了。 當錯誤地使用興奮劑時，它會導致兒童心律失常和心臟驟停的風險增加。
Clonidine, an antihypertensive drug, also has been used in the treatment of mania. Sudden withdrawal can produce a rebound hypertensive crisis. Consistent with the brain-disabling principles, it can produce a variety of psychiatric symptoms, including sedation, vivid dreams or nightmares, insomnia, restlessness, anxiety, and depression. More rarely, it can cause hallucinations. Unfortunately, this drug is too commonly used as a so-called mood stabilizer in children. When mistakenly prescribed with stimulants, it causes an elevated risk of cardiac arrhythmia and cardiac arrest in children.

一些臨床醫生會在雙相情感障礙患者的治療中添加多種抗抑鬱藥，包括百憂解等 SSRIs。 幾乎所有的抗抑鬱藥都會引起或加重躁狂症（第 7 章）。 儘管如此，禮來公司還是成功獲得了 FDA 對 Symbyax 的批准，Symbyax 是 Zyprexa 和 Prozac 的組合，用於治療與雙相情感障礙相關的抑鬱發作。 實際上，考慮到 SSRI 引起和加劇躁狂反應的頻率，不應將百憂解開給雙相情感障礙患者。
Some clinicians will add a variety of antidepressants, including SSRIs like Prozac, to the treatment of patients with bipolar disorder. Nearly all antidepressants can cause or worsen mania (chapter 7). Nonetheless, Eli Lilly managed to obtain FDA approval for Symbyax, a combination of Zyprexa and Prozac, for the treatment of depressive episodes associated with bipolar disorder. In reality, Prozac should not be prescribed to patients with bipolar disorder, given the frequency with which SSRIs cause and exacerbate manic reactions.

一長串試圖替代鋰的嘗試再次表明，它幾乎不是治療躁狂症或雙相情感障礙的特定靈丹妙藥。
The lengthy list of attempts to substitute for lithium suggests, once again, that it is hardly a specific magic bullet for mania or bipolar disorder.

為什麼有這麼多“雙相”患者？ (p. 214)
WHY SO MANY “BIPOLAR ” PATIENTS?

當我接受精神病學培訓時，我們很少看到病人經歷過劇烈的躁狂發作。 一個案子一入院，就會成為大查的題目，供大家看、評。 在精神病院工作近4年的時間裡，我只記得少數這樣的案例。 如今，雙相情感障礙的診斷已成為一種時尚，許多患者在不符合診斷標準的情況下就給了它。 但許多其他病例確實涉及經歷過躁狂發作的患者。 為什麼增加？ 正如我們在第 6 章和第 7 章中看到的，較新的抗抑鬱藥通常會引起躁狂症。
When I was in my psychiatric training, we rarely saw a patient undergoing a fl orid manic episode. When a case was admitted, it would become a subject for grand rounds for everyone to see and evaluate. I can remember only a handful of such cases during nearly 4 years working in psychiatric hospitals. Nowadays, the diagnosis of bipolar disorder has become a fad, and many patients are given it without meeting the diagnostic criteria. But many other cases do involve patients who have undergone maniclike episodes. Why the increase? As we saw in chapters 6 and 7, the newer antidepressant drugs commonly cause mania.

根據美國精神病學協會 (2000) 官方診斷手冊，當患者出現類似躁狂的藥物不良反應時，正確的診斷是物質誘發的情緒障礙。 然而，我無法回憶起在我的臨床或法醫經驗中以這種方式正確診斷的單個患者（Breggin，印刷中）。 醫生不想承認自己的錯誤，也不想透露同事的錯誤，因此診斷患者是否患有躁狂發作或雙相情感障礙比診斷為藥物不良反應要容易得多 躁狂的特徵。
When a patient develops a maniclike adverse drug reaction, the correct diagnosis, according to the official American Psychiatric Association (2000) diagnostic manual, is substance-induced mood disorder. Yet I cannot recall a single patient who was properly diagnosed in this manner in either my clinical or forensic experience (Breggin, in press). Doctors do not want to admit to their own mistakes, and they do not want to disclose the mistakes of their colleagues, so it is so much easier to diagnose the patient as having a manic episode or bipolar disorder than as having an adverse drug reaction with manic features.

即使藥物是如此明顯的罪魁禍首，它的作用是不可否認的，典型的醫療保健提供者可能會告訴患者和家人，這種藥物只是暴露了潛在的疾病。 醫療保健提供者可能會增加劑量或添加另一種藥物，而不是將患者從違規藥物中撤出，最終使患者的病情惡化。 但正如第 6 章和第 7 章的研究表明，許多過去沒有躁狂發作史的人被抗抑鬱藥物驅使進入類似躁狂的狀態。
Even when the drug is such an obvious culprit that its role cannot be denied, the typical health care provider is likely to tell the patient and the family that the drug merely unmasked an underlying disorder. Instead of withdrawing the patient from the offending agent, the health care provider is likely to increase the dose or to add another drug, ultimately worsening the patient’s condition. But as the research in chapters 6 and 7 shows, many people with no past history of manic episodes are driven into maniclike states by antidepressant medication.

第 10 章將探討我的精神病學職業的一大恥辱：越來越多的兒童被診斷出患有雙相情感障礙並使用成人情緒穩定劑和抗精神病藥。
Chapter 10 will examine one of the great shames of my profession of psychiatry: the increasing numbers of children diagnosed with bipolar disorder and medicated with adult mood stabilizers and neuroleptics.

結論（第 215 頁）
CONCLUSION (p.215)

鋰是一種高度神經毒性物質，在通常規定的治療範圍內對神經元功能和精神功能具有普遍抑製作用。 它對腦細胞有毒。 鋰和其他“情緒穩定劑”以某種方式“保護”腦細胞的廣為宣傳的概念是荒謬的。
Lithium is a highly neurotoxic substance with a generally suppressive effect on neuronal function and mental function in the commonly prescribed therapeutic range. It is poisonous to brain cells. The much-promoted concept that lithium and other “mood stabilizers” are somehow “protective” of brain cells is fantastical.

鋰對躁狂症或其他過度興奮狀態沒有特定的治療作用。 它的大腦致殘作用並不是針對被診斷為躁狂或雙相情感障礙的患者。 鋰將抑製或抑制動物、服用鋰的母親的新生兒和哺乳嬰兒、正常志願者以及被診斷患有精神疾病的人的身心功能。 接受鋰治療的志願者對他們的聯繫能力和智力運作能力造成毀滅性影響。
Lithium has no specific therapeutic effect on mania or other states of overexcitement. Its brain-disabling effect is not specific for patients diagnosed as manic or bipolar. Lithium will subdue or suppress the mental and physical functioning of animals, newborn infants and nursing infants of mothers who take lithium, and normal volunteers, as well as people diagnosed with psychiatric disorders. Lithium-treated volunteers suffer devastating effects on their ability to relate and to function intellectually.

Animals show similar taming effects.

鋰具有很強的吸引力。 正常志願者無法察覺自己的受損程度，而給予治療劑量的患者很容易變得嚴重中毒，而不會察覺到他們正在惡化的臨床狀況。 長期接受鋰治療的患者通常無法感知他們變得多麼柔和或他們的記憶已經變得多麼受損。
Lithium is highly spellbinding. Normal volunteers fail to perceive how impaired they have become, and patients given therapeutic doses easily become severely toxic without perceiving their deteriorating clinical condition. Patients treated long term with lithium typically fail to perceive how subdued they have become or how impaired their memories have become.

鋰的各種替代品都有自己的大腦功能障礙，而且沒有一種藥物是專門針對躁狂症的。
The various alternatives to lithium have their own brain-disabling effects, and none of the drugs is specific for mania.

儘管鋰具有這些抑制特性，但它在控制躁狂方面不如精神安定藥有效，尤其是在急性躁狂或嚴重的複發性躁狂中。 這部分是因為鋰的毒性太大，足以製服嚴重不安或叛逆的人。
Although lithium possesses these suppressive properties, it is not as effective in controlling mania as the neuroleptics, especially in acute mania or in severe, recurrent mania. This is partly because lithium is too overwhelming in toxicity in doses sufficient to subdue severely disturbed or rebellious individuals.

聲稱鋰是躁狂症或躁狂抑鬱症（雙相情感障礙）的疾病特異性療法的說法實際上沒有根據； 它是一種腦殘劑。 它的功效被誇大了，它對大腦和思想以及整個身體的不利影響也經常被最小化。
The claim that lithium is a disease-specific therapy for mania or manic-depressive (bipolar) disorder has no basis in fact; it is a brain-disabling agent. Its efficacy has been exaggerated, and its adverse effects on the brain and mind, as well as the body as a whole, have been too frequently minimized.

NOTE
1. 我從一位作者那裡獲得了原文的翻譯。
1. I obtained a translation of the original article from one of the authors.

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