精神病学、疯人院、精神疾病、电休克、脑叶切除术、Freud与Jung|Lex Fridman Podcast #502
- 历史学家 Andrew Scull 的核心判断是:精神病学正同时在诊断、药物和研究策略等所有战线上陷入危机。 Steven Hyman 和 Thomas Insel 任职期间,NIMH 将「200亿美元」投入遗传学和神经科学;两人离任时都承认,经过13年「真正酷的科学研究……精神病患者的处境一点也没有改善」,而 Hyman 认为,今天的药物「并没有真正超越我们在1950年代偶然发现的那些药」。
- 大型药企已经大幅撤出精神科药物研发。 在因隐瞒数据、炮制研究而支付数十亿美元和解金之后(仅 Vioxx 就是50亿美元),而神经科学又迟迟找不到新的药物靶点,大型药企「认为研究其他疾病能赚更多钱」,把新药开发留给了「小型初创公司」——尽管 Scull 表示,如果主要精神疾病没有生物学成分,他会「感到非常惊讶」。
- 遗传学正在瓦解这个领域赖以建立的诊断分类。 使用300个基因组变异位点的 GWAS 只能解释约10%的精神分裂症,而精神分裂症、双相情感障碍和自闭症之间的易感基因高度重叠;这让一些精神科医生推测,10年内「精神分裂症这种东西不存在了,双相情感障碍这种东西也不存在了」。Scull 警告,这会打击公众对该领域的信任,尽管「科学可能正把他们带向那里」。
- 精神病学炒作反复出现的信号,就是80%治愈率;Scull 将这一判断直接套用到今天的氯胺酮和迷幻药热潮上。 「Cotton 的疗法80%治愈、胰岛素昏迷疗法80%治愈、早期疯人院80%治愈。这是夸大的修辞」——至于把迷幻药说成抑郁症奇迹疗法,他认为「证据极其薄弱……这部电影我已经看过太多次了」;不过他也承认,严肃的临床试验(Lex 提到 Johns Hopkins 的裸盖菇素研究)值得以严谨态度检验,而不是直接否定。
- 现有药物的硬疗效数据,比市场叙事更糟糕。 NIMH 资助的 CATIE 研究(2005年发表于《新英格兰医学杂志》)发现,第二代抗精神病药有时价格是第一代的10倍,但疗效并不更好;67%-82%的患者因药物无效或副作用退出,副作用包括增重10-50磅、代谢综合征。SSRIs 在统计上优于安慰剂,「但未必达到临床显著差异」;超过40%的患者没有反应,也没有生物标志物能预测谁会受益,药物基因组学的反应预测仍只是一张「未来兑现的承诺票据」。
- 尽管背负着这个领域最沉重的文化包袱,ECT 对难治性抑郁和有自杀倾向的抑郁仍有一些证据支持。 患者「有人对 ECT 赞不绝口,也有人对它破口大骂」:记忆丧失是真实的,《飞越疯人院》重塑了它的惩罚性形象,而「我们完全不知道它为什么有效。这是一种纯经验性治疗」;但 Lex 一位「什么都试过」的朋友认为 ECT 改变了自己的人生,Scull 表示,「这种故事并不少见」。
- 今天的黑暗时代不只是精神病学造成的,公共政策同样负有责任:美国最大的3家住院精神病治疗机构,是洛杉矶县监狱、库克县监狱和赖克斯岛。 严重精神疾病患者平均比其他人早死「15-25年」,而且差距还在扩大;去机构化承诺的替代性社区服务从未兑现——「社区照护是一场没有豆子的障眼法」。
- Scull 对未来的判断是:为被忽视的社会心理维度提供资金,保护公众对科学的信任,并保留更好治疗出现的可能性。 当前的资金削减意味着「一个10年正在被浪费,而损失之所以看不见,是因为它属于反事实」;解决办法是「更多谦逊、更少傲慢……当有人告诉我们某件事是突破时,要更加怀疑」。Lex 将 AI 视为「另一个潜在的双刃剑」,但 Scull 坚持认为,「绝不能变得愤世嫉俗」地看待进步。
1. 只有对症治疗,没有治愈
- Scull 的开场框架是,现代精神药理学在1950年代初出现,「是一件偶然事件……几乎是意外发生的」;而今天所有可用疗法依然只是缓解症状——「我们没有针对接下来要讨论的任何一种疾病的精神科青霉素」。
- 反复出现的代价是医源性伤害,即由干预本身造成的问题。他举的例子是 PTSD 暴露疗法:让患者直面创伤,「对很多患者而言,实际上会让事情变得更糟;对一些患者而言,则会让他们变好」。
- 至于两大药物类别,抗精神病药和抗抑郁药「充其量只有部分疗效」,相当一部分患者不会受益,精神科医生也「事先不知道谁会反应良好……谁会反应糟糕」——风险收益判断就悬在一个没有明确标记的中间地带。
2. DSM建立的目标是可靠性,而不是效度
- 诊断曾经混乱到令人难堪:1960年代的专业文献已经记录了这一点,后来 David Rosenhan 的《在疯人院里保持清醒》又将其公之于众。Scull 直斥这项研究是「科学欺诈」,但它仍然引发了恐慌。Robert Spitzer 领导的 DSM-III 工作组在1980年给出的回应,是一套「逐项勾选」症状、按数量计数的系统。
- 这套系统之所以扎根,是因为所有人都需要它:药企需要按诊断开发对应药物,保险公司需要「一个稳定的基础」,患者和家属则在「拼命寻找」确定性。
- 关键区别在于:可靠性意味着 Walla Walla 和纽约的医生能够得出同一个结论;效度则意味着这个分类确实对应现实。Scull 认为,DSM 的标签就像18世纪医生诊断「发热」一样——把「一组截然不同的东西放在同一个标签下」。
3. 认为精神疾病是脑病的200亿美元豪赌
- 在 Steven Hyman、随后 Thomas Insel 任职 NIMH 的约13年间,资金大量流向遗传学和神经科学,前提是精神疾病属于脑部疾病;这种路径「很受医学院院长们欢迎,因为……钱涌了进来」。Scull 转述 Insel 离任时的结论:「花了200亿美元之后,精神病患者的处境一点也没有改善。」「我当时觉得,这是一个相当毁灭性的判断。」
- Leon Eisenberg 贯穿职业生涯的一句话概括了整个过程:「我进入精神病学时,那是没有大脑的精神病学;我离开时,它变成了没有心智的精神病学。」
- Scull 更深层的反对点,是不接受 Lex 将大脑与心智二分的框架:那是「范畴错误」。大脑具有可塑性,会在环境中发育——「社会和心理因素嵌入了我们的大脑」——而流行病学也显示,社会因素会推动疾病发生。把两者硬性分开,不成立。
4. DSM-5的病理学重启失败,药企撤退
- DSM-5 原本想借助已经破译的基因组、PCR 和神经递质科学,根据潜在病理重新定义诊断。「到了2008年前后,他们已经举手投降」,继续沿用1980年建立的症状分类。Spitzer 和 DSM-IV 负责人 Allen Frances 批评了不透明的制定过程;Insel 和 Hyman 则称该文件「不科学、毫无用处」。Scull 的判断是:「如果连这样的顶尖人物都在抨击它的诊断体系」——这就是危机所在。
- 与此同时,大型药企被曝「隐瞒东西……炮制研究……操纵数据」,支付数十亿美元赔偿;在神经科学始终找不到新药物靶点后,它们把研发投入转向其他疾病,新药开发被留给小型初创公司。
5. 监狱成了美国最大的精神病院
- 严重精神疾病患者平均比其他人早死「15-25年」,而且「这个差距一直在扩大,而不是缩小」。Scull 认为,主要责任在公共政策而不只是精神病学:街头精神病患者在短暂住院后不断循环于「沟渠、廉价旅店和监狱」之间。
- 今天美国最大的3家住院精神病治疗机构——「如果你还能把它们称为治疗机构」——分别是洛杉矶县监狱、库克县监狱和赖克斯岛;这些机构从性质上就不具备收治严重精神疾病患者的条件。
- 用 Scull 的话说,去机构化的前提是:「社区照护是一场没有豆子的障眼法……从来没有为真正严重的精神病患者建立替代性的社区设施。」
6. 庇护院的乐观主义如何发酵成“退化论”
- 早期精神病学家曾宣称,只要尽早送入,疯人院可以治愈「60%、70%、80%,甚至可能更多」的患者。现实却只有35%-40%的出院率,慢性患者年复一年地累积,最终让机构的典型形象变成:患者「只有躺进棺材才会离开」。
- 面对「你们承诺的是一回事,交付的却完全不同」的质问,这个职业选择了责怪受害者:把患者说成「进化上的倒退者」、拥有「低劣的生物学」,之所以无法出院,是因为「他们会像兔子一样繁殖」。退化论于是把治疗机构变成了「把他们隔离起来」的场所。
7. 美国优生学通向T4毒气室
- 语言在政策之前就已经变得杀戮化:一名英国精神科医生说,如果他接收的患者是小狗,「我们会把它们塞进袋子,绑上几块铅,然后扔进池塘淹死」。绝育政策沿着同一逻辑展开:截至1960年代,美国已有超过60,000人被绝育,其中加州占比尤其高。Scull 说,他所在的州直到约1960年仍在为精神病患者实施绝育。
- Lex 问纳粹是否受到美国叙事影响,Scull 的回答是:「是的,绝对是。」在缺乏民主制衡的情况下,「无用的食客」最终演变为 Hitler 的 T4 计划,名称来自 Tiergartenstraße 4。约25万名精神病患者可能被杀害,他们是「最终解决方案」最早的受害者;伪装成淋浴间的毒气室技术也在这一过程中发展出来。当地人把运送受害者的巴士称为「杀戮箱」,而德国精神病学界「在很大程度上选择了合作」。
- Rockefeller Foundation 约在1930年将精神病学列为资助重点,部分原因是多名受托人都有直接的家庭经历,包括妻子被收治入院;该基金会资助了德国遗传学家 Ernst Rüdin。Rüdin 后来成为绝育法的设计者之一,也是「支持杀害精神病患者」的人。
8. 脑叶切除术:冰锥、露营车与诺贝尔奖
- Egas Moniz 在1935年开始实施手术,Walter Freeman 在1936年接手;Moniz 凭借「14年的经验」获得1949年诺贝尔医学奖。Scull 说:「我相信这是他们希望撤回的一项决定。」
- Freeman 的女儿说,他「立志成为脑叶切除术领域的 Henry Ford」。他发明了冰锥版本:先用2-3次电击让患者失去意识,再把冰锥从眼眶穿入并来回搅动。他开着一辆称为 Lobotomobile 的露营车巡回州立医院,一个下午就做「20或30例脑叶切除术」,一只手累了就换另一只手,还吹嘘说:「我可以在20分钟内教会任何一个该死的傻瓜做脑叶切除术,哪怕他是精神科医生。」
- 这项手术最终因代际更替而消亡:年轻精神科医生看到后院里那些失败病例——失禁、基本上已经变成「僵尸」的患者——同时又有了看起来更接近正规医学做法的抗精神病药作为替代。一些脑叶切除术医生仍然做到1970年代初。
9. 用疟疾治梅毒性疯狂
- 全身性麻痹性痴呆曾占20世纪初疯人院入院患者的25%,患者既有宏大妄想(认为自己是 Napoleon、Jesus Christ),又逐渐瘫痪。Rockefeller Institute 的研究人员发现,这些患者的大脑里存在梅毒病原体;这是精神病学少见的病理学胜利,证明感染可以造成严重精神症状。
- Wagner-Jauregg 将从一名被俘的意大利士兵身上抽取的疟疾血液注射给患者,并宣称能够治愈;他后来承认疗效「被严重夸大」。他在1937年获得诺贝尔奖,是历史上仅有的2项精神病学创新诺贝尔奖之一,另一项就是脑叶切除术。精神病院甚至饲养真正的疟蚊,给穿着约束衣的患者叮咬;青霉素最终终结了这种疗法。
10. Henry Cotton的外科细菌学
- Cotton 曾师从 Kraepelin 和 Adolf Meyer,1916年开始主持 Trenton 医院;他接受局灶性感染理论,认为潜伏的低度感染会毒害大脑。在没有抗生素的年代,他提出的答案是「外科细菌学」:先拔牙,再切除扁桃体,之后扩大到胃、脾脏和结肠,同时宣称治愈率达到80%。现实是,45%的腹部手术患者在1年内死亡。他曾在 Princeton 最负盛名的系列讲座中授课,《纽约时报》还称其为重大突破。他的原话是:「胃就像建筑工地上的水泥搅拌机,完全可以不要。」
- 这套做法在 Cotton 去世后仍延续下来,他的继任者一直拔牙拔到1960年。Scull 采访过医院牙医;这名牙医「肯定拔过几十万颗牙」,仍然坚信 Cotton 本该获得诺贝尔奖。
- 在关于安慰剂效应的讨论中,Scull 解释了集体错觉如何形成:白大褂医生实施大规模、亲密且侵入性的干预,可能放大安慰剂效应。Lex 说:「对我来说,即使你告诉我这是安慰剂,安慰剂效应也会起作用。」Scull 的回应是,医生和患者都会陷入其中——「欺骗自己、只看见自己想看见的东西,是很容易的」。
11. 胰岛素昏迷:80%治愈、1%-5%死亡率与 John Nash
- Sakel 将成瘾治疗中的轻度戒断昏迷改造成治疗精神分裂症的深度低血糖昏迷,从1933年开始使用;一个疗程最多60次,患者「真的悬在生死边缘」,死亡率为1%-5%,还会出现脑损伤和肥胖,但他反复宣称治愈率达到80%。有人告诉他这种疗法会杀死脑细胞,他回答:「是的,这可能是真的。它们杀死的是精神分裂症患者的脑细胞。」Scull 说:「当然,这完全是胡说。」
- 这项疗法让 Sakel 致富,到1960年代初留下约200万美元遗产;直到1950年代才接受随机对照试验,结果失败,随后逐渐消亡。John Nash 曾在 Cotton 旧日工作的 Trenton 医院接受胰岛素昏迷治疗,并在那里面临脑叶切除术风险。
12. 从Metrazol恐怖到ECT:诞生于屠宰场
- 一名奥地利精神科医生认定精神分裂症和癫痫不可能共存(Scull 说:「这不是真的,但他就是这么相信的」),因此认为人工诱发癫痫发作可以把精神病赶出去。Metrazol 引发的大发作剧烈到足以让大腿骨穿出髋关节;据发明者自己承认,患者还会经历几分钟「感觉自己处在死亡边缘」的状态。
- Cerletti 和 Bini 最初尝试电击替代方案时进展糟糕:从头部通到肛门的电极让狗的心脏停跳。后来他们去了罗马屠宰场,发现用颅部电极击晕的猪会抽搐但不会死亡。他们的第一个人类受试者,是从罗马火车站带来的流浪汉;第一次电击失败后,他听到两人讨论加大电流,便说:「不,再来一次,那会要命。」他们还是继续了;患者抽搐、停止呼吸,随后恢复,并重新与现实建立联系。
- ECT 价格低廉、操作简单,很快扩散开来;但后来发现,它「对精神分裂症并不是很有用」——这正是它最初被发明来治疗的疾病——反而似乎对抑郁症有效,尤其是「有自杀倾向的抑郁症」。
13. ECT的两副面孔:管教工具、文化反派与性别账本
- 在1940-50年代的精神病院里,未经改良的 ECT「更多被用来控制人的行为,而不是作为治疗干预。它具有很强的惩罚性」;《飞越疯人院》进一步固定了这种形象。Scull 认可电影对病房贫困、工作人员蔑视的描写,也指出片中的首席精神科医生原型就是 Oregon State Mental Hospital 的实际负责人。
- 这段历史之所以难以被好莱坞拍成电影,是因为一名对他的《Madhouse》感兴趣的制片人问:「第三幕在哪里?」意思是要一个大团圆结局;Scull 只能回答:「这个故事没有大团圆结局。」
- 这些绝望疗法都呈现出相同的性别结构:Cotton 的患者约70%是女性,脑叶切除术记录中女性反复占60%-70%,ECT 患者也明显以女性为主;男性则更容易被归入其他诊断,包括人格障碍和 ADHD。
14. ECT平反:疗效确实存在,机制无人知晓
- 肌肉松弛剂(最初使用的是箭毒)消除了骨折,但代价是需要麻醉师和呼吸支持;记忆问题和脑损伤担忧仍然存在,而且疗效往往需要反复维护。Scull 的平衡判断是:有些患者和精神科医生「对 ECT 赞不绝口,也有人对它破口大骂」。如今加州几乎禁止对非自愿患者实施 ECT,这类法律限制在医学领域相当罕见。
- 真实的恐怖与真实的疗效并存:CIA 资助的 Ewen Cameron 每天多次实施 ECT,直到患者「无法行走、无法说话、无法自己进食」。但 Lex 提到一位20年前因抑郁症「什么都试过」的朋友,最终认为 ECT 改变了自己的人生;Scull 回应:「这种故事并不少见。」近期对照试验也为它治疗深度痛苦患者提供了「相当不错的证据」。
- 未解决的不适感在于:「我们完全不知道它为什么有效。这是一种纯经验性治疗。」这种未知本身就会让人抗拒,不像切除一个看得见的肿瘤那样直观。
15. 信任、炒作与反复出现的80%治愈率
- 过去2个世纪反复出现的信号是:「Cotton 的疗法80%治愈、胰岛素昏迷疗法80%治愈、早期疯人院80%治愈。这是夸大的修辞。」Scull 将这一判断用于当下:氯胺酮和迷幻药「被吹捧成抑郁症的奇迹疗法,而证据极其薄弱……这部电影我已经看过太多次了」。Lex 补充说,Johns Hopkins 目前正在进行严肃的裸盖菇素研究,Scull 对此表示同意:应当严谨、谨慎,而不是炒作。
- 腐败的不只是科学新闻:Science 和 Nature「会选择要把什么放到前台」,追逐轰动效应;而负面结果——「帮助我们避免犯错的东西」——往往不是最容易发表的内容。多中心研究是制约热情的办法,但资助机构仍然在饿死异见者。
- 谈到资金削减,Scull 说,进行中的临床试验被迫中止,一条需要「至少6或7年」的培训链条也被打断——「你说的是一个10年正在被浪费,而损失之所以看不见,是因为它属于反事实」。而且,「一旦信任丧失,就很难恢复」。
16. 遗传学可能让“精神分裂症”本身消失
- 人们期待的、导致精神分裂症的孟德尔基因从未出现。使用300个微小变异位点的全基因组关联研究「只能解释约10%的精神分裂症。这并不算很有力」。更令现有分类难堪的是,双相情感障碍、精神分裂症和自闭症之间的易感基因高度重叠——「它们并不是彼此独特的实体」。
- 他的朋友 Robin Murray 将精神分裂症描述为「似乎确实是精神病的极端端点……处在一条连续谱上」。如果正如一些顶尖精神科医生推测的那样,10年后精神病学宣布「精神分裂症这种东西不存在了,双相情感障碍这种东西也不存在了」,Scull 预计会对公众信任造成「相当糟糕的影响——但科学可能正把他们带向那里」。
17. Freud之前:祈祷、卧床与加餐
- 19世纪美国的新宗教填补了门诊治疗的真空:Mary Baker Eddy 创立的 Christian Science 认为「疾病这种东西并不存在……可以通过祈祷消除」;Scull 指出,如果这种信仰疗法真的有效,它对精神疾病的效果可能比对癌症更好。源自 Adventist 的 Kellogg 疗养院曾接待过 Lincoln 的遗孀、Tarzan 和 Henry Ford。
- 南北战争后的神经科医生,其专业能力建立在「子弹穿过大脑、留下窟窿」之上,随后发展出门诊实践:补药、静电疗法,以及 Silas Weir Mitchell 的休息疗法——让患者完全卧床并大量进食,主要针对女性。Virginia Woolf 认为,这种疗法「几乎把她逼疯了,或者让她变得更糟」。
- Mitchell 的畅销书《Wear and Tear》(磨损与疲惫)和《Fat and Blood》(脂肪与血液)认为,电报和铁路带来的现代生活让神经系统不堪重负。Lex 由此指出,1900年前后的焦虑叙事与今天关于社交媒体的讨论几乎逐字相同。Scull 的回应是:「他们认为现代生活正以完全相同的方式带来压力。」
18. 1909年:Freud登陆Clark,用德语演讲
- 机构内部的历史叙述把它称为 Freud 会议,但事实并非如此;Freud 在约30名演讲者中「几乎只是个附带人物」,其他人包括2位物理学诺贝尔奖得主和 Franz Boas。他用德语演讲,而当时的听众都受过世界最先进医学文献的训练,语言并非障碍。William James 参加了会议,却「没有留下深刻印象」;Harvard 的 James Jackson Putnam 则转向支持 Freud,而他在 Boston Brahmin 精英圈的地位很重要。
- Freud 鄙视那个让自己变富的国家,认为美国「应该改名叫 Dollaria,因为它只对美元感兴趣」;他「非常记仇」:一旦与他决裂,就会被逐出教门,Jung 尤其如此,最终导致1913年的分裂。
- 最有钱的患者都去了 Jung 那里,Scull 怀疑这「可能加剧了」两人的分裂。Edith Rockefeller McCormick 的广场恐惧症严重到这种程度:她的司机要开着 Rolls-Royce 沿铁路跟随她乘坐的火车,以防她必须跳车;后来她成为 Jung 学派分析师,并向 Jung 开出巨额支票。Mellon 家族的资助则最终让 Jung 的著作进入 Princeton University Press。
19. 从Anna O到本我:精神分析为何无法规模化
- 最早的典型患者是 Breuer 的 Anna O,即 Bertha Pappenheim。Breuer 和 Freud 将她照护生病父亲后出现的症状解读为受压抑的创伤——「潜伏在无意识中的半记忆,以扭曲的形式浮现出来」。Freud 按自己的说法是「非常笨拙的催眠师」,于是用自由联想取代 Charcot 的催眠表演;后者如今已知「是伪装出来的」,患者只是「把自己的表演排练出来」。梦和口误成为泄露无意识的出口,本我、自我和超我则承诺把怪诞的不幸转化为普通的不幸。
- Freud 自己也感叹其文学性:「我的病例记录读起来像短篇小说……缺少严肃科学的印记。」这恰恰是小说家、剧作家和超现实主义者拥抱他的原因;而疯人院里的精神科医生则认为,面对他们眼中的生物性疾病,谈话疗法并不值得认真对待。
- 真正决定规模的是算术:约1930年,北美只有约300名分析师;每名患者每周要消耗5次、每次50分钟的治疗时间。相较于数十万名住院患者,这只能覆盖几千人。到1940年,因 Hitler 的迫害,美国分析师人数增加了一倍以上;但这些机构拒绝进入大学,在战后大学成为知识生产工厂之后,这种选择变成了「结构性弱点」。
20. 战争建立门诊精神医学,也造就心理学竞争者
- 二战期间,美国以心理不适任为由拒绝了175万名新兵,但即便入伍,崩溃仍然发生:在战斗环境下,比例最高达到25%的士兵。(纳粹的替代方案是「直接把人枪毙」。)战前美国约有2,000名精神科医生;战争结束时,仅军队系统就有超过2,000名精神科医生,他们在 Bill Menninger 的心理治疗和创伤导向体系下仓促受训。到1958年,约80%的精神科医生在门诊工作,而不是医院里。
- 心理学家被征召来填补治疗缺口后发现:「等等,我们也可以做这个。」他们建立了一套训练模式:先用2年学习科学心理学和研究方法,再进入临床工作。这让他们熟悉如何申请联邦研究经费,而「精神分析师完全不知道怎么申请」。
- 分析师还抵制 Rockefeller Foundation 一再要求证明疗法有效:「没有简单的衡量方式,因为我们做的是重建完整人格。」面对那些说「我们会测量用这种方式治疗后发生了什么」的竞争者,这个回答显得很无力。
21. CBT:治疗症状,衡量结果
- 在分析师看来,治疗症状就像「打地鼠」——压下一个,另一个又冒出来。Aaron(Tim)Beck 曾接受精神分析训练,后来感到失望;他最近去世,可能活到100岁。他一方面在1960年代记录了诊断的不可靠性,为 DSM-III 提供了推动力;另一方面加入了心理学家构建短期、标准化、可复制、可检验疗法的队伍。
- Scull 对证据的诚实判断是:CBT 治疗精神分裂症的记录「相当糟糕」,Cochrane 对整体证据的评价最多只有「低到中等置信度」。但他认为,对较轻的抑郁症,CBT 可能比药物更有效,而且没有部分药物副作用,这也是英国 NICE 将其列为一线治疗的原因。
- Lex 的框架得到了认可:觉察自己的思维模式、触发因素和习惯,是一个「把自己的生活重新整理好」的过程,确实可能帮助一部分人;但随着疾病严重程度上升,证据就越来越不确定。
22. Chlorpromazine:无人规划的革命
- Rhône-Poulenc 手里有一种老式抗组胺药(合成于1880年代),却不知道该拿它做什么——止吐药?治疗湿疹?那是一个药物研究「像狂野西部一样」的时代。法国海军中尉 Henri Laborit 将其用于增强麻醉,注意到术前患者突然变得漠不关心:「这东西就像化学脑叶切除术。」Sainte-Anne 医院的 Delay 和 Deniker 开始给精神病患者增加剂量;经由魁北克的 Heinz Lehmann,它进入北美。两家公司先后拒绝后,Smith, Kline & French 买下了它,并在2年内让200万人服用。
- 推动普及的是药企而不是医院精神科医生:药企把躁动患者变得平静的动态影像带到州议会播放。Lex 问:「所以这已经是大型药企的运作机制了?」1955年 Miltown 紧随其后,由电视节目里的「Uncle Miltown」Milton Berle 推广;1960年代初,「主要镇静剂」被重新命名为「抗精神病药」,暗示它们攻击的是潜在的精神病。
- 实际情况是,这些药物能让相当一部分患者的阳性症状——幻觉、妄想、激越——变得迟钝;但对阴性症状,即冷漠、语言贫乏和主动性丧失,「作用不大,或者完全没有作用」。相当一部分精神病患者根本不会对药物产生反应。
23. 迟发性运动障碍、clozapine与CATIE判决
- 这些副作用大约被忽视了20年,直到 George Crane 在《Science》发表论文:严重坐立不安、帕金森症状和迟发性运动障碍——舌头伸出、步履蹒跚,以至于路人会主动避开。「你看到的其实是他们正在服用的药物造成的医源性影响。」
- Clozapine 于1957年问世,后来被撤出市场,也一直没有进入美国,部分原因是它不会造成迟发性运动障碍——「当时业内很多人认为,如果没有这些症状,就说明你没有攻击到问题。很荒谬,对吧?」另一部分原因是它会破坏一些患者的白细胞,导致死亡。它在1980年代末复活,用于难治性病例,但要求每周检查血液;随后,「第二代」抗精神病药类别由此诞生。
- NIMH 资助的 CATIE 研究于2005年发表在《新英格兰医学杂志》上,给出了判决:这些新型专利药有时价格是第一代对照药的10倍,但疗效并不更好;67%-82%的患者因药物无效,或因增重10-50磅、代谢综合征和糖尿病等副作用无法忍受而退出。与此同时,FDA 只要求2项阳性试验就能批准药物,即便15项试验中有13项失败。
24. SSRIs:统计显著,临床有限
- 抗抑郁药的起点也是一次意外:晚期结核病患者服用新药后「开始表现得很开心,到处跳舞」。约1960年,药企认为抑郁症只是住院忧郁症患者构成的小市场;如今「抑郁症是精神病学的普通感冒」——一部分源于理解加深,另一部分则如 Lex 未遭反驳的概括,是「药企说服了整个世界」。
- SSRI 的故事——抑郁症源于血清素缺乏、Prozac 可以修复、Tipper Gore 公开支持——跑在了数据前面:SSRI 在统计上优于安慰剂,「但未必达到临床显著差异」,在一项60分量表上往往只高出1或2分。超过40%的抑郁症患者没有反应,而观察到的疗效中有很大一部分来自安慰剂。
- 代价包括情绪麻木,「把一切都压平」;性欲下降,有时停药后也不会恢复;对一些人而言,戒断过程「简直糟透了」,让他们被困在药物上。如今大部分处方来自基层医疗,而不是精神科。
25. 诊断扩张——真正的希望在哪里
- Nick Haslam 将其称为「诊断扩张」:一个明确的疾病核心,逐渐吸附出一圈模糊的外围。DSM-5 曾争论丧亲是否应被算作抑郁症;Allen Frances 坚信,自闭症诊断数量的大幅增加,更多是因为他放宽了诊断标准,而不是因为真实病例增加。Scull 指出,NAMI 这样的家庭组织并不等同于患者,其利益可能不同。Michael MacDonald 经 Scull 转述的一句话值得保留:疯狂「对患者而言是最孤独的痛苦,对身边人而言却是最具社会性的疾病」。
- 对正在受苦的人,实际建议是:「你可能需要尝试药物,因为痛苦非常强烈。但你需要了解其中的问题,也需要一名非常仔细监测你的临床医生。」从结构上看,应当为社会心理维度提供资金——无家可归、家庭负担等领域,目前学术精神科医生无法据此建立获得研究经费支持的职业。
- 关于 AI 治疗,Lex 认为,系统如果能听到那些「即使对治疗师也不会说出的最深秘密」,就进入了 Freud 和 Jung 的领域;Scull 承认,疫情期间的远程治疗已经显示,其中一部分「确实可能被机械化」。Lex 称 AI 是「另一个潜在的双刃剑」。精神分析本身如今已经是「面向富人的小众产品」。
- Scull 的收束立场是:「如果主要精神疾病没有生物学成分,我会感到非常惊讶……但我不认为那会是全部故事。」那些拥有最多资金的公司放弃了相关研究,这「令人沮丧」;修正方向是建立一个更少技术官僚色彩、更加关怀患者的职业体系——而且「绝不能变得愤世嫉俗,不能放弃希望,不能否认进步的可能性,因为可能性始终存在」。
完整逐字稿
The following is a conversation with Andrew Scull, a historian of psychiatry and mental health. He has authored many books that I highly recommend, including Madness in Civilization: A Cultural History of Insanity from the Bible to Freud, from the Madhouse to Modern Medicine and Desperate Remedies: Psychiatry's Turbulent Quest to Cure Mental Illness. Andrew Scull has spent decades studying how societies have understood madness, how psychiatry rose to authority, and how often that authority was used with false confidence and catastrophic consequences. In this conversation, we'll trace the long arc from the asylum era to eugenics, from lobotomy and insulin coma therapy to electroconvulsive therapy, psychoanalysis, antipsychotics, antidepressants, and the modern crisis of mental health. It is in part a story about the terrifying history of bad ideas in medicine, but it is also about the fascinating mystery of the human mind and the difficult journey to understand it.
1. Crisis in Psychiatry
Is it fair to characterize your view on psychiatry and mental illness as that there's a crisis in modern psychiatry? We have made some progress—
Yes.
—over the past century, but mostly we still are not good at treating mental illness, either via drugs or talk therapy—meaning psychopharmacology or psychotherapy—or, as you put it, the brain or the mind route. So let's start at the end of our story. Let's start where we stand before we go into the rich history that you so eloquently write about.
So psychiatry is a profession that tries to deal with an enormously complicated thing: the human mind, the human emotions, and the human ability to attempt to understand the world. In particular, obviously, it focuses on people whose common-sense approach to the world seems to break down. These are people whose emotional life is filled with turmoil, whose ability to relate to others is badly damaged, or who see things in the world that the rest of us simply think aren't there. They're illusions, they're hallucinations, they're delusions, and this is a subject that has occupied some very clever minds over the years.
There's no question that in the course of at least the last 3 quarters of a century, there has been some limited progress in dealing with the problems that mental illness creates. Some of that is confined to the milder forms of mental distress. The more serious forms of psychosis and breakdown of emotional control are areas where I think, again, there's been some progress, but it's easy to overstate how much of that there has been.
As we'll see probably later in our conversation today, the advent of modern psychopharmacology, which occurred in the early 1950s, was a serendipitous event. It wasn't planned for. It happened almost by accident, and it did mark, in some ways, an advance over some of the things that psychiatry had engaged in before that. There's no question that, for some people, that revolution and a parallel revolution in the psychotherapeutic realm have created some advance for patients, and we should not minimize that.
What we have available to us are symptomatic treatments, not cures. We don't have a psychiatric penicillin for any of the conditions we're going to be talking about. That doesn't mean we can't do some things that help, but the help is quite limited, and it's important to understand both the ways in which we have progressed and the limits of that progress. It's also important to understand that when we treat something, sometimes we create new problems—what we call iatrogenic problems, things caused by the interventions that we use. That's true of some psychotherapeutic interventions and most certainly true of the drugs we use to treat mental illness these days.
So, for example, in treating PTSD, we often get patients to confront the episode—the trauma—which provoked their distress. That is often a very, very fraught process, and for many patients it actually makes things worse. For some patients, it makes them better. So that's a situation where you could see problems with both antipsychotics and antidepressants, the 2 main classes of psychotropic drugs that we use.
They're at best partially effective, and they don't work for a significant fraction of patients who are given them. One of the big problems psychiatry faces is that psychiatrists don't know in advance who's going to respond well to the drugs, who's going to respond badly, or for which group of patients in the middle the side effects and the main effects—if that's what we want to call them, the therapeutic effects—are finely balanced. Making those judgment calls about what to do is very, very difficult.
Now, in terms of the crisis psychiatry faces at the moment, as I see it, there are a number of strands that point to this. Psychiatry's diagnostic system is still used. I mean, the fundamental basis of psychiatric diagnosis today was really first formulated in 1980 with the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders—
DSM-III.
—and then there's been DSM-III-R, DSM-IV, DSM-IV-TR, and now DSM-5. Finally, not with a Roman numeral, but with an Arabic numeral. So they thought with DSM-5, when they needed to modify it, it would be like a piece of software. You have Windows 10, Windows 11, and so on, right?
Now, that diagnostic system came into being because psychiatrists had a very hard time agreeing with one another about what was wrong with somebody. That became embarrassingly clear, first in the professional literature, which outsiders didn't read, and then via a very famous study that was a scientific fraud by David Rosenhan called On Being Sane in Insane Places. He claimed to have sent pseudo-patients to the hospital, and all but one of them were diagnosed as schizophrenic, the other as somebody with bipolar disorder. They were fake patients.
So, almost in a panic after that study appeared in Science, and because there was an abundant professional literature from the 1960s showing the same thing—that diagnosis was a very erratic process—the DSM-III task force, led by Robert Spitzer, who was then at Columbia, was explicitly set up to try to create a sort of tick-the-boxes approach to deciding which box a patient belonged in.
Were you schizophrenic? Were you this type of schizophrenic or that type of schizophrenic? Were you manic-depressive or bipolar? Did you have various forms of depression? To construct those boxes, what they relied upon was a list of symptoms. If you had 6 or more of 10 symptoms of a certain sort, you could be diagnosed with major depression, for example.
So that system came into being. It was partially embedded because it appealed to drug companies that were developing drugs to treat these various disorders. It appealed to insurance companies because it gave them a stable base to look at. It appealed, as diagnosis always does, to patients and their families, who are scrambling to deal with these enormous upsets in the mental life of either themselves or a family member. So it provided some sense of certainty around diagnosis.
But that was always based simply on symptoms, in the way an 18th-century doctor might diagnose dropsy or fever, for example. Fever and other diseases they talked about in the 18th century are really a constellation of very different things under one label. I think that's what is turning out to be true of the DSM labels.
That approach was really all that psychiatry could come up with if it wanted to make sure that, whether you were in Walla Walla, New York, San Francisco, or Atlanta, you reached the same conclusion when faced with the same patient. You had a reliable diagnostic system. That didn't necessarily mean it was a valid diagnostic system, if you understand the distinction between validity and reliability.
Reliability means you and I, faced with the same sets of facts, reach the same conclusion. But that conclusion may or may not reflect the underlying reality of things, right? So you had this diagnostic system, and it went through various iterations. Each time it went through an iteration, the number of possible psychiatric disorders you could get grew and grew and grew, and it became difficult to believe in some of those categories, shall we say—that they were really illnesses rather than some sort of social construct.
But beyond that, psychiatrists wanted to be more like other medical doctors, to root their diagnoses in an understanding of the underlying pathology of the disorder. What was it that caused people to become schizophrenic? The sense was that if we could grasp that, we'd have a better handle on how to attack it, how to treat it.
When DSM-5 was mooted—the 5th edition—in the early 2000s, NIMH was then under the leadership of Steven Hyman, who's at Harvard now, and was succeeded by Thomas Insel, who ran NIMH for about 13 years. The 2 of them had pushed psychiatry and psychiatric research in a very particular direction.
On the one hand, toward understanding the genetics of mental illness, and on the other, toward looking at what the new discipline of neuroscience could contribute to understanding things. Both of them were heavily invested in the idea that mental illness was brain disease. If it was brain disease, then the question was: What was making the mechanism here go awry? What was causing people's emotions, their cognitive skills, or their sense of the world to become so disordered? They invested a lot of money in that approach.
When Insel stepped down, he gave an interview, actually, to somebody at MIT, and he's repeated it since in a book he wrote about his experiences, where he said, "Well, you know, as I look back on my 13 years, I funded an enormous amount of scientific...
really cool scientific research. I funded geneticists and neuroscientists, and they did a lot of really interesting science. And after spending $20 billion, the lot of the mentally ill has improved not one bit, right? Which was a pretty devastating statement, I thought.
And NIMH is the National Institute of Mental Health.
National Institute of Mental Health, yes. I shouldn't resort to jargon. But the National Institute of Mental Health had been founded in the late 1940s with the goal of improving care, doing basic research, training people in the field, advancing the care of the mentally ill, and, obviously, producing cures and advances. Its mission has varied widely over the years, but starting in the 1990s—the period when George H. W. Bush declared the Decade of the Brain—NIMH increasingly focused on the idea that mental illness was purely a brain disease. There's something to that, and there's also some mistake in thinking about it that way.
This is, by the way, as we will talk about, this distinction between seeing mental health—the maladies of the human mind—as a problem of the brain, like neurobiology and neuroscience, versus the problem of the mind, which is more in the cognitive and psychotherapeutic realm and less amenable to scientific rigor. So I think what's appealing about studying the brain, neurobiology, and neuroscience is that there's data. Yes, it's more rigorous. You can do science.
It’s the kind of thing that really appealed to medical school deans because once the NIH and the drug companies, too, were funding basic research on neurobiology and basic research on genetics, the money flooded in. Psychiatry, which had been something of an orphan, became much more popular.
And we should say that this is something you write a lot about. There are all these factors to consider: cultural elements, political and public-policy elements. Then, at a certain point, drug companies and insurance companies come in, of course, and all the human beings around somebody who's suffering with a mental health issue—family factors, and that's connected to cultural stuff.
It's a very complicated area, and oversimplification is a real problem, I think. And I think even that dichotomy you just drew between the brain and the social or psychological—some mix of those things—I think in some ways that's a category mistake, a mistaken way of looking at the world, because the brain you have today, you're not born with. Human brains are remarkably plastic things. They develop in response to the environment. Social and psychological factors are embedded in our brains. A rigid separation, saying one or the other—no. There's abundant evidence from epidemiology that social factors play an important role in the development of illness.
Nevertheless, in the history of psychotherapy, for example, the human mind is complicated, with all these factors. To say anything helpful, you have to simplify. Freud famously simplified a lot toward a particular view of the human mind. That simplification, actually—we'll talk about whether it's correct in a deeper sense—was productive.
Yes. In fact, whenever you're trying to deal with a very complicated set of issues, you have to simplify. You have to make heuristic decisions about what you're going to neglect and what you're going to emphasize. But what I'm trying to say—well, you asked me about the crisis in psychiatry, and the simplest way for me to encapsulate the issue and the problem, as I see it—one of the problems that has arisen—is a quote by Leon Eisenberg, who had a very long career at Harvard.
Eisenberg said toward the end of his career, “When I entered psychiatry, it was brainless psychiatry, and I leave it mindless psychiatry.” That sums up the way the field, to a large degree, has moved. In the process, insights are lost, though in other ways, things are being gained.
Freudians tended to neglect the biological, to suggest that the brain as a biological organism was not something we needed to worry about. We worried at the level of a psychological model of how our minds work. And all too often—not exclusively, because some of the psychiatrists I'm friends with are very sophisticated men and women and do grasp that you can't move in these bipolar directions; you've got to meet somewhere in the middle—but that sort of thing got lost, I think, in all the enthusiasm for neuroscience.
When antipsychotic drugs were discovered in the early 1950s, we had no clue how they worked. And one of the things that they helped us spawn, as people began to say, “Well, why did these drugs work? What did they do?” was to begin to understand that the brain wasn't just a set of electrical signals, as had been thought in the first half of the 20th century and before. Rather, there was this very interesting chemical soup running around in our brains, with neurotransmitters that help the brain work the way it did and perhaps explained why it went awry. So it was one of the many factors that gave rise to neuroscience.
The first neuroscience conventions were in the 1970s, and they attracted a few hundred people. Now it's tens of thousands of neuroscientists. It's a huge enterprise.
Diagnosis has come under threat. The categories that we've all become familiar with, that we're told are real diseases—like bipolar disorder, schizophrenia, and major depression—are beginning to falter, and we're beginning to worry about whether those diagnoses are real ways of thinking about the world and may, in fact, mislead us. Because if we think there's something called schizophrenia, or the schizophrenias, as the inventor of that term put it, and we try to research where it comes from, but that's not really what's going on, obviously we're probably not going to make the progress we could be making if we had a better diagnostic system. And that's what DSM-5 thought it was going to be able to do and discovered it couldn't. So it stayed basically with the symptomatic approach.
If we can just be really brief, I'd love to talk a little bit more about the DSM, but just to give a history here, looking it up on Perplexity: DSM-I in 1952 was a 32-page pamphlet with 106 diagnoses, heavily influenced by psychodynamic concepts and etiology, using broad, often vague categories like reactions. DSM-II in 1968 expanded to 185 diagnoses, still psychodynamically flavored and with poor reliability, but added more attention to childhood disorders and later removed homosexuality as a disorder in the 1974 printing.
Then came the revolution, as you mentioned. DSM-III in 1980 introduced explicit symptom-based diagnostic criteria, a multiaxial assessment system, and an officially atheoretical stance about causes, aiming to improve reliability and research utility. DSM-III-R in 1987 revised criteria and expanded to around 297 diagnoses. DSM-IV in 1994 and DSM-IV-TR in 2000 focused on literature-driven empirical revisions, added and deleted some disorders, increased coordination with ICD-10, and so on.
Finally, in 2013, DSM-5 came out, which eliminated the multiaxial system, integrated most information into a single nonaxial diagnostic list, with separate notations for psychological and medical factors. It reorganized chapters—for example, neurodevelopmental; obsessive-compulsive and related; trauma- and stressor-related disorders—introduced new and refined entities, and so on. But the big-picture trajectory conceptually was that the DSM moved from cause-focused and psychoanalytical to symptom-based, atheoretical, and reliability-driven over time. There has been growth in the number and granularity of categories, closer alignment with ICD, and ongoing controversy over medicalization, validity, and the balance between categorical and dimensional approaches.
Yes. It feels like that description doesn't necessarily fully get to the core of why the DSM-5 doesn't quite get the full scope of the problem.
You invest more than $20 billion in a particular approach. And at the time you're constructing this, you say, “Finally, because of all the work that's being done in genetics, we now have decoded the human genome. We have PCR, so we can chop it up and look at bits of it. We have a lot more understanding of the role of neurotransmission in the brain. Surely we're going to be able to recast our diagnostic system based on underlying pathology so that we won't be worrying about symptoms anymore. We'll be looking at the actual underlying pathological changes that have taken place.”
But in the event, it turned out they couldn't do that. By about 2008, they had thrown up their hands and said, “No, we're going to have to continue to rely upon the same basic approach that we developed in 1980.”
When that document came out, there had been a lot of criticism, some of it from Robert Spitzer, who had been largely in control of DSM-III and DSM-III-R, and his successor, Allen Frances, who'd run DSM-IV. They both were fiercely critical of what was going on and said it was being done in the dark, in secrecy, and that it wasn't scientific. When it was about to come out, Thomas Insel and Steven Hyman, the then-current and preceding directors of the National Institute of Mental Health, denounced the document as unscientific and useless.
So if you're talking about a crisis, that's a crisis for the field. If its diagnostic system is being dissed by leading figures like that, what else was a problem? The difficulties with the existing drug therapies, particularly, had become more and more manifest.
To make matters worse, partly because Big Pharma had sometimes behaved, shall we say, rather unethically with these drugs, it had hidden things that undercut their claims. It had manufactured studies. It had manipulated data. And it got caught out, and it paid billions of dollars in damages for some of the tricks it had got up to.
Not just in psychiatry—I mean, Vioxx, for example, the painkiller, was another huge scandal, and it was a $5 billion settlement.
But the drug companies had suffered some reputational damage. Beyond that, they didn't have any real clues. Unfortunately, neuroscience hadn't thrown up new targets for different forms of drug development, and they decided they could make more money by spending their money on research on other diseases, not mental illness.
The crisis was that you were stuck with a set of drugs that Steve Hyman says “aren't really any advance on the ones we found by accident in the 1950s.”
Mm-hmm.
And there isn't new research unless small startups are going on to develop new ones. So you have an increasing sense that your diagnostic process is falling apart, your drug treatments' limitations are becoming more manifest, and, as well, for people with serious mental illness, public policy has screwed things up badly.
If you are a person with serious mental illness, you will die, on average, 15 to 25 years before the rest of us. That gap has been growing rather than diminishing. So that's not a good thing.
It's not something I want to lay entirely at the door of psychiatry, so don't get me wrong. I think a lot of this is public policy that has really abandoned treatment for the seriously mentally ill. You see it on the streets of our cities. You see the sidewalk psychotics. You see people who are cycling between brief periods of inpatient care, the gutter or the flophouse, and the jail.
You see the 3 largest centers of inpatient psychiatric care, if you can call it that, in the United States today: the Los Angeles County Jail, Cook County Jail in Chicago, and Rikers Island in New York. That's shocking because, by their very nature, of course, prisons aren't equipped to deal with serious mental illness.
Some dark ways to return to the asylum era.
Yeah. Well, you know, the asylums had acquired a very bad reputation, and I've written about some of the reasons why that happened. But when asylums were founded, it was a period of enormous optimism that we were going to be able to cure these people, that we would rescue them from attics and from jail cells, and, through providing a therapeutic environment, coaxing them to work and creating a system where they learned to control themselves, not necessarily to drive their demons out, but to keep them under some sort of wraps.
The expectation when the asylums came along was that they'd not only rescue people from horrendous conditions in the prisons and the jails, but they'd actively cure them. The earliest alienists, as they called themselves then, thought that they could cure 60, 70, 80 percent, maybe even more, of patients, as long as they came in early.
Really, asylums were built out of that sense of optimism—that sense that so much was environmental, and that not exacerbating the condition by treating people like animals, beating them, and otherwise horrifically maltreating them would create a sense of cure. That really underlay the construction of the asylums.
Now, having abandoned the asylums—which we did starting a little bit in the 1950s, but really from the late 1960s onward—that was because there was going to be something miraculous called community care. But community care is a shell game without a pea. It's like one of those confidence tricks. There were no substitute community facilities for dealing with the really seriously mentally ill.
So now we're truly in this crisis, in this essentially dark age. In part, I think our conversation—our journey through the history of psychiatry—is an exploration of some gigantic mistakes, but also an exploration of where some hope for the future might lie. We'll talk quite a bit about this.
2. Categories of Mental Illness
I was wondering if you can also lay out what the big categories of mental illness are that we're referring to. You've already hinted at them, but what are the levels of seriousness and the categories of illness, like psychosis and depression and so on?
Going back to the early 20th century, the German psychiatrist Emil Kraepelin, working with thousands of records in German asylums, inductively developed a distinction between 2 very broad categories of mental illness. One he called dementia praecox, or early dementia, and the other he called manic-depressive illness, which was a more remitting illness that sometimes went away entirely, other times went back and forth, whereas dementia praecox was a one-way ticket down.
That label was transformed by a Swiss psychiatrist, Bleuler, into the term we use today, schizophrenia, although Bleuler talked about the schizophrenias because he thought that under that broad label there was a diverse group of things running around. I think that was an important insight that tends to get lost sometimes.
This was jamming together people with very serious psychosis—that is, people who'd lost touch with what we like to think of as reality, whose emotional and cognitive lives were in total turmoil, and who had lost the ability to connect with other human beings. Their social skills atrophied. Well, this is something contemporary psychiatrists would refer to as the positive and negative symptoms of schizophrenia.
But underlying the definition of schizophrenia here is a detachment from reality. So you're hearing voices, you're seeing visions.
You're thinking people are plotting against you. You think the television is talking directly to you.
And because of that, it has these consequences for how you're connected to the rest of the world and what your emotional life is like, all that kind of stuff.
Yes. Your emotional life flattens out. Your language capacity deteriorates. Your ability to relate to other people either vanishes or becomes caught up in the web of delusions, where you think people around you are plotting against you or doing terrible things to you.
And is that a different world than the world of bipolar disorder and the world of depression?
Yes. The Greeks and the Romans—ancient Greece and ancient Rome—recognized different forms of insanity, as they called it. Melancholia would have been the term the Greeks and the Romans would have used, and it survived and was very much around. I think that is a form of depression.
What's happened now is that major depression has become a catchall category. It embraces both what we might think of as milder forms of emotional distress, along with what melancholia referred to, which was really a kind of depression that had psychotic features: this loss of contact, as it were, with everyday reality.
Something you would talk about maybe as clinical depression. By the way, we should mention that this field in the 21st century is like a minefield.
Yes, very much so. Here's a very strange bit of historical record.
The other distinction—and the distinction we're grappling with—is that we have people whose depression is of such a scale that they're threatening to do away with themselves. They've retreated into complete, almost immobility. They're overwhelmed by senses of sadness and loss, and if they're religious, then they're damned to hell and all those kinds of things. So we have this psychosis that we've been talking about.
We have something else that the ancients recognized: dementia, the loss—really, the loss—of our mind, as it were. But then we also have other kinds of disturbance of our mental faculties that generally we think of as more minor. I don't want to make light of them, because people genuinely suffer pretty badly from these things.
Those are things we in the 20th and 21st centuries tend to talk about as neuroses, neurotic diseases, and psychotic diseases. In the 19th century, neurosis was a term that meant things rooted in the brain, as you can see from the root of the word, and psychosis was stuff that came from the mind, the psyche. Yet sometime in the late 19th century, those things crossed over.
When we talk in the present, we do tend to distinguish between the core, really the most severe forms of mental disorder. That would include things like Alzheimer's disease and other forms of dementia, very serious depression, and bipolar disorder, where people oscillate or have extreme mania. They're not getting any sleep. They're talking at an extraordinary rate. Their behavior is very hard to tolerate, and they're exhausting themselves. They may even die from exhaustion if it's not controlled.
Very often, that alternates with periods of depression. So that was a category that was captured initially as manic-depressive illness and later evolved into bipolar disorder, with depression and major depression separated out separately.
But then there are a whole bunch of other things, like phobias. People can't go outside because they find it too frightening. Milder phobias: “I can't get in an airplane because it's gonna crash,” or “I can't go to school because it's overwhelming for me.” So school phobia emerges as a diagnosis.
A disorder that at first attracted Freud was hysteria.
And now we should say you wrote a book on hysteria.
Oh, I did indeed, yes.
You mentioned—I mean, hysteria, every classification we're talking about has been used and abused by every layer of society, including institutions.
Yes.
Including just culturally, the word hysteria has been applied disproportionately to different races, to different—
Genders particularly, yes, yes.
Genders disproportionately. So we're in this crisis of trying to figure out what to do with this super-complicated human mind.
Yes.
And everybody is dogmatically creating narratives that take hold, and in so doing can lead to some abuses—
Yes, they do. Yes, they do.
—as you document.
3. Asylums, Eugenics, and the Nazis
If you look back at the asylum era, born in this period of intense optimism, the claims to be able to cure these vast numbers of patients were overblown. I do believe the early asylums actually did good work, and that some patients did very well and recovered as a result of their stays.
But what happened was that they weren't discharging 80% of their patients. They were discharging 35% or 40% of their patients, and what that meant was that every year, left behind, was a batch of chronic patients. Then the next year, you repeated it. Over time, what that means is that the ratio of new patients to chronic patients gets worse and worse.
More and more, the image of the asylum was defined by the chronic patient who hadn't recovered, who maybe spent years or decades there, and who only left in a pine box. The image of the asylum declined drastically. As the asylums became more and more overcrowded, conditions in them deteriorated. Patients were often abused, and psychiatrists didn't know what to do with them.
They faced a problem in the late 19th century. You'd promised 70% or 80% cures, but we weren't seeing that. In fact, when we calculated cures based on the numbers of people in the asylum, it was more like 10% or 12%. That's the way you could play with statistics, because that's all the old patients mixed with the new. But still, it looked very bad. How do you explain this, doctor? You've promised us one thing, and you've delivered something quite different.
The answer came in a way of blaming the victim, in a way of saying, “Well, what we didn't understand was that mental illness is a fundamentally biological condition. These people are evolutionary throwbacks.” Evolution was generally thought of as a progression onward and upward, but these people had fallen back into a lesser form of existence. They'd lost their essential humanity because their brains were defective.
So what emerged then was the idea of degeneration—the idea that these patients were degenerates. They were people with an inferior biology. You couldn't release them because they bred like rabbits. They didn't have any self-control because of their diminished humanity.
This is the narrative.
This is the narrative. And so what it did was provide a justification for locking up people in asylums that wasn't therapeutic at all. It was just keeping them out of the way.
And then it led to the justification of sterilization—
Exactly.
—based on the same argument.
So maybe we can release them if we make sure they can't breed.
This is the beginning of the darkness.
It is the beginning of the darkness. My own state was one of the pioneers in this process, and it continued to sterilize mental patients up until about 1960.
By the 1960s, over 60,000 sterilizations had been performed in the United States, with California performing a disproportionately high number.
That's correct. But even more serious consequences could flow from this set of issues. When you start talking—as one British psychiatrist said—if his patients coming into the asylum had been puppies, we'd have tied them up in a sack because they were some horrible mongrel, not a purebred dog, tied them up in a sack with some lead weights, and thrown them in a pond and drowned them.
Man.
That kind of language is very, very dangerous. And what happened was that California's law surrounding sterilization was advocated for in the West. By that I mean North America, Britain, and much of Europe. There were enough checks and balances in a democratic system that, even though there were enthusiasts—the eugenicists who said, “Best get rid of these people, put them to death”—that never really acquired mass support.
But what happened in Germany once the Nazis came to power is that they seized on these notions: the idea that the mentally ill were, as they put it, “useless eaters,” people consuming resources but never going to get better, just a burden on the state. Their lives weren't worth living because, after all, they had this serious mental illness.
So first you sterilize, and then you go, “But we're still supporting all these people.” Hitler starts something called the T4 program, after the street name of the house where this was concocted: Tiergartenstraße 4. The mentally ill were the first people to suffer from the Final Solution.
It was in the mass killing of the mentally ill, which may have been as many as 250,000 people, that the technology of the gas chamber was developed, and the technology of disguising the gas chambers as showers was developed. Patients were taken away to a number of psychiatric centers and systematically put to death. They had the crematoriums and the black smoke, and local people talked about the buses that were bringing them in as killing crates. So they were aware of what was going on.
Were they influenced by the narratives that were born in the United States?
Yes, absolutely.
About this kind of—
About that sort of thing. And lacking the checks and balances that, at least until recently, this country had, it was relatively easy for Hitler to do that. Particularly with the war looming, the idea was, “We're going to support all these useless people? Let's kill them.” And German psychiatry, for the most part, collaborated with that process.
I wonder how many people throughout that whole journey in the psychiatry profession were brave enough to speak up and say, “Hey, maybe the sack-of-puppies kind of language is a problem?”
Oh, yes. Oh, yes.
That kind of language is a problem?
That's the really nasty direction that that language could lead to. And it was symptomatic of the kind of stigma that tends to attach itself to mental illness and this sense of hopelessness.
But if you're a healing professional—if you enter psychiatry thinking, “I'm going to do this to help people, to cure people, to make their lives better”—to just become a glorified boarding-house keeper, keeping them under lock and key, or, in the alternative, to collaborate in the sorts of awfulness that the Nazis perpetrated, that's something from which decent human beings tend to recoil, and decent psychiatrists tended to recoil.
Still thinking, as they did by the end of the 19th century, that mental illness was predominantly a biological problem, some of them began to say, “Well, maybe biology, as well as being the problem, could provide the solution. Maybe we should look for ways to intervene in the biological systems of these people and make them better.” The same logic that applies, I would say, in the present—
For many working in the field—but in a cruder form.
But in a very different form, exactly.
Yeah. If we can just speak about the Nazis a bit more, you highlight that America financially supported the German psychiatric researchers with deep Nazi ties, like Ernst Rüdin, who was the key architect of Hitler's mass sterilization and extermination laws.
So it seems like the Nazis borrowed the American narrative that these were lesser biological beings, and then this financial support and these ties continued.
Yeah. One of the organizations that recognized that mental illness was an acute social problem, very costly to the state and inflicting all kinds of suffering on people, was the Rockefeller Foundation.
What we don't realize today is that the involvement of the federal government in medical research, and indeed scientific research, is a World War II and postwar development, partly the Cold War, Sputnik, and all of that. That's when big science and big medicine got funded in extravagant ways.
Before the war, science was an orphan. It didn't get much money from the government, and medicine even less so. To the extent that medical training was reformed, that was the product of investment by the Rockefeller Foundation, which was enormously wealthy by the standards of the time.
Around 1930, the Rockefeller Foundation decided it needed to concentrate its resources and pick priorities for the money it was investing. It may seem a rather strange thing, within the whole range of medical areas it could choose, that it chose psychiatry as the one in which it was going to invest.
I think it did so in part precisely because scientific research in psychiatry was so backward, partly because it was such a pressing public problem, and partly—and this was less public but nonetheless, I think, played an important role—because several of the trustees of the Rockefeller Foundation had direct experience of mental illness in their families.
There were wives who'd been institutionalized as schizophrenic. In one case, a wife murdered the children and killed herself, leaving her husband, a major actor in the Rockefeller Foundation, bereft and, of course, inclined then to support research in this area.
The Rockefeller Foundation spread its money very widely, precisely because it didn't know where to spend most of its money. So it provided some support for psychotherapeutics. It supported a number of the therapeutic experiments then going on, and it supported work in genetics.
One of the geneticists it supported was Ernst Rüdin in Germany, who was the leading German researcher in genetics and mental disorder. And Rüdin, because he had absorbed the lessons from California about sterilization, became a very enthusiastic proponent of that, and then a supporter of murdering mental patients.
And we should say, we'll probably talk about the complicated nature of science: that it sometimes can be captured by certain ideologies and, in so doing, do a lot of damage to humanity.
But ultimately, the beacon of hope for the future of humanity lies in the scientific method, as flawed as it is. So everything we're talking about lets us see how you F up in major, dark, disturbing ways throughout the 20th century, in the psychiatric profession. But that should be an instructive lesson in how we proceed forward to do better and better and better.
4. The Ice Pick Lobotomy
We can discuss a series of therapeutic experiments on people who were shut up in a double sense. They were locked away, and their voices were not heeded because they were the product of their madness.
So what we see in the first 5 decades of the 20th century is people with a variety of motivations, including the desire to improve the lot of the mentally ill, engaging in uncontrolled experiments that had terrible results.
And the science behind it was shaky, but nonetheless it existed. It wasn't just plucked out of the sky. And yes, eventually those things break down. The clearest case of that, because it's the most extreme of these, at least in the public imagination, is lobotomy.
The idea was to solve psychotic breakdowns in people by excising part of their brain—initially by drilling holes in the skull and injecting alcohol, or using what looked like a butter knife to break connections between the brain. Later, when that process seemed to be too slow, there was the Henry Ford of lobotomy. His daughter said Walter Freeman aspired to be the Henry Ford of lobotomy, the one who could mechanize its production and get it done fast.
He invented the ice-pick lobotomy, where you used an ice pick in the orbit of the eye after rendering somebody unconscious with 2 or 3 electric shocks. You banged it through the bone, wiggled it about, and severed—I mean, it's just hard to even describe.
So this was from the 1930s to the 1970s?
Yes. Freeman started his work in 1936, borrowing from the work of the preceding year by a Portuguese neurologist named Egas Moniz. Moniz won the Nobel Prize in Medicine in 1949 for lobotomy. It's important to see that: That was 14 years of experience, and yet that won a Nobel Prize. I'm sure that's one they'd like to retract.
So Walter Freeman popularized the ice pick?
His particular specialty after the war became this ice-pick lobotomy, because there were over 500,000 patients in America's mental hospitals. Freeman was convinced this operation was a cure-all, and so he traveled around in a camper truck, which he called the Lobotomobile. He would descend on state hospitals in the summer and teach them how to do this ice-pick lobotomy.
This is, by the way, an image of the tool.
Yes, those are the tools he used. Originally, he used an actual ice pick, and then he developed this—
This is what he developed. This is the state-of-the-art technology.
This is the state of the art, with a hammer or a mallet.
Oh, no!
Yes, I'm sorry. It's very distressing.
Having to write about this, by the way, is a lot.
Well, it's really very, very, very, very difficult. I came across, for example, a picture of a naked woman being dragged away by attendants to be lobotomized. She's resisting with all her might and to no avail.
You have a picture there of Walter Freeman lobotomizing a patient in Washington State. Freeman was ambidextrous. When he taught neurology, he would draw simultaneously with his left and right hand, and he could do it perfectly. When he was performing lobotomy, when his right hand got tired, he switched to his left hand. He sometimes did 20 or 30 lobotomies in an afternoon.
He boasted, “You know, I could teach any damn fool to perform a lobotomy in 20 minutes—even a psychiatrist.” Freeman was a neurologist, and he had a lot of contempt for psychiatrists.
So this was a very ugly episode. How did it die away?
It really took generational change. Some of these lobotomists continued to operate into the 1960s, even into the early 1970s, but the younger generation became acquainted with the really worst failures of that regime: the people on the back wards who were incontinent, who were basically zombies, who had lost all mental power. They rebelled against this.
By then, they had a different treatment in the form of antipsychotic drugs, which looked much more like what regular medicine was doing and didn't have these horrible overtones.
In the popular mind, probably the most famous instance of telling the public about some of these interventions was the film of Ken Kesey's novel One Flew Over the Cuckoo's Nest. You see Jack Nicholson giving, I think, the performance of a lifetime. He is given ECT, electroconvulsive therapy, in a very dramatic rendition of what that was—not really what was going on with ECT by the 1970s, but certainly what had been going on in the past.
Finally, when ECT doesn't smash him to bits, they lobotomize him, and the film ends, obviously, with him being smothered to death because Chief can't bear to see him in the state that he's in. That fixed in the public mind some of the images of these things. It is one of the things that gave electroconvulsive therapy such a bad name.
5. Malaria "Cure" for Syphilis
So, actually, not to fast-forward too quickly, let's talk about the full journey of everything we've been talking about. We mentioned the asylum era that began in the mid-19th century and went into the 20th century, and we talked about the narratives.
And we talked about sterilization.
Sterilization. And let's look at insulin shock therapy, from 1933 to the 1960s, where you were putting patients into deep hypoglycemic comas using large doses of insulin.
Yeah. As I mentioned, for psychiatrists who went into the field and were ambitious, but who also wanted to think of themselves as therapeutic agents, to just sit there passively and contain the patients was very unattractive. They looked around for ways in which biological interventions could perhaps be used to ameliorate this condition, which they still saw in largely biological terms.
One of the crucial early ways in which this thinking developed, and which affected a large number of patients, was this: One of the few diagnostic triumphs of psychiatry in the early 19th century, as the profession began to emerge, was that it began to distinguish a group of patients who were deemed to be suffering from something called general paralysis of the insane.
That encapsulates 2 things about what was going on. First of all, paralysis: the gradual loss of motor control—the ability to walk, the ability to swallow, the ability to talk. Those are primarily what we'd think of these days as neurological issues. But they were accompanied by bizarre psychiatric symptomatology. These were people who thought they were Napoleon, or Jesus Christ, or the richest and sexiest man in the world, or Mary, the mother of God.
They were primarily men, but there were also female victims. At the turn of the 20th century, as many as 25% of the people being admitted to asylums were suffering from general paralysis of the insane, or GPI for short.
There had been a lot of suspicions about this being connected somehow to sex and moral dissolution and so forth, but what evolved in the early 20th century was the discovery of the actual origins of this disorder. I've said that psychiatry has been looking for the underlying pathology that lies behind mental diseases. This was one where researchers at the Rockefeller Institute discovered that the organism that causes syphilis was residing in the brains of people who were suffering from GPI.
This was, in fact, the tertiary stage of syphilis. Syphilis is still a real public health problem. It was like AIDS in the late 19th century. It was everywhere. When you first contract syphilis in the primary phase, you have pain, but then it goes underground and you think it's gone. It lurks the way the chickenpox virus lurks and can surface years later, right?
It's insidiously damaging. Sometimes it attacks the heart, and people drop dead of a heart attack in their 40s. “Oh, he died of a natural heart attack,” but in fact it was the syphilis. Or it attacks the central nervous system, the spinal column, and the brain. Then you get the paralysis, and you also get the psychiatric symptomatology.
When that was discovered, it suggested that mental illness might have an infectious origin. A treatment for GPI, tertiary syphilis, went on to win its developer a Nobel Prize—one of only 2 awarded for psychiatric innovations. One was a lobotomy; the other was giving people malaria to cure their syphilis.
In case people didn't hear that: giving people malaria in order to cure syphilis.
There was an Austrian doctor, Julius Wagner-Jauregg, who had long thought that fever could be used to cure mental illness. He tried rat-bite fever. He tried giving people typhoid vaccine, which creates a fever, to no avail.
Toward the end of World War I, the Italians were fighting on the side of the British, the Americans, and the French. They captured an Italian soldier who had malaria. Malaria was endemic in Italy in those years. They brought him to Wagner-Jauregg, and he extracted the malarial blood and injected it into a series of patients with GPI, with general paralysis of the insane, and claimed it cured them.
We know from later on, when he fessed up, that those claims were wildly exaggerated, but they were widely accepted. Malarial treatment spread to Britain, Germany, and the United States. Sometimes it was administered through vials of malarial blood, but very often mental hospitals had actual colonies of malarial mosquitoes.
Imagine you're a mental patient, and you're put in a straitjacket and put in a room. You can't move, and mosquitoes are buzzing around. They bite you, and then you develop malaria.
And he got a Nobel Prize for this?
Yes, in 1937, he got a Nobel Prize. This was a condition that was invariably fatal, and the claim was that somehow the malarial fever worked.
There were 2 possible ways. Wagner-Jauregg thought it stimulated the immune system to attack whatever it was that was causing the insanity. But the other possibility was the following: When you have the malarial parasite in a test tube and heat the test tube to about 105 or 106 degrees, it dies. So the idea, potentially, was that you were burning the parasites out of the brain with this agent.
Because people were pretty unsophisticated about statistics, and because the idea of a controlled trial had not yet come to pass, this treatment was used extensively for a couple of decades.
What caused it to stop—and this speaks to the progress of science—was the discovery of penicillin, which was a real magic bullet. Once you had penicillin, you weren’t going to continue treating people with malaria, so it died away. But it was the first such treatment, and here’s the other way this feeds into the narrative of these desperate remedies that developed in the period between the mid-1910s and, say, 1950.
The discovery of the syphilitic origins of general paralysis of the insane occurred at a time when medicine had undergone a profound transformation. In the late 19th century, the work of Louis Pasteur, who was a chemist, not an MD, and the work of Robert Koch in Germany had uncovered the origins of a variety of diseases and suggested that bacteria were the reason why people got sick. That led, of course, to a whole series of public health triumphs, because initially it didn’t lead to antibiotics. But for a lot of these diseases, even viral diseases like rabies, you could develop a vaccine. The vaccines were phenomenally effective.
That was one way in which the new germ theory of disease transformed medicine and tied it into the laboratory and into science in a new way. The other was the adaptation of Pasteur’s theories by a British surgeon named Lister. Previously, when pus developed after surgery, people had thought that was a good sign. Lister said, “No, I don’t think so. These are actually nasty germs causing this, and so we’re going to do antiseptic surgery.”
He sprayed carbolic acid on the wounds to try to kill the microbes. Most of his colleagues thought he was nuts. They thought, “This is ridiculous, these microorganisms. You couldn’t even see them.” Well, you could with a microscope, but Lister prevailed. Eventually, we moved from antiseptic surgery to aseptic surgery, which is what we have now, where you try to have a sterilized set of instruments in a sterilized environment so you don’t infect things, right?
By the way, these are definitive examples of progress in medicine.
Absolutely.
Penicillin—
Yes.
—and making sure there are no germs during surgery.
Associated with wounds, yes.
So these are all just refreshingly clear examples of progress. The reason I say it’s refreshingly clear that there’s progress is that there’s not a refreshingly clear progression in the history of psychiatry. Maybe a few hints.
Some bits, yes. There haven’t been the dramatic breakthroughs that I think everybody in the field would hope for. There’s some debate about how powerful what we have done is, and I think it’s reasonable to debate that and to also acknowledge that there is important progress, limited as it is.
Now you have 25% of the admissions to a mental hospital actually suffering from an infectious disease. Medicine in general has now tied its fortunes to the laboratory. The idea that disease is caused by bacteria—we can’t yet see viruses—is a very powerful one, and that notion that disease is caused by bacterial infection acquires great momentum. But it hasn’t touched psychiatry.
Medicine now has interventions that work, and sometimes quite dramatically. The first patient given the diphtheria antitoxin—diphtheria causes a leather-like membrane to grow over your throat, and you die choking to death. If you have a child and you watch that child die like that, you will never be over it. So when you had something that warded that off, that improved medicine’s image dramatically and improved its financial prospects dramatically, particularly as medical training became reformed and more involved with science.
That hadn’t applied to psychiatry until syphilis came along. Now we have the model that an infectious agent can cause people’s minds to go amok. The very person who invented the basic distinction between the kinds of psychoses we still use today—schizophrenia and bipolar disorder—Emil Kraepelin, began to think, “You know, there may be something infectious about the mental illnesses we’re treating.”
One of the people he trained was a young psychiatrist from the United States named Henry Cotton, who had also been trained by Adolf Meyer, the leading American psychiatrist of the first 40 years of the 20th century. When Cotton came back from Germany, having spent a year there, Meyer secured him a position as head of the New Jersey State Mental Hospital at Trenton.
Cotton was an ambitious, reforming man. He wanted to bring psychiatry back to medicine. He also wanted to chuck out all the old stuff. He didn’t want chains in his hospital. He didn’t want straightjackets, if he could help it. So that went away. But nothing seemed to change fundamentally. He still wasn’t curing patients.
Then he came across this idea of focal sepsis: the idea that low-grade infections can lurk in the body, and what they do is release toxins into the bloodstream and the lymph. Imagine if those toxins get to the brain. What’s it going to do? It’s going to poison the brain, and the brain is then going to act up.
We didn’t have antibiotics, so what were we going to do about this? Well, we could perhaps locate the bacterial infection and get rid of it. We could engage in what he called surgical bacteriology.
The first obvious target here was teeth. Your teeth look close to your brain. They’re often infected, and that infection often goes untreated for a time. So we pulled a lot of teeth. Patients didn’t get better.
Maybe the theory was wrong. No. Tonsils—well, they were getting infected, so we removed them. They still didn’t get better. Well, they were swallowing the bacteria, so we removed stomachs, spleens, and colons. And we claimed to be curing 80% of our patients. Rich patients came from all over America to be treated with this novel treatment.
Crazy.
Cotton gave a series of lectures at Princeton. These weren’t just ordinary lectures; they were given by Nobel Prize winners. It was a very prestigious series. They were published by Oxford University Press and Princeton University Press. The New York Times hailed it as a great breakthrough.
In reality, 45% of the people who got the abdominal surgery died within a year.
They’re cutting out stomachs.
Yep. He was cutting out stomachs. There’s this passage in one of his papers where he says, “Stomachs are like cement mixers on a construction site and could be dispensed with.”
When you think about it, oh my God—if you were released from Trenton and you had no teeth, people immediately knew you were an ex-patient because the word had spread. This went on starting in 1916. Cotton dropped dead of a heart attack in 1933, but he was succeeded by 3 people he had trained.
They dropped the abdominal surgery. They used colonic irrigation, but the teeth and the tonsils kept being pulled. I interviewed the dentist who had come to the hospital in 1916 and must have pulled several hundred thousand teeth. He retired in 1960, which was when that finally stopped. And he was convinced Cotton should have won the Nobel Prize for this.
Can you give us some intuition and help us put ourselves in that mind space? Presumably, these were smart human beings. Why were they fraudulent in their reporting of how effective it was? Why were all the people who were participating—both the doctors and general culture—
It’s extraordinary. Obviously, many of the interventions I’m talking about are very powerful interventions conducted by people in white coats and with stethoscopes and scalpels.
Powerful, by the way, in terms of the amount of impact they have on the human body, not powerful in terms of how effective they are.
Yes, powerful as well in terms of the placebo effect. “Look, what I am going to do to you—and yes, it’s going to hurt, and it’s very intimate—but it’s going to make you better.” So that’s always—this is a problem that persists in contemporary psychiatry: trying to figure out how much of the improvement we’re seeing is the placebo effect and how much of it is the active effect of whatever we’re doing.
But, by the way, on that small tangent, let’s return to that perhaps later.
Yes.
I, for one, can tell you that for me, for my mind, the placebo effect—even when you tell me it’s a placebo—will work.
Yes.
But now, if you have combined an actual gigantic operation that is physically, mentally, in every way life-changing—
Everybody around you is in lab coats, and all of society is telling you this is going to be life-changing.
I get it. That’s the purest kind of placebo effect.
It’s a placebo effect that comes both from the patient, who wants to be better and wants to believe this is going to make them better, and from the person conducting it. It’s easy to deceive yourself, to see what you want to see.
6. Insulin Coma Therapy
So anyway, that was one episode. We’ve talked about triumphs of medicine, so let me talk about one of the real triumphs of 20th-century medicine, which is interesting to refer to because it wasn’t a cure, just like psychiatric drugs aren’t a cure for mental illness. It was a symptomatic treatment, but it transformed lives. That was the discovery of insulin in the 1920s.
Previously, particularly what we now call Type 1, or juvenile, diabetes was a death sentence. You got it, and whatever you did—you tried various quack remedies, you tried diet, you tried all sorts of things—the inevitable thing was that it killed you. And then came insulin.
Now, insulin doesn’t mean you’re cured of your diabetes, but what it means is you can live a relatively normal life and your lifespan is greatly expanded. So by any measure, you have to say that’s dramatic progress.
But insulin is something our bodies produce, we hope, unless we’re seriously diabetic. Those of us with Type 2 diabetes have bodies that resist insulin, and we have to resort to other ways of trying to cope. But if you get too much insulin, it makes you unconscious, and that’s how another one of these desperate remedies came along.
A man named Sakel, working in a German clinic for drug addicts, was putting people under mild comas to help them through the withdrawal symptoms once they got over their addiction.
So he was familiar with that. When he moved to Austria, he decided he’d try this as a treatment for schizophrenia. He put people into comas—sometimes comas that would last hours or days. They would be revived by giving them glucose, usually intravenously, sometimes not. During the time they were in comas, they often had seizures. He saw that as a therapeutic sign.
He claimed that his insulin coma treatment cured 80% of his patients. Eighty percent tends to come up again and again in these treatments as a sort of percentage that you cure. He was invited to New York and demonstrated this at the Harlem Valley Mental Hospital. It spread. This is in the ’30s? This was starting in 1933. The visit to America was, I believe, in 1936, and Sakel ended up settling here.
He had a very lucrative private practice in New York, and when he died, he left his partner, I think, an estate of about $2 million, which in the early 1960s was a very substantial amount of money that he’d earned from practice. Insulin coma therapy was widely adopted. What kept it from being a large-scale thing was that it required an enormous amount of nursing and medical attention, because people were literally hovering on the brink of life and death. They could go into a permanent coma; they could just die.
Their vital signs had to be monitored. They had to be brought around very quickly, if need be. There’s some evidence that the treatment killed brain cells. When Sakel was told that, he said, “Yes, that’s probably true. They’re killing the schizophrenic brain cells.” That’s just nonsense, of course. That’s just nonsense, but that was his rationale.
Insulin comas weren’t subjected to a randomized controlled trial until the 1950s. When they were subjected to a controlled trial, they failed it, and so it died out. That’s scientific progress again, in a way, but it took a long time.
One of the people who received insulin coma therapy—have you seen the film “A Beautiful Mind”?
Mm-hmm. He did receive insulin coma therapy.
Ironically, at Trenton State Hospital, where Cotton had been. John Nash got insulin comas, and they were going to lobotomize him, and they didn’t, but he was at risk of that.
We should say that with this treatment, patients would thrash, moan, and convulse before falling into a coma. The treatment required a course of up to 60 comas. It turned out to have a mortality rate of 1% to 5% and caused significant brain damage and obesity.
Yeah, yet it was hailed as a miracle cure for schizophrenia.
Yes, that’s right.
It was performed on John Nash, one of the great minds of the 20th century.
Yes, and Nash clearly did become delusional, but that was one of the treatments he was subjected to, and it’s well represented, actually, in the film “A Beautiful Mind.”
So I mentioned seizures. Also in Hungary in this period, another psychiatrist decided that you couldn’t be both schizophrenic and epileptic, that there was somehow an antagonism between the two. If you had epilepsy, you didn’t have schizophrenia. If you had schizophrenia, you couldn’t have epilepsy. I should say at the outset, that’s not true, but that’s what he believed.
The logical next step was, “Well, if we could create an artificial epileptic seizure, maybe we would drive out the schizophrenia.” So what to do? He first tried injecting camphor, a natural substance. Natural substances aren’t necessarily benign substances. That caused abscesses, and it wasn’t very effective.
He sought an alternative, and he settled on something called Cardiazol, or Metrazol, depending on which side of the Atlantic you were on. Injecting that into a patient usually caused a seizure—a big seizure, like a grand mal seizure, where your body arcs back and your legs contract dramatically.
You can fracture spines, hips, and bones.
And you ended up, yes, with fractures of the vertebrae and fractures of the hip socket. When muscles in the thigh contract that badly, what happens? The thigh bone is driven into the socket at such a rate that it fractures. So these were among the complications that Metrazol produced.
More than that, he himself conceded that between the injection and the seizure, the patient felt as though he or she were on the brink of death. Now imagine—pretend you’re a mental patient. You’re brought in in a straitjacket. A man in a white coat with a big hypodermic injects something into you. You feel as though you’re going to die. Maybe that lingers for 2, 3, or 10 minutes, and then you seize, with those possible fractures following.
Violent seizures.
It’s violent and hard to witness, and it’s very unpredictable. So it’s used, but people are not very happy, and that’s how we get electroconvulsive therapy—electroshock, as it’s first called.
7. Electroconvulsive Therapy (ECT)
Two Italian psychiatrists, Cerletti and Bini, experimented with electricity, and they first experimented on dogs. They made a mistake initially. They had an electrode on the head and an electrode on the anus. The electric current passed through the body, stopped the heart, and the dogs died. So that seemed a dead end.
Then somebody said to them, “You know, you should go to the Rome slaughterhouse and see the pigs being slaughtered, because you’ll learn something very interesting.” So they went, and the pigs were dangling by their hind legs. As they came by, 2 electrodes crossed their heads. With electroshock, they convulsed, became unconscious, their throats were slit, and pork arrived.
They tried that on dogs, and it turned out that current passing through the brain didn’t kill them. So they decided to try it out. They picked up a transient homeless person at the Rome train station and brought him in. They tried it, and at first they didn’t use enough current, so nothing very much happened.
They were very white-faced and quite worried, off in the corner. We have descriptions of this, and they were talking: “What should we do?” “Well, we’ll up the current.” The patient heard that and said, “No, another one, that’s deadly.” They did it anyway, and he convulsed—another grand mal seizure, with the same problems of spinal fractures and hip fractures, and so on.
He stopped breathing. You can imagine the scene. Then he spontaneously started breathing again, and when he came around, he was in contact with reality. They had this miracle cure, and it was very easy to administer, cheap, and didn’t involve injecting things into people’s bodies. So it quickly spread across the Atlantic and to other parts of Europe, and ECT became a very widely used intervention.
A couple of things to say about this. It turns out it’s not very useful for schizophrenia. Remember the connection between seizures and schizophrenia that was originally posited. But it seems to work in cases of depression, particularly suicidal depression.
Fast-forwarding to the modern day.
Mm-hmm.
This is something I learned by reading a bunch recently. It seems to be one of the few evidence-based, scientifically backed methods that actually worked for clinical depression—for serious depression.
Yes, if we fast-forward, we’re looking at, in some respects, a different animal, for reasons I’ll explain.
This is unmodified ECT.
Yeah, so we’re talking about unmodified ECT, which ruled the roost well into the 1950s, and in some places even into the 1960s. It was associated with all the problems of fractures that we’ve talked about. It was also associated with memory problems. People often lost memory. There’s some dispute about how serious that is, but it’s pretty widely recognized that’s one of the prices you’re going to pay for that treatment.
The thing is, for mental hospitals in the ’40s and ’50s, ECT was used much more as a device to control people’s behavior than as a therapeutic intervention. It was quite punitive and seen as such. Patients didn’t want it repeated, and so they controlled themselves a bit.
But yes, we don’t know why it, quote, “works.” More recent work, starting probably in the 1990s—and I’m going to get in trouble with some people for saying this, because you mentioned patients and psychiatrists who swear by ECT—has led to a split in opinion. There are others who swear at it, partly because of the memory problems I alluded to, and partly because of claims that it may cause brain damage.
Passing an electric current through the brain is possible. What changed ECT a bit—quite a bit, actually—was giving muscle relaxants so that people didn’t thrash about, and the fractures were largely a thing of the past. When they introduced these muscle relaxants, they originally used curare, but then they used other, more modern drugs to paralyze the muscles temporarily.
The problem is that this would also paralyze your breathing muscles, so that’s not too good. It became a more complicated procedure because you needed anesthesiologists, breathing support, and so forth during the procedure. But it did eliminate the fractures.
It was still a very widely disdained practice, I think, particularly when they had drugs available. The thinking was that, well, we’d sooner use those. But the drugs turned out to be only partially effective, and pretty ineffective very often for suicidal cases or in cases of extreme melancholia.
Now, a couple of things to say: Very often, ECT has to be repeated at intervals as a kind of maintenance therapy. So it hasn’t cured things, but it temporarily alleviates the symptoms. The temporary relief may be fairly lengthy, but nonetheless, very often things will recur.
The memory problems can be quite severe. The worries about brain damage are, I think, certainly things we have to be very cautious about. When we talk about treatment-resistant depression, that’s an interesting concept to me. What it means is that those are the patients who don’t respond to drugs. They may not have a different disease, but the drugs don’t work for them—hence, treatment-resistant.
And the numbers of psychiatrists who are willing to give ECT are rather small, and in many states it’s hedged around with lots of legal restrictions. In California, for example, ECT now almost can’t be given to involuntarily confined patients because you have to volunteer for it. So it’s unusual in that most medical procedures aren’t hedged about by legal constraints like that.
There clearly is a very powerful group of people—some of them psychiatrists, many of them ex-patients, many of them other people who are just suspicious of modern medicine and science—who are very powerfully opposed to ECT. So although it’s fair to say there are trials now that seem to provide decent evidence that, for some patients, this works, and that those patients are deeply distressed before the treatment, it’s also still a controversial treatment, I think it’s fair to say.
Like basically every single topic, treatment, problem, and subfield of psychiatry today.
Yes, yes.
For everything we say today, there will be at least 1 person upset—
—and writing a letter. I think lots of people are upset. So if we talk about drugs, there’ll be 2 kinds of people who will be upset: those who think the drugs are more powerful than they are, or who have been successfully treated by the drugs and go, “Well, it worked for me, so stop criticizing it, because it really is an effective treatment.”
Then, on the other side of the coin, there are those for whom the drug treatment has failed, or who are left with terrible side effects that don’t go away. Or they’re part of a general group of people that, unfortunately, is of a growing number these days, who are so suspicious of medical science and the drug companies that no amount of evidence will sway them. They’re convinced that the drug treatments are poisonous.
The Scientologists are a very extreme example of that. They have a whole museum in Los Angeles, and the title is “Psychiatry: An Industry of Death.” Then, if you think about all the resistance that has surfaced to vaccination in the contemporary United States and how the trust in vaccination has been destroyed for a substantial number of people, it’s very difficult to convince them that they’re mistaken.
And it’s not just the trust in vaccination; the consequence of that is a general distrust in science—
A general distrust, exactly.
—and distrust in medicine and so on.
That’s 1 of my great worries about our contemporary situation. We’re less than a year in. After 4 years of this, first of all, the degree of mistrust will have grown exponentially, and once trust is lost, it’s very hard to recover.
Secondly, the science itself is being destroyed. Clinical trials that were midway through were aborted, so that knowledge has been lost. You would have to start from square 1, and that’s years of work. Scientists aren’t being trained because funding has been cut. Scientists with successful careers no longer have the funding necessary to do their work, and it takes at least 6 or 7 years to train a scientist at the beginning of their career.
If you have 4 years with nobody being trained, you’re talking about a decade being lost. And what’s lost is invisible because it’s counterfactual. We don’t know what that science will lead to or what that medical treatment might lead to, and very many times they fail. That’s the nature of science. It’s the nature of medicine and medical research that not every bright idea we have is going to eventuate in a breakthrough.
It would be really simple and wonderful if the opposite were the case. But the reality is we have to go down lots of blind alleys, we have to try lots of different things, and we have to take years to move from the laboratory to practical application. When we eliminate a whole segment of that, and when on top of that we diminish people’s trust in science, that’s a really, I think, profoundly devastating thing that, given my advanced age, I won’t live to see the consequences of, but my children and grandchildren will.
It really is something cultural: you’ve got to build up trust, and it can be destroyed very easily. So 1 of the things, to go back to the very first question you asked me about—“Is psychiatry in crisis?”—is that genetics was supposed to provide a clear picture of the origins of various mental diseases, because they do seem to run in families.
The expectation was that once we decoded the human genome and could examine bits and pieces of it, we would very quickly find a Mendelian gene or set of genes for schizophrenia, let us say. That hasn’t happened. We now use genome-wide association studies—that is, throwing everything but the kitchen sink into the picture, without any preconditions, and seeing what relates to what. If we use 300 small variations in the genome, we can account for about 10% of schizophrenia. That’s not very powerful.
Beyond that, what psychiatric genetics has tended to throw up is something that undermines the distinctions that we’ve made based on symptomatology. If you look, there is a great deal of overlap in the kinds of genetic abnormalities that heighten the susceptibility to bipolar disorder, schizophrenia, or autism. There’s a lot of overlap there.
What that suggests is that these aren’t distinctive entities in the way that, you know—schizophrenia, as my friend Robin Murray, a British psychiatrist, has said, really seems to be the extreme end of psychosis, the most serious. But it’s sort of on a continuum.
If psychiatry has to say in 10 years, as some leading psychiatrists are speculating, that there’s no such thing as schizophrenia, there’s no such thing as bipolar disorder, that will tend, I suspect, to have pretty bad effects on people’s trust in psychiatry. And yet that’s where the science may lead them.
So it’s a complicated picture, but this issue of trust and its absence is vital, I think, in looking at not just what we’re talking about today, but across a whole spectrum of things, even outside the medical realm altogether. If you lose trust in institutions, trust in science, trust in history, then I think more humility and less arrogance, more willingness to confess the limits of what we can do, more awareness of the dangers of enthusiasm, and more skepticism when we’re told something is a breakthrough are all necessary.
One of the things I worry about is the tendency of science journalism and medical journalism to hype things. Then, when the hype turns out to be just that, it undermines trust. Be cautious when things come along. Don’t be so sure that something represents a breakthrough.
I’m very worried at the moment. I see ketamine and psychedelics being propounded as a miracle cure for depression, and the best way to put it is that the evidence for that is enormously weak. I’ve seen this movie before too many times. I mentioned the 80% cure rate for Cotton’s work, the 80% cure rate for insulin coma therapy, and the 80% cure rate for the early asylums. This is overblown rhetoric, and the reality is that progress usually comes in small steps.
Sometimes it comes in big steps. Penicillin, I think, was a huge step. I was lucky enough to grow up in the era when penicillin and other antibiotics became widely available. They hadn’t been overused by then, and so if I had a strep throat, I had something that got rid of it right away. I didn’t run the risk of heart valve damage, which in previous times would’ve been the case.
Once in a while, you do have these dramatic shifts, and maybe AI will help us in that regard, but maybe it won’t. It’s another potential double-edged sword.
I should mention that psychedelics, psilocybin in particular, have been demonized for a long time. There are now studies out of Johns Hopkins doing serious research on cases where it is effective. I think it’s nice to give different treatments a chance with the rigor of science, but with caution.
And basically ignore, as you’re saying, science journalists who are hyping every new thing because they have to get clicks and all this kind of stuff. Look at the actual science in the modern day. In the past, the rigor was not there; in the modern day, there’s more.
Yes. We can add beyond the realm of science journalists. I think Science and Nature make choices about what they’re going to foreground, and they too have this tendency to look for things that make a big splash.
Oh, you mean the editors of the major journals.
I think the editors of the major journals—that’s what they’re looking for. Negative findings are very important in science. They’re the things that help us avoid mistakes, but they’re not the things that are going to get you published in the journal.
Right. So it’s not just the surface-level science journalism. It’s also the major journals, the conferences, and the publication process.
Having lots of scientists working on these problems at different sites and in different places turns out to be very important, I think, as a check on enthusiasm and as a check on premature claims that turn out to be unfounded. It’s also because you’re often partially right, but you’re not fully right, and someone else following the same idea is perhaps going to be a little closer to the truth than you were.
So it’s very helpful to have multicentered studies and not everything under 1 all-knowing entity. That’s a problem with funding agencies. The maverick scientist has a hard time, very often, getting a hearing.
We know of lots of examples of that in history where, after the fact, we go, “Oh, well, yes, we should have supported that line of research, but we didn’t.”
Very well put.
So what can we say about that little cultural moment, one of the most famous moments about psychiatry? First of all, Ken Kesey wrote this book about his own experience in a mental institution.
Yeah, Menlo Park. Yes.
How representative is it of the system at the time?
Mental hospitals have had a very patchy and complicated history. He was actually working in a hospital for veterans. Those were largely created after the Second World War, when there were very many more psychiatric casualties among American troops than even in the First World War.
The interesting thing is we all, by osmosis, know that in the First World War there was something called shell shock that afflicted the troops, and that the military initially resisted recognizing it and ultimately was forced to grasp it. But in World War II, American psychiatric casualties among the troops were 2 to 3 times as high as in World War I, and that's an important part of the history of psychiatry.
The upshot of that was that postwar, the VA was heavily involved, first of all, in paying to train psychiatrists and even psychologists, and then had, in its mental hospital system, a considerable involvement with psychiatric disorders.
The book is different from the film, is the first thing to say. Obviously, the film is heavily indebted to the book, but it changes various things.
If I may just go into Perplexity: “The book and the 1975 film tell the same basic story of McMurphy challenging an oppressive psychiatric ward, but they differ sharply in point of view, tone, and what the story is about. The novel is weirder, more political, and more about Chief Bromden's inner world and the Combine, while the film is more naturalistic, character-driven, and turns McMurphy into the central hero.”
Yes, I think that's right.
McMurphy is the person who received ECT, played by Jack Nicholson.
Yes. And you have a nurse figure in Nurse Ratched.
Yeah, yeah. Louise Fletcher's, I think, is an equally powerful performance.
It's one of the greatest films of all time, which happens to be about psychiatry—which is unfortunate for, you know, maybe psychiatry.
Psychiatry, yes. It's very interesting. I used to teach a class called Madness in the Movies, and I didn't just use— in fact, I used relatively few contemporary films. Of all the films from back then, the one almost everybody in the class had seen was One Flew Over the Cuckoo's Nest.
So 18-, 19-, and 20-year-olds in 2015—if I showed them Alfred Hitchcock's Spellbound, no chance they'd ever seen that. Maybe one, because they were a class of people interested in film. But everybody had seen One Flew Over the Cuckoo's Nest.
On that tangent, really quick, what is the greatest film on madness in your view?
Oh, well—
Would that be One Flew Over the Cuckoo's Nest?
I think One Flew Over the Cuckoo's Nest. I think, oddly, a very different film appeared at about the same time: I Never Promised You a Rose Garden, which is a much more sympathetic portrait of a different kind of psychiatry—a very Freudian psychiatrist, really about Frieda Fromm-Reichmann, who worked at Chestnut Lodge in Maryland and treated schizophrenia with psychotherapy rather than with drugs or other forms of physical intervention.
That was a bestselling novel by a young girl who had been her patient, with some fairly serious delusions and a very complicated family background. Again, the film changed a lot of things in the novel. That's what films do.
My book Madhouse at one point interested Hollywood, and one of the two principals said to me, “I really like this story. It's got a great first act and a great second act, but where's the third act?” Meaning, “Where's the happy ending?” And I had to say there wasn't any happy ending to that story. It was just rather grim.
Madhouse: A Tragic Tale of Megalomania and Modern Medicine is the book you're referring to. Yes, that's right. Now that reminds me of Flowers for Algernon. That doesn't have a happy ending, and it's not about mental health necessarily, but it's about the journey of an institution in relation to the health of a patient.
Yes, Pat Barker's trilogy of novels about World War I was turned into a film. I think it was called Regeneration, and that was quite powerful. It was about World War I and the treatment of shell shock. I thought it was quite well done.
My friend Patrick McGrath, who's a novelist, wrote a book called Asylum. Patrick grew up in the grounds of Broadmoor. Broadmoor is England's premier hospital for the criminally insane, and he was babysat by some of the patients. When you read his novels, you can see how that upbringing affected his rather macabre imagination.
But anyway, One Flew Over the Cuckoo's Nest—the poverty of the environment, the room that the patients were in, I think, fairly successfully recreates the way in which staff very often put patients down, didn't listen to them, poked fun at them, or even were physically abusive, although you don't see that. Those were all features of mental hospitals.
The general boredom of life is sort of there, but, yeah, hard to represent. Putting boredom on the screen will turn an audience off rather fast.
What about nurses and this kind of abusive element, you know?
Yeah, I think there was an abusive element in a lot of mental hospitals, and it was almost inevitable. Look at who had the most contact with the patients: it was the lowest-paid, least-respected ward attendants, very few even RNs. And, you know, the ratio of doctors to patients in the large state mental hospitals meant that patients hardly ever saw a physician.
One remarkable thing about the film, among the many remarkable things about it as well as its polemical edge, I think, is that the chief psychiatrist you see in the film is the real head of Oregon State Mental Hospital. It really was his introduction to acting, and I thought he was pretty remarkable, actually.
Obviously, there's a lot of exaggeration there, but ECT was used in the fifties and sixties as a tool of discipline in the hospitals. It was also used therapeutically, but overwhelmingly it was used as a tool of discipline and control. And that's true to life.
One of the interesting things we haven't talked about with all these treatments we've been discussing is that, almost invariably—except in the case of syphilitic patients, for obvious reasons, since men were more troubled by that condition than women—it was women who got the brunt of these experiments.
With Henry Cotton, about 70% of his patients who were treated were female. With lobotomy patients, it's hard to get overall numbers, but those of us who've looked at the records of a number of different hospitals again and again discover that 60% or 70% of the patients are female.
ECT tends to be heavily female. That's complicated by the fact that it's used primarily, as we were discussing, in serious cases of depression and so-called treatment-resistant depression, and depression is a diagnosis that is more to be found among women than men. Not that there aren't very many men with depression, but again, the ratio is such.
Men tend to get different diagnoses. Personality disorders, for example, are very, very common and are more a male diagnosis. ADHD is more male than female, and so on. So it's good to point that out.
I think that film helped end interest in ECT for decades, except among a small handful of enthusiasts. Probably even now, it creates hesitation in people about the treatment. So it's one that has had a very powerful and long-lasting effect, I think.
I think the surprising thing is I recently learned that a friend of mine tried everything about 20 years ago for depression, and ECT was the last thing he tried. It changed his life for the better.
That's not an uncommon story. Yeah.
And then I looked online, and there are a lot of stories like this. Before learning of that, I'm embarrassed to say, my knowledge of ECT was just “One Flew Over the Cuckoo's Nest.”
You know, it has a terrible history in the '40s, '50s, and '60s. There are lots of abuses. The CIA funded Ewen Cameron up in Canada, and he was giving multiple ECT treatments a day and reducing people to the point where they couldn't walk, they couldn't talk, they couldn't feed themselves, and they were incontinent. Then he built them back up, or so he claimed, but in many cases they were left permanently damaged.
So I could recite lots of real horror stories about ECT, but if you're honest about the thing, what you just described—patients who were on the brink of suicide, who had long-running depressions, some of them had ECT, and they describe it as lifesaving—is also true.
As I say, when more controlled trials have been done recently, there's enough evidence now that it's hard to say, “This never works. This is just one of these desperate remedies we should consign to the Dark Ages.” The complicating thing is we have no clue why it works. It's a purely empirical treatment.
Right. Right.
And that itself, I think, tends to put people off. If you have a curable form of cancer and the surgeon says, “Well, I'm going to remove it,” and she does, that's that.
But because we understand even a little bit—even if our knowledge of human biology is pretty primitive—we do understand a little bit that cancer is cells dividing uncontrollably, taking up space, doing damage to the body, and eventually killing you. The fact that we can surgically remove it is a big deal.
There are lots of disorders. I have high blood pressure. If untreated, my blood pressure is like a 20-year-old's, thanks to treatment. It's an ongoing thing. I take the damn pill every day, and it has a few minor side effects, but for me, very minor ones.
And it turns what could have killed me via a stroke or a heart attack into a condition that's very well controlled. All of these things—they're a complicated picture. It's easy with some of these things, with lobotomy, with insulin comas, deep sleep treatments, and Henry Cotton's endeavors. You can just say, “Well, we'll throw them away.” And for a long time, I think ECT would have formed part of that cast of characters.
So when I first conceived the idea of writing Desperate Remedies, the book, it was back in 1981, and I was in London on a Guggenheim Fellowship at the Wellcome Institute. I hadn't done research in detail, but I was aware there were all these things lurking about that had happened in the 1920s and ’30s, and I thought that would be a very interesting thing to study.
Luckily, I didn't do it right away. I did it piecemeal over the years, and I ended up writing a much more comprehensive look at psychiatry, really from its origins to now. I couldn't have written that book back then, and I would've missed all the developments from 1980 onwards, which are very, very important to the overall picture.
So, 40 years later: 2022.
Yes. Yes, exactly.
Your own Desperate Remedies: Psychiatry's Turbulent Quest to Cure Mental Illness—
Yeah. Yeah.
Desperate Remedies: Psychiatry's Turbulent Quest to Cure Mental Illness.
I've written a lot of books and, along the way, I think I've been productive and kept interested. I always had at least 2 projects on the go at once. You can't simultaneously write 2 things, but I'd have one and I'd work on it, and if I got tired of it, I'd pick up the other one for a bit and then go back.
It also meant that when I was working on one main project, I had other things percolating in my head. I would come across things that were relevant to them, make a note, and then go back. So when I finally did Desperate Remedies, I'd been thinking about those issues for 40 years, and that made a big difference, I think, to the way I approached things and to what I thought.
Because you either, like Thomas Szasz says, say the same thing over and over and over again for 40 years, or you learn new things and broaden what you know. You think about things in a different way because you realize you haven't grasped the full complexity of what you're looking at.
What I found with psychiatry is there are really a couple of fundamental things that have kept me engaged with the field. One, it's an arena where there's tremendous human suffering, and it spreads out. As far as I know—and I wrote a big book called Madness in Civilization, about the period from the ancient Greeks and ancient China to now—in every society I've studied, they have to cope with this.
It takes different forms. It's regarded in different ways. It's treated differently. But people who deviate so far from the norm of what we regard as culturally appropriate exist everywhere. So there's the suffering, the difficulty of studying it, and then the fact that it is such a complex and difficult subject to understand.
The very fact that we have such limits to our knowledge means there's space there to examine things in what needs to be a very complicated way. And so its intellectual puzzles attracted some very, very smart people, but there's a long way to go.
Yeah, we have glimmers of insight about how the mind works, but if you look at the span of human history, we're probably in the very early days of understanding this particular one.
8. Freud and Psychoanalysis
If it's okay, since we've been carrying multiple threads together, one of the threads that I think is really exciting to me and really important to the history of psychiatry is the psychotherapy side. We've mentioned psychopharmacology, and it would also be nice to discuss when the two clash and there's a revolution where psychopharmacology kind of wins over psychoanalysis for a time.
But let us start at the beginning, in the 19th century, when talk therapy starts coming to life, maybe in the religious context with Christian Science and then in the psychoanalytic context.
Yes. So I'd mentioned late-19th-century psychiatry, confined as it was to the mental hospital and to people incarcerated in those places, had become very biological. But there were people experiencing mental troubles of various kinds—sadness, confusion, loss of social relationships that were troubling them, grief, all sorts of things like that—that didn't involve time in a mental hospital but nonetheless involved a good deal of distress, as they continue to do.
One of the things that was interesting about 19th-century America was that it spawned a number of new religions, sort of variants of Christianity. You had a Seventh-day Adventist group that still exists, which actually spawned a sanitarium for their depressed congregants that was later taken over by 2 prominent members of the Adventist Church, the Kellogg family. Everybody knows them through cereal.
They ran a huge sanitarium to which Abraham Lincoln's widow went, Tarzan went, Henry Ford went, and lots of very prominent industrialists and politicians. It was kind of a farm to go and recover your mental stability and health, and it was all bound up also with beliefs about diet and defecation and all sorts of things.
There were the Mormons, or the Church of Jesus Christ of Latter-day Saints. Many Christians don't believe they're really Christian, but they think they are and call themselves such. So you have a number of these, and one of them was Christian Science, which was the invention of a woman named Mary Baker Eddy.
She developed the idea—and there are still Christian Science churches and Christian Science reading rooms all across America—that there wasn't such a thing as disease, that it could be prayed away, that it was just a lack of sufficient faith. Faith healing tended to work, I think, better, if it worked at all, for psychiatric problems than it did if you had, say, cancer.
Christian Science achieved a considerable number of followers, disproportionately women, but not only women. It began to treat many of the people suffering from what we would think of as the milder mental disorders. And it attracted both adherents and severe critics. Mark Twain, for example, was thoroughly dismissive of Mary Baker Eddy. But it was very successful for a time.
There were other religiously based attempts to join in. The most important of these in New England was something called the Emmanuel Movement, centered around Emmanuel Church in Boston, which was an attempt actually to bring medical and religious approaches to helping the mentally troubled.
Rather quickly, the doctors involved decided this was veering too much in the direction of medically based therapeutics. They kind of withdrew from the enterprise. It dispensed talk therapies, obviously, with a strong religious component around them.
This was also at a time when some—I guess we can call them psychiatrists, though they were often neurologists—were beginning to get lots of patients with these kinds of difficult-to-treat disorders. Neurology had emerged in America after the Civil War. The Civil War provided a lot of naturalistic experiments on what happens to the human brain and the human nervous system when trauma affects them. I don't mean psychological trauma; I mean bullets blowing holes in your brain.
A group of new specialists emerged after the Civil War who claimed expertise in the brain and the nervous system. One of the other parts of that is insanity, because insanity is also seen as a brain disease. So there is a conflict that erupts in the 1870s and ’80s between neurologists and psychiatrists.
But the neurologists can't, for the most part, get into the asylum where the most seriously ill patients are. Gradually, what comes to their waiting room, along with people suffering from things like multiple sclerosis, are people with functional mental disorders.
There's the beginning of an outpatient practice, which initially involves some drugs and the use of electricity—not ECT, but the use, for example, of static electricity, because it produces obvious physiological responses. Electricity is seen as dominating the workings of the body. Sometimes there are tonics of one sort or another.
Most notoriously of all, there was something called the rest cure. Silas Weir Mitchell, one of the leading lights of American neurology, developed complete bed rest, lots of calories, lots of food, and a complete lack of intellectual stimulation. Supposedly, this was going to cure you. It was mainly aimed at women.
I feel like that's another evidence-backed technique that works well. I've partaken in this, and I know it has helped me: lying in bed doing nothing, eating snacks.
Virginia Woolf was one of the people subjected to this. She claimed it practically drove her mad or made her worse.
Just to clarify, we're talking about lying in bed, eating snacks.
Eating lots of snacks. Very high-calorie.
Okay, Weir Mitchell wrote 2 popular bestsellers, self-help books, I suppose you'd call them in the modern genre. One was called Wear and Tear. The pace of modern life—the telegraph, the railway—was all too much. Your nervous system was overstressed. Either your batteries ran down, that was one analogy, or you overtaxed your system and went bankrupt. Wear and Tear—that was the problem.
The solution was Fat and Blood. That was the title of the other book. You got scrawny, neurotic, nervous, twitchy, and what you really needed was to build back up your strength, including your nervous strength.
Isn't it fascinating to look at that, more than 120 years ago? They're talking about how anxiety-inducing society is, how much is going on. And we in the modern day talk in the exact same way about social media, the internet, and all that kind of stuff.
Yeah, yeah, it is. We look back on the 19th century and think of it in idyllic terms, as a much slower pace of life, but people thought it was stressful in exactly the ways we do.
There was a class of potential patients. Some of them were seeking help from neurologists and from a few psychiatrists who had moved out of the asylum. But there were also these religious mental-healing groups, and they were all around at the beginning of the 20th century.
In 1909, a Viennese gentleman and 2 of his close colleagues traveled across the Atlantic on a German steamer. They arrived in New York and then transported themselves up to Worcester, Massachusetts, where Clark University was celebrating its 20th anniversary.
Clark University still exists, but it was set up to copy the German research university. The only comparable example at the time was Johns Hopkins in Baltimore, and Hopkins developed the leading medical school of the time by borrowing from that German concept of mixing research, teaching, and patient care.
I like how you're telling this in a cinematic way—the story of Sigmund Freud and Carl Jung coming to America to give a lecture. I like how it's like the movie opens and there—yeah.
Yeah, well, here he is, you know.
How do you feel about who he is? He's fairly obscure. We should say the reason you're actually telling it that way is that America has been a really defining place for psychiatry.
Yes. Freud had his own views on America and so on, but this was, in terms of the history of psychiatric medicine, America as central.
Right.
Many of the in-house histories of psychiatry portray this as a Freud conference. But it wasn't. Freud was almost an afterthought of the conference.
The head of Clark was a psychologist, and he was interested in Freud, but there were about 30 speakers at the Clark conference, including 2 Nobel Prize winners in physics, Franz Boas, who was the leading anthropologist of his generation, and a host of other scholars. There were also a couple of Freud's fierce critics, one of whom, Stern, was on the same boat as him. They avoided one another like the plague.
But anyway, it's important to see that Freud's presence was a mark of how important German science and German medical science were in the late 19th and early 20th centuries, when German science was the most advanced in the world. Freud delivered his lectures in German, and that wasn't a problem for the audience because they had all learned German so they could read the German literature on medicine. It's quite an extraordinary thing.
William James attended one of Freud's lectures and had a conversation with him. William James was one of the people thinking about the psychology of the human mind in interesting ways. He wasn't impressed by Freud, and he also had a bad heart condition. He died not all that long afterward, but he wasn't impressed by Freud. A handful of people were, including some of the neurologists.
Freud's lectures explicitly attacked religiously based psychotherapy. He said psychotherapy was like a surgical operation on the mind, and that only doctors or thoroughly trained people should practice it, although he didn't believe that psychoanalysis was something that could only be practiced by medically qualified people. The lecture was on psychoanalysis.
It was 5 lectures, published subsequently, and Freud made a very important convert there. James Jackson Putnam was a Boston Brahmin, one of the upper-class Bostonians who was extremely well connected and was a professor of neurology at Harvard. He became a Freudian at that conference.
Mainstream American psychiatry paid very little attention to Freud's arrival on the scene. When he became a bit more visible, they tended to be very dismissive. They regarded the idea of talk therapy for something they regarded as a biological condition as ridiculous.
Maybe just mention a few things. Sigmund Freud, of course, is widely acknowledged to be the father of psychoanalysis. He had a bunch of ideas, one of which was that there was this unconscious mind that was the source of many of our behaviors. Exactly. Psychoanalysis is a way to delve deep into that mind, and the tool he used to do that was talking.
Yes. Freud was trained as a neurologist himself and studied under the most famous late-19th-century neurologist, Jean-Martin Charcot, in Paris. He translated Charcot into German and endeared himself to Charcot by doing that—a clever way to help your career along.
But Freud's Viennese colleagues didn't think much of Charcot, and they didn't think much of Freud's ideas either. So he had a bit of a hard time, but he did develop a successful practice in the sense that patients came to him.
He was accompanied by 2 of his close disciples to the Clark conference, one of them Carl Jung, who was then anointed the crown prince. He was supposed to inherit Freud's enterprise until the 2 men had a very serious falling out a little bit later, in 1913, and Freud and Jung went their separate ways. That's a complicated story.
Freud, as one of his close friends and collaborators put it, was a great hater. If you fell out with Freud, it was bad news.
Hater. If you fell out with Freud, it was bad news.
Oh, yeah. You were excommunicated if you were Adler, but especially if you were Jung. Jung was Swiss, and he worked in the major mental hospital in Zurich. He was attracted to psychoanalysis and to Freud, and for the first few years there was this obvious close alliance.
Jung was the person who actually persuaded Freud to go to America. Freud initially had a very low opinion of America. He said it should be renamed Dollaria because it was only interested in the dollar. American women were far too pushy and powerful, American food was dreadful and poisoned him, and so on.
So, as you said, Freud was a master hater.
Yeah, he was. One of the things he hated was America, even though America brought him some fairly rich patients. But the richest patients of all went to Jung, not to Freud, and I think that probably exacerbated the split.
Let's actually focus first, before the conference, on the actual ideas of psychoanalysis. Freud was the originator of psychoanalysis. This was in the 19th century. Tell me about the original case of Anna O. and what psychoanalysis is.
Freud's academic career had been failing in Vienna, and he faced the prospect of either having to emigrate to America, which he regarded with horror in the 1880s, or perhaps reviving his career by going and studying under the most famous neurologist of the era, Jean-Martin Charcot, who was then delivering lectures on hysteria in Paris.
Freud went and spent some months there, came back imbued with Charcot's ideas about hysteria, and found a Viennese medical establishment. He started a consulting career, and that involved a close friend named Josef Breuer. Breuer was more senior, had a very large practice, and referred patients to Freud. The 2 of them began to be interested in this problem of hysteria.
Breuer had treated a woman who is now known as the foundation patient—the Ur-patient—for psychoanalysis, who was known to us as Anna O. We actually know she was Bertha von Pappenheim, but that was hidden for a long time. A lot of these patients had pseudonyms because the cases exposed a lot about their inner psychology, and quite reasonably, even without the modern concerns about privacy, there was a reluctance to identify them.
Anna O. had nursed her father through an illness, and he ended up dying. She developed various physical symptoms that troubled her a great deal and was also somewhat depressed. Breuer and Freud dealt with that by developing the notion that what she was suffering from was repressed memories and trauma.
This would become central to psychoanalysis: the idea of half-remembered memories lurking in your unconscious that emerged in distorted forms as psychological symptoms and ways of being in the world that were disruptive. Freud, of course, developed a much more elaborate theory of this in the years to come.
Breuer and Freud collaborated on a book called Studies on Hysteria, and there is a series of case vignettes in it of patients Freud had treated. He developed the notion that people had these past experiences. Initially, he thought they were real—for example, that they had been sexually assaulted as children and couldn't face that, so they hid it away from themselves. But they couldn't completely hide it, so it emerged in a tortured series of forms.
As things developed, the notion of resistances emerged: You couldn't easily retrieve these memories, and indeed, you resisted their surfacing. You had a hard time acknowledging them. Only with long and painful work would it become possible to bring them from the unconscious into the conscious world. As you brought them into the conscious world, you learned to cope with them in a different way, your personality was transformed, and you were made better.
But crucially, the stuff that happens in childhood is important.
Yes. The early experiences have a dramatic effect, and I think even some biological psychiatrists would agree with that notion these days. To the extent that we abolish this distinction between mind and body and acknowledge that they are closely tied together, traumatic experiences in childhood, various socialization experiences, loss, and so on deeply mark the human psyche, I think, and can have long-term effects that are very powerful.
Of course, Freud added a bunch of stuff in the realm of psychosexual stages of childhood.
Yes. As he began to develop his theories, he more and more came to see the libido—which gets transformed into the sex drive—and sexual experiences, the repression of sexuality, and the modification of sexuality as people grow. All of that enters the picture.
It's one of the things that ends up dividing Freud and Jung, partly because Jung downplayed that sexual side of things after the break.
Freud develops a very complicated theory of mind, initially reflecting his training as a neurologist. He tries to write an essay called Project for a Scientific Psychology, which survives, and the scientific psychology is going to tie psychology back into neurology. But he abandons that, and once he has abandoned it, he goes on to develop an increasingly elaborate theory.
He writes The Interpretation of Dreams, for example, because he begins to regard dreams as an arena where hidden memories, these suppressed things, reemerge in disguised form in your dream life. That book marks an important step forward. He becomes interested in things like slips of the tongue, so-called Freudian slips, seeing those as revealing what really is hidden from you. There is this very elaborate dissection of things that relies upon long, extended talk therapy.
Of course, underlying it, he’s building a model of how this whole mind thing works. There are 3 interacting parts of the personality. First, the id, which is primitive, entirely unconscious, driven by the pleasure principle, seeking immediate gratification or basic drives such as sex and aggression. There’s the ego, which is the rational mediator operating under the reality principle, balancing the id’s demands with external reality. And finally, the superego, which is the internalized moral standards and ideals, producing guilt or pride and striving for perfection. So that’s the structure.
Yeah. That is, broadly speaking, the structure that Freud ends up with, and the conflicts between these entities and the ways they interact are obviously the thing that creates your mental universe, your way of being in the world, and in many cases creates pathology, which through the process of psychoanalysis you can transform grotesque unhappiness into ordinary unhappiness, or something like that. You know?
Yeah, sure.
Yes, you get that. Initially, Jung gets one of the heirs to the International Harvester fortune as a patient, and the McCormick family are as rich as the Rockefellers, the Carnegies, and the Vanderbilts of that world. This guy is a US senator who ends up committing suicide in 1925 after a lot of treatment from Jung, when he fails to win reelection to the US Senate. He kills himself in Washington during the interregnum.
But he also gets another one of that brood. One of the Rockefeller daughters, Edith Rockefeller, marries a McCormick. She has a lot of psychological issues, and she tries to get Jung to move to Chicago, promising him she’ll set him up in a mansion with lots of her friends as his patients, and Jung has no interest. So she finally persuades him to come to New York and accompany her on the liner across to Zurich to be treated.
She’s agoraphobic, and so she has a hard time being out of her little cocoon. She’s treated there as an example of how peculiar she was. I mentioned the agoraphobia. She occupies a huge array of suites with all her servants and so on in Zurich. She takes a train journey—it’s a stopping train—and her chauffeur follows the train in the Rolls-Royce in case she has to jump out of the train at a station because she can’t bear it anymore.
She becomes a Jungian analyst, but she’s very wealthy and she writes big checks to Jung, which is the important thing. Then Jung attracts Paul Mellon and his wife, Mary. Jung’s works are published by Princeton University Press with a subvention from that Mellon Foundation. So it’s a long-running thing. Freud doesn’t get patients quite that rich. He gets some rich Americans.
We should say that Freud’s ideas became quite popular among the intellectual and artist class in the 1920s in America.
Another thing happened. World War I saw the breakdown of many soldiers from something that came to be labeled shell shock. The label “shell shock” intimates the first theories about its origin, which was that shells bursting near you and bombs bursting near you shook up your body and your brain and created some physical damage that then accounted for the symptoms of shell shock: your mutism, your blindness, your constant shaking, your nightmares, all of that.
But it became increasingly apparent that shell shock was actually a psychological thing. The trauma of war, in a significant number of cases, brought about mental breakdowns. In thinking about that, Freud’s ideas about the unconscious mind and trauma and its connection to symptomatology acquired a new significance for a lot of people in that period. After the war, you’re absolutely right: among a certain smart section of society, those ideas developed considerable purchase.
Psychiatrists who were mostly stuck in the asylums dealing with psychotic patients wanted nothing to do with these ideas and this talk therapy.
Mainstream psychotherapy was mostly in a clinical setting.
Yeah, Freud’s ideas were not popular.
No.
The only partial exception to that was the mental hospital in Washington, DC—the only federal mental hospital, St. Elizabeths. William Alanson White, who was then the superintendent, was somewhat sympathetic to Freud’s ideas and tried a bit, but you’re talking about thousands of patients, and the idea of talk therapy for them is obviously out of reach. Plus, they are much more severely disturbed, so it does happen.
Novelists, painters, artists, playwrights, and the audience for those elite forms of culture do tend to embrace Freudian ideas. Sex sells in the theater and in the movies, obviously. But beyond that, part of Freud’s appeal to everybody was something he lamented at one point. He said, “You know, my case histories read like short stories, like works of fiction. And in that sense, people think they lack the stamp of serious science. But I’m driven to that because that’s how I unpack what’s going on.”
Well, psychoanalysis is telling stories. It’s getting people to recover stories, recover memories, to rebuild, right? Its elements of psychological conflict and hidden motives and so forth are naturally very appealing to people writing novels, people writing plays, and people doing screenplays.
9. WWII and Cognitive behavioral therapy (CBT)
For artists of the modern sort, the idea that we can extract things from the subconscious—Surrealism and the like, for example—is clearly very heavily influenced by Freudian ideas. But it’s important to know that, circa 1930, there are probably 300 psychoanalysts in North America. If they each practice classical psychoanalysis involving 5 hours a week, they can’t treat that many patients—a few thousand when there are hundreds of thousands in the hospitals.
Right. Mm-hmm.
So what changes that? Hitler starts killing off Jews and killing off psychoanalysts. The ones who can escape, some of them go to England and some come to America. The most famous escapee is Freud himself and his daughter, Anna. Princess Marie Bonaparte, who’s one of Freud’s great supporters, bribes the Nazis to get him out. He travels by train to London, very sick with cancer of the jaw, as he has been since the mid-1920s.
He sets up shop in London, and Anna succeeds him, really, as one of the central figures in British psychoanalysis. Other analysts come here to America. The numbers of analysts, probably by 1940, when America’s not yet in the war, have a bit more than doubled. More importantly, psychoanalytic training has become much more organized here.
The institutes outside the universities control psychoanalytic training. Universities are not yet the knowledge factories they become after the war, and that’s a crucial mistake that psychoanalysis makes. It’s great because it controls its training completely. The bad thing is that when the center of gravity moves to the university, it’s not there, and either it resists being incorporated or the university resists incorporating it. So I think that’s a structural weakness for it.
But what really transforms things is World War II.
5 fifty-minute hours, famously.
They last 50 minutes because then there are 10 minutes for 4 analysts to recover before the next patient arrives.
Yes. You are free-associating on the couch and gradually being coaxed to see, as material emerges, what you’re hiding from yourself.
I mean, initially they tried—this is in their early, early days—they tried hypnosis.
Yes.
But this is where Freud took the big leap and expanded free association.
Right.
So I mentioned Freud training under Charcot. Charcot hypnotized his hysterical patients. We now know a lot of that was fakery. I don’t think he was conscious of the fakery, but the patients were on display over and over again, and they worked their routines up very well. They deceived him and they deceived the audience.
But Freud came back from Paris bringing with him the idea that hypnosis was the way forward. After the break with Breuer—Breuer had a general medical practice and lost interest in hysteria and didn’t want anything to do with the revisions of Freud’s work on hysteria—Freud, who was a very clumsy hypnotist by his own account, began to develop this alternative of free association and getting people to speak whatever came into their head without a censor.
That was the important thing: the half-remembered memories were being hidden from you, and the constellation of psychological forces in your unconscious was squashing them down, but they were reemerging as other kinds of symptoms.
So how well does psychoanalysis work? How much do we understand? We’ve talked about all these approaches that didn’t work. How well did it work at that time?
One of the things after World War II, when psychoanalysis was making great strides in America and the Rockefeller Foundation was still heavily involved in promoting psychiatry and developing what it hoped would be new tools for it, was that the then heads of the funding program, Alan Gregg and Robert Morison—especially Morison—kept pressing the analysts: “Provide us proof that what you do works.”
The analysts kept resisting and resisting and resisting, saying, “It’s much more complicated than that.”
There's no easy measure because what we're doing is reconstructing entire personalities, entire ways of being. People sense themselves, their ways of being in the world. We don't have easy ways to measure that.
To contrast that with the 80% promises, over and over and over and over. Yes, yes, yes.
And it's a long and complicated process. That was very important, because another kind of psychotherapeutics is emerging during and in the aftermath of the war as a rival for both psychiatry and psychoanalysis. Initially, it's not terribly successful, but as time goes on, it becomes a more and more important part of the story.
So, to focus on the war for a minute, America's psychiatrists went to the military brass and to the politicians before America entered the war. They had some advance warning because America didn't enter until Pearl Harbor, but the European war had been going on. They said, "Look, if we have to fight, we're going to have the same problem we had in the First World War. We're going to train these soldiers, equip them, put them on the battlefield, and the psychologically vulnerable among them are going to break down."
"They'll have shell shock all over again, so we should screen all recruits to make sure they're not psychologically weak and susceptible." They screened out 1.75 million people and said, "These men are not fit. So now we won't have the problems we had in World War I."
Except it quickly turned out that those problems reemerged. Industrial warfare exposes people to seeing things and doing things that all of us in normal life would recoil from. When we're forced to do them as soldiers, many of us—I can't speak from experience, but from talking to people who've gone through all this—find the experiences and the memories those experiences create intolerable. They emerge in symptoms, and they break down.
So it became a huge problem for the American Army, as it did for all the armies. Actually, the Nazis just shot people. If you broke down, bang, you're dead. They weren't dealing with you. Obviously, the Allies' response was not that. They quickly had to try to treat these troops, maybe get them back into the fighting lines, maybe get them into support positions—something to cope with the problem.
It created extraordinary morale problems among the troops, and it invited malingering: claiming you had these conditions when you didn't. It obviously cost a lot of the fighting force. In combat conditions, as much as 25% of the soldiers broke down. So it was a big, big problem.
Before the war, there were about 2,000 psychiatrists in North America, in the United States. At the end of the war, there were more than 2,000 psychiatrists in the US military. You had to train people in a hurry, and even still, it was hard to get enough people trained.
It turned out that the head of US military psychiatry—not the first one, because the first one died, but the second one—was a man named William Menninger from the Menninger Clinic in Kansas, where he and his brother ran a psychoanalytic treatment facility. Bill Menninger became the head of Army psychiatry. He concluded that the best treatment for these soldiers breaking down was psychotherapeutic in nature. The origin of their condition was trauma, and so, in a watered-down way, Freud's ideas were the ones that the people who were recruited quickly and retrained as psychiatrists absorbed.
They formed, after the war, a fairly coherent group of people, separate from the psychiatrists in the state hospitals who were still very biologically oriented. Another group emerged during the war precisely because you couldn't produce enough psychotherapists who were MDs quickly enough. Psychologists were drafted in and asked to treat people.
What the psychologists discovered was, "Hey, we could do this stuff too, and we really like it. It's interesting. It's challenging. We should do that."
So after the war, there was a similar kind of problem. Mental illness was a massive problem. The returning soldiers were a big problem, but it was also a problem in the community. These guys—the psychiatrists—didn't go and work in the mental hospital. They started outpatient treatment.
By 1958, about 80% of psychiatrists were working in outpatient settings rather than in hospitals. The psychologists organized themselves, and federal money said, "We need you. We need you. We need more of you." So the VA, the Veterans Administration, and then, once the National Institute of Mental Health was established, started providing a lot of money for training. They trained not just psychiatrists; they trained psychologists.
So the question was: How were the psychologists going to set up clinical training? What the clinically oriented psychologists came up with was a training program where would-be clinical psychologists spent 2 years learning basic scientific psychology and research methods, and then had 2 or 3 years of clinical work and experience.
That's very clever, because it meant that when they started looking for grants, they knew how to do that. The psychoanalysts didn't have a clue how to apply for federal grant money, and they got almost none.
Beyond that, these people began to work on treating symptoms. The psychoanalysts thought that treating a symptom was playing Whac-A-Mole. If you didn't deal with the underlying problems of the personality—the interactions between your id, ego, and superego—you suppressed that symptom, and another one would pop up over here.
The clinical psychologists said, "We're going to treat the symptoms of what's troubling people. We're going to treat the symptoms, and we're going to develop techniques that allow people to cope with those symptoms and eliminate them."
How were they going to do that? Primarily through what initially was cognitive behavioral therapy, and later interpersonal therapy and some other variants emerged. Basically, what they tried to do with those techniques was develop things that worked relatively quickly, worked specifically on one set of problems or a small subset of problems, and tried to get those under control.
How did it work? You'd developed really bad habits. The way you react to being socially snubbed or ignored, the way you deal with your coworkers, or the trouble you're having with your disruptive child would help you see the patterns that you'd fallen into and would give you exercises that would help you develop a better way of coping with those things—ways that didn't produce these symptoms.
I'm oversimplifying, obviously, but that's basically the fundamental thrust of it.
And one of the other contrasting things about CBT, cognitive behavioral therapy, is that it doesn't necessarily have that heavy requirement of 5 hours a week.
Exactly. These therapies could be packaged. They could be reproduced. They could be tested to see whether they worked, so they had an evidentiary foundation. The psychoanalyst would say, "It's going to take us years, and it's hard to measure." These guys went, "Well, we'll measure what happens when we treat people this way."
Psychologists.
Yes. The symptoms are what matter, not the underlying, more complex thing that psychoanalysts claimed to be treating. So it's shorter and reproducible, whereas in psychoanalysis, every patient is a new patient with a new set of complicated things going on. Here we are: We're going to do this.
And the key figures here are Albert Bandura, Albert Ellis, and Aaron Beck.
Yes. Bandura and some other psychologists launched this movement, and then later on, Aaron Beck, who went by Tim Beck and just recently died. I think he was 99.
No, no, I think he crossed 100.
Maybe 100. Yes, maybe 100.
There's video of him talking at that age, and he's still killing it. So wise.
Aaron Beck is a remarkable figure because he was also one of the first, in the 1960s, to look at psychiatric diagnosis and show how unreliable it was—how difficult it was to get psychiatrists to agree on what was wrong.
So he was a psychoanalyst, right?
He had been trained as a psychoanalyst, became disillusioned with it, and so there were 2 important strands that stemmed from his work.
First, he was one of the people within the community itself who said to his fellow psychiatrists, "You know, we're not very good at this diagnosis business, and maybe we need to work on that." That was very important for the movement toward DSM-III.
The other side of the coin was that he broke with the idea that treating symptoms was a waste of time and joined with the psychologists, who had already embarked on that journey, to say, "How can we develop techniques to overcome these self-destructive ways in which people are responding? How can we help with their ability to interact?"
Interpersonal therapy is much more concerned with the way in which, if your relations with other people break down, that damages your emotional stability. If you repair those relationships, that helps your emotional stability come back.
So all of this develops, and Americans are unusual. Most of the rest of the world has what we call socialized medicine. America doesn't have that, so we're used to paying for medical care. Americans were more willing, I think, to pay for clinical psychologists, and they attacked some of the problems of everyday living—the more minor problems, I was going to say, but these are often quite distressing things.
Those were the things they were most successful at doing. If I look at the literature on CBT, for example, and its uses in cases of schizophrenia, the evidence is pretty poor that it works. Even the evidence for the milder conditions is a bit more ambiguous than they like to pretend.
The Cochrane Reviews, which are a systematic attempt to assess how strong the evidence is for particular approaches to disease of all sorts, say that, at best, the evidence for CBT is of low or medium confidence. But I think, again, there are patients for whom this helps. Indeed, for the milder forms of depression, I think CBT works better than the drugs, without some of the side effects that the drugs have.
And indeed, NICE, which is the British organization that determines which treatments the National Health Service will support and which ones are sufficiently evidence-based, has come to that same conclusion.
So I think one thing to say about cognitive behavioral therapy is that it has some elements of surface-level, intuitive things, like being aware of and adjusting your thought patterns, being aware of triggers that get you into a negative spiral—
Exactly.
—and then basic behavior changes, habit changes that lead to a healthier life. So I think this kind of “getting your life together” process is intuitive, that it would have a positive effect on some percentage of the population. But as you get more and more serious into the land of mental disorders, it starts to be a little bit less conclusive.
Yes. I think that’s an accurate statement of the way I read the literature. It’s not a cure-all, but for some patients, this really does seem to improve things quite a lot. And it does make sense that you have developed poor ways of responding to signals from the outside world, and they’ve become habitual. Habits, as we know, are very hard to break.
There’s a lot of homework and a lot of exercises you have to do to try to reconfigure the ways you deal with the world. It’s not for everybody, and it doesn’t work for everybody, but there’s some subset of people for whom this seems to have positive effects.
10. Antipsychotics
So this is the lay of the land. We talked about some of the darkness, lobotomies and so on. There are some talk-therapy ideas, psychoanalysis, and then there is, from the clinical psychology side, cognitive behavioral therapy. Then psychopharmacology starts to emerge, challenging this whole shebang of talk therapy, period. Can you talk about the accidental origins of psychopharmacology, which challenges this whole thing?
Hardly anybody had conceived of the idea that drugs could be used to treat mental illness. Drugs had been used in the mental hospitals back in the 19th and 20th centuries, but they were usually things that were used to control patients, to calm them down. Opiates, for example, and various hypnotics that would put people to sleep when they were extremely agitated, and so forth. Sometimes marijuana was experimented with, as was alcohol in the 19th century, interestingly enough, given the revival of psychedelics.
But the idea that a drug might be used to actually attack the underlying problem emerged by accident in the following kind of way. The drug industry in general had emerged mostly in Germany, where, as I’d mentioned, the most advanced medicine was being practiced in the late 19th century. It grew out of the chemical industry—for example, refining coal tar into different substances. That’s where we got aspirin and a whole bunch of drugs. Gradually, drug companies became more organized and differentiated themselves from all the quack remedies that were around.
World War II greatly accelerates things, not least because we discover a real magic bullet called penicillin and then the other antibiotics that we subsequently come across. Penicillin had been observed by Alexander Fleming, famously, in his lab in some Petri dishes where bacteria had been killed. He later became one of the co-winners of the Nobel Prize and made a lot of capital out of that discovery.
It was really Howard Florey and his team at Oxford who developed the therapeutic potential of penicillin. Florey actually flew some of it in his jacket across the Atlantic to America, and it was the Americans who solved the critical problem. It took Florey and his team weeks to develop enough penicillin to treat a single mouse. What America learned how to do was mass-produce penicillin, and that was critical because it was vital to the war effort.
After the war, it was vital to the civilian population because it was such an important breakthrough. So drug companies grew fatter on that. They embarked on research to try to find new substances they could use to treat things, and a French company named Rhône-Poulenc came across a chemical that had actually been synthesized back in the 1880s in Germany. It was an antihistamine, chlorpromazine.
They didn’t know what to do with it, but other kinds of antihistamines had been used effectively during the war, and they thought, “Well, let’s look and see if we can find a market for this drug.” The interesting thing to remember is that, in those days, investigating the properties of new drugs was a Wild West phenomenon. There were no controls. You could do whatever you wanted, and you handed stuff out and said, “Why don’t you try this and see if it works?”
So Rhône-Poulenc did that. They thought this might work as an antiemetic. If you have a child who’s prone to car sickness, you give them an antiemetic drug. That was one possibility. Another possibility was that it might work for eczema, so that people didn’t scratch themselves. Somebody said, “Well, maybe it will work as an anesthetic potentiator,” meaning that if you gave someone some of it, you’d need to use less anesthetic. It would act like a catalyst because it tended to make you sleepy.
If you read the leaflets on Dramamine, one of the cautions is, “It’ll make you sleepy; don’t drive,” right? So why don’t we give it to some surgeons and see if they can find a use for it? Literally, it’s like that. One of the people who gets that drug is a lieutenant in the French Navy, Henri Laborit. He tries it as an anesthetic potentiator, and he also gives it to some of the patients who are awaiting surgery.
Normally, when you’re awaiting surgery, you’re a little bit anxious. These patients stop being anxious. This was the era of lobotomies, and he wrote to one of his relatives who worked in one of the Paris mental hospitals. He said, “This works like a chemical lobotomy. These people don’t care anymore about their surgery.”
And that’s supposed to be a good thing, right?
Well, lobotomy hadn’t become the nasty word it would become in a few years. One of his colleagues contacts Delay and Deniker, who work at Sainte-Anne, which is the biggest mental hospital in Paris, and says, “Hey, guys, this might work on your psychiatric patients. You should give it a try.”
And they do. When it doesn’t work, they give a larger dose, and when it doesn’t work, they give an even larger dose. Sure enough, patients stop acting out. They stop smashing furniture. They’re still sort of conscious, but they’re less mobile and much calmer.
This is why, in the early stages, chlorpromazine—which becomes known as Largactil in Europe and Thorazine here—is known as a major tranquilizer, because it has this tranquilizing effect. The hospitals see it as a boon because it helps control the patients. They’re not yet thinking of it as more than that. So that’s the accidental way it’s discovered.
It comes to North America via Quebec, where there’s a psychiatrist, Heinz Lehmann, who works at the Protestant Hospital. Quebec in those days is dominated by its Anglophone elite, who oppressed the French Canadians pretty mightily. But because of the French connection, he gets some of the drug.
Rhône-Poulenc has had to sell the rights to an American company. In those days, American physicians don’t trust European science or European medicine—especially European medicine. The first 2 drug companies it approaches say, “No, thank you. This doesn’t look very interesting to us. I don’t think there’s much of a market.”
Then Smith, Kline & French buys it up, and within 2 years, 2 million people are taking this drug. It’s a bonanza for them, right? It isn’t an accident, because they put their best salesman on the job of selling this, and they realize the hospital psychiatrists mostly aren’t interested. They haven’t yet gotten to this idea of a chemical cure or a chemical treatment.
So it’s the companies that wake up to this?
The companies wake up. They sell it to the politicians. They go to the state legislatures. They have moving pictures of an agitated patient who turns calm.
So this is already the mechanism of big pharma?
Yeah. So it’s starting to be big pharma. It transforms Smith, Kline & French from a small operator into a big company. Then, of course, once that’s successful, it turns out that chlorpromazine can be easily tweaked as a molecule, and so copycat drugs emerge on the scene.
This happens in America in 1954. The following year, in 1955, we get the so-called minor tranquilizers invented and brought to market.
This is Miltown.
Yeah, this is Miltown, heavily promoted by the first major television star of the mid-1950s, Milton Berle, who calls himself Uncle Miltown and promotes the drug heavily on his show.
So these are mostly tranquilizer-type effects?
They’re muscle-relaxant types of things, and later on, in the 1960s, we get Valium and Librium coming on, adding to or replacing those first-generation drugs. So you have major tranquilizers and minor tranquilizers. And guess what? The Freudians don’t really want anything to do with these drugs.
Right. Of course.
The hospital psychiatrists wake up to the usefulness of Thorazine and its analogues and do start using the drugs a lot. That’s really important. In the early 1960s, they change their name. Instead of being major tranquilizers, they become antipsychotics.
Right.
So that suggests they actually attack the underlying psychosis.
Is there any evidence of that for them?
They do change the forms of psychosis in important ways, some good and some they fail to attack. They reduce the agitation, the delusions, and the hallucinations—the things psychiatrists call the positive symptoms of schizophrenia. Those they help with, not every patient, but a significant number of patients, and that’s very important.
Why are they called the positive symptoms?
The positive symptoms add things. They add the hallucinations and the delusions. Those are challenging, and they're visible usually because, if somebody's deluded or hallucinating, you know about it pretty quickly, right? The negative symptoms are things like apathy, loss of ability to interact with people, poverty of language, and lack of initiative. All of those things are devastating.
Just to state it out loud and clear: Both the positive and negative symptoms of schizophrenia, as psychologists call them, are devastating and both negative.
Yes, yes. I think that's right.
In the common parlance of what “negative” means.
It's a very strange choice of language, but it's been there for a long time, so it's embedded. Now, to the extent antipsychotics work, they work on the positive symptoms. They either dull them down so you're still hallucinating a bit and you're still delusional, but it's much less, and you are somewhat pacified. You're less overtly disturbed.
But the negative side of things, not so much or not at all. Then, on top of that, the drugs work for some people and they don't work for others, and a significant number of psychotic patients are non-drug responders, just as a significant number of people with depression are not responsive to antidepressants.
Moreover, initially, in the enthusiasm for these drugs, everybody neglected the fact that they have serious side effects. Many people argued that the side effects were an essential part of the treatment and you just had to put up with them. So what are we talking about when I say there are nasty side effects?
Well, among others, you may become incredibly restless. So you're constantly in motion, moving around, never still. If you're in the presence of somebody like that, it becomes unbearable after a fairly short while, and it's unbearable often to the person who can't control it.
Other patients develop Parkinson's disease symptoms, which is an awful affliction. It unfortunately affects a significant number of people each year, and we have, through L-DOPA, a means to delay its impact, but eventually that loses its efficacy, and unfortunately we don't have a cure. So you have those.
And then perhaps the nastiest is what's called tardive dyskinesia. Tardive because it's late-developing, it doesn't happen right away, and dyskinesia because what it involves is jerky, uncontrolled movements of the body, particularly of the facial muscles. So your tongue will protrude, you'll make strange noises, you'll twitch, and you'll stagger about when walking.
If somebody like that is walking down the street toward you, you will think there's a mentally ill person, and you'll cross to the other side of the street. Yes, they probably are a mentally ill person, but what you're seeing is the iatrogenic effects of the drugs they're on. Okay?
So that problem was ignored for about 20 years. A paper appeared in Science by George Crane, a Maryland psychiatrist, in which he said, “We, as a profession, have been ignoring this terrible problem.” Yes, the drugs do some good, but they're also creating a lot of harm, and we need to focus more on that.
It took a few years, but by the 1980s, I think the American Psychiatric Association was very worried by that problem. The drug companies were worried about it, too, but didn't have any obvious solution until, toward the end of the 1980s, something happened.
In 1957, when people were developing copycat versions of Thorazine, clozapine was developed by a small company, which was subsequently bought up by a bigger company and introduced in Europe. It never came to America for 2 reasons.
First, it tended not to produce tardive dyskinesia, and at that time many in the profession thought that if you didn't get those symptoms, you weren't attacking the problem. Bizarre, right? Secondly, in a significant number of patients, it destroyed the patients' white blood cells, and they died. Okay? Not a good outcome.
So it was quickly withdrawn from the market, and it never made it to this side of the Atlantic. However, as this tardive dyskinesia problem became more acute, there was an attempt to revive clozapine, and it turns out it tends to work better in treatment-resistant cases, meaning cases that don't respond to the other antipsychotics that we have.
It could be revived, but at the cost of weekly blood checks, because you had to be very careful. If your white blood cell count started to drop, you had to stop. Right? So it came to market in the late 1980s, and very quickly other drug companies tried to find other compounds, chemically not related to it, but that's hardly the point.
The whole class of drugs became known as second-generation antipsychotics.
So clozapine, Risperdal—
Yes, those kinds of ones.
Zyprexa.
Zyprexa, among others.
Zyprexa.
Yes. So there were a number of these, and they have actually—because they are chemically quite different from each other—but they're classed together in the public mind—
…and in the professional mind.
They tend to have different side-effect profiles, slightly different modes of action, and differing levels of efficacy, I think.
Of course, there wasn't, at that time or even now, a real science of, when a human being comes to you, what the actual protocol is for figuring out which drug to give.
Right. Once the drug revolution came along, increasingly the studies were funded by the drug companies, who owned the data and controlled the data, and only released what they chose to release—what was helpful for them and not what wasn't.
And they were heavily marketing stuff.
Oh, yeah, very heavily marketed. And then, to get FDA approval of efficacy and safety, you needed 2 trials. You might have conducted 15 trials and 13 of them had been failures, but if you had 2 that worked, that was enough. That's what you needed. That was the gold standard.
In 2005, the National Institute of Mental Health funded this drug study, not an industry study. What it wanted to look at was that the first-generation drugs were now out of patent and they were cheap, while the second-generation drugs were patented and quite expensive—10 times as expensive in some cases.
So we did something called the CATIE Study, and it was published in the New England Journal of Medicine. There were 2 interesting findings. You had 1 first-generation antipsychotic, one of those very early drugs, and 4 more recent drugs that you were looking at. And you asked a number of questions.
Are the new drugs more efficacious than the old drug? No. Hmm. Were patients willing to tolerate these drugs? That was a finding that I thought was much underreported at the time. Between 67% and 82% of the patients, depending on which drug they were on, dropped out of the trial because either the drug wasn't working or they couldn't stand the side effects.
So that tells you these are our best drugs. There are real complications here. And then, as we delve further into it, do they have nasty side effects? Well, somewhat less tardive dyskinesia, but a whole new set of side effects.
If you take these pills, you will gain, in most cases, a lot of weight: 10, 20, 30, 40, 50 pounds. What does that do? That gives you metabolic syndrome; it gives you diabetes; it gives you heart trouble.
It's important to state this when we're looking at it, because there is no free lunch with medicine. If you take an aspirin, it may cause your stomach to bleed, sometimes enough to really put you in serious jeopardy. Most of the time it's fine.
Every drug that's brought to market has the main effect we're looking for and some side effects, which may be minimal for most people, but for some people may be worse than that. So we've got to—it's one of these cost-benefit analyses, right? You're getting some relief from your psychiatric symptoms, but you're courting these other dangers that may or may not arise, and going in, we don't know where you're going to fall. We don't know. It's trial and error.
You mean every individual that walks into the picture, they don't know where on the distribution they fall?
Right. And we have no biological markers at the moment that would tell us. One or 2 of my friends in the psychiatric genetics industry, if that's the right term for it—but, you know, in that research area—are saying, “Well, we haven't done very well to find the genetic roots of mental illness, but maybe we can learn to distinguish which patients are going to respond well to drugs and which shouldn't be given them because they're not going to.”
That's a promissory note. It's not something that they actually can do now. It's just that we hope we'll be able to do this, and I hope they're able to do it, too. But you can't have an enormous amount of confidence in that.
Maybe it'll happen, or maybe some other mechanism will emerge that allows us to see who the responders and nonresponders are, and who's going to suffer the worst side effects if they're put on these medications. The side effects do vary, so although a lot of what I've described is common to this class of drugs—
And sometimes it's hard to describe the side effect. You're talking about the human mind.
Yeah, yeah.
So describing the side effects, it's not like bleeding or diarrhea or—
Well, yeah.
Weight gain, that's describable, but the effect on your personality—
Yep, that's much harder. People, some of the patients who drop out do so because they find the richness of their mental life is completely gone, and they don't want to tolerate that. They'd sooner tolerate some hallucinations. That's a hard one.
11. Antidepressants
So there's that picture: the SSRIs that also came to be known as Prozac, Zoloft, and Paxil during that time.
Yes, Paxil, all of that. Well, again, they're the second generation of antidepressants.
Mm-hmm.
So that's a complicated story.
Again, it's an accident. They're treating patients with advanced tuberculosis in the 1950s. That's a very unpleasant thing that's also going to kill you, so these are very advanced cases of tuberculosis. You're coughing your lungs up. You're depressed as all get out.
And here we have 2 new drugs, iproniazid and imipramine, that maybe will treat the condition. When you give them to the patients, these depressed tuberculosis patients start acting happy, dancing about. Their mood changes. Bingo! We've got something that maybe we can use over here to treat depression.
However, the drug companies around 1960 think of depression as a small market because what they're talking about is the kind of melancholic psychotic depressions that lead people into the mental hospital. That's not an insignificant group, but it's not a huge group. So it's really much later on that things begin to change. Right now, it's fair to say depression is the common cold of psychiatry. It's abundant there, the depressive diagnosis, probably the most commonly given among psychiatrists.
Well, it's transforming, yes. So part of that is a deeper understanding of the human mind, and a big part of that is probably the drug companies convincing the world.
So there were big disputes, for example, when DSM-5 was being contemplated, about whether grief or bereavement would count as a mental disorder, would count as a form of depression if you lose a parent, or, even worse, a child. It's deeply upsetting, yes. Some psychiatrists say yes and some no, but it's an example of what happens in psychiatry repeatedly, what I would call diagnostic creep, which is a term an Australian named Nick Haslam came up with. But it's a phenomenon I described before that.
You start with a core of unambiguous deviations from the norm that are so serious that any competent member of the culture knows that's that. But then you begin to say, "Well, there's this penumbra," you see, and just outside that core, there are people who are also disturbed, not perhaps sufficiently disturbed that you actually recognize it, but it's happening. So that has tended to happen over and over again.
Parents with an autistic child won't necessarily agree with what I'm about to say, but the chief editor of DSM-IV, Allen Frances, is convinced the huge increase in the number of diagnoses of autism is more driven by the fact that he loosened the criteria for the diagnosis than it is because there are more actual cases. Autism used to be a fairly rare phenomenon, and now, sadly, it's a very broad one. I understand why parents react very negatively to that because the diagnosis is the key to all sorts of social supports and educational supports and all the rest, and they're dealing with a child who is extremely difficult.
But there is a real difference between the most severe forms of autism, where people lose the capacity to speak and very often any ability to interact with other people, and the other cases, which are still serious but milder. Diagnostic creep is not driven just by psychiatric imperialism—the desire for more territory, more patients. It's driven as well by patients and people, and they resist it being pushed back very often. So families have formed organizations like NAMI, but those aren't the mentally ill. Those are the family members of the mentally ill, and there are differences in the perspectives and the interests of the family members and the patients. That's easy to forget.
I think one of the things you talk about is—I mean, the quote you had used the word "madness." But that madness, or mental health maladies, if you're suffering from them, is a deeply lonely experience. And then, if you're around somebody suffering from it, it's a very social experience.
Yeah, this is actually a paraphrase. I was quoting one of my friends and fellow historians of psychiatry, Michael MacDonald: "The most solitary of afflictions for the sufferer and the most social of maladies for those around them."
There are lots of ways in which you can see that very powerfully, and that's why I think there are a ton of people who suffer in various ways from mental disturbances of one sort and another. But the effects aren't confined to them. They extend out to everybody else around them, and that's really powerful.
So, in this first generation, there were actually 2 different kinds of antidepressants: MAOIs, as they're called in the trade, and tricyclics, which were called tricyclics because they had three rings of carbon atoms in their molecule. Those had, as I say, a limited market, but there were also complications associated with them. It was easy to overdose and die, so giving a depressed patient a bunch of pills that, if they took too many of them, would kill them was tricky.
They could kill you another way, too, because, for example, certain dietary items—cheese, cured meats—in combination with them were very health-threatening, maybe even fatal. Now, in the late 1980s, the drug companies came across a new class of antidepressants that didn't have those side effects. As we'll see, they had other side effects, but not those. The most famous of those was Prozac.
There was a class of drugs called SSRIs, and again, forgive the acronyms, but what it means is selective serotonin reuptake inhibitors. Serotonin is something manufactured in our bodies, actually in our digestive system, and it performs a variety of functions in the body. But it's also one of the neurotransmitters in our brains. The way these drugs worked was by slowing the reuptake of serotonin in the brain, which was marketed by the drug companies as the solution to depression.
When you got depressed, it was because you didn't have enough serotonin in your brain, and these pills solved that problem. Tipper Gore, Al Gore's ex-wife, was like many politicians' wives, depressed for reasons I fully understand, or at least partially understand. She went to her psychiatrist, and that was one of the things she was given. She became one of the big public advocates for SSRIs, which still are the most prescribed antidepressants.
Do they work? And what are the side effects?
Yeah. So here's where we get into slippery territory. Every time you do a controlled study of these antidepressants, they beat placebo by a statistically significant margin, but not necessarily by a clinically significant margin. When you see drug ads, be very careful: "This one significantly improves X or Y." Does that mean clinically, or does it mean statistically?
When we measure improvement with depression, we tend to use rating scales of various sorts. If you improve on one of the major scales that's used by 1 or 2 points on a 60-point scale, it may be enough to show statistical significance. These drugs look a little better than placebo, but they don't really affect your quality of life much.
For most patients, antidepressants are marginally better than placebo, but a lot of the effect is the placebo effect. They come with very difficult side effects. A lot of people describe them as numbing drugs. They flatten everything out, so you can't experience the highs and lows that we normally take as part of human experience.
The numbing extends elsewhere in your body. In particular, lots of patients find a complete loss of libido. They can't get an erection. They can't climax if they're a woman. Their sex life just goes away, and sometimes it doesn't come back after you stop the drugs.
The next layer of problems is that getting off the drugs, for some people, turns out to be hell on wheels. They get worse depression than they had before. They get terrible feelings. Their brain is sparking; something's wrong. Many patients find themselves trapped on those drugs for a long time, and we don't know what the effects of that are going to be.
So it's a very mixed picture. That's why I think groups like NICE in England are saying, "Use CBT as the first line, not drugs." But again, it's also fair to say—I think what we find, and there was a recent Lancet study that I think was revealing on this point, is that it's like this with both antipsychotics and antidepressants.
You have a group of people who respond pretty well, and the side effects for them are bearable, or they don't experience them. That's great. You have a group of people—and it's significant. With depressed patients, we're talking 40 percent or north of 40 percent who aren't responding. The drugs aren't doing anything for them, and they're running a risk.
Then, in the middle, you have a group of people who get some positive improvement, but they also get side effects. That's where this cost-benefit analysis, if we can call it that, comes into play, and it's very difficult. The problem is that, going in, you don't know which group you're going to fall in, and your doctor doesn't know which group you're going to fall in.
More importantly, one of the things the drug revolution did was move the diagnosis and the prescribing of things away from psychiatry alone. Many of these things, particularly antidepressants, are dispensed by primary care docs, not psychiatrists.
12. Future of Psychiatry
Let's zoom out. We did say that there's a real crisis. From an individual perspective, suffering from psychosis or suffering from depression, what are you supposed to do? What works, and what is the hope for the future over the next 10 or 20 years?
So you probably need to try the drugs because the suffering is very intense. But you need to be aware of things, and you need a clinician who's monitoring very carefully. More generally, psychiatric research needs to broaden.
We have spent all our money on drugs, neuroscience, and genetics, but there are other things we could do that would improve the lives of families and patients more immediately.
So we need to spend some time on the psychosocial dimensions of mental illness and allow psychiatrists to build careers in those fields. One of the problems, if you're an academic psychiatrist, is that your whole future is dependent on bringing in grant monies, and there aren't grant monies available to study whether there are better ways we could cope with the problem of homelessness or better ways we could ease the problem for families who are having to cope with somebody in their midst who's hallucinating. That sort of thing, I think, would help.
What about talk therapy, both CBT, cognitive behavioral therapy, and psychoanalysis? We left psychoanalysis in this place where society left it behind. I think, with the advent and rapid improvement of artificial intelligence systems that are able to communicate with individual humans, learn a lot about them, and have conversations about the deepest secrets that you sometimes would even be uncomfortable telling a therapist, that starts to go into the realm of Freud and Jung and psychoanalysis. Do you think there's a future in it?
I think it's become a niche product now. Only the very wealthy can afford to do it, and some of them do make use of it, and some of them claim that it helps them.
Well, yes, and we did see, actually, with COVID, the isolation that it produced and the fact that people couldn't go to their therapists directly. We saw the rise of some of this distance therapy, and some of it may indeed be mechanizable in the way you described. It's very important that psychiatrists broaden their perspective on these things, and some already have.
I think public policy is in a mess when it comes to serious mental illness, but I'm pessimistic about fixing that because it would cost bunches of money. If we were talking about something where we could cure people, transform them from, as they used to say, tax eaters to taxpayers, there'd be an incentive to do it. But the honest answer is, right now, that's not where we are, and so we face dilemmas.
I think helping people as much as we can with social supports—and social interaction is tremendously important to people's mental health. If they lack it, if they're lonely, if they're isolated, it does bad things to people. Somehow providing that kind of support, providing some sense of agency to people who often lack it, would be very helpful.
I hope somebody has a breakthrough and produces a better drug because, unlike some people, I would be astonished if the major forms of mental illness didn't have a biological component to them. I don't think that's ever going to be the whole story, but it's going to be an important part of the story. Therefore, the fact that major drug companies have abandoned research in this area—they've been bad actors in many ways, but the drugs have had some positive effects—and the fact that there's no research being done by the people with the most money to develop better treatments is, well, one word for it would be depressing. That's not what we want to see.
So the path forward is a mix of continued research on drugs, but from a patient perspective, extreme caution in the use of those drugs; talk therapy, whether it's CBT or psychoanalysis; further investigation and research on that front; and the psychosocial component of social and family support—people around you, less loneliness. Investigating how, from a cultural and social perspective and from a public policy perspective, we can increase the amount of social connections that people who suffer have, and all of that together.
Yes. And a breakthrough with people who have a very hard time making those connections or who've lost the ability to make them.
If we can zoom out, looking back at this rich history of human beings—we did look at the darkness, but I think there's a very large number of people that want to help those who suffer. Looking at the history of people trying to figure out how to help those who suffer, what gives you hope about our future? What gives you real hope for the future of psychiatry, that we can actually help people who suffer?
Well, I think we have a profession with many very well-meaning people who see the suffering on a day-to-day, face-to-face basis. I like to think that among them will be people who move this thing forward. The fact is, we have moved things forward.
We have tended to dwell a lot on some of the very unsavory aspects of the past, and even some of the drawbacks of what we have available to us in the present. But it is important to see that, at times, highly motivated people have been able to do very good things to help people with these conditions. There is, I think, hope in the future that we will see more of that than has been the case.
That involves, in some senses, a shift in the mentality of a whole profession in a more caring kind of direction, or a less technocratic kind of direction, with less reliance on something as simple as giving people pills. That can help, but it's clearly not going to be the solution to the whole thing.
We need a system that is aware of and caters to the suffering that people experience, and finds ways, if it can't eliminate it entirely, to ameliorate it in ways that people will sense are actually of help to them. It's a very difficult area, this one. It's one that touches some of the most profound aspects of ourselves as human beings, and I think, as difficult as this problem is, it's very important not to be cynical, not to give up hope, and not to deny the possibility of progress, because that's always there, has happened, and I hope will happen with increasing pace in the years ahead of us.
And if you're listening to these words and you're right now in this moment of your life where you yourself are suffering, please know we're with you. We're in this together. Stay strong. There's hope. Legitimately, as one human to another, I love you. Brother, sister, if you're listening to this, stay strong.
Andrew, thank you for this incredible work of history that you do, this incredible work of raising awareness, stepping into a difficult topic, and trying to find the wisdom and insights in it. Thank you for this incredible conversation today.
Lex, thank you for having me. I felt you were remarkably prepared to push me in various directions, so you'd obviously done a lot of preparation to get this in the right frame. I hope that people will get something positive from this conversation, along with some of the darkness we've inevitably had to talk about.