原文標題:ADHD Drugs Linked to Psychosis and Mania
In one analysis, those on a high dose of prescription amphetamines were more than 13 times more likely to develop psychosis and mania.
根據一項分析，服用高劑量處方安非他命的患者出現精神病和躁狂的可能性是普通人的 13 倍以上。

By Peter Simons -September 23, 2024
彼得·西蒙斯 – 2024年9月23日
文章來源:
https://www.madinamerica.com/2024/09/adhd-drugs-linked-to-psychosis-and-mania/

In a new study, researchers compared people who were hospitalized for psychiatric reasons. They found that people taking prescription amphetamines (Adderall) were more than twice as likely to develop psychosis or mania; those on high doses were more than five times as likely.
在一項新的研究中，研究人員比較了因精神疾病住院的患者。他們發現，服用處方安非他命（如 Adderall）的患者發展出精神病或躁狂的可能性是普通人的兩倍以上；而服用高劑量的患者，發病的可能性更是高出五倍以上。

However, when the researchers included outpatients as well—essentially, those with less severe psychiatric problems—they found that those taking a high dose of amphetamines were more than 13 times as likely to develop psychosis/mania.
然而，當研究人員將門診病人也納入研究時——這些患者通常有較輕微的精神問題——他們發現，服用高劑量安非他命的患者發展出精神病或躁狂的可能性高達 13 倍以上。

“The results of this study suggest that high doses of prescription amphetamines are associated with an increased odds of incident psychosis or mania,” the researchers write.
研究人員寫道：“這項研究結果表明，高劑量的處方安非他命與精神病或躁狂事件的發生概率增加有關。”

The study was led by Lauren V. Moran, with joint senior authors Dost Ongur and Roy Perlis. It was published in The American Journal of Psychiatry.
這項研究由 Lauren V. Moran 主導，Dost Ongur 和 Roy Perlis 共同擔任資深作者。研究發表在《美國精神病學期刊》上。

Moran is an employee of pharma company Sage Therapeutics. She is affiliated with Brigham and Women’s Hospital. Moran is also affiliated with Harvard Medical School as a psychiatrist at McLean Hospital in Belmont, MA, as is Ongur. Perlis is affiliated with Harvard Medical School and Massachusetts General Hospital.
Moran 是製藥公司 Sage Therapeutics 的員工，她隸屬於布萊根婦女醫院 (Brigham and Women’s Hospital)，同時也是哈佛醫學院的成員，並且在馬薩諸塞州貝爾蒙特的麥克萊恩醫院擔任精神科醫師，Ongur 亦然。Perlis 則隸屬於哈佛醫學院和麻省總醫院 (Massachusetts General Hospital)。

In the United States, prescription amphetamine salts (Adderall) are the most common treatment for ADHD, and, according to the researchers, high doses are common. Yet this isn’t the first study to find a connection between ADHD drugs and psychosis and mania. A study in the New England Journal of Medicine found such a link, as did a study in Pediatrics. Moreover, one partial explanation for the dramatic rise in pediatric bipolar disorder diagnoses is the similarly dramatic jump in stimulant prescriptions. A study in Bipolar Disorders found that 62% of adolescents who had a bipolar disorder diagnosis had been using stimulants before developing psychosis/mania. (The increase in children prescribed antidepressants may also partially explain the increase.)
在美國，處方安非他命鹽（如 Adderall）是治療 ADHD 的最常見藥物，並且根據研究人員的說法，高劑量的使用非常普遍。然而，這並不是首次有研究發現 ADHD 藥物與精神病和躁狂之間的聯繫。《新英格蘭醫學期刊》中的一項研究發現了這種聯繫，《小兒科》期刊中的一項研究也有類似發現。此外，兒童雙相情感障礙診斷激增的部分原因可以歸結於興奮劑處方數量的同樣急劇增長。《雙相情感障礙》期刊的一項研究發現，62% 的被診斷為雙相情感障礙的青少年在出現精神病或躁狂之前曾使用過興奮劑。（兒童抗抑鬱藥處方的增加也可能部分解釋了這一增長。）

In most other countries, methylphenidate (Ritalin) is a more commonly prescribed stimulant drug than Adderall. In this analysis, the researchers found that Ritalin was not associated with an increase in psychosis/mania risk. They write that this is consistent with most other studies. (However, there have been studies to suggest that Ritalin, too, can cause psychosis/mania.)
在大多數其他國家，哌甲酯（利他林）比 Adderall 更常被處方作為興奮劑藥物。在這項分析中，研究人員發現利他林與精神病/躁狂風險的增加無關。他們寫道，這與大多數其他研究的結果一致。（然而，也有研究表明，利他林也可能導致精神病/躁狂。）

The Results
In the current study, Moran et al. investigated the connection between ADHD stimulant drugs and psychosis/mania. They examined the records of people ages 16-35 hospitalized at McLean Hospital for the first time between January 1, 2005, and December 31, 2019. They compared 1,374 people hospitalized for psychosis or mania to 2,748 people hospitalized for other psychiatric diagnoses (serving as the control group). Those who were hospitalized for psychosis/mania were more likely to be male, Black, Hispanic, and on public health insurance; they were also more likely to have used cannabis, tobacco, and hallucinogenic drugs.
研究結果

在目前的研究中，Moran 等人調查了 ADHD 興奮劑藥物與精神病/躁狂之間的聯繫。他們檢視了2005年1月1日至2019年12月31日期間，首次在麥克萊恩醫院（McLean Hospital）住院的16至35歲患者的記錄。他們將1,374名因精神病或躁狂住院的患者與2,748名因其他精神科診斷住院的患者（作為對照組）進行了比較。那些因精神病/躁狂住院的患者更可能是男性、黑人、拉丁裔，並使用公共醫療保險；他們也更可能使用大麻、煙草和迷幻藥物。

The researchers included these factors while accounting for age, family history, and current college attendance, among others, in their statistical analysis.
研究人員在統計分析中納入了這些因素，同時考慮了年齡、家族史和當前大學就讀情況等。

Twice as many people with psychosis/mania had taken amphetamine salts (Adderall) in the past month compared to those hospitalized for other reasons: in total, 204 out of 1,374 (14.8%) people with psychosis/mania compared to 211 out of 2,748 (7.7%) hospitalized for other reasons. Almost all had used them as prescribed.
與因其他原因住院的患者相比，過去一個月內服用安非他命鹽（Adderall）的精神病/躁狂患者人數是前者的兩倍：在1,374名精神病/躁狂患者中，有204人（14.8%）服用了安非他命鹽，而在2,748名因其他原因住院的患者中，只有211人（7.7%）服用了該藥。幾乎所有人都是按照處方使用的。

A high dose of amphetamines was defined as 40 mg of mixed amphetamine salts (Adderall) and 100 mg of lisdexamfetamine (Vyvanse). This was relatively common (24.2% of those taking stimulants in the psychosis/mania group; 16.9% of those taking stimulants in the control group).
高劑量的安非他命被定義為40毫克的混合安非他命鹽（Adderall）或100毫克的右旋苯丙胺（Vyvanse）。這種情況相對普遍（在精神病/躁狂組中，24.2%的興奮劑使用者；在對照組中，16.9%的興奮劑使用者）。

In the main analysis, Moran et al. found that people taking amphetamines were 2.13 times as likely to develop psychosis or mania; those on high doses were 5.28 times as likely.
在主要分析中，Moran 等人發現，服用安非他命的人發展出精神病或躁狂的可能性是普通人的2.13倍；服用高劑量的人可能性更是達到5.28倍。

Those who took Adderall were about four times as likely to develop psychosis/mania than those who took Ritalin.
服用 Adderall 的人發展出精神病/躁狂的可能性約為服用利他林（Ritalin）者的四倍。

It gets worse, though: After conducting sensitivity analyses, the researchers concluded that their study hugely underestimated the risk.
然而，情況更糟的是：在進行敏感性分析後，研究人員得出結論，他們的研究大大低估了風險。

“After adjusting for selection bias, the observed odds ratio from the main study increased from 2.13 (unadjusted) to 6.05, suggesting that use of hospitalized control subjects underestimated the effect of amphetamine use on the odds of psychosis or mania,” Moran et al. write.
Moran 等人寫道：“在調整了選擇偏差後，主要研究中觀察到的比值比從未調整的2.13增加到6.05，這表明使用住院對照組低估了安非他命使用對精神病或躁狂發生概率的影響。”

And when comparing the ADHD drug users to outpatients only (rather than inpatients) in order to account for the bias toward more severe symptoms, the researchers found that a high dose led to a 13.6-fold increased risk of psychosis/mania.
當僅將 ADHD 藥物使用者與門診患者（而非住院患者）進行比較，以考慮對更嚴重症狀的偏差時，研究人員發現，高劑量導致精神病/躁狂風險增加了 13.6 倍。

The low-dose group did not consistently exhibit a risk of psychosis/mania in sensitivity analyses. However, in the main analysis, the risk was increased with any dose of amphetamines, not just high doses:
在敏感性分析中，低劑量組並未持續顯示出精神病/躁狂的風險。然而，在主要分析中，任何劑量的安非他命都增加了風險，而不僅僅是高劑量：

“The attributable risk percentage was 62.7% for those exposed to any prescription amphetamine, and 81.0% for those exposed to high-dose amphetamines,” the researchers write.
研究人員寫道：「對於接觸任何處方安非他命的人，歸因風險百分比為 62.7%；對於接觸高劑量安非他命的人，則為 81.0%。」

Ultimately, the researchers’ takeaway was to try your best to avoid high doses of amphetamines.
最終，研究人員的結論是盡量避免高劑量使用安非他命。

“The clinical utility of prescribing doses of amphetamines that exceed 30 mg dextroamphetamine equivalents is unproven; coupled with the elevated risk of inducing psychosis or mania, we recommend minimizing this practice,” the researchers write.
研究人員寫道：「開具超過 30 毫克右旋安非他命等效劑量的安非他命，其臨床效用尚未證明；再加上誘發精神病或躁狂風險的增加，我們建議盡量減少這種做法。」

Moran et al. note some limitations to their study. As it was not a randomized, controlled trial, it is difficult to draw causal conclusions. The number of participants with stimulant use was small, particularly for comparisons between smaller subgroups. The participants themselves were a unique group of people hospitalized at a private psychiatric hospital in the US, so it is unclear how well the results will generalize to the broader public or internationally. And the data comes from the electronic health record, which can always have errors, missing information, etc.
Moran 等人指出了他們研究的一些局限性。由於這不是一項隨機對照試驗，很難得出因果結論。使用興奮劑的參與者數量較少，特別是在較小的子群組之間的比較。參與者本身是在美國一家私人精神病院住院的特殊人群，因此不清楚結果能在多大程度上推廣到更廣泛的公眾或國際上。而且，數據來自電子健康記錄，可能存在錯誤、信息缺失等問題。

ADHD and Stimulant Use

Beyond the question of high doses, the diagnosis of ADHD itself—and the prescription of stimulants at any dose—has received significant criticism from prominent figures in psychiatry.

For instance, take Allen Frances, the man who spearheaded the creation of the fourth edition of psychiatry’s bible as Chair of the DSM-IV Task Force. He argues that the diagnosis is overly broad and medicalizes normal aspects of childhood, such as being unable to sit still for eight hours of school lectures. Supporting this notion, dozens of studies have found that younger children in the classroom are much more likely to receive a diagnosis of ADHD and take stimulant drugs. And take Keith Conners—the namesake of the primary measure for diagnosing ADHD, and prominent early Ritalin proponent—also argued that the current ADHD diagnosis was based on “shoddy science.”

Worse, the diagnosis and treatment of ADHD are not leading to better outcomes. In fact, in a recent study comparing kids with the same symptoms, those who received the ADHD diagnosis ended up with a worse quality of life, not better—and were more than twice as likely to self-harm—than kids with the same symptoms who went undiagnosed.

The large, NIMH-funded MTA study is often cited as evidence that stimulant drugs work. Indeed, the short-term results appeared positive. However, by the 22-month mark, the benefit of stimulant drugs vanished. The authors wrote that “the MTA medication algorithm was associated with deterioration rather than a further benefit.” Ultimately, they added, “extended use of medication was associated with suppression of adult height but not with reduction of symptom severity.”

Other studies have contradicted the notion that stimulants can improve academic performance and even support the notion that kids are more likely to drop out of school after taking the drugs. One study noted that Ritalin was associated with an 18-fold increase in depression, which returned to baseline once kids stopped taking the drug.

And despite claims to the contrary, researchers have been unable to find a single biomarker, nor any brain differences, to define the supposed neurobiological condition of ADHD.
ADHD 與興奮劑的使用

除了高劑量的問題外，ADHD 的診斷本身——以及任何劑量的興奮劑處方——都受到了精神病學領域知名人士的嚴重批評。
例如，擔任《精神疾病診斷與統計手冊》第四版（DSM-IV）工作組主席的艾倫·弗朗西斯（Allen Frances）就指出，該診斷過於寬泛，將童年的正常特徵醫學化，如無法在學校八小時的課堂上安靜坐著。

支持這一觀點的是，數十項研究發現，班級中年紀較小的孩子更有可能被診斷為 ADHD 並服用興奮劑藥物。

再以基思·康納斯（Keith Conners）為例——他是診斷 ADHD 的主要量表的創建者，也是早期利他林（Ritalin）的著名支持者——他也認為當前的 ADHD 診斷基於“劣質的科學”。

更糟糕的是，ADHD 的診斷和治療並未帶來更好的結果。

事實上，在一項最近的研究中，對比具有相同症狀的孩子，接受 ADHD 診斷的孩子最終生活質量更差，而非更好——並且自我傷害的可能性是未被診斷孩子的兩倍以上。

由美國國家精神衛生研究所（NIMH）資助的大型 MTA 研究經常被引用為興奮劑藥物有效的證據。

的確，短期結果看起來是積極的。

然而，到第22個月時，興奮劑藥物的益處消失了。

作者寫道：“MTA 藥物算法與病情惡化相關，而非進一步的益處。”

最終，他們補充道：“延長使用藥物與抑制成年身高有關，但與症狀嚴重程度的降低無關。”

其他研究則與興奮劑能提高學業表現的觀點相矛盾，甚至支持孩子在服用藥物後更可能輟學的說法。

一項研究指出，利他林與抑鬱症發生率增加18倍有關，當孩子停止服藥後，這一數據會回到基線水平。

儘管有相反的說法，研究人員仍未能找到任何生物標記或大腦差異來定義所謂的 ADHD 神經生物學狀況。

Moran, L. V., Skinner, J. P., Shinn, A. K., Nielsen, K., Rao, V., Taylor, T., . . . & Ongur, D. (2024). Risk of incident psychosis and mania with prescription amphetamines. The American Journal of Psychiatry. Published online 12 September 2024. https://doi.org/10.1176/appi.ajp.20230329 [Link]
Moran, L. V., Skinner, J. P., Shinn, A. K., Nielsen, K., Rao, V., … & Ongur, D.（2024）。處方安非他命與新發精神病和躁狂的風險。《美國精神病學期刊》。2024年9月12日在線發表。https://doi.org/10.1176/appi.ajp.20230329

Peter SimonsPeter Simons was an academic researcher in psychology. Now, as a science writer, he tries to provide the layperson with a view into the sometimes inscrutable world of psychiatric research. As an editor for blogs and personal stories at Mad in America, he prizes the accounts of those with lived experience of the psychiatric system and shares alternatives to the biomedical model.