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据路透社报道，多位患者在服用诺和诺德公司生产的用以治疗糖尿病及肥胖的药物后,出现了自杀倾向。具路透社检索了美国食品药品监督管理局不良反应数据库,发现自 2010 年以来,有 265 份报告提到 GLP-1 类药物可能引发自杀思想。目前,欧洲药品管理局也在调查这一问题。
Dawn Heidlebaugh felt trapped in a disturbing pattern while taking Ozempic, the popular drug used to treat diabetes and obesity.
在服用诺和泰（Ozempic，司美格鲁肽）这种用于治疗糖尿病和肥胖症的热门药物期间，Dawn Heidlebaugh 陷入了一种令人不安的困境。
Each Sunday for more than a year, the 53-year-old Ohio real estate agent took her weekly injection to help control her blood sugar. Then every Tuesday, she felt lethargic, depressed and sometimes suicidal, thinking her husband and four children might be better off without her. These feelings would last a few days, and the cycle repeated every week — except when she skipped a dose.
在一年多的时间里，这位 53 岁的俄亥俄州房地产经纪人每个星期日都要注射诺和泰，以帮助控制她的血糖。然后，每到星期二，她就会感到无精打采、情绪低落，有时甚至产生自杀念头，认为自己的丈夫和四个孩子没有她也许更好。这种情绪会持续几天，然后每周重复一次——除非她跳过一次用药。
“I knew it was the drug,” said Heidlebaugh, who said she had not previously suffered from depression.
“我知道是药物的原因，”曾表示从未有过抑郁症的 Heidlebaugh 说。"
Heidlebaugh is one of four U.S. patients who told Reuters about experiencing suicidal thoughts while taking Novo Nordisk’s popular Ozempic drug, approved to treat type 2 diabetes, or Wegovy, another Novo top-seller approved for weight loss. A fifth patient said he experienced depression and suicidal thoughts after taking Mounjaro, a similar diabetes medicine from Eli Lilly , which is also used for weight loss. All three drugs are GLP-1 receptor agonists, which slow digestion and reduce hunger.
Heidlebaugh 是四名向路透社报告在使用诺和诺德（Novo Nordisk）畅销药物诺和泰时产生自杀念头的美国患者之一，该药物已获批用于治疗 2 型糖尿病，或者是同样畅销的减肥药 Wegovy。第五名患者表示，在服用礼来（Eli Lilly）的类似糖尿病药物 Mounjaro 后，他出现了抑郁和自杀念头，该药物也用于减肥。这三种药物都是 GLP-1 受体激动剂，可以减缓消化并降低食欲。
The U.S. Food and Drug Administration has received 265 reports of suicidal thoughts or behavior in patients taking these or similar medicines since 2010, Reuters found in an examination of the agency's adverse-event database. Thirty-six of these reports describe a death by suicide or suspected suicide. The FDA monitors such reports to help decide whether to further investigate a drug’s safety and take action to protect patients, such as mandating a warning label.
路透社在对美国食品药物管理局的不良事件数据库进行检索时发现，自 2010 年以来，已有 265 份关于服用这些或类似药物的患者产生自杀念头或行为的报告。其中 36 份报告描述了自杀或涉嫌自杀的死亡事件。美国 FDA 监测此类报告，以帮助决定是否进一步调查药物的安全性，并采取行动保护患者，例如强制要求警示标签。
Accounts of suicidal thoughts linked to this class of drugs are drawing increasing scrutiny, including an investigation by European regulators announced in July. In a statement to Reuters, the FDA said it is evaluating such reports and will decide on what action, if any, to take after a thorough review.
与这类药物有关的自杀念头的报告正在引起越来越多的关注，包括欧洲监管机构在 7 月宣布的一项调查。美国 FDA 在向路透社发表的声明中表示，正在评估这类报告，并将在经过彻底审查后决定是否采取任何行动。
Many beneficial drugs have rare and sometimes dangerous side effects that have to be carefully assessed by regulators and managed by physicians, making clear warnings essential in such cases, said Thomas J. Moore, faculty associate at the Johns Hopkins Bloomberg School of Public Health, who has studied the incidence of rare psychiatric side effects.
约翰斯·霍普金斯大学布隆伯格公共卫生学院的教职工 Thomas J. Moore 表示，许多有益的药物都具有罕见且有时危险的副作用，这些副作用必须由监管机构进行仔细评估，并由医生进行管理，因此在这种情况下明确的警告至关重要。摩尔教授曾研究罕见的精神副作用的发生率。
“This doesn’t mean to automatically blame the drug,” he said. “It does mean that a patient's complaint should not be automatically dismissed.”
“这并不意味着自动归咎于药物，”他说。“但也并不意味着患者的投诉可以被自动忽略。”
The Reuters review is the first exhaustive examination of FDA adverse-event reports involving incidents of suicidal thinking linked to GLP-1 drugs. The news organization also filed public records requests to obtain 113 more-detailed narratives for individual incidents among the 265 reports in the FDA database. The experiences of the five patients who spoke with Reuters have not been previously reported.
路透社对涉及与 GLP-1 药物相关的自杀思维事件的 FDA 不良事件报告进行了首次详尽检索。该新闻机构还提交了公共记录请求，以获取 FDA 数据库中 265 份报告中更详细的 113 份个体事件叙述。与路透社交谈的五名患者的经历以前尚未报道过。
More than half of the narrative summaries describe suicidal thoughts appearing shortly after the person started the medicine or increased the dose. About two fifths of them said symptoms ceased after the patient stopped taking the drug or lowered the dose.
超过半数的叙述摘要描述了自杀念头在人们开始服药或增加剂量后不久出现。其中约五分之二的人称症状在患者停止服药或减少剂量后消失。
Thirty of the 113 narratives described patients with a history of depression, suicidal thinking or another mental-health condition. Another five reports explicitly said the patient had no history of psychological issues. Most reports don’t address that medical history.
113 份叙述中的 30 份描述了曾经有抑郁症、自杀思维或其他心理健康问题的患者。另外五份报告明确表示患者没有心理问题的病史。大多数报告没有提到医疗史。
Adverse-event reports provide a warning system for the medical community but aren't considered definitive scientific evidence. Submitted by doctors, patients, drugmakers and others, they often lack key details and do not on their own establish that a drug caused the potentially dangerous health events. Reuters identified the 265 reports by searching the government database for key words involving suicide and self-harm; it’s possible that additional reports of these side effects exist.
不良事件报告为医疗界提供了一个警示系统，但并不被视为明确的科学证据。这些报告由医生、患者、制药公司等提交，通常缺乏关键细节，不能单独证明药物导致了潜在的危险健康事件。路透社通过搜索政府数据库中涉及自杀和自伤的关键词来识别了这 265 份报告；还有可能存在其他有关这些副作用的报告。
It’s also possible that the reports identified in these searches contain multiple submissions describing the same incident.
这些搜索所识别的报告也可能包含多次提交，描述了同一事件。
In a statement, Novo said it takes “all reports about adverse events from use of our medicines very seriously,” and that it would continue to monitor clinical data and collaborate with authorities. The company said it remains confident in the benefit-risk profile of the products and that its own safety monitoring has found no “causal association” between the drugs and thoughts of self-harm.
诺和诺德在一份声明中表示，该公司非常重视关于使用其药物的不良事件的所有报告，并将继续监测临床数据并与相关部门合作。该公司表示，对其产品的风险利益概况仍然充满信心，其自己的安全监测未发现药物与自残思维之间的“因果关联”。
Eli Lilly said in a statement that it was working closely with regulators on potential safety issues involving Mounjaro and that it would continue to review data on “suicidal ideation, thoughts of self-harm and depression.”
礼来在一份声明中表示，该公司正在与监管机构密切合作，就 Mounjaro 可能存在的安全问题进行调查，并将继续审查与“自杀念头、自伤念头和抑郁症”有关的数据。
Dr. Erick Turner, a former FDA medical officer who reviewed psychiatric drugs, said cases such as Heidlebaugh’s are cause for concern. Regulators should pay attention to cases where patients have no history of depression, experience suicidal thoughts suddenly after starting or increasing their dose, and then see symptoms subside after stopping.
Erick Turner 博士是一名曾审查精神药物的前 FDA 医疗官员，他表示像 Heidlebaugh 这样的案例是令人担忧的。监管机构应关注患者没有抑郁症状的情况，突然在开始或增加剂量后出现自杀念头，然后在停药后症状减轻的情况。
“That makes it harder to explain away the suicidality,” said Turner, a professor of psychiatry at Oregon Health & Science University. “It makes any occurrence of those safety signals more credible.”
“这使得很难解释自杀念头，”Turner 说道，他是俄勒冈健康与科学大学的精神病学教授。“这使得这些安全信号的发生更加可信。”
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Millions of patients are being encouraged to try drugs such as Wegovy, which led to an average loss of 15% of a person’s body weight in clinical trials, making it the most effective approved weight-loss treatment to date. Its 2021 approval kickstarted a new market for obesity drugs that is estimated to reach $100 billion within a decade. Novo Nordisk says additional trials, which it plans to publish soon, show the drug can also help protect patients against heart attacks and strokes.
数百万患者被鼓励尝试像 Wegovy 这样的药物，该药在临床试验中平均使患者体重减轻了 15%，使其成为迄今为止最有效的获批准的减肥治疗方法。其在 2021 年的批准开启了一个新的肥胖药物市场，估计在未来十年内将达到 1000 亿美元。诺和诺德表示，他们计划很快发布的额外试验显示，这种药物还可以帮助患者预防心脏病发作和中风。
Trials of Mounjaro showed even more weight loss, and Eli Lilly has said it expects the FDA to approve the drug for that purpose this year.
Mounjaro 的试验显示了更多的体重减轻，礼来表示预计 FDA 将在今年批准该药物用于减肥治疗。
Ozempic, Wegovy and Mounjaro have so far proved relatively safe. Their clinical trials did not show suicide risk, according to the FDA. But doctors are on the lookout for previously undocumented dangers as hundreds of thousands of new patients start taking these drugs to lose weight. Heightened suicide risks have caused regulators to issue strong warnings on obesity drugs in the past.
到目前为止，诺和泰、Wegovy 和 Mounjaro 已经被证明相对安全。根据 FDA 的说法，它们的临床试验没有显示出自杀风险。但随着数十万新患者开始服用这些药物以减肥，医生们正在寻找以前未记录的危险。在过去，增加的自杀风险曾导致监管机构对肥胖药物发布强烈警告。
Wegovy’s U.S. prescribing label, produced with FDA approval, says suicidal thoughts or attempts have been reported in clinical trials for other weight-loss medicines. It recommends that patients starting Wegovy be monitored for such behavior and calls for those with a history of suicide attempts or active suicidal thinking to avoid the drug.
Wegovy 的美国处方标签是经过 FDA 批准的，它表示在其他减肥药物的临床试验中曾报告有自杀念头或企图。它建议对开始服用 Wegovy 的患者进行此类行为的监测，并要求那些有自杀企图或有积极自杀念头的人避免使用这种药物。
Novo’s Saxenda, a GLP-1 approved in 2014 for weight loss and included in the Reuters analysis of adverse event reports submitted to the FDA, contains an FDA warning because suicidal thoughts or behaviors were seen in some patients during the company’s clinical trials.
诺和诺德的 Saxenda，这是一种 2014 年获得减肥批准的 GLP-1 药物，已包含在提交给 FDA 的不良事件报告的路透社分析中，因为在该公司的临床试验中曾看到一些患者出现自杀念头或行为，所以含有 FDA 警告。
Dawn Heidlebaugh looks out of the window of her home in Findlay, Ohio, U.S., September 19, 2023. REUTERS/Megan Jelinger
2023 年 9 月 19 日，Dawn Heidlebaugh 在美国俄亥俄州芬德利的家中望向窗外。路透社/Megan Jelinger
There’s no such language on the U.S. label for Ozempic, which was approved for treating diabetes in 2017. Suicidal behavior isn’t listed as a potential side effect for any GLP-1 drugs in the European Union.
Ozempic 在 2017 年获得了治疗糖尿病的批准，美国标签上没有这样的语言。在欧盟，自杀行为没有被列为任何 GLP-1 药物的潜在副作用。
Scrutiny of GLP-1 drugs intensified in July after the European Medicines Agency (EMA) announced an investigation of suicide risk from Ozempic, Wegovy, Saxenda and other GLP-1 drugs. It later said it was analyzing about 150 reports of suicidal thinking. Health agencies in the UK and Canada are also reviewing the drugs’ suicide risk. The drug manufacturers have said they are cooperating with the probes.
在欧洲药品管理局（EMA）宣布对诺和泰、Wegovy、Saxenda 和其他 GLP-1 药物的自杀风险进行调查后，对 GLP-1 药物的审查在 7 月份加剧。后来，它表示正在分析大约 150 份关于自杀念头的报告。英国和加拿大的卫生机构也正在审查这些药物的自杀风险。药物制造商表示他们正在配合调查。
The European regulator expects to conclude its review in November. The agency told Reuters that such reviews can result in regulators requiring a warning on the product, issuing urgent safety restrictions or asking drugmakers to conduct a more extensive safety study.
欧洲监管机构预计将在 11 月完成其审查。该机构告诉路透社，这种审查可能会导致监管机构要求在产品上发出警告，发布紧急安全限制或要求药品制造商进行更广泛的安全研究。
If the FDA finds that GLP-1 drugs increase suicide risk, it could also require warnings. In the case of Wegovy, the agency could strengthen the existing warning by requiring more explicit language linking the drug to suicide risk. The agency’s strongest action, short of banning a drug, is to issue a so-called black-box warning, which could prompt some doctors and patients to avoid the medicine.
如果 FDA 发现 GLP-1 药物增加了自杀风险，它也可能要求发出警告。在 Wegovy 的情况下，该机构可以通过要求更明确地将该药与自杀风险联系起来来加强现有的警告。该机构最强有力的行动，除了禁止药物之外，就是发布所谓的黑匣子警告，这可能会促使一些医生和患者避免使用这种药物。
Novo Nordisk itself submitted 180 of the 265 reports to the FDA describing suicidal thinking or behaviors that Reuters found. Among the 113 detailed case narratives, 91 were filed by Novo. In nearly all of those, the company wrote that there weren’t enough details to determine what happened. In three reports, the company sought to explain the experience of the patient by saying overweight people are at higher risk of depression or suicidal ideation. Novo declined to comment further on its statements in these reports.
根据路透社发现的 265 份报告中，诺和诺德公司自己提交了 180 份报告，描述了自杀念头或行为。在 113 份详细的案例报告中，有 91 份是由诺和诺德提交的。在几乎所有这些报告中，该公司都写道没有足够的细节来确定发生了什么。在三份报告中，该公司试图通过称超重的人患抑郁症或自杀念头的风险较高来解释患者的经历。诺和诺德公司拒绝进一步评论其在这些报告中的说法。
It’s difficult to gauge whether or how quickly such reports will spur FDA action. As Reuters reported earlier this year, it took the agency 12 years after launching a safety review of the allergy-and-asthma drug Singulair before it required a black-box warning about serious neuropsychiatric side effects, including suicidal thinking, in 2020. By that time, the FDA had received more than 80 reports of people killing themselves while taking the medicine, including 31 children and teenagers.
很难估计这些报告是否会或以何种速度促使 FDA 采取行动。正如路透社今年早些时候报道的那样，FDA 在启动了对过敏和哮喘药物 Singulair 进行安全审查后，花了 12 年的时间，直到 2020 年才要求在该药物上加上黑匣子警告，警告有严重的神经精神副作用，包括自杀念头。在那之前，FDA 已经收到了 80 多份有人在服用这种药物时自杀的报告，其中包括 31 名儿童和青少年。
Reports of suicidal thinking have previously dogged other weight-loss medications. Sanofi's Acomplia, which never won U.S. approval, was withdrawn in Europe in 2008 after being linked to suicidal thoughts. The weight-loss drug Contrave carries a black-box warning about suicidal thinking, and another obesity medicine, Qsymia, carries a warning telling patients to stop taking it if they experience suicidal thoughts.
自杀念头的报告以前曾困扰其他减肥药物。赛诺菲的 Acomplia 从未获得美国批准，在 2008 年被与自杀念头联系在一起后在欧洲撤回了市场。减肥药 Contrave 上有关于自杀念头的黑匣子警告，另一种肥胖药物 Qsymia 则有一个警告，告诉患者如果出现自杀念头就停止服用。
Sanofi and Currax Pharmaceuticals, the maker of Contrave, said their drugs shouldn’t be compared to GLP-1 drugs because they contain different active ingredients. John Amos, chief executive of Vivus LLC, which sells Qsymia, said patients should consult health-care providers on the benefits and risks of various weight-loss medicines.
赛诺菲和 Contrave 的制造商 Currax Pharmaceuticals 表示，它们的药物不应与 GLP-1 药物相比，因为它们含有不同的活性成分。Vivus LLC 的首席执行官约翰·阿莫斯（John Amos）表示，患者应咨询医疗保健提供者，了解各种减肥药物的益处和风险。
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GLP-1 drugs reach the brain, according to pharmacology reports Novo and Lilly submitted to the FDA. That may account for their effectiveness in influencing hunger signals, but could also increase risks of neuropsychiatric side effects.
根据诺和诺德和礼来提交给 FDA 的药理学报告，GLP-1 药物可以抵达大脑。这可能解释了它们在影响饥饿信号方面的有效性，但也可能增加神经精神副作用的风险。
Patients who spoke with Reuters described suicidal or panicked feelings that came on quickly after either starting the medicine or increasing the dosage.
与路透社通话的患者描述了在开始服用药物或增加剂量后迅速出现的自杀或惊恐的感觉。
None were aware of their experiences being reported to the FDA, underscoring how the FDA’s adverse-event database often doesn’t capture the full scope of a drug’s potential problems. Some people do not connect medical or psychological issues to their medicines. Some patients interviewed by Reuters weren’t aware of the FDA process for reporting them.
他们中没有人意识到自己的经历已被报告给 FDA，突显了 FDA 的不良事件数据库通常无法捕捉药物潜在问题的全部范围。有些人不会把医疗或心理问题与他们的药物联系起来。一些接受路透社采访的患者不了解向 FDA 报告这些问题的程序。
Three of the patients, including Heidlebaugh, described becoming scared after experiencing impulses to kill themselves by crashing their cars.
其中三名患者，包括 Heidlebaugh，在经历了决定撞车自杀的冲动后感到害怕。
“I was driving and thought: ‘What if I just jerked the wheel while on this bridge?’” said Lisa Wood, a 33-year-old North Carolina ultrasound technician who lost 70 pounds on Wegovy. “It didn’t occur to me that it was the Wegovy.”
“我正在开车，突然想：‘如果我在这座桥上突然拧方向盘会怎样？’” 33 岁的北卡罗来纳州超声波技术员 Lisa Wood 说道，她通过服用 Wegovy 减掉了 70 磅的体重。“我没有意识到这是因为 Wegovy。”
Wood said her symptoms subsided after she stopped taking the medicine.
Wood 说，在她停止服用药物后，症状有所缓解。
Sarah Sobol of Buffalo, New York, age 40, said she had panic attacks, hallucinations and suicidal thoughts after increasing her dose of Ozempic, which she took in 2021 for weight loss. She later found patients posting on Facebook about similar symptoms, stopped the medication and began to feel better.
40 岁的纽约布法罗市的 Sarah Sobol 说，在 2021 年因体重问题开始增加她的诺和泰剂量后，她出现了惊恐发作、幻觉和自杀念头。后来，她在 Facebook 上发现有患者也报告了类似的症状，于是停止了药物，感觉好了起来。
“If someone had said: ‘This is a side effect; you’re not losing your mind,’ it would have really helped me,” said Sobol, who sought therapy to deal with her symptoms. “I thought I would end up in the psych ward. I was terrified I would not be normal again.”
“如果有人告诉我：‘这是一种副作用；你不是要发疯了，’那真的会帮助我很多，”Sobol 说，她寻求心理治疗来应对自己的症状。“我以为我会被关进精神病院。我真的害怕我再也无法恢复正常。”
Some patients told Reuters they stuck with the therapy, despite the suicidal thoughts, because doctors assured them the drug didn’t cause them. Katherine, a 37-year-old North Carolina nurse and mother of two who spoke on condition she be identified only by her first name, said she repeatedly visualized shooting herself while taking Wegovy. One night she went to the emergency room. She was given anxiety medicine and quickly released. She said an ER staffer told her: “‘You’re a mom. This happens when you get over-tired.’”
一些患者告诉路透社，尽管有自杀念头，但他们仍然坚持治疗，因为医生向他们保证这种药物不会引发这种情况。Katherine 是北卡罗来纳州的一名 37 岁的护士和两个孩子的母亲，她要求只提供她的名字，不愿透露全名。她表示，在服用 Wegovy 期间，她多次想象自己开枪自杀。有一天晚上，她去了急诊室。她服用了抗焦虑药后很快出院。她说，急诊室的一名员工对她说：“‘你是一个妈妈。当你过度疲劳时，这种情况就会发生。’”
Katherine had lost 70 pounds while on Wegovy but switched to Mounjaro. She said she has not experienced any suicidal thoughts on that drug.
Katherine 在服用 Wegovy 期间减掉了 70 磅，但后来换成了 Mounjaro。她说，在那种药物上她没有经历过任何自杀念头。
Some patients in reports to the FDA and interviews with Reuters said they had experienced depression in the past, but that the feelings they experienced on the GLP-1 drugs felt more intense.
一些向 FDA 报告和接受路透社采访的患者表示，他们过去曾经历抑郁，但在使用 GLP-1 药物时，他们的感觉更加强烈。
Jayson Chesnutt, a 49-year-old patient on Mounjaro, told Reuters that his dark thoughts prompted him to check himself into the Indiana psychiatric hospital where he works as a nurse. He ultimately decided to continue the medicine, however, because his blood sugar levels had improved and he had lost 75 pounds in five months.
49 岁的患者 Jayson Chesnutt 正在使用 Mounjaro，他告诉路透社，他的阴暗思维促使他入住了印第安纳州一家精神病医院，他在那里担任护士。然而，他最终决定继续服药，因为他的血糖水平有所改善，他在五个月内减掉了 75 磅。
Chesnutt continues to feel depressed and, at times, suicidal. But he says he can manage these feelings now that he is aware of the possible cause. He favors a stronger warning for consumers.
Chesnutt 仍然感到抑郁，有时甚至有自杀念头。但他说，现在他知道了可能的原因，所以可以应对这些感觉。他支持为消费者发布更强烈的警告。
“People need to know their feelings may not be them,” he said.
“人们需要知道，他们的感觉可能不是他们自己的，”他说。
Reporting by Robin Respaut and Chad Terhune; additional reporting by Maggie Fick and Ludwig Burger; editing by Michele Gershberg and Brian Thevenot
报告由 Robin Respaut 和 Chad Terhune 撰写；Maggie Fick 和 Ludwig Burger 提供额外报道；Michele Gershberg 和 Brian Thevenot 编辑
