The data, released in a report Thursday, is a sign that medication abortion has become the most accessible and preferred method for terminating pregnancy.More than half of recent abortions in the United States were carried out with abortion pills, according to preliminary data released on Thursday, a sign that medication abortion has increasingly become the most accessible and preferred method for terminating pregnancy.The report, issued by the Guttmacher Institute, a research organization that supports abortion rights, found that in 2020, medication abortion — a two-pill method authorized in the United States for pregnancies up to 10 weeks’ gestation — accounted for 54 percent of all abortions. The figure represents a substantial increase from the institute’s previous report, which found that the method accounted for 39 percent of abortions in 2017.The increase in medication abortion is most likely the result of several factors. The method — which is less expensive and less invasive than surgical abortions — had already become increasingly common before the coronavirus pandemic, driven partly by restrictions from conservative states that imposed hurdles to surgical methods, especially later in pregnancy.As of 2017, according to the Guttmacher Institute, which collects data by contacting every known abortion provider in the country, nearly a third of clinics offered only medication abortion. In 2019, according to data from the Centers for Disease Control and Prevention, which did not include California, Maryland and New Hampshire, pills accounted for 42 percent of all abortions — and 54 percent of abortions that were early enough to qualify for medication because they occurred before 10 weeks’ gestation.The pandemic fueled that trend, as medical groups filed a lawsuit asking the federal government to lift the Food and Drug Administration’s requirement that the first of the two abortion pills, mifepristone, be dispensed to patients in person at a clinic or doctor’s office. Citing years of data showing that medication abortion is safe, the medical groups said that patients faced a greater risk of being infected with the coronavirus if they had to visit clinics to obtain mifepristone and pointed out that mifepristone was the only drug that the F.D.A. required patients to get in person from a medical provider but that patients were also allowed to take at home on their own without having the provider present.A judge granted the request that summer, allowing patients to see a physician by telemedicine and receive pills by mail, but, after a challenge by the Trump administration, the Supreme Court reinstated the restriction early last year.Under the Biden administration, however, the F.D.A. permanently lifted the in-person requirement in December and also said that pharmacies could begin dispensing mifepristone if they met certain qualifications. The F.D.A.’s action means that medication abortion will become more available to women who find it difficult to travel to an abortion provider or prefer the privacy of being able to terminate a pregnancy in their homes.As a result, while the new report from the Guttmacher Institute is preliminary — only reflecting information from 75 percent of the clinics and including only percentages, not raw data — the proportion of abortions carried out with pills is expected to increase further.Nearly 80 percent of all abortions in the C.D.C.’s 2019 data occurred before 10 weeks’ gestation, suggesting that there were many more women who might choose abortion pills over an in-clinic procedure if they could.At the same time, the growing interest in medication abortion has made it a focus of the highly polarized abortion debate.In 19 states, mostly in the South and the Midwest, telemedicine visits for medication abortion are banned, and so far in 2022, according to the Guttmacher Institute report, 16 state legislatures have introduced bills to ban or limit medication abortion.With the Supreme Court now considering whether to roll back abortion rights or even overturn the 1973 Roe v. Wade decision, which legalized abortion, experts and advocates on all sides expect medication abortion to play an even more pivotal role in the divisive abortion debate.

Though public health experts have long advised the use of condoms for anal sex to protect against H.I.V. and other infections, regulators did not have enough data to allow marketing for that use.For the first time, U.S. regulators have officially authorized a condom to be used for anal sex, not just vaginal sex.The decision, announced by the Food and Drug Administration on Wednesday, has long been sought by sexual health experts, who said it could encourage more people who engage in anal sex to use condoms to protect themselves against H.I.V. and other sexually transmitted infections.The risk of sexually transmitted diseases is “significantly higher” during anal sex than vaginal sex, an F.D.A. official said Wednesday. But until now, there has not been enough data to show that condoms are safe and effective during anal sex.“The F.D.A.’s authorization of a condom that is specifically indicated, evaluated and labeled for anal intercourse may improve the likelihood of condom use during anal intercourse,” Courtney Lias, director of the F.D.A. office that issued the approval, said in a statement. The decision applies to a condom manufactured by Global Protection Corp. called the ONE male condom. Last year, the company asked the F.D.A. to allow it to add anal sex to the intended use of the condom on the product label, based on a study showing the failure rate, defined as slippage or breakage, to be less than 1 percent during anal sex.The F.D.A. said in the statement that other condom companies would now be able to apply for similar approval by submitting claims that their condoms demonstrated “substantial equivalence” to the evidence shown for ONE condoms.“I don’t think this is viewed as something that should be restricted, but rather something that opens the door for other companies to rigorously assess their condoms and show that they also perform well for anal sex,” said Aaron Siegler, an epidemiologist at Emory University who helped lead the study that prompted the F.D.A. decision.Davin Wedel, president and founder of Global Protection Corp, said, “I think most people would be surprised to know that condoms are not approved for anal sex. With this new designation from the FDA, consumers will have important information about the safety and effectiveness of condoms for anal sex.”The federal agency had previously said that condoms needed to have less than a 5 percent failure rate, and earlier studies of condoms for anal sex had shown failure rates higher than that.As a result, while using condoms for anal sex is recommended by public health authorities like the World Health Organization and the Centers for Disease Control and Prevention, it has been considered an “off-label” use in the United States. Companies have not been able to market condoms for anal sex, said Dr. Kenneth Mayer, the medical research director for Fenway Health, a community health center in Massachusetts that has long been a leader in treating patients who identify as L.G.B.T.Q.“It’s a great thing if the package inserts could indicate anal sex because it might create an incentive for the companies to do more marketing,” Dr. Mayer said. “You don’t see condom ads on gay social media, for example, so this would incentivize that as part of part of the conversation.”“And it’s not just gay men.” Dr. Mayer continued. “It’s not that heterosexuals who engage in anal sex are unaware that condoms exist, but there’s been very little education, so it’s somewhat out of sight out of mind.”Condom use during anal sex has declined in recent years, since the advent of a method to prevent H.I.V. infection called pre-exposure prophylaxis, or PrEP, which involves taking a daily pill. According to the most recent statistics from C.D.C.’s National H.I.V. Behavioral Surveillance data, about 46 percent of men who have sex with men were having anal sex without condoms in 2017, compared to 28-to-40 percent in 2011.But although PrEP is very effective, there can be issues with cost and access. Currently, only about a third of men who are at high risk for H.I.V. infection are taking the drug, the C.D.C. reported.“That’s hundreds of thousands of people,” said Dr. Mayer, who was not involved in the study that led to the F.D.A.’s decision. “And certainly those are individuals who would benefit from condoms.”He added that condoms are the most effective protection against other sexually transmitted infections, including syphilis, which has been increasing in the United States.To try to amass data that could lead to the approval of condoms for anal sex, the company teamed up with researchers at Emory University, met with the F.D.A. and designed a study.Funded by the National Institutes of Health, the study, the largest to date on condom effectiveness during anal sex, was conducted between May 2016 and May 2017. It involved 504 men, half of whom had sex with men and half of whom had sex with women, and the researchers took several steps designed to encourage more consistent and accurate data than previous studies, Dr. Siegler said.After being trained in proper condom use, the men were given condoms and asked to fill out a daily diary on a phone app, to answer questions about whether they had had sex that day and whether the condom they used broke or slipped. The participants reported 2,351 anal and 2,533 vaginal sex acts during the study period.Dr. Siegler said that the team had hypothesized that the condom failure rate during anal sex would be low enough to pass muster with the F.D.A., but had not expected it to be as low as it was — 0.7 percent — or that it would be lower than the failure rate during vaginal sex, which was 1.9 percent.The researchers attribute the higher failure rate during vaginal sex to the fact that the study encouraged lubricant appropriate for condoms to be used for every instance of anal sex, but, adhering to public health guidelines, only encouraged lubricant to be used during vaginal sex “as needed or desired.” So, while 98 percent of people who had anal sex used lubricant, only 42 percent of those who had vaginal sex did. When the researchers looked only at people who used lubricant, the failure rate in the vaginal group was 1.1 percent, making the odds of failure in each group essentially the same, the study reported.Public health experts said that suggests that lubricant was critical to the study’s results, and in its statement, the F.D.A. said that during anal sex, the condom “should be used with a condom-compatible lubricant.”The study involved three different types of the One condom — standard, thin and fitted, which comes in 54 different sizes. They did not have ribbing or other characteristics, Dr. Siegler said. Each participant was given five samples of each type of condom to use for two to four weeks. The researchers had expected the fitted condoms to have the lowest failure rate, but the study found there was no difference, an outcome that Dr. Siegler said he thought reflected that all three varieties had to meet the same manufacturing and durability standards.Dr. Siegler, who specializes in research on PReP, said that before conducting the condom study, the Emory team wondered whether adding anal sex to a condom label would encourage more men to use condoms.“Does this matter? Would it change use?” he asked. The team conducted a survey of more than 10,000 men who had sex with men and found that 69 percent said that if the F.D.A. approved condoms for anal sex, they would be more encouraged to use them.“I don’t see condoms versus PReP as kind of mutually exclusive options, I see them as options that can support each other and that allow people that choice,” he said. “There isn’t perfect use of any one technology. But if we optimize people’s access to and understanding of different prevention options, I think we can increase the overall population level protection against H.I.V.”Dr. Mayer said he also saw adding the label to condoms as an additional tool that could help improve the use of all protective measures.“It’s definitely not a one-size-fits-all kind of kind of environment,” Dr. Mayer said. “It will help normalize the conversation because there’ll be an economic incentive for the companies to advertise condoms for anal sex.”

Social isolation, economic stress, loss of loved ones and other struggles during the pandemic have contributed to rising mental health issues like anxiety and depression.But can having Covid itself increase the risk of developing mental health problems? A large new study suggests it can.The study, published Wednesday in the journal The BMJ, analyzed records of nearly 154,000 Covid patients in the Veterans Health Administration system and compared their experience in the year after they recovered from their initial infection with that of a similar group of people who did not contract the virus.The study included only patients who had no mental health diagnoses or treatment for at least two years before becoming infected with the coronavirus, allowing researchers to focus on psychiatric diagnoses and treatment that occurred after coronavirus infection.People who had Covid were 39 percent more likely to be diagnosed with depression and 35 percent more likely to be diagnosed with anxiety over the months following infection than people without Covid during the same period, the study found. Covid patients were 38 percent more likely to be diagnosed with stress and adjustment disorders and 41 percent more likely to be diagnosed with sleep disorders than uninfected people.“There appears to be a clear excess of mental health diagnoses in the months after Covid,” said Dr. Paul Harrison, a professor of psychiatry at the University of Oxford, who was not involved in the study.

A new, large study found that in the year after getting Covid, people were significantly more likely to be diagnosed with psychiatric disorders they hadn’t had than people who didn’t get infected.Social isolation, economic stress, loss of loved ones and other struggles during the pandemic have contributed to rising mental health issues like anxiety and depression.But can having Covid itself increase the risk of developing mental health problems? A large new study suggests it can.The study, published Wednesday in the journal The BMJ, analyzed records of nearly 154,000 Covid patients in the Veterans Health Administration system and compared their experience in the year after they recovered from their initial infection with that of a similar group of people who did not contract the virus.The study included only patients who had no mental health diagnoses or treatment for at least two years before becoming infected with the coronavirus, allowing researchers to focus on psychiatric diagnoses and treatment that occurred after coronavirus infection.People who had Covid were 39 percent more likely to be diagnosed with depression and 35 percent more likely to be diagnosed with anxiety over the months following infection than people without Covid during the same period, the study found. Covid patients were 38 percent more likely to be diagnosed with stress and adjustment disorders and 41 percent more likely to be diagnosed with sleep disorders than uninfected people.“There appears to be a clear excess of mental health diagnoses in the months after Covid,” said Dr. Paul Harrison, a professor of psychiatry at the University of Oxford, who was not involved in the study. He said the results echoed the emerging picture from other research, including a 2021 study on which he was an author, and “it strengthens the case that there is something about Covid that is leaving people at greater risk of common mental health conditions.”The data does not suggest that most Covid patients will develop mental health symptoms. Only between 4.4 percent and 5.6 percent of those in the study received diagnoses of depression, anxiety or stress and adjustment disorders.“It’s not an epidemic of anxiety and depression, fortunately,” Dr. Harrison said. “But it’s not trivial.”Researchers also found that Covid patients were 80 percent more likely to develop cognitive problems like brain fog, confusion and forgetfulness than those who didn’t have Covid. They were 34 percent more likely to develop opioid use disorders, possibly from drugs prescribed for pain, and 20 percent more likely to develop non-opioid substance use disorders including alcoholism, the study reported.After having Covid, people were 55 percent more likely to be taking prescribed antidepressants and 65 percent more likely to be taking prescribed anti-anxiety medications than contemporaries without Covid, the study found.Overall, more than 18 percent of the Covid patients received a diagnosis of or prescription for a neuropsychiatric issue in the following year, compared with less than 12 percent of the non-Covid group. Covid patients were 60 percent more likely to fall into those categories than people who didn’t have Covid, the study found.The study found that patients hospitalized for Covid were more likely to be diagnosed with mental health issues than those with less serious coronavirus infections. But people with mild initial infections were still at greater risk than people without Covid.“Some people always argue that ‘Oh, well, maybe people are depressed because they needed to go to the hospital and they spent like a week in the I.C.U.,’” said the senior author of the study, Dr. Ziyad Al-Aly, chief of research and development at the V.A. St. Louis Health Care System and a clinical epidemiologist at Washington University in St. Louis. “In people who weren’t hospitalized for Covid-19, the risk was lower but certainly significant. And most people don’t need to be hospitalized, so that is really the group that’s representative of most people with Covid-19.”The team also compared mental health diagnoses for people hospitalized for Covid with those hospitalized for any other reason. “Whether people were hospitalized for heart attacks or chemotherapy or whatever other conditions, the Covid-19 group exhibited a higher risk,” Dr. Al-Aly said.The study involved electronic medical records of 153,848 adults who tested positive for the coronavirus between March 1, 2020, and Jan. 15, 2021, and survived for at least 30 days. Because it was early in the pandemic, very few were vaccinated before infection. The patients were followed until Nov. 30, 2021. Dr. Al-Aly said his team was planning to analyze whether subsequent vaccination modified people’s mental health symptoms, as well as other post-Covid medical issues the group has studied.The Covid patients were compared with more than 5.6 million patients in the Veterans system who did not test positive for the coronavirus and more than 5.8 million patients from before the pandemic, in the period spanning March 2018 through January 2019. To try to gauge the mental health impact of Covid-19 against that of another virus, the patients were also compared with about 72,000 patients who had the flu during the two and a half years before the pandemic. (Dr. Al-Aly said there were too few flu cases during the pandemic to provide a contemporaneous comparison.)The researchers tried to minimize differences between groups by adjusting for many demographic characteristics, pre-Covid health conditions, residence in nursing homes and other variables.In the year after their infection, the Covid patients had higher rates of mental health diagnoses than the other groups.“It’s not really surprising to me because we’ve been seeing this,” said Dr. Maura Boldrini, an associate professor of psychiatry at NewYork-Presbyterian Columbia University Medical Center. “It’s striking to me how many times we’ve seen people with these new symptoms with no previous psychiatric history.”Most veterans in the study were men, three-quarters were white and their average age was 63, so the findings may not apply to all Americans. Still, the study included over 1.3 million women and 2.1 million Black patients, and Dr. Al-Aly said “we found evidence of increased risk regardless of age, race or gender.”There are several possible reasons for the increase in mental health diagnoses, Dr. Al-Aly and outside experts said. Dr. Boldrini said she believed the symptoms were most likely influenced by both biological factors and the psychological stresses associated with having an illness.“In psychiatry, it almost always is an interplay,” she said.Research, including brain autopsies of patients who died of Covid-19, has found evidence that Covid infection can generate inflammation or tiny blood clots in the brain, and can cause small and large strokes, said Dr. Boldrini, who has conducted some of these studies. In some people, the immune response that is activated to fight against a coronavirus infection may not shut down effectively once the infection is gone, which can fuel inflammation, she said.“Inflammatory markers can disrupt the ability of the brain to function in many ways, including the ability of the brain to make serotonin, which is fundamental for mood and sleep,” Dr. Boldrini said.By themselves, such brain changes may or may not cause psychological problems. But, if someone is experiencing stress from having felt physically ill or because having Covid disrupted their lives and routines, she said, “you may be more prone to not being able to cope because your brain is not functioning 100 percent.”Dr. Harrison, who has conducted other studies with large electronic medical databases, noted that such analyses can miss more granular information about patients. He also said that some people in the comparison groups might have had Covid and not been tested to confirm it, and that some Covid patients might have been more likely to receive diagnoses because they were more worried about their health after Covid or because doctors were quicker to identify psychological symptoms.“There’s no one analysis that tells you the whole story,” Dr. Al-Aly said. “Maybe all of us or most of us experienced some sort of an emotional distress or mental health stress or some sleep problem,” he added. “But people with Covid did worse.”

If further study confirms the findings, they could lead to ways to prevent and treat the complex condition.It is one of many mysteries about long Covid: Who is more prone to developing it? Are some people more likely than others to experience physical, neurological or cognitive symptoms than can emerge, or linger for, months after their coronavirus infections have cleared?Now, a team of researchers who followed more than 200 patients for two to three months after their Covid diagnoses report that they have identified biological factors that might help predict if a person will develop long Covid.The study, published Tuesday by the journal Cell, found four factors that could be identified early in a person’s coronavirus infection that appeared to correlate with increased risk of having lasting symptoms weeks later.The researchers said they had found that there was an association between these factors and long Covid (which goes by the medical name post-acute sequelae of Covid-19, or PASC) whether the initial infection was serious or mild. They said that the findings might suggest ways to prevent or treat some cases of long Covid, including the possibility of giving people antiviral medications soon after an infection has been diagnosed.“It’s the first real solid attempt to come up with some biologic mechanisms for long Covid,” said Dr. Steven Deeks, a professor of medicine at the University of California, San Francisco, who was not involved in the study.He and other experts, along with the study authors themselves, cautioned that the findings were exploratory and would need to be verified by considerably more research.Still, Dr. Deeks said: “They’ve identified these four major factors. Each is biologically plausible, consistent with theories that other people are pursuing, and importantly, each is actionable. If these pathways get confirmed, we as clinicians can actually design interventions to make people better. That is the take-home message.”One of the four factors researchers identified is the level of coronavirus RNA in the blood early in the infection, an indicator of viral load. Another is the presence of certain autoantibodies — antibodies that mistakenly attack tissues in the body as they do in conditions like lupus and rheumatoid arthritis. A third factor is the reactivation of Epstein-Barr virus, a virus that infects most people, often when they are young, and then usually becomes dormant.The final factor is having Type 2 diabetes, although the researchers and other experts said that in studies involving larger numbers of patients, it might turn out that diabetes is only one of several medical conditions that increase the risk of long Covid.“I think this research stresses the importance of doing measurements early in the disease course to figure out how to treat patients, even if we don’t really know how we’re going to use all that information yet,” said Jim Heath, the principal investigator of the study and president of the Institute for Systems Biology, a nonprofit biomedical research organization in Seattle.“Once you can measure something, then you may be able to start doing something about it,” Dr. Heath said, adding: “We did this analysis because we know patients will go to physicians and they’ll say that they’re tired all the time or whatever, and the physician just tells them to get more sleep. That’s not very helpful. So, we wanted to actually have a way to quantify and say that there’s actually something wrong with these patients.”The complex study had several components and involved dozens of researchers at several universities and centers including the Institute for Systems Biology, the University of Washington and Swedish Medical Center in Seattle, where the study’s lead medical author, Dr. Jason Goldman, is an infectious disease specialist.The primary group of patients included 209 people, ages 18 to 89, who were infected with the coronavirus during 2020 or early 2021 and were seen at Swedish Medical Center or an affiliated clinic. Many were hospitalized for their initial infections, but some were seen only as outpatients. Researchers analyzed blood and nasal swabs when patients were diagnosed, during the acute phase of their infections and two to three months later.A tattoo of the demon Mr. Gillotte hallucinated during the Covid delirium he experienced after he was taken off the ventilator.Joshua Bright for The New York TimesThey surveyed the patients about 20 symptoms associated with long Covid, including fatigue, brain fog and shortness of breath, and corroborated those reports with electronic health records, Dr. Heath said.He said that 37 percent of the patients had reported three or more symptoms of long Covid two or three months after infection. A further 24 percent reported one or two symptoms, and 39 percent reported no symptoms. Of patients reporting three or more symptoms, 95 percent had one or more of the four biological factors identified in the study when they were diagnosed with Covid-19, Dr. Heath said.The most influential factor appeared to be autoantibodies, which were associated with two-thirds of the cases of long Covid, Dr. Heath said. Each of the other three factors showed up in about a third of the cases, he said, and there was considerable overlap, with several factors identified in some patients.The researchers corroborated some of their findings in a separate group of 100 patients, many with mild initial infections, from research led by Dr. Helen Chu at the University of Washington. The researchers also compared their results to data from 457 healthy people.“The study is large and comprehensive and is a great resource for the community studying long Covid,” said Akiko Iwasaki, an immunologist at Yale, who was not involved in the research.Dr. Avindra Nath, who is chief of the section on infections of the nervous system at the National Institute of Neurological Disorders and Stroke and was not involved in the study, called the study well designed but pointed out several weaknesses, including the fact that patients had been followed for only two to three months. “This might be too short a time frame,” he said. “Some might just improve spontaneously with time.”Dr. Iwasaki noted that 71 percent of the patients in the primary group had been hospitalized, limiting the ability to conclude that the biological factors were equally relevant for people with mild initial infections. The Coronavirus Pandemic: Key Things to KnowCard 1 of 4Omicron in retreat.

If the preliminary decision is finalized this spring, it would sharply limit the number of patients who use the expensive drug.Medicare officials have decided that the federal health insurance program should only cover the controversial new Alzheimer’s drug Aduhelm for patients who are participating in approved clinical trials. The preliminary decision, reached after lengthy deliberations, was released on Tuesday by the Center for Medicare and Medicaid Services, or C.M.S. If it is finalized later this year, it would significantly limit the number of patients who could use the expensive drug.The decision said that coverage should be provided for patients in “C.M.S. approved randomized controlled trials” and trials supported by the National Institutes of Health. The decision said “all trials must be conducted in a hospital-based outpatient setting.”The agency added that Aduhelm of other similar drugs for Alzheimer’s that are provided outside of these trials “are nationally non-covered.”“Alzheimer’s disease is a devastating illness that has touched the lives of millions of American families. Throughout this National Coverage Determination process, CMS has been and remains committed to providing the American public with a clear, trusted, evidence-based decision that is made only after a thorough analysis of public feedback on the benefits and risks of coverage for Medicare patients,” said the C.M.S. administrator, Chiquita Brooks-LaSure. “C.M.S. has proposed an evidence-based coverage policy after experts reviewed all relevant publicly available evidence and feedback received from stakeholders.”Whether Medicare ends up covering Aduhelm is considered pivotal to the future of the drug, which is made by Biogen and priced at $28,200 a year per patient. Roughly 80 percent of the 1.5 million Americans who have the type of condition the F.D.A. approved the drug to treat — mild Alzheimer’s-related cognitive decline — are old enough to receive coverage under Medicare.For the next 30 days, C.M.S. will have a public comment period on the preliminary decision, and the agency is expected to announce its final decision about covering the drug by mid-April.The fact that Medicare is conducting an extensive review of Aduhelm is itself unusual. The program almost always pays for F.D.A.-approved drugs, at least for the medical conditions designated on their label, health policy experts said.Biogen initially priced the drug at $56,000 a year, but slashed the price in half last month after months of weak sales. Before Biogen’s price cut, Medicare’s actuarial division, acting without knowing what the coverage decision would be, imposed one of the biggest-ever increases in Medicare Part B premiums for 2022, partly driven by the possibility of Aduhelm coverage.After Biogen’s price cut, advocacy groups for Alzheimer’s patients urged C.M.S. to lower the premium increase. On Monday, the secretary for health and human services, Xavier Becerra, said that he was instructing C.M.S. to re-examine the premium hike “given the dramatic price change of the Alzheimer’s drug, Aduhelm.”Aduhelm was approved by the Food and Drug Administration in June in a decision vigorously criticized by many doctors and Alzheimer’s experts because clinical trial results showed it had significant safety risks and unclear benefit to patients.Congress is investigating whether the F.D.A. worked too closely with Biogen and why Aduhelm was approved despite strong objections from some senior F.D.A. officials and the agency’s independent advisory committee.So far, only a small number of patients — a fraction of the number Biogen and industry analysts had initially expected — have used Aduhelm, a monoclonal antibody administered as a monthly infusion. Many large American health care systems have declined to offer the drug, citing questions about its benefits and risks. Medicare officials are supposed to determine coverage based on whether a drug is a “reasonable and necessary” treatment, a phrase that usually “means adequate evidence of improved health outcomes,” said Dr. Sean Tunis, a former official with C.M.S. who is now a senior fellow at the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center.Medicare’s decision on Aduhelm will also establish standards for evaluating several similar Alzheimer’s drugs in the pipeline.The F.D.A. itself acknowledged in its approval of Aduhelm that there was insufficient evidence it would help patients. Instead, it greenlighted the medication — the first new treatment for Alzheimer’s in 18 years — under a program called “accelerated approval,” which allows authorization of unproven drugs for serious diseases with few treatment options if the drug affects a biological mechanism in a way considered “reasonably likely to predict clinical benefit.”The F.D.A. said it based accelerated approval on Aduhelm’s reduction of a protein, called amyloid, that clumps into plaques in the brains of people with Alzheimer’s. But many Alzheimer’s specialists say that extensive research has shown little evidence that reducing amyloid slows cognitive decline. The F.D.A. also required Biogen to conduct another clinical trial to determine if the drug provided any evidence of benefit. In the years it will take for that trial to be completed, Aduhelm will be available to patients.

A group of Alzheimer’s experts and health advocates called on the F.D.A. to withdraw its approval of the drug, the latest of several setbacks for the treatment.Biogen slashed the price of its controversial new Alzheimer’s drug Aduhelm on Monday as the drug faces weak sales and mounting criticism.The price was reduced to $28,200 a year from $56,000 on the same day that a group of Alzheimer’s experts and health advocates called on the Food and Drug Administration to pull the drug off the market and said they were supporting an effort to file a formal petition with the agency to withdraw it.“The F.D.A.’s decision to approve Aduhelm is indefensible in both scientific and clinical terms,” said a statement signed by 18 scientists, most of them doctors. “This drug should be withdrawn from the market immediately.”The agency approved Aduhelm in June, even though a council of senior F.D.A. officials, an advisory committee of outside experts and many Alzheimer’s specialists said the scientific evidence showed that the drug did not provide a clear benefit to patients and that it carried risks of dangerous side effects.Major health systems, including Cleveland Clinic, Mount Sinai Health System, Mass General Brigham and the Department of Veterans Affairs have declined to offer Aduhelm, citing questions about its benefits and risks. In October, Biogen reported that Aduhelm had brought in just $1.9 million in revenue through September, a strikingly small amount given that about 1.5 million Americans have the mild Alzheimer’s-related dementia that makes them eligible for the drug.In a statement about the price-cutting on Monday, Michel Vounatsos, Biogen’s chief executive officer, said the company had “listened to the feedback of our stakeholders” and believed that “too many patients are not being offered the choice of Aduhelm due to financial considerations.”But Brian Skorney, an analyst at Robert W. Baird & Company, said after the price announcement: “For the broad majority of people who are critical of Aduhelm, $56,000 and $28,000 are both exceptionally high prices for a drug that a lot of people perceive doesn’t work at all.”The statement from Alzheimer’s experts and health advocates calling on the F.D.A. to withdraw Aduhelm grew out of a three-hour video meeting among the scientists last week.“We’re not just saying the approval was probably the worst decision the F.D.A. ever made,” Dr. Peter Whitehouse, a neurologist and Alzheimer’s expert at Case Western Reserve University who led the Dec. 15 meeting, told attendees during the session. “It’s so bad that we should advocate for withdrawal.”The doctors and scientists who signed the statement also agreed to provide their expertise to support the filing of a citizen petition, a formal process to seek reversal of the F.D.A.’s decision. The petition will be filed by the Right Care Alliance, a coalition of clinicians, patients and community members, which is also circulating a pledge for physicians who promise not to prescribe Aduhelm and for patients and family members who say they will not request it.Dr. Vikas Saini, chairman of the Right Care Alliance and president of the Lown Institute, a health care think tank, said that while the citizen petition process can take months or years, it can prompt F.D.A. action.Dr. Saini, who helped organize last week’s meeting, said that out of 45 citizen petitions filed since 1971 by the group Public Citizen, in 27 cases the F.D.A. withdrew drugs from the market and in seven other cases the agency sharply restricted a drug’s use.In response to the call to withdraw approval of Aduhelm, also known by its scientific name, aducanumab, an F.D.A. spokeswoman said that “the data set for Aduhelm was very complex, and our review has been thorough.”The spokeswoman also said that “careful analyses of the Phase 2 and Phase 3 clinical trials support the conclusion that it is likely that Aduhelm provides clinical benefit — although the data currently available do not provide substantial evidence of effectiveness on clinical benefit.”Aduhelm has also been encountering resistance in other countries. On Friday, reviewers at the European Union’s drug regulator, the European Medicines Agency, recommended against approving Aduhelm, a decision that Biogen said it would ask to be re-examined.Aduhelm is a monoclonal antibody, given as a monthly infusion. In clinical trials, 41 percent of patients receiving the F.D.A.-approved higher dose experienced brain swelling or brain bleeding, often mild, but serious in some cases.Pool photo by Jessica RinaldiSeveral months ago, leading Canadian Alzheimer’s research organizations said that approving the drug in Canada “cannot be justified.”Dr. Howard Chertkow, scientific director of the Canadian Consortium on Neurodegeneration in Aging, was one of three Alzheimer’s experts from outside the United States who signed the statement calling on the F.D.A. to withdraw the drug. “We feel it’s an abrogation of our responsibility as physicians to allow a marginal medication with a very high cost associated with it to come into the country, so we’re quite active in trying to block what has happened in the states from occurring in Canada,” he said at last week’s meeting.Two nearly identical clinical trials of Aduhelm, a monoclonal antibody given as a monthly infusion, were stopped early because an independent data monitoring committee concluded that the drug didn’t appear to be beneficial. A later analysis by Biogen found that participants receiving the high dose of the drug in one trial had experienced a very slight slowing of cognitive decline but that participants in the other trial had not benefited at all.About 41 percent of patients receiving the high dose — the dose the F.D.A. approved — experienced brain swelling or brain bleeding, side effects that were often mild or asymptomatic, but were sometimes serious.Monday’s statement also objects to the F.D.A.’s justification for its approval. Acknowledging there was insufficient evidence that Aduhelm would help patients, the agency greenlighted it under a program called “accelerated approval,” which allows authorization of drugs without proof of benefit for serious diseases that have few treatment options if the drug affects part of the disease’s biology (known as a surrogate endpoint) in a way that is “reasonably likely to predict clinical benefit.”The F.D.A. based its approval on Aduhelm’s ability to reduce a protein called amyloid that forms plaques in the brains of people with Alzheimer’s. But experts say years of studies have not shown that reducing amyloid helps memory or thinking problems.Approving the drug because of amyloid reduction “will have huge and wide-ranging negative implications for patients, families” and dementia research, Dr. Kenneth Langa, a professor of medicine at the University of Michigan, said in last week’s meeting. The group’s statement, which includes a section for others to sign their names in support, plays on the F.D.A.’s language by calling for “accelerated withdrawal.”“Reading the justification of the F.D.A. was like watching a ‘Saturday Night Live’ skit for data nerds.” Dr. Saini said. “I mean, I had trouble believing it.”The agency’s approval requires that Biogen conduct another trial to see if Aduhelm works. In its response Monday, the F.D.A. spokeswoman said “we believe that the data support accelerated approval while holding the company accountable for conducting an additional study.” Last week, Biogen said that it had developed a protocol to get that trial completed in 2026, several years before the F.D.A.-imposed deadline.Before he signed Monday’s statement, Dr. Sam Gandy, director of Mount Sinai’s Center for Cognitive Health, who helped organize the meeting, said that with advocacy groups like the Alzheimer’s Association still supporting the drug’s approval, he had a “concern that calling for something may trigger a backlash that undoes where we really want to go.”But Dr. Jerry Avorn, a professor of medicine at Harvard Medical School who also signed the statement, said that while it was unlikely that calling for withdrawal would make F.D.A. officials say, “‘Yeah, they’re right, we goofed, we better undo this decision,’” the action was nonetheless important. “We’re taking a stand and saying the process was terrible and the outcome was terrible, and even if they don’t listen to it, it’ll be kind of a shot across the bow.”Rebecca Robbins contributed reporting.

Scientists who injected idle mice with blood from athletic mice found improvements in learning and memory. The findings could have implications for Alzheimer’s research and beyond.What if something in the blood of an athlete could boost the brainpower of someone who doesn’t or can’t exercise? Could a protein that gets amplified when people exercise help stave off symptoms of Alzheimer’s and other memory disorders?That’s the tantalizing prospect raised by a new study in which researchers injected sedentary mice with blood from mice that ran for miles on exercise wheels, and found that the sedentary mice then did better on tests of learning and memory.The study, published Wednesday in the journal Nature, also found that the type of brain inflammation involved in Alzheimer’s and other neurological disorders was reduced in sedentary mice after they received their athletic counterparts’ blood.Scientific results with mice don’t necessarily translate to humans. Still, experts said the study supports a growing body of research.“We’re seeing an increasing number of studies where proteins from outside the brain that are made when you exercise get into the brain and are helpful for improving brain health, or even improving cognition and disease,” said Rudolph Tanzi, a professor of neurology at Massachusetts General Hospital and Harvard Medical School. He led a 2018 study that found that exercise helped the brains of mice engineered to have a version of Alzheimer’s.The most promising outcome would be if exercise-generated proteins can become the basis for treatments, experts said.“The demonstration that there are transferable factors in the blood that seemed to convey beneficial effects on the brain that improve learning and memory is by far the most interesting aspect of the work,” said Dr. Madhav Thambisetty, a neurologist and senior investigator at the National Institute on Aging, who was not involved in the new research.The study, led by researchers at Stanford School of Medicine, found that one protein — clusterin, produced in the liver and in heart muscle cells — seemed to account for most of the anti-inflammatory effects. But several experts noted that recent studies have found benefits from other proteins. They also said more needs to be learned about clusterin, which plays a role in many diseases, including cancer, and may have negative effects in early stages of Alzheimer’s before brain inflammation becomes dominant.“It’s far too premature to conclude that higher or lower levels of clusterin might be either beneficial or not,” said Dr. Thambisetty, who has studied clusterin. “I don’t think we’re at the stage yet where people can trade in their treadmills or cancel their gym memberships for a clusterin pill or a clusterin injection.”The study was led by Tony Wyss-Coray, a professor of neurology and neurological sciences at Stanford, who had previously done research finding that the blood of young mice can reverse age-related cognitive impairment in old mice.Dr. Wyss-Coray said he wanted to see “if exercise produced factors that would also accumulate in the blood and that you could then transfer them.”The study involved mice that were about three months old — roughly the equivalent of 25-to-30-years-old for humans. Some of the mice, nocturnal animals that love to run, could freely use exercise wheels in their cages and logged about four to six miles on the wheels each night. The wheels were locked for other mice that could scoot around their cages but could not get an extended cardio workout.After 28 days, the researchers took a third group of mice that also did not exercise and injected them with blood plasma, the liquid that surrounds blood cells, from either the runner mice or the non-runner mice. Mice receiving runner blood did better on two tests of learning and memory than those receiving blood from the non-runner mice.In one test, which measures how long a mouse will freeze in fear when it is returned to a cage where it previously received an electric foot shock, mice with runner blood froze 25 percent longer, indicating they had better memory of the stressful event, Dr. Wyss-Coray said. In the other test, mice with runner blood were twice as fast at finding a platform submerged in opaque water, he said.The team also found that the brains of mice with runner blood produced more of several types of brain cells, including those that generate new neurons in the hippocampus, a region involved in memory and spatial learning.A genetic analysis showed that about 1,950 genes had changed in response to the infusion of runner blood, becoming either more or less activated. Most of the 250 genes with the greatest activation changes were involved in inflammation and their changes suggested that brain inflammation was reduced.The team tested whether removing any of the four most significant proteins in the runner blood would matter, and found that if clusterin was removed, anti-inflammatory effects disappeared. And when mice engineered to have a type of brain inflammation or a version of Alzheimer’s were injected with clusterin, it lessened their brain inflammation.In the only part of the study involving humans, 20 military veterans with a pre-dementia condition called mild cognitive impairment who had participated in a six-month exercise program were found to have high levels of clusterin in their blood.Kaci Fairchild, associate director of the Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education and Clinical Center, and an author of the new study, said the veterans, ranging in age from 50 to 89, exercised three times a week, combining cardio with weight training.Dr. Fairchild said that in results that have not yet been published, besides having elevated clusterin, the veterans did better on tests involving word memory and story recall.“Across the board, veterans had improvements in cognitive function, largely related to learning and memory,” Dr. Fairchild said. Noting that some people have disabilities or limitations that prevent them from exercising, she said she hoped that “the implications from this clusterin is that we can develop a medication targeting this protein for persons who weren’t able to engage in physical activity.”In the brain, clusterin binds to cells that line the blood vessels, cells that become inflamed in Alzheimer’s disease, Dr. Wyss-Coray said, suggesting that a potential drug might bind to those cells and “mimic the anti-inflammatory effects.”Still, experts who study Alzheimer’s disease and neuroinflammation said much more research is needed before therapies can be developed.“Not everything that works in mice works in humans, and we don’t know if there are other unexpected side effects that could make it untenable in humans,” said Mark Gluck, a professor of neuroscience and public health at Rutgers University in Newark, N.J., who was not involved in the study.Dr. Michael Heneka, the incoming director of the Luxembourg Centre for Systems Biomedicine who was not involved in the study, said the role of inflammation in diseases processes can change over time, being protective early on and detrimental later, so it is important to target inflammation at the appropriate time.It’s also unclear if clusterin is the optimal protein for a therapy.Other proteins linked to physical exercise have been shown in recent studies to improve cognition in mice. One, irisin, released by muscles, was found to reduce neuroinflammation and help mice perform better on memory and learning tests. Another, called Gpld1, an enzyme produced in the liver, was shown to increase after exercise and to correlate with better cognitive function in elderly mice.Whichever proteins end up being promising, it would be safer to develop a medication than to try to transfuse blood, which would contain other things beside the proteins, said Dr. Tanzi, who was not involved in the new study. “The big question,” he added, “is which proteins are the winners and how do we take advantage of them to provide new therapies?”

Newly published safety data shows that 41 percent of patients in key clinical trials of the Alzheimer’s drug experienced brain bleeding or swelling, though many cases were asymptomatic.Concerns about safety risks of the controversial new Alzheimer’s drug Aduhelm have intensified in the wake of the death of a 75-year-old woman who experienced brain swelling after receiving infusions of the drug as a participant in a clinical trial.The death of the woman, who lived in Canada, occurred in late September and was reported by a doctor to the Food and Drug Administration’s adverse event reporting system this summer. It is being investigated by both the F.D.A. and Biogen, which makes the drug, also known by its scientific name, aducanumab.In a statement Biogen said: “The cause of death is unknown at this time. We know the 75-year-old clinical trial patient was admitted to the hospital with a seizure” and diagnosed with brain swelling.“Following a prolonged hospitalization, the patient was being prepared for discharge when she deteriorated and was transferred to another facility,” the statement continued. “We have requested missing information, including brain imaging, from the critical last nine days of hospitalization.”Last week, Brian Abrahams, a biotech analyst with RBC Capital Markets who has a medical degree, wrote to clients that he had obtained the woman’s case report through a public records request and had concluded that the brain swelling probably caused the woman’s death and “that this is likely to have been caused by aducanumab.”In its statement, Biogen said that “the RBC report only provides a partial view of the case,” adding, “We take this event very seriously and continue to work with the reporting investigator.”In a note earlier this month, Dr. Abrahams, whose assessments of the case were reported previously by Endpoints News, Fierce Pharma and other publications, wrote that the report suggested that the patient “did not appear to have any other contributing conditions listed.”Brain swelling and brain bleeding are known to be possible side effects of Aduhelm, a monoclonal antibody that is administered as a monthly infusion. The F.D.A. approved the drug in June even though a council of senior F.D.A. officials, an advisory committee of outside experts, and many Alzheimer’s specialists said it was unclear whether Aduhelm could benefit patients and that the drug carried serious risks of harm.On Aduhelm’s label, the F.D.A. warns about these brain side effects, known as amyloid related imaging abnormalities (ARIA), and advises physicians to monitor patients and obtain two M.R.I. brain scans during the first year of treatment. The label does not say that people with ARIA should necessarily be taken off the drug. Many cases of ARIA are mild or asymptomatic, but some can be serious.Between July and September, three other cases of ARIA were reported to the F.D.A.’s adverse event database, all requiring hospitalization. Biogen said it was also reviewing those cases.In a recent statement, the American Academy of Neurology noted that “the F.D.A. label calls for less frequent monitoring than was performed in clinical trials” and said that “additional MRIs will often be needed in response to changes in patients’ clinical condition.”The academy said that when talking with patients and families, “neurologists must communicate information about potential adverse effects and the burdens of monitoring.”Dr. Sam Gandy, an Alzheimer’s clinician who is director of the Mount Sinai Center for Cognitive Health, said that another major concern is that the patients in the Aduhelm clinical trials were healthier than many people with Alzheimer’s who might use the drug now that it is available. People were excluded from participating in the trials if they had medical issues that many older people experience, including previous cardiac problems, any indication of impaired liver or kidney function or if they were taking blood thinners.The F.D.A. label does not exclude any of these conditions. “Now if those common comorbidities are not excluded and it’s sort of all comers,” Dr. Gandy said, “I worry that things may look worse in the real world than they did under these very controlled conditions.” He said one of the patients in his private practice, a man in his 80s, participated in an Aduhelm clinical trial and experienced 10 microbleeds in his brain over about a year, causing him to be dismissed from the trial. Since the drug’s approval, Dr. Gandy said, several patients have sought his opinion and have decided against getting the drug in part because of safety concerns.Most data available about Aduhelm comes from two nearly identical Phase 3 clinical trials that Biogen conducted before applying for F.D.A. approval of the drug. Both trials were shut down in 2019 because an independent monitoring committee concluded that the drug did not appear to be helping patients. A later analysis by Biogen found that participants receiving the highest dose of the drug in one trial experienced a very slight slowing of cognitive decline, but participants in the other trial did not benefit at all.Safety data from those trials was published Monday in the journal JAMA Neurology in a study whose authors included eight Biogen employees.The data showed that 425 of 1,029 patients, or 41 percent, who received the high dose of the drug — the dose that the F.D.A. later approved — experienced either brain swelling or bleeding. Sixty-four patients had to stop participating in the trials because of swelling or bleeding.Most of the affected patients, 362, experienced swelling, and 94 of those reported symptoms, according to the study, which also said that most cases of brain swelling resolved within 16 weeks. In a statement, Biogen noted that most swelling emerged early in the treatment period, either while patients were being ramped up to the high dose or shortly after they reached that dose.The study, which reported on the same safety data Biogen presented to the F.D.A. during the drug review process, said that symptoms like headaches, confusion, dizziness or nausea occurred in 103 patients receiving the dose that was later approved. Less frequent symptoms included fatigue, visual impairment, blurred vision and gait disturbance.Biogen said that M.R.I.s showed that swelling or bleeding was mild or moderate in most patients with those side effects. Still, the study reported that scans showed severe effects in 12 percent of patients with swelling, 12 percent of patients with microbleeds and 22 percent of patients with a type of slow brain bleeding.The study said that people with moderate or severe swelling were taken off the drug until their episode resolved. Those with mild swelling and no symptoms could stay on the drug, and the study said their swelling did not get worse. There were no deaths as a result of brain swelling or bleeding in the two trials, the study said. In an earlier safety study, one participant died. The 75-year-old woman who died in September was participating in an extension trial of the drug, Biogen said.More of the patients with brain swelling or bleeding were carriers of a gene mutation, APOE4, which also increases a person’s risk of developing Alzheimer’s disease. While patients in the trials appeared more likely to experience a slowing of decline if they carried the APOE4 mutation, the data suggests they also face greater safety risks from the drug.

It’s the first study of individualized brain stimulation to treat severe depression. Sarah’s case raises the possibility the method may help people who don’t respond to other therapies.Driving home from work in Northern California five years ago, a young woman was so overwhelmed with depression that all she could think about was ending her life.“I couldn’t stop crying,” recalled Sarah, now 38. “The thought that consumed me the entire way on that road was just driving my car into the marshland so I can drown.”She made it home, but soon after, moved in with her parents because doctors considered it unsafe for her to live alone. No longer able to function at work, she quit her health technology job.She tried nearly every treatment: roughly 20 different medications, months in a hospital day program, electroconvulsive therapy, transcranial magnetic stimulation. But as with nearly a third of the more than 250 million people with depression worldwide, her symptoms persisted. Then Sarah became the first participant in an unusual study of an experimental therapy. Now, her depression is so manageable that she’s taking data analysis classes, has moved to her own place and helps care for her mother, who suffered a fall.“Within a few weeks, the suicidal thoughts just disappeared,” said Sarah, who asked to be identified by only her first name to protect her privacy. “Then it was just a gradual process where it was like my lens on the world changed.”Researchers at the University of California, San Francisco surgically implanted a battery-operated, matchbook-sized device in Sarah’s brain — a “pacemaker for the brain” some call it — calibrated to detect the neural activity pattern that occurs when she is becoming depressed. It then delivers pulses of electrical stimulation to stave off depression.Twelve days after Sarah’s device was fully operational in August 2020, her score on a standard depression scale dropped to 14 from 33, and several months later, it fell below 10, essentially signaling remission, the researchers reported.“The device has kept my depression at bay, allowing me to return to my best self and rebuild a life worth living,” Sarah said.Sarah’s is the first documented case of personalizing a technique called deep brain stimulation to successfully treat depression. Much more research is needed before it’s clear how effective the approach could be and for how many patients. But several teams of scientists are now working on ways to essentially match the electrical stimulation to what happens in an individual patient’s brain.Deep brain stimulation is used to treat Parkinson’s disease and several other disorders, but isn’t approved by federal regulators for depression because results have been inconsistent. While some previous studies suggested benefits, two trials sponsored by U.S. device companies were stopped in the last decade because stimulation seemed no better than the placebo effect of a “sham” implant that provided no stimulation.But those studies didn’t target individualized locations or patterns of electrical activity in people’s brains. It was “one size fits all,” said Dr. Darin Dougherty, director of neurotherapeutics at Massachusetts General Hospital, who worked on one of the halted trials. He called the personalized approach with Sarah, which he wasn’t involved in, “very exciting.”“One person’s depression might look very different from another person’s depression,” said Dr. Katherine Scangos, an assistant professor of psychiatry at U.C.S.F. and an author of a report about Sarah’s case, published Monday in the journal Nature Medicine. The senior authors were Dr. Andrew Krystal, an expert in neuro-modulation and mood disorders, and Dr. Edward Chang, whose work includes brain implants for paralyzed patients who cannot speak.To identify the specific brain activity pattern linked to Sarah’s depression, researchers conducted an intensive 10-day exploration of Sarah’s brain, placing multiple electrodes in it and asking about her feelings when they applied stimulation to different locations in varying doses.“One person’s depression might look very different from another person’s depression,” said Dr. Katherine Scangos, a researcher on a new study using deep brain stimulation as a personalized treatment.Mike Kai Chen for The New York TimesSarah remembers an “aha moment” when she felt like “the Pillsbury Doughboy,” emitting a “giant belly laugh,” which she said was “the first time I spontaneously laughed and smiled” in five years. Another feeling resembled “being in front of warm fire and reading a comforting book,” while a negative sensation felt like “nails on a chalkboard.”Eventually, the team identified a specific pattern of electrical activity that coincided with Sarah becoming depressed.The exploratory phase guided the researchers to place the stimulation device in Sarah’s right brain hemisphere linked to electrodes in two regions. One was the the ventral striatum, involved in emotion, motivation and reward, where stimulation “consistently eliminated her feelings of depression,” and the other the amygdala, where changes could “predict when her symptoms were most severe,” Dr. Scangos said.While deep brain stimulation is typically delivered continuously, Sarah’s device is set to supply only a six-second burst when it recognizes her depression-linked brain activity pattern. The goal, said Dr. Dougherty, is that stimulation will disrupt or shift the neural activity to produce a healthier pattern that will ease depressive symptoms.Sarah has continued taking psychiatric medications, and the stimulation hasn’t eliminated depression-causing activity in her brain. But she can manage her illness much better, she said, instead of being unable to make even the smallest decisions, like what to eat.Now, “you’re experiencing that whole negative, depressive, whatever the triggering thing is, and then it’s like suddenly the ultra-rational side of you comes on and those emotions can be separated,” she said in an interview, wearing a T-shirt that said “Take it easy lemon squeezy.”That separation helps her productively use tools from talk therapy, like staying calm and maintaining perspective.About 30 percent of people with depression don’t respond to standard treatments or find the side effects intolerable. Deep brain stimulation wouldn’t be appropriate for all because it costs tens of thousands of dollars and brain surgery to implant the device carries risks like infection. But if the new attempts work, it might help a significant number, experts said. Dr. Chang said the research may also lead to noninvasive approaches that would help more people.“Our job now is really to figure out what is it that identifies who needs this kind of intervention,” said Dr. Helen Mayberg, director of the Center for Advanced Circuit Therapeutics at the Icahn School of Medicine in New York City, who pioneered the concept of deep brain stimulation for depression nearly 20 years ago.Dr. Mayberg uses a different method of individualization. With imaging, she finds the location in each person’s brain where four white matter bundles intersect near a key depression-related region. After implanting electrodes and a stimulation device, “we pretty much set it and forget it,” delivering stimulation continuously, while also helping patients with conventional therapy.Dr. Scangos examined a graph of Sarah’s brain activity. Mike Kai Chen for The New York TimesNeural activity is monitored “to learn the brain signature that heralds an impending depressive relapse or need for a dose adjustment or just indicates that the person is just having a bad week,” Dr. Mayberg said. She led one of the halted trials, but her work has also allowed patients to experience improvements that continue for years if stimulation is sustained.In another approach, Dr. Sameer Sheth, an associate professor of neurosurgery at Baylor College of Medicine, and colleagues study a patient’s specific brain activity pattern to identify which of billions of combinations of stimulation characteristics, like frequency and amplitude, improve that patient’s depression.He then tunes electrodes in two regions and applies that specific combination as continuous stimulation.Dr. Sheth said the first patient, given the device in March 2020, “is remarkably well” now, maintaining a relationship and becoming a father. To test for a placebo effect, researchers gradually stopped stimulation to one brain region without the patient knowing when. His depression “got worse and worse” said Dr. Sheth, until he needed “rescue.” After stimulation restarted, he improved, suggesting the effect “is definitely stimulation-related.”Several months ago, Sarah needed a rescue too. Shortly after entering a study phase where the device is either turned off or left on for six weeks without the participant knowing which, “the suicidal thoughts were back,” Sarah said. Her family tried to get her hospitalized, but hospitals were full. “Things were really bad,” Sarah said.“She did have a very severe worsening of her depression,” said Dr. Scangos. She said she couldn’t disclose whether stimulation had been off or on, but said a device company technician was sent to Sarah’s home to “make a rescue change.”Afterward, Sarah said, she improved again.Over the year, the number of times a day that Sarah’s device has detected depression-linked brain activity and delivered stimulation has decreased somewhat, but is still substantial, Dr. Scangos said. Still, some days Sarah doesn’t need the maximum amount the device is set to provide: 300 times or 30 total minutes daily. (It automatically stops around 6 p.m. because evening stimulation made her too alert to sleep.)Longer-term and more detailed data on Sarah will be published later, said the researchers, who have two other participants so far. The device is intentionally tuned so Sarah cannot feel the stimulation, but she believes she knows that it’s occurred because she subsequently develops a sense of “emotional distance” that keeps negative feelings “compartmentalized,” she said.Also, “I feel alert,” she said. “I feel present.” That’s “a really good sign,” said Dr. Dougherty, who is considering using a similar approach for depression and possibly addiction. “The emotions are still there, but instead of sticking like mud, it’s running off like water.”To help researchers correlate brain activity with emotional states, two or three times a day, Sarah holds a doughnut-shaped magnet to her head, triggering the device to save the next 90 seconds of neural activity, and she completes a mental health survey. She’s been encouraged to pick moments “when she’s in a very good mood or a bad mood,” Dr. Scangos said. Also, twice daily, 12 minutes of neural data are automatically relayed to the device company and researchers.One question, experts said, is whether Sarah’s results support the theory that stimulating briefly whenever depression begins works because it keeps the brain from becoming accustomed to the treatment. Or, Dr. Sheth asked, does Sarah’s need for many daily doses after a year suggest continuous stimulation would be as or more effective?Another question is whether the therapy can prompt lasting brain changes to eventually avert depression with little or no continuing stimulation.Because of her implanted device that delivers deep brain stimulation, Sarah has been able to move to her own apartment and take classes in data analysis.Ruth Fremson/The New York TimesResearchers, several of whom consult for device companies or have patents related to deep brain stimulation, expect it will take years to learn if individualized approaches are effective enough to be approved. Different methods might work for different people’s depression, and individualized stimulation might eventually help other psychiatric disorders, researcher say. The most elemental things have improved for Sarah, who said she’s started to “relearn my life” and that “hobbies I used to distract myself from suicidal thoughts suddenly became pleasurable again.” When depressed, Sarah, a passionate cook and foodie, had such slow reflexes and trouble functioning that she’d cut or burn herself in the kitchen and doctors told her it wasn’t safe to cook anymore. Foods had little flavor. But after receiving the device, she ate Vietnamese pho in the hospital cafeteria and was thrilled she could taste “the brightness and the herbs,” she said. While being driven home from the hospital, she saw the marshes and exclaimed: “God, the color differentiation is gorgeous.” Now, she said, she’s “seeing things that are beautiful in the world, and when I was in the depths of depression, all I saw was what was ugly.”If you are having thoughts of suicide, call the National Suicide Prevention Lifeline at 1-800-273-8255 (TALK) or go to SpeakingOfSuicide.com/resources for a list of additional resources.