In a small, preliminary study, an experimental gene-editing treatment dramatically lowered cholesterol levels, perhaps permanently, after just one infusion, scientists reported on Monday.

If confirmed in larger studies, researchers hope the findings may lead to a one-and-done way to prevent heart disease in large numbers of people. Most gene therapies target rare diseases, but cardiovascular disease kills nearly 800,000 Americans a year.

“We have these debates and new guidelines that we should be treating people earlier,” said Dr. John H. P. Alexander, a cardiologist at Duke University who was not involved with the study. “A curative therapy would change the game.”

The study, published in The New England Journal of Medicine, was an interim analysis of 35 patients in a trial that will involve as many as 85 participants. All have genetically high levels of LDL cholesterol — the bad kind — or heart disease.

In the 35 patients, a single infusion of the highest dose of the treatment reduced LDL cholesterol levels by as much as 62 percent. The change has been sustained in a subgroup whose members were treated 18 months ago.

It will be followed by a larger study of 200 patients.

It is unusual for The New England Journal of Medicine to publish such a preliminary result. But “it looks like it works pretty well,” said Dr. Eric Rubin, the editor in chief. Moreover, he noted, the trial is an ambitious attempt to apply cutting-edge gene therapy to the leading cause of death in the United States.

Still, “we need much more safety data,” said Dr. J. Michael Gaziano, the director of preventive cardiology at the Boston V.A. health care system, who was not involved in the new study. The Food and Drug Administration requires that all patients in gene therapy studies be followed for 15 years.

Patients in the trial received an infusion containing a gene editing “machine,” or a tiny molecular factory wrapped in a cloak of fat. The fat-coated particles travel through the blood directly to the liver, where they are taken up by cells that remove the fatty wrapper.

The editing machine then crawls along the liver cell’s DNA until it finds its target, a gene called PCSK9. It stops there and erases one DNA letter in the gene, replacing it with another.

That simple change disables the PCSK9 gene and prevents cells from making the PCSK9 protein. Without it, the liver pulls more LDL cholesterol out of the bloodstream, keeping the levels lower.

The study was led by Dr. Sekar Kathiresan, the chief executive at Verve Therapeutics, now a subsidiary of Eli Lilly. Dr. Kathiresan, a cardiologist, said he was motivated by personal history.

His grandmother, father, uncle and brother all had heart attacks. His brother died of cardiac arrest at age 42, just after returning from a run.

Gene therapies for rare diseases carry multimillion-dollar price tags. But Dr. Daniel Skovronsky, chief scientist at Eli Lilly, said that would not be the case if this treatment were eventually approved.

“That’s not what we’re going for here,” he said. “We’re going for a medicine that someday could be part of primary care.”

High LDL levels are eminently treatable with an array of medicines, including the old standbys, daily statin pills. More recent advances include injected drugs that block the protein made by the PCSK9 gene, creating the same effect as gene editing.

But too many people cannot or will not take the drugs. Between one third and a half of patients stop taking cholesterol-lowering medications within a year of starting them, even people who have had heart attacks.

Kristy Faulkner, 45, who lives in Guilford, Conn., is among those who need treatment but are reluctant to take a powerful drug. Heart disease runs in her family, and she had a heart attack when she was 42.

“There’s some sort of internal denial, like I can’t be on these meds every day of my life,” she said.

“I understand the importance,” she added, “and I feel ashamed.”

Her cardiologist, Dr. Erica Spatz, at Yale University, is hoping Ms. Faulkner’s insurance will pay for a PCSK9 inhibitor that only has to be administered every six months. Her medical history means there is “no margin for error,” Dr. Spatz said.

But a gene-editing treatment that is administered just once?

“This kind of therapeutic breakthrough could be a game changer for people like her,” Dr. Spatz said.

Alice Thomas, 64, of Lexington, N.C., would love to take cholesterol-lowering drugs but can’t get them. Her sole source of income is Social Security, and while statins are cheap, she was unable to tolerate them.

Her insurance did not approve the injectable drugs that might have helped. She has had two strokes, and a few months ago, her LDL cholesterol level was dangerously high at 190.

“I didn’t have anything,” Ms. Thomas said. “Then I found out about this study.”

She received the infusion in Dr. Kathiresan’s trial on March 30. Two weeks later, her cholesterol level was 50.

“This is great,” she said. “One time and it’s over.”

Most years, when thousands of psychiatrists gather for the annual meeting of the American Psychiatric Association, they walk past a scattering of protesters. There are Scientologists with megaphones; Falun Gong groups doing their exercises; and, often, former patients, saying they have been harmed by medications or electroconvulsive therapy.

This year, though, the profession is facing criticism from the highest levels of the federal government. The American Psychiatric Association gathered just 10 days after Health Secretary Robert F. Kennedy Jr. announced a set of policies to encourage doctors to deprescribe, or assist patients in stopping, the most widely prescribed class of antidepressants.

A current of anxiety ran through the meeting, held here this week. Many physicians in the crowd said they worried that Mr. Kennedy’s statements would prompt people to refuse medications, or to quit them and relapse. The plenary session erupted in applause when Dr. Marketa Wills, the organization’s chief executive, declared, “We will never support governmental interference in the practice of medicine.”

“We are standing tall for evidence-based care,” she continued. “We are standing tall against stigma, oversimplification, and anything that would move patients further away from the care that they need.”

But there were also signs that the field’s leaders are engaging, albeit cautiously, with Mr. Kennedy’s effort to curb overprescribing. Numerous sessions offered training in helping patients taper off medications. In July, the association’s president will take part in a panel convened by the Department of Health and Human Services to develop clinical guidance on tapering antidepressants.

In an interview, Dr. Wills said she had been “encouraged” by the invitation to participate in the panel, and she credited the administration with “putting mental health front and center.”

“It feels like the beginning of a conversation, one that we welcome,” Dr. Wills said. She added, “It would be odd to have that conversation without psychiatrists at the table.”

Outside in the corridors, some rank-and-file attendees were less diplomatic.

Many providers took issue with Mr. Kennedy’s negative characterization of selective serotonin reuptake inhibitors, or S.S.R.I. s, the most widely prescribed class of psychiatric medications. Clinical trials have found that most patients’ depressive symptoms improved with S.S.R.I.s, and they are considered safe enough to be prescribed by general practitioners.

A 2026 study found that 16.6 percent of U.S. adults, or roughly one in six, reported currently taking an antidepressant.

“He just doesn’t like S.S.R.I.s,” said Dr. Sung Hyon, a psychiatrist from Pasadena, referring to Mr. Kennedy. Dr. Hyon said S.S.R.I.s had been “foundational” in his practice — “boring drugs that are well established, have good safety evidence and have zero chance to cause addiction.” He called them “God’s gift to psychiatry.”

And patients know it, he added. “So many millions” of Americans already take S.S.R.I.s, he said, and the vast majority are fully aware of their downside, like sexual side effects and withdrawal symptoms.

“And they say, ‘You know what? It’s worth it,’” Dr. Hyon said. “Because there are so many of them, it would be a pretty big political firestorm if he really tried to restrict access. And there is very, very little medical evidence to do so.”

Mr. Kennedy has long signaled that curbing the use of psychiatric drugs was a goal of his. Earlier this month he began taking steps in that direction, announcing guidelines and regulatory changes meant to provide an incentive for clinicians to help patients taper off psychiatric medications. The steps would not affect patients’ access to antidepressants.

Andrew Nixon, a spokesman for the Department of Health and Human Services, said the agency had had no discussions about banning S.S.R.I.s., “and any claims suggesting otherwise are false.” The aim of the new initiative, he said, is to “promote appropriate psychiatric prescribing and drive deprescribing when clinically indicated.”

Some psychiatrists said they worried that Mr. Kennedy’s deprescribing initiative was the beginning of a wider effort that might, in later stages, discredit psychiatry more broadly and restrict access to care.

“I think it is actually putting more questions in people’s minds about whether psychiatric treatment is safe or effective,” said Dr. Eric Rafla-Yuan, who chairs the A.P.A.’s caucus on the social determinants of health. “The data has not changed on S.S.R.I.s. It’s the narrative that has changed.”

He said the A.P.A. should be pushing back forcefully against Mr. Kennedy’s claims about psychiatric treatments, and should steer clear of seeming to endorse any part of the initiative.

“It’s a fine line between having a seat at the table and being used as a tool to legitimize their agenda,” he said.

‘Much Too Medicated’

At the same time, deprescribing seemed, at the meeting, to be on everyone’s lips. A new book, “Stahl’s Deprescriber’s Guide,” was selling like hot cakes in the exhibition hall. There were panels titled, “Deprescribing Antipsychotics,” “The Much Too Medicated Patient” and “Stimulants for A.D.H.D.: Did We Get It Wrong?”

Dr. Chris Aiken, who delivered an address about multidrug cocktails, said a generational change is moving through the psychiatric association, as a younger cohort of physicians, in their 30s and 40s, take a more prominent role.

Millennials were part of the first generation to be prescribed stimulants and antidepressants as children and teens, he said, and physicians in that group are more conscious of poor outcomes years later. “Meds are not the answer, and they have seen this in their own lives,” he said.

Some senior physicians had a similar message.

“If I have any regrets about my recommendations as a physician, it’s about the medications that I did not withdraw sooner,” said Dr. Ronald Winchel, an assistant clinical professor of psychiatry at Columbia University’s medical school, at one panel.

He said a number of concerns had prevented him from doing so: Sometimes, patients were taking multiple medications and it was difficult to say which was effective. Sometimes, patients were doing well, and he was afraid of setting them back. And there was a dearth of research on how patients do after they quit medications.

“The fear of withdrawing medications has really complicated our work,” he said.

Dr. Winchel compared this year’s churning discussion to a watershed moment in the A.P.A.’s history: In 1973, sustained pressure from protesters caused the organization to reverse its century-old position and declare that homosexuality was not a mental disorder.

“Instead of getting into a defensive crouch, they looked at themselves and they made progress,” Dr. Winchel said. The same kind of advancement, he added, could result from a rigorous discussion about prescribing practices. “If some of this agitation is coming from outside,” he said, “what is wrong with that?”

In his presentation, Dr. Aiken urged colleagues not to dismiss the stories Mr. Kennedy has highlighted of patients who have encountered serious difficulties quitting antidepressants.

“I don’t really know how common it is, but I do know that when it does happen, it can be quite severe,” he said. “It may be rare, but let’s take it seriously, because it can really burn people when it happens.”

Others said working with Mr. Kennedy around mental health policies was a matter of simple pragmatism.

“There’s definitely a need for us to be talking to the people who are making decisions,” said Dr. Hammad Khan of Sacramento. “We can’t let Joe Rogan decide what the F.D.A. approves or doesn’t approve.”

An Inflection Point

Dr. Awais Aftab, the author of “Psychiatry at the Margins,” a popular mental health Substack, said he expects the H.H.S. effort to focus on raising awareness about tapering off medications. There are few pathways for the government to reduce the prescription of drugs like S.S.R.I.s, which have gone through F.D.A.-approval pathways and are widely used by the public, he said.

He described “a sense of alarm” among psychiatrists at the virulent critique of the field coming from Mr. Kennedy’s circle. Psychiatry, he said, has been late to acknowledge the complaints of patients like Laura Delano, an author and activist, who say they were overmedicated as children or teenagers and got little support from doctors when they wanted to reduce or stop the drugs.

“The mainstream psychiatric community has been fairly insulated, and suddenly they are hearing now about this issue,” said Dr. Aftab, a psychiatrist at Case Western Reserve University.

He added that he believes that the use of antidepressants in the United States may have reached a natural limit. “The demand is going to, at some point, go into an equilibrium with the reality of the lack of effectiveness and the reality of the tolerability issue,” he said.

But the experience of some other countries suggests that the demand for antidepressants may continue to rise, even amid warnings about overprescribing.

In 2017, Britain commissioned a major report on overprescribing and then followed up with a series of reforms, including updating clinical guidelines to require regular prescribing reviews and instituting a national audit program to monitor drug use.

But a study of prescribing in Britain found that the use of antidepressants continued its steady rise through 2023, the last year for which data was available. In contrast, recent years have seen a decline in the use of anxiety medications and hypnotics, which were also the subject of updated clinical guidelines.

The study’s authors said the rise was most likely driven by patient demand, reductions in stigma and the lower cost of antidepressant medications available in generic form.

Many psychiatrists at the conference in San Francisco said that they routinely urge patients to try therapy as an alternative or a complement to medications, but that many patients have no access to that care, because their insurance will not pay for it.

Dr. Michael Bostwick, a suicide researcher and professor of psychiatry at Mayo Medical School, in Rochester. Minn., said it remained unclear what alternative treatments Mr. Kennedy is recommending to patients who quit antidepressants.

“Toward what end?” he said. “Is he going to put more resources toward therapists? Is he going to tell us to eat more red meat, or work out more, or take psychedelics, like the president has advocated? There is no alternative plan.”