They went out in their thousands and camped overnight along a coastal road in the cold Gaza night, huddled around small fires, waiting for supplies so they could feed their families.

What they encountered were hundreds of dead and wounded, according to witnesses and a doctor who treated the wounded, when Israeli forces opened fire on desperate Palestinians who rushed forward as aid trucks finally arrived before dawn on Thursday.

“I saw things I never thought I would see,” said Mohammed Al-Sholi, who had camped overnight to get food for his family. “I saw people fall to the ground after being shot, and others just grabbed the food they had with them and kept running for their lives.”

Amid the chaos and bloodshed, some people were run over by the emergency trucks, he said.

On Friday, President Biden said the United States would start dropping aid to Gaza to help ease suffering there, as European leaders condemned Israel for the deaths of dozens of hungry Palestinians killed as they surrounded the aid convoy.

Gaza health authorities have said Israeli forces killed more than 100 people and injured 700 others in a “massacre” as the convoy rolled down a dark road, a version of events that Israel disputed.

An Israeli military spokesman, Vice Admiral Daniel Hagari, said Thursday that Israeli soldiers had tried to secure the convoy and fired “when the crowd moved in a way that endangered them.” But he said the soldiers had not shot at people seeking help. The army has said most of the people were killed in a stampede and some were run over by the trucks in Gaza City.

About 150 injured and 12 of the dead were taken to Kamal Adwan Hospital in northern Gaza, Dr. Eid Sabbah, the head of nursing there. He said about 95 percent of the injuries resulted from gunshots to the chest and abdomen.

The deaths sparked global outrage and increased pressure on Israel to agree to a ceasefire with Hamas that would allow more aid to Gaza.

French Foreign Minister Stéphane Séjourné called for an independent investigation, saying the violence surrounding the convoy was the result of a humanitarian catastrophe that left people “fighting for food.”

“What is happening is indefensible and unjustifiable,” Mr Séjourné told radio station France Inter on Friday. “Israel must be able to hear it, and it must stop.”

Annalena Baerbock, Germany’s foreign minister, called on the Israeli army to “fully explain” the killings and joined calls for a ceasefire.

“People in Gaza are closer to death than to life,” Ms. Baerbock said in a statement. “More humanitarian aid needs to come in immediately.”

Mr. Biden said the United States would work with Jordan in the coming days to land aid to Gaza.

“Innocent people got caught up in a terrible war and couldn’t feed their families, and you saw the response when they tried to get help,” Biden said at the White House before meeting Prime Minister Giorgia Meloni of Italy. “But we must do more, and the United States will do more.”

Samantha Power, the administrator of the U.S. Agency for International Development, said that regardless of how people near the convoy died, it was clear they were trying to get food.

“That can’t happen,” she said. “Desperate civilians trying to feed their starving families should not be shot at.”

British Foreign Secretary David Cameron said Israel has a duty to ensure significantly more humanitarian aid reaches civilians in Gaza.

“A sustained pause in the fighting is the only way to receive life-saving aid on the scale needed and to free the hostages cruelly held by Hamas,” he said. a statement.

Palestinians, especially in the north, have suffered from famine and regularly gather in the relatively few aid trucks that have entered the area. Aid groups and the United Nations have accused Israel of blocking aid to northern Gaza, which Israel has denied. Aid groups have also reported widespread looting of aid trucks in the area.

A small number of police from the Hamas-led security forces have arrived in Gaza City in recent weeks but have largely failed to restore basic security, residents said. Last week, the World Food Program, a United Nations agency, joined UNRWA, the UN agency serving Palestinians in Gaza, in blocking aid shipments to the north, citing lawlessness in the area.

On Friday, the European Union said it plans to significantly increase funding for UNRWA this year, giving it 50 million euros, or about $54 million, next week.

The announcement was a lifeline for the agency, which has been fighting for its survival after some donor countries suspended their funding, citing Israeli accusations that a dozen of the agency’s 13,000 employees were involved in the Hamas-led attacks of 7 October.

The number of aid trucks entering Gaza fell significantly in February, data show, even as humanitarian leaders warned of famine and said some people had resorted to eating birdseed and leaves.

Through February 27, an average of 96 trucks entered Gaza per day, a 30 percent drop from the January average and the lowest monthly average since before the ceasefire in late November, according to UNRWA. Before the war, about 500 aid trucks entered Gaza every day.

The drop partly reflects Israel’s insistence on inspecting every truck at the Kerem Shalom intersection in southern Israel, which has served as the main entry point since reopening in December. Aid is also entering Gaza from Egypt through a border crossing near the city of Rafah, after Israeli officials inspected the cargo for weapons and other contraband.

Aid officials said the inspection system, while necessary, had caused significant delays, resulting in less overall aid.

On Thursday, Israeli soldiers provided security for the convoy entering Gaza City, with private vehicles distributing food from international donors, said an Israeli military spokesman, Lt. Col. Peter Lerner. told Great Britain Channel 4.

Edited drone video footage released by the Israeli military, along with social media videos of the scene analyzed by The New York Times, do not fully explain the sequence of events. The videos show hundreds of people surrounding and climbing on trucks, and people crawling and diving for cover.

Mr Al-Sholi, a 34-year-old taxi driver, said he went to meet the convoy because he and his family, including three young children, had been surviving on little more than the spices, chopped wheat and wild vegetables they could find.

On Wednesday he had heard that people had received bags of flour from relief trucks and there were rumors that another convoy was coming. So he went with friends to a roundabout to wait. He said he had never seen so many people gathered in one place.

“Just before the trucks arrived, a tank started coming towards us — it was around 3:30 a.m. — and fired a few shots in the air,” Mr. Al-Sholi said in a telephone interview, referring to Israeli tanks. ‘That tank fired at least one shell. It was dark and I ran back to a destroyed building and took refuge there.”

When the trucks arrived shortly afterwards, people ran to them to get food, drinks and whatever else they could get, said Mohammad Hamoudeh, a photographer in Gaza City. But when the people reached the trucks, he said, “the tanks started shooting directly at the people.”

He added: “I saw them firing direct machine gun fire.”

The witnesses said Israeli tanks shot at people even as they started to run away. Israeli forces continued to fire regularly at Gazans between 3 a.m. and 4 a.m., when they first arrived, until about 7 a.m., the witnesses said.

On Thursday, Admiral Hagari, Israel’s military spokesman, said troops “did not fire on those seeking help despite the accusations.”

“We did not fire at the humanitarian convoy, either from the air or from land,” he said. “We secured it so it could reach northern Gaza.”

Mr Hamoudeh said despite the panic on the ground, many were still rushing to get supplies. “People were terrified, but not everyone,” he said. ‘There were people who risked death just to get food. They just want to live.”

Reporting was contributed by Victoria Kim, Shashank Bengali, Abu Bakr Bashir, Approach Ibrahim, Julian E Barnes, Lauren Leatherby, Gaya Gupta, Monika Pronczuk, Zolan Kanno-Youngs And Adam Sella.

On the last day of 2023, Thierno Sadou Barry walked from his homeless shelter near Times Square to Harlem, looking for cheap suitcases he could fill with all his belongings.

Mr Barry and his wife, Oumou Barry, had fled political persecution in Guinea. Now the couple and their infant daughter had to leave the homeless shelter where they had lived since arriving in New York City nine months earlier, under recent city rules that limit shelter stays and have forced thousands of families to move.

As he walked, Mr. Barry cursed himself for leaving Guinea and coming to this cold, unforgiving place.

At home he risked death – and what good would a dead man have done for his family, he wondered? And so he had abandoned his elderly parents, his toddler daughter and his young sons. But now he lost hope that he would ever be able to send for them. He couldn't even send money home to support them.

“I can't even tell you how anxious, stressed and desperate I am right now,” he said in French. He had heard that some families were sent to tent shelters after being evicted. “Can you imagine, with an 8-month-old baby?”

The Barrys are among tens of thousands of migrants who have filled homeless shelters across the city over the past year and a half. But in recent weeks, many have received letters telling them it's time to move.

The expulsions are part of an effort by the Adams administration to reduce rising costs for migrant shelters and free up space for new immigrants who continue to come from the border.

The Barrys have applied for asylum and are awaiting a work permit. Their claim to political persecution seems strong. But the process is long and uncertain. So, like the tens of thousands of other migrants in the city, they're stuck waiting in a bureaucratic purgatory, increasingly concerned that the place they've traveled so far to doesn't want them.

“The problem with all this waiting is: wait until when?” Mr Barry said, adding: 'Because you were kicked out of the place where you thought you would at least be safe. It's like being told that my future is much more uncertain than I could have imagined.”

The Barrys arrived in New York City by plane on March 26, via Brazil, Nicaragua and California. They had to leave three of their children with relatives and friends, but two days after arriving in California after crossing the southern border, Mrs. Barry gave birth to a new daughter, Adama.

A taxi driver at the New York airport where they arrived asked where they wanted to go, but they had no idea. The driver dropped them off at Row NYC in Midtown Manhattan.

The Row was a four-star hotel converted into a homeless shelter. Nobody spoke French. But they found help from volunteers working at the nearby bus station. Mr. Barry got a MetroCard and signed up for food stamps. They contacted Andrew Heinrich, a lawyer and executive director of the nonprofit Project Rousseau, who provided them with pro bono legal assistance in managing the asylum application process.

They felt happy, but also isolated and haunted by guilt.

“Leaving your children, it's really not easy to live with,” Ms Barry said. “I want to talk to my kids, but it's so hard. So I look at pictures of them. I'll settle for that.”

On the day Mr Barry applied for asylum in August, he told his lawyer it felt like another birthday. The day he would receive his papers would be like a baptism.

But first there would be months of waiting for an uncertain outcome. About half of asylum applications were rejected last year.

Many migrants work off the books while waiting for legal approval. The Barrys didn't, terrified of jeopardizing their business. “I'm not going against the law,” Mr. Barry said.

Instead, the Barrys signed up for English classes so they would have more options once they got a work permit. They expected the permits to arrive in March, 180 days after they submitted their asylum applications.

One day in English class, Mr. Barry said his teacher was explaining the stages of culture shock that people can experience when they arrive in new places. First comes the honeymoon. “It's the excitement phase. When you see the big buildings, you're really overexcited,” Mr. Barry recalled one day in October, as he walked down a noisy stretch of Eighth Avenue next to Port Authority as Times Square glowed nearby.

The second phase was frustration, Mr. Barry said, which he felt acutely toward the end of the fall.

His lawyer, Mr. Heinrich, encouraged him to focus on gathering evidence for his asylum case. So in December, Mr. Barry told his story while Mr. Heinrich typed.

Coming to New York City had never been his plan. Mr Barry studied for four years at university in Conakry, the capital of Guinea, before opening a shop selling imported textiles from China.

But in January 2023, he and his wife knew they had to leave as soon as possible. A coup had taken place in September 2021 and a military junta that promised reforms had instead stepped up political persecution of opposition groups. Mr Barry had taken part in protests and members of the military came to his house looking for him.

Mr and Mrs Barry's relatives had also pressured them to have their four-year-old daughter's genitals cut. “The parents say it's tradition, that we should do it too,” Mrs. Barry said. “It still bothers me to this day. I don't want my daughters to experience what I did.”

Mr. Heinrich asked if Mr. Barry could think of any evidence of political persecution that he could present to a judge.

“I think it can be done with articles,” Mr. Barry replied, referring to news reports, adding: “A lot of markets were set on fire. Everyone knows that, you can Google it.”

Mr. Barry searched his phone for photos. Sometimes he would stand and stare into space, his hands folded in his lap. When they started talking about his four-year-old daughter and the female genital mutilation, Mr. Barry began to cry. He brought his right hand to his temple and covered his face and eyes.

“Every time I talk to her she asks me, 'Why did you abandon me, why did you abandon me?'” he said softly.

On Jan. 30, just after 8 a.m., the Barrys left the Row hotel with most of their belongings — three backpacks, a crib, a car seat, a stroller, a large suitcase and a shoulder bag with baby supplies — and loaded up in an Uber.

Mr. Barry had heard a rumor at the shelter that if they showed up at the Department of Homeless Services family intake center in the Bronx, they could avoid another eviction notice and get permanent placement in a shelter.

There was something to that rumor. The city now has two systems for homeless families, one for migrants and one for everyone else. In January, there were 15,000 families in the new migrant system. The migrants are subject to rolling deportation orders, while this is not the case for families in the regular system.

The Barrys waited in the Bronx center for five hours until a worker led them out the door. “They told us to wait, so we waited, and now they're telling us to go,” Mr. Barry said.

No one told them why they had to leave, but after gathering their belongings, they were sent to a van with another migrant family. The van dropped them off on 45th Street in Manhattan, outside the Roosevelt Hotel, the city's main migrant shelter.

New arrivals go there to be placed in shelters, but in recent weeks it has become a holding area for families who have been kicked out and hope to reapply for shelter. When the Barrys entered the hotel, they found hundreds of families in front of them. Hours passed.

Just before 2 a.m., a worker told Mr. Barry that the family would be assigned a room at the Americana Inn, eight blocks from where they were staying at the Row hotel.

The room was small, with room for a single bed, right against the walls, and a sink. There was no room for the crib. Mr Barry slept on the floor so his wife and baby could share the bed.

In the morning, Mr. Barry begged the hotel staff for a bigger room. They assigned him a room where they could cram in the crib. “We'll deal with it while we wait,” he said.

He had numbered the days. By the time the next 60 days were up, his work permit would be on its way.

The incessant buzz of an Israeli drone fills the room.

On one large wall, scenes of death and desperate rescue operations through twisted metal and broken stone play in a video loop. A large pile of rubble – metal bars, bricks and broken plaster – stretches almost the entire length of the exhibition hall.

Along blue walls meant to evoke Gaza's sky and sea, hang paintings that mostly evoke life before Israel's intense bombardment and invasion: Palestinian still lifes, native cacti, music, cats and cows, and even one Catwoman.

The work of more than a hundred artists from Gaza adorns the walls of this exhibition, on view at the Palestinian Museum in the Israeli-occupied West Bank, a protest collection that is as much about the art that is not there and that has been lost in the war. raging in Gaza, but also about the art on display there. Most artists are trapped in the enclave and struggle to survive, let alone create.

“We resist with our colors and our canvases to convey our message to the world,” said Basel El Maqosui, an artist who left his home in northern Gaza and whose work is on display.

“They destroyed our entire civilization and destroyed our modern and ancient artifacts,” he said in an interview. “Each one carries with it a memory full of love and joy, and another memory full of sadness and tears.”

High on the wall in the hall hangs his painting of a Palestinian woman, her head, face and shoulders framed by layers of colorful scarves – red, yellow and blue.

Mr El Maqosui said he was inspired by his neighbor in northern Gaza, a young Bedouin woman who had a unique style of wearing brightly colored Palestinian clothes, wearing four to five colorful scarves around her, regardless of the occasion or weather.

The artists' work in the exhibition, called 'This Is Not an Exhibition', seeks to reflect the texture of Palestinian life, which can be both political and apolitical at a time when Israel's declared war against Hamas is taking a horrific human toll has caused enormous destruction in Gaza.

The exhibition's organizers say they see the show as an act of solidarity with artists in Gaza, offering a way to draw attention to the cultural costs of the war. The exhibition points to a shared experience between Palestinians in the West Bank and Gaza who, although divided in geography and governance, are united by common aspirations for statehood after decades of living in various forms under Israeli control.

“Killing the Palestinians, killing the artists, destroying their works, attacking the cultural institutions,” said Ehab Bseisso, a member of the museum's board of directors, “is a primary part of the genocidal erasure of history, memory and creativity.”

“This is about serving the colonial narrative that Gaza had no life, no art, no culture,” he added.

During more than four months of war, Israeli airstrikes in Gaza have destroyed many artists' studios and works, as well as most museums and cultural institutions – a loss to the area's cultural life that experts say could take more than a generation to reverse. to rebuild it.

UNESCO, the United Nations cultural organization, has expressed concern about the impact of the war on Gaza. The agency has documented damage to at least 22 heritage sites, including 10 buildings of historical or artistic interest, one museum and three archaeological sites.

Standing in the exhibition hall and speaking over the sound of the drone, Mr. Bseiso called the works of art hanging around him “survivors” because they were sold to collectors, universities and cultural centers outside the Gaza Strip before the start of the war.

Many represent joyful aspects of Palestinian life, while others represent the struggle of what organizers call “the harshness of reality” and the “ugly cruelty of the occupation.”

One painting from 1982 shows a body holding its dismembered head, wrapped in a black-and-white checked scarf known as a kaffiyeh. Another copy, from the 1970s, shows a man in chains and a dead pigeon. Below it hangs a painting from 2016 showing a person whose face is covered by a red bandana with white underwear on it, with the word “return” spray-painted in Arabic.

“This is the voice of Gaza that they are trying to silence,” Mr Bseisso said.

Some of those voices have been lost.

According to organizers, at least four of the artists with works in the exhibition were killed in Israeli airstrikes. Their names are marked on a contributor wall with a black line in the corner of their nameplate.

Mr. El Maqosui has come a long way from the days when he would teach art at a school by day and create colorful art in his home studio by night. His house and studio were razed in an Israeli airstrike, he said.

More than two decades of works were destroyed. “I lost everything I had,” he said.

Now he spends much of his days fetching and filtering water, lining up for food and keeping his family's rickety plastic-sheet tent intact from the cold, wind and rain in the southern city of Rafah.

He still makes time for art, sitting in the tent, wrapped in blankets, sketching with pen in a notebook, his colorful subjects replaced by black-and-white representations of the bleak reality in which he and more than two million others now find themselves. live yourself.

“In these difficult circumstances that are difficult to describe in words, I try to hold on to my humanity through drawing,” he said. “Drawing doesn't change what we experience, but it is a way to convey our suffering to the world.”

When the war began, the Palestinian Museum was preparing an exhibition on music that would open in November. But seeing the death and destruction in Gaza prompted organizers to make a U-turn.

They tore down the walls of the music exhibit and used the rubble to create a pile of rubble in the center of the museum hall.

Shareef Sarhan, co-founder of Shababek, an artist collective and gallery in Gaza City, said the effect “makes you feel like you are entering Gaza with all its destruction.” Mr Sarhan, who lives in Istanbul and Paris, helped put together the exhibition remotely, including suggesting the drone sounds and rubble.

Before the war, the top floor of Shababek was used for artists in residence to focus on their art. It was destroyed by an Israeli attack, said Mr. Sarhan, who was outside Gaza when the war began.

The bottom two floors – where some of the enclave's most renowned artists displayed their sculptures, paintings and mixed-media art installations – remain intact and for weeks housed families who had fled their homes and sought shelter there.

Mr Sarhan says he does not know what happened to many of the paintings, but he believes the families used the wood and canvases to start fires to keep warm amid an acute fuel shortage caused by the near complete siege of Israel.

The exhibition, he said, will allow Gaza's artists to communicate with people outside despite the war, at a time when most of the population is cut off from the rest of the world.

During the war, telephone and internet connections have been frequently cut, either by military airstrikes, power outages or, according to senior US officials, directly by Israel.

“People lose their connection with the outside world, but art can play a role that the artist cannot play,” Mr Sarhan said. “People can see their message and feel your situation. It becomes like a reflection, like an official spokesperson for them.”

In early 2020, the Food and Drug Administration responded to decades of escalating concerns about a commonly prescribed drug for asthma and allergies by deploying one of its most potent tools: a stark warning on the drug’s label that it could cause aggression, agitation and even suicidal thoughts.

The agency’s label, which was primarily aimed at doctors, was supposed to sound an alert about the 25-year-old medication, Singulair, also known by its generic name, montelukast. But it barely dented use: The drug was still prescribed to 12 million people in the United States in 2022.

Children face the greatest risks of the drug’s ill effects, and while usage by minors did decline, it was still taken by 1.6 million of them — including Nicole Sims’s son. Ms. Sims had no idea why, at 6, her son started having nightmares and hallucinations of a woman in the window. When he told her that he wanted to die, Ms. Sims went online, desperate for answers.

Only then did she learn about the F.D.A. warning. She also found a Facebook support group with 20,000 members for people who had experienced side effects of the drug. Members of the group recounted a haunting toll that they linked to the drug with the help of peers, not their doctors.

“It’s a mental health crisis that nobody is recognizing,” said Anna Maria Rosenberg, an administrator of the group.

The F.D.A.’s handling of Singulair illustrates systemic gaps in the agency’s approach to addressing troubling side effects from medicines approved long ago — and to warning the public and doctors when serious issues arise. The agency had flagged the 2020 warning label, known as a “boxed warning,” to physicians’ groups, but it had not required that doctors be educated about the drug’s side effects.

Federal regulators in 1998 initially dismissed evidence that emerged during the approval process about the drug’s potential to affect the brain and did not revise their assessment until two decades later. The F.D.A. was slow to alert the public as reports of psychiatric problems surfaced, highlighting deficiencies of a drug-monitoring system that puts the onus on drugmakers to report problems.

Federal regulators themselves can be blind to the full scale of a problem: The F.D.A. discovered nearly a decade ago that Merck, the maker of Singulair, received thousands more reports of side effects from the drug than the agency or its global counterpart. And after a teenager’s high-profile suicide in 2007, the F.D.A. stopped short of forcing Merck to conduct more rigorous and expensive studies that could have made clear how common bad reactions were.

Prescribing of the drug has remained at high levels, raising questions about whether the alert reached enough doctors and patients, who often don’t read the fine print on the drug’s tightly folded label, tucked into a bag at the pharmacy. (Prescribing data was provided to The New York Times by Komodo Health.)

Many doctors support the drug’s availability and see existing cautions as sufficient. But researchers have grown increasingly alarmed about its effects, especially on children, and about what they see as the F.D.A.’s failure to determine how many have been harmed or to get the word out to doctors.

“What are the great studies that tell us how often it happens? There aren’t any,” said Thomas Moore, of the Johns Hopkins Center for Drug Safety and Effectiveness, who has long tracked reports of montelukast’s psychiatric effects. “This is a structural problem.”

Dr. Reshma Ramachandran, a Yale University assistant professor and family doctor, said that the warning had not broken through to channels that doctors notice and that the agency “needs to do much more in terms of direct communication to clinicians and through more active channels.”

‘Searching for answers’

In issuing the warning in March 2020, the F.D.A. required pharmacists to hand out a medication guide and added the warning, with a thin black line as a border, to the drug label. The agency also sent a safety alert to email subscribers, flagged the warning to dozens of professional and patient groups, and published an article in a medical journal on its reasoning.

But it did not use its authority to require monitoring of side effects or the education of doctors. Rarely are approved drugs with known side effects fully barred from sale.

While researchers see evidence that points to a link between the drug and psychiatric side effects, studies vary significantly on how frequently they appear — or, in some cases, whether they appear at all. Reports include a wide range of psychiatric effects, making it challenging to pinpoint the cause.

The agency’s risk-benefit calculus for montelukast has weighed its psychiatric risks against its wide use in treating many patients for asthma, which can be deadly.

F.D.A. officials said they had taken appropriate action. In an interview, officials said that a number of compelling reports of psychiatric problems seemed drug-related and that the boxed warning was meant to raise awareness.

The agency is continuing to study notes in electronic health records for clues about side effects, and officials said it “continues to monitor and investigate this important issue.” But pinpointing the risks may not be feasible: It would take a large study to capture events such as suicides that remain rare, said Dr. Sally Seymour, director of the F.D.A.’s pulmonary drugs division.

With concerns lingering, researchers, including some at the F.D.A., have returned to basic animal studies to examine possible effects of montelukast in the brain, a quest that could take a decade to complete.

Merck, which reaped billions of dollars in revenue from the drug, spun it off in 2021 to the company Organon. Merck referred comment to Organon, but in an April 2023 court filing denied “a significant link between Singulair and neuropsychiatric events.”

Organon said in a statement that the company had communicated appropriate information to patients and health providers about the drug’s risks and benefits. “Nothing is more important to Organon than the safety of our medicines and the people who use them,” the company said. Other generic companies also sell the drug.

The warning was added before Ms. Sims’s son began talking about hearing scary voices and seeing walls that appeared to be melting. If she had known, she said, she would have stopped the drug right away.

Ashley Bracken also wishes her family’s allergy practice in Utah had alerted her to the boxed warning.

Ms. Bracken’s daughter, Genevieve, had been on the medication since age 7 and grew increasingly depressed after a doctor increased her dose to the adult level in April 2021, when she was 13. Her mother initially attributed her daughter’s obsessive hand washing to the pandemic. She wrote off her daughter’s moodiness to teenage angst.

Ms. Bracken said she first saw a list of the drug’s side effects, which include obsessive compulsive disorder, in a screenshot on Genevieve’s phone from October 2021.

She and her husband had been scouring the device for any clue to why the girl, then 14, had killed herself days before Christmas that year. The F.D.A.’s warning included suicide, though the agency has said no studies have definitively assessed the risk. The family’s medical practice declined an interview request.

“It sickened us,” Ms. Bracken said. “In the moment, we were searching for answers, because what she did didn’t make sense.”

Rising sales, growing concerns

Approved in 1998, Singulair soon became a top-selling drug. With a market of 25 million people battling asthma and more with allergies, sales representatives blanketed doctors’ offices. They promoted the drug as a once-a-day alternative to inhaled corticosteroids, which are considered more effective but also more cumbersome. Singulair came in a chewable, cherry-flavored pill for children.

Concerns surfaced within Merck: A whistle-blower claimed in a 2008 lawsuit that the company improperly paid doctors to prescribe drugs, including Singulair, and that the drug “leads to aggressiveness and attention deficit problems” in children. Merck settled the claims, largely related to other drugs, and admitted no wrongdoing.

Merck promoted the medication to parents, in 2009 partnering with the TV personality Jo Frost, known as “Supernanny” on reality television. Merck, which also made an inhaler for asthma, funded the American Academy of Pediatrics to train doctors about asthma diagnosis and prescribing, a Fox affiliate reported in 2010. (An NBC affiliate has also reported on problems with the drug.)

A worldwide success, the drug would earn Merck an estimated $50 billion in revenue, according to a recent Reuters analysis of the drug’s troubled history.

In 2007, its possible drawbacks drew wider attention when Elizabeth Little, a New York state senator, contacted the F.D.A. about a 15-year-old on Singulair who became hopeless and anxious, agency records show. The teenager killed himself 17 days after starting the drug.

Rather than mandating fresh studies of Singulair, the F.D.A. allowed Merck to review its existing trials. The company concluded in 2009 that those trials were not devised to identify psychiatric problems or suicides, and few had been noted. An F.D.A. examination of reports of side effects prompted Merck the same year to add warnings about hallucinations, hostility, anxiety and suicide to the label.

As of 2019, the F.D.A. had documented 82 suicides of people on montelukast. More than 500 suicide attempts have also been linked to the drug in unverified reports to the agency.

Problems drew notice worldwide. Researchers examining side effect reports sent to the World Health Organization in 2015 discovered outsize rates of anxiety and suicidal behavior among children on montelukast, a finding researchers deemed “striking” in young children.

A 2022 review of the same type of reports found high rates of aggression and agitation. Nightmares were reported 25 times as frequently as expected and suicidal thinking 18 times as frequently.

Such studies based on voluntary reports can identify problems, but not pinpoint how often they appear. Research trying to do so using more detailed health records is mixed. Studies of older adults and of U.S. veterans and an F.D.A. study on depression and suicide found few problems.

Some doctors cite those studies in arguing the F.D.A.’s warning in 2020 was sufficient. They said montelukast remained popular because it addressed asthma and allergies at the same time, with no side effects for some people. The drug eases breathing by suppressing inflammation in the airways.

“In some studies, they find increased risk, and in others, not,” said Dr. John Kelso, an allergist at the Scripps Clinic in San Diego.

Some reviews continue to find problems. A 2021 study of Korean health data found that older adults who had asthma and then developed psychiatric problems were 70 percent more likely to have taken montelukast-type drugs than those who had not. Younger adults in Denmark who were prescribed the drug were 38 percent more likely to soon need psychiatric or A.D.H.D. medications, a 2023 study found.

Even such “observational” reports can be biased by the unique features of people taking a drug, Mr. Moore, of Johns Hopkins, said.

Still, he said other evidence suggested the drug was causing the problems: They crop up in children with no psychiatric history. They go away when the drug is stopped. They tend to return if it’s restarted.

Settling the question of how common the problems are remains unlikely, said Dr. Daniel Benjamin, a Duke University researcher who helps distribute the scarce federal funds allocated to studying older pediatric drugs.

“There’s just a tsunami of drugs where we don’t really know what they’re doing in children,” he said.

Drug targeted at the airway goes into the brain

F.D.A. scrutiny of montelukast has brought new information to the fore and shed fresh light on older data.

In records approving the drug in 1998, the agency said only a “trace” amount of the drug crossed into the brain, though its data showed lingering levels in a rat’s brain 24 hours after a dose. That remained its stance for decades.

The agency reversed that conclusion in 2020. It cited a 2015 study — which highlighted the agency’s 25-year-old data — saying it showed “significant” penetration of the blood-brain barrier in rats. The agency concluded anew that “montelukast could act directly on cells in the brain” in rats and updated the drug label in 2020.

The F.D.A. has also struggled to get a handle on how many patients experienced harm.

In 2014, as Merck unsuccessfully sought approval to sell Singulair over the counter, F.D.A. records for an oversight meeting showed that Merck had data on about 46,500 cases with adverse events. U.S. officials and the World Health Organization knew about only 14,000.

Though Merck was not required to report nonserious side effects or those listed on the label from outside the United States, the agency noted that the tally from regulators was “still far lower” than Merck’s.

The breadth of problems remained urgent for leaders of the Facebook group, which in 2017 urged the F.D.A. to consider a boxed warning. That led to an emotional hearing in 2019.

A Massachusetts mother testified that when her 12-year-old daughter’s dose was raised, she began to hear voices telling her to harm herself; she dreamed about people being tortured and decapitated.

A Wisconsin mother said her son, 11, dreamed about his family being murdered. An Arizona mother said her 7-year-old developed severe tics, a problem one French study has tied to the drug.

Months later, the F.D.A. announced the boxed warning and began studies of the drug’s interactions with the brain.

‘Leave this Drug to Adults’

Other scientists, too, have been examining the effect of the drug on the central nervous system and its potential to accumulate in the brain.

One Swedish study found that mice taking the drug for two weeks had impaired cell growth in the hippocampus, a brain region critical for memory and learning. A 2022 study in Portugal found altered levels of dopamine and serotonin in rats, as well as lowered defenses against stress, said Gonçalo Justino, a biochemistry researcher at the University of Lisbon.

Dr. Justino said he was haunted by numerous case studies in the medical literature of distressed children. Given the degree of harm to some children, he said, doctors should “leave this drug to adults.”

Dr. Marc Flajolet, a Rockefeller University neuroscientist, said evidence suggesting that the drug could affect developing brains meant that “it will be probably safer at this point not to use that in kids until we know more.”

Other researchers have examined the drug’s interaction with genes or discussed its potential to release toxins or accumulate in the brain, especially in children.

Parents of children who’ve struggled on the drug urge caution.

In Tennessee, Ms. Sims’s son, now 8, has been off the drug for nearly two years. His drawings of red-eyed demons gave way to sketches of a smiling boy fishing under the sun.

Ms. Sims still worries about signs of lingering depression. After what seem to be great days, he will comment, “It wasn’t fun.” Few studies examine whether there are long-term effects.

Ms. Bracken said she and her husband learned more about their daughter’s mental state after her death. Her suicide note referred to “loud voices.” Texts to friends mentioned nightmares.

Ms. Bracken said she would like to see prescribing curtailed among children and, if it continues, mandatory communication about the risks.

“Who does it fall on?” she asked. “Why is it me, after losing my daughter, that I feel the need to go and put a PowerPoint together and present this to doctors to save lives?”