In the months after 24-year-old D.J. was diagnosed with schizophrenia, he searched online for answers to questions that felt urgent and existential.

Does it get really bad over time? Will I be able to live a normal life?

He'd read the statistics. He'd seen the news stories. Freshly graduated from University of Washington, the new diagnosis, he said, was "pretty devastating."

He was nervous about his career prospects and scoured Reddit and YouTube for stories from people who'd experienced frightening symptoms like his own. Seeing disturbing specters with no eyes. Feeling invisible bugs biting his skin. Getting stuck in "forgetfulness loops," like losing his keys 20 times over before leaving the house.

One day online, D.J. saw an ad for a new medication. Local researchers were running a clinical trial for a drug that worked differently from the ones with debilitating side effects he'd recently been prescribed.

"I was trying to see if I could make the symptoms go from 60%-70%," said D.J., who requested to use his nickname to protect his future employment opportunities, "to something closer to zero."

D.J. became one of the first in line to try the new antipsychotic, called Cobenfy — a potentially life-changing drug for one of psychiatry's most intractable mental illnesses, but whose long-term side effects are still unknown.

Cobenfy was approved by the Food and Drug Administration in fall 2024 and represents the first novel approach in decades to treating schizophrenia, which affects an estimated 3.7 million American adults. The drug is now beginning to make its way into the hands of Washingtonians. Psychiatrists here report that pharmaceutical sales reps are dropping off brochures at their offices, that patients are slowly starting to ask about the medication and that, in certain circumstances, they're beginning to write Cobenfy scripts.

"There's been interest, definitely," said Dr. Swapna Vaidya, a psychiatrist in private practice in Seattle and behavioral health medical director for care coordination at Optum, who has had a couple of patients ask about the drug over the past few months.

Psychiatrists have for decades had a limited choice of drugs to treat the serious hallucinations, apathetic feelings and flat affect tied to schizophrenia. At least some of schizophrenia's symptoms are thought to be related to excessive dopamine activity. All prior antipsychotics have, in large part, relied on blocking this chemical messenger's receptors.

How is Cobenfy different from other antipsychotics?

Unlike previous generations of antipsychotics, Cobenfy doesn't directly interact with dopamine or serotonin receptors.

Although they're relatively effective at dimming hallucinations, antipsychotics struggle to manage so-called "negative symptoms" — social withdrawal, memory problems and lack of motivation so powerful they prevent many from holding down jobs or keeping up with daily routines. Some cycle through several antipsychotics without finding relief from any of their symptoms. Others stop taking medications or avoid them from the outset because they don't believe they're unwell, a common symptom known as anosognosia.

These drugs can also cause extreme fatigue, permanent movement disorders, weight gain and deadly cardiovascular diseases, side effects so intolerable that people often abandon their meds periodically or altogether.

Cobenfy may offer a more hopeful promise, though many aspects of the drug are unclear, like whether it works better than previous generations of antipsychotics. The drug, which is being manufactured by Bristol Myers Squibb, has so far been tested in a handful of short-term trials and yearlong follow-ups. But it hasn't yet been measured for effectiveness in a head-to-head trial against leading antipsychotics like aripiprazole, risperidone or clozapine. It comes with its own set of side effects, like nausea, vomiting, hypertension and risk of liver disease. And it's expensive, with a monthly list price starting at $1,850.

It may have at least a few big advantages, though: It doesn't appear to trigger the kind of significant weight gain, metabolic changes or fatigue seen in other antipsychotics.

"Patient tolerance is excellent ... Anything you can do to improve the tolerance is key," said Dr. Arif Khan, medical director at Northwest Clinical Research Center, a research facility in Bellevue that's helping run Cobenfy clinical trials.

Local physicians like Vaidya say they're cautiously optimistic, especially for patients who haven't responded to other options.

"I'm not going to be somebody who just wants to start a person on this medication until I have enough data to absolutely say this might be the right choice," said Vaidya, who hasn't yet prescribed the medication. But, she said, "It's certainly promising. At least from a scientific point of view."

"Feeling of helplessness"

Dr. Peter Loeffler had exhausted his options.

Antipsychotics, including clozapine. Electroconvulsive therapy. Combining several drugs at once. By the time Cobenfy came to market, he'd been considering last-resort sedatives like benzodiazepines for his 60-something patient, who was by all measures treatment resistant and had been hospitalized several times over the past three years.

A "feeling of helplessness" led Loeffler to write her a Cobenfy prescription.

"Yesterday actually is the first time that there's been any kind of dip in (her symptom) scores," Loeffler, a fourth-year psychiatry resident at Providence Sacred Heart Medical Center in Spokane, said a few weeks after his patient started Cobenfy. "I'm just now getting my feet wet, but I'm imagining the future where it's as promising as it seems to be. As I hope it is."

Psychiatrists and their patients are suddenly living in a moment that, five or 10 years down the line, could be considered an extraordinary inflection point.

There's been no significant improvements for treating schizophrenia since the introduction of the first antipsychotic, chlorpromazine, in the 1950s. The drug helped spark a psychopharmacological revolution — as researchers in the 1950s began to better understand the underlying causes of mental illness, more and more drugs for psychosis, depression and anxiety came to market. Antipsychotics, in particular, gave some people the ability to manage serious symptoms on their own, and played a central role in emptying government-run psychiatric institutions.

Newer iterations of antipsychotics have been shown to cause fewer side effects, but these drugs are far from perfect. Some people with uncontrolled symptoms end up hospitalized, in jail or on the streets. And while medication is often the first-line treatment, therapy, lifestyle changes and stress management are typically also part of living a stable life with a diagnosis like schizophrenia.

Unlike other antipsychotics, Cobenfy doesn't directly block dopamine or serotonin.

Cobenfy's therapeutic properties were discovered through "serendipitous observation," said Dr. Steve Paul, professor of psychiatry and neurology at Washington University in St. Louis, and former CEO of the small pharmaceuticals startup, Karuna Therapeutics, that developed the drug.

When Paul first became interested in the compounds that would eventually become Cobenfy, it was the early 1990s. Paul, a former scientific director at the National Institute of Mental Health, was working for Eli Lilly on a drug for Alzheimer's disease. But it had gastrointestinal side effects so serious they never brought it to market.

The researchers noticed, though, that the drug seemed good for something else.

Some patients who tried the compound had symptoms related to schizophrenia — suspiciousness, agitation, hallucinations — and saw substantial improvements. Researchers decided to combine the drug with one they hoped would prevent their initial compound's nasty side effects, and eventually began testing it in people with schizophrenia.

Findings from the resulting placebo-controlled clinical trials and 52-week follow-ups are encouraging, Paul said. But, he added, "There's a lot that's going to be learned in the real world."

In Spokane, group home staff tell Loeffler his patient is spending more time outside her room and is working with a community specialist who is helping her get connected to volunteer opportunities.

He's still waiting to hear from her, though, that her hallucinations are less intense. That during their visits, she's aware that he's her doctor.

"I would love for her to have a sense of, oh, things are getting better," he said. "She hasn't said that yet."

"An opportunity lost"

Researchers, physicians and patients are facing down a mountain of unanswered questions. Ones that, if history tells us anything, won't be answered for years or even decades.

For example, it's unclear if the drug can cause involuntary and repetitive facial tics and limb spasms — permanent symptoms of previous classes of antipsychotics that often take years to develop — or other slow-to-detect or rare symptoms.

Cobenfy doesn't come with a black box warning, the most serious FDA label for drugs that can cause significant or life-threatening side effects. But about one-third of medications approved by the FDA result in later safety concerns that prompt the agency to add such a warning, remove a drug from the market or note new side effects, a 2017 study shows. Psychiatric drugs were more likely than several other classes of drugs to trigger new safety warnings after their approval.

Whether the drug outperforms existing drugs or makes a significant dent in schizophrenia's negative and cognitive symptoms, often the most disabling ones for people with this illness, is also unsettled. And whether patients can get it covered by their insurance — many insurers are requiring preauthorization paperwork for the drug, psychiatrists say — is another question. The drug's list price is more than $22,000 a year compared with roughly $600-$3,200 for a year's supply of clozapine pills.

"Boy, I thought when I was looking at this drug that they had an opportunity to go, 'We could make ourselves the first (choice) antipsychotic,' and they didn't price themselves that way," said Dr. David Rind, chief medical officer for the Institute for Clinical and Economic Review, an independent nonprofit that analyzes clinical evidence and cost effectiveness of prescription drugs and other treatments.

"I do think it's an opportunity lost."

Patients prescribed drugs requiring preauthorization are sometimes forced to slog through bureaucratic red tape every year, a stressful process that can pause or delay treatment, said Dr. Claire Brutocao, a psychiatrist at Providence who supervises Loeffler's work. She said it would be a "hard sell for me to choose this earlier down the line over other things that are more readily available, at least at this point."

For D.J., the medication is free, at least for now: For the next several months, he'll continue receiving the drug as a paid clinical trial participant.

He has more energy, he's less forgetful and his hallucinations have quieted, though it's hard to know if the improvements are from the medication or life changes he's going through, he said.

"What me and many other people worry about ... is the possibility of some kind of irreversible damage that we do not know about." But, he said, "I feel good that I'm first in line. I'm really trying to be on top of this illness."

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