Look for Hope and You Will Find It: Outlook for First-Episode Psychosis Has Never Been Better

Advances in the early treatment of patients with first-episode psychosis offer a more promising trajectory for young people than ever before, said Dost Ongur, M.D., at APA’s 2024 Annual Meeting. He was the recipient of APA’s Alexander Gralnick Award and presented an award lecture titled “Early Intervention in Psychotic Disorders: Where Are We and Where Are We Going?”

The period after the onset of psychosis remains challenging for young people and their families, but there is enough known about first-episode psychosis now that treatment can lead to better outcomes, and the sooner treatment begins, the better the outcomes will be, said Ongur, who is chief of the Psychotic Disorders Division at McLean Hospital in Belmont, Mass., and editor of JAMA Psychiatry.

“The field has traditionally thought of the emergence of schizophrenia as an inexorable decline, a steady downward progression of a bad illness,” he said, but that should no longer be the prevailing approach with young patients and families. “The idea is not that everyone is going to get better—but if we look for hope, we will find it,” he said.

Coordinated specialty care (CSC)—a multidisciplinary approach offering psychotherapy, medication management, family education and support, case management, and work or education support—is the standard of care for first-episode patients, Ongur said. CSC grew out of the National Institute of Mental Health’s (NIMH) landmark RAISE (Recovery After Initial Schizophrenia Episode) study, which showed the success of a version of CSC called NAVIGATE.

“CSC is team based, multidisciplinary, intensive, person centered, and recovery oriented,” Ongur said. “It’s not heavy-handed with medication, and it’s time limited. CSC is not something you do for life—probably the longer the better—but it has a beginning, a middle, and an end.

“This is very different from the typical scenario in which a young person comes out of the hospital and is told ‘Go see this doctor in the community somewhere’ or ‘Here is the phone number for a clinic. Call and maybe you can get an assessment,’ ” he said. “That scenario doesn’t match the urgency of the situation. With CSC, a team will meet with the young person, in his or her home if that is what it takes. Together they will talk about school, work, substance use. It’s intensive and assertive, similar to assertive community treatment. It’s youth oriented and designed to meet the needs of an 18-year-old.”

In addition to helping establish an effective standard of care, NIMH has invested in research designed to gather and share real-world data on how patients with first-episode psychosis respond to this care. The Early Psychosis Intervention Network (EPINET), initiated in 2019, is a national learning health care system that links over 100 early psychosis clinics through standard clinical measures, uniform data collection methods, data-sharing agreements, and integration of client-level data across service users and clinics. “The goal is to create a learning health care network,” Ongur said.

Ongur also highlighted the work of the Laboratory for Early Psychosis (LEAP) at Mclean Hospital, which he directs. LEAP is one of NIMH’s Advanced Laboratories for Accelerating the Reach and Impact of Treatments for Youth and Adults With Mental Illness (ALACRITY).

The LEAP Center coordinates 14 statewide early psychosis centers in Massachusetts. Ongur said the center is undertaking research projects to better understand outcomes among people who are referred to first-episode clinics but never show up and to test the effectiveness of treatments for affective psychosis.

An especially important LEAP project is a clinical trial to compare patient retention with standard coordinated specialty care (medication management, psychotherapy, and supported employment or education) and an enhanced version of the model (CSC +) that includes peer support, outreach using digital technology, cognitive remediation, and multi-family group therapy.

Important questions about treatment of first-episode psychosis are still to be resolved, Ongur said. “Some of the open questions include: When do we declare victory? When do we say our early intervention is done? Is there a time limit to early intervention or do we try to keep young people in the clinic for as long as possible? The best we can tell right now is that two years [the standard for CSC] appears to be too short.”

Moreover, the course of early psychosis appears to be quite variable and dependent on any number of factors in a patient’s life. “In this field there has been an unspoken assumption with chronic patients that [psychosis] symptoms emerge slowly and become florid, but in fact, it’s a much more dynamic and malleable process,” he said. “We need to better understand the sequence of events—what is leading to what—so we can intervene in the smartest way possible.”

Ongur especially emphasized the hazards of substance use—particularly use of cannabis—for young people at risk for psychosis. He cited a 2019 editorial in the Journal of Child and Adolescent Psychiatric Clinics that stated, “The time is right for the United States … to invest in public health education and messaging regarding cannabis as legal but not safe for young users, particularly of high potency products.”

Finally, Ongur presented evidence from his own research on the relationship between energy metabolism and psychosis. A January 2021 report in Schizophrenia Bulletin looked at the role of creatine kinase—an enzyme that is pivotal in providing adenosine triphosphate (ATP) to cells and maintaining its levels when energy demand is increased. ATP is the source of energy use and storage in cells.

The study found that creatine kinase was significantly reduced in patients with first-episode psychosis compared with healthy controls. “Generation of energy is critical for normal brain function as for the rest of the body,” Ongur said. “If you don’t have enough ATP, brain function starts to suffer. That leads to problems with information processing and neuronal dysfunction and probably also underlies some of the process of psychosis.”

He added that deficits in energy metabolism likely represent a “general vulnerability to complex brain disorders”; it is found in patients with epilepsy and other brain disorders, he said.

“The early phase of psychotic illness is a critical period for intervention,” Ongur concluded. “There is much more to learn, but it’s an exciting time in early psychosis.” ■