Early Psychosis Intervention Shows Robust Real-World Effectiveness

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Health professionals know that the results of clinical trials—which often involve motivated patients and doctors—don’t always translate when applied in real-world settings.

But a real-world test of OPUS, an intervention for people with first-episode psychosis, found it is as effective—and in some cases superior—as researchers had found when the intervention was evaluated in clinical trials.

The findings were a bit surprising to the study team from Copenhagen University Hospital in Denmark. “Early intervention services for psychosis are, by definition, a complex psychosocial intervention, and, once implemented, they may not be delivered with the same rigorous attention to program fidelity, low caseload, motivation … as they had in the controlled environment of a randomized trial,” wrote Christine Merrild Posselt, M.Sc., a psychologist at the Copenhagen Research Center for Mental Health, and colleagues.

OPUS, developed at Copenhagen University Hospital, is a modified form of assertive community treatment for psychosis that includes family involvement and social-skills training provided by a multidisciplinary team of psychiatrists, psychologists, nurses, social workers, physiotherapists, and vocational therapists. A clinical trial of 547 adults conducted between 1998 and 2001 demonstrated that OPUS was superior to standard care in reducing psychosis symptoms and substance use and improving functioning. The success of the trial led to the broad implementation of OPUS across Denmark in 2003, as well as making OPUS a model for early psychosis programs in other countries.

For the current study, Posselt and colleagues compared the five-year outcomes of 3,328 patients who had received OPUS between 2003 and 2014 (after the national implementation) with those of 545 of the original clinical trial participants. Data for all patients was obtained from Danish medical registers. This period included two years of OPUS intervention followed by three years of standard care for all patients.

The researchers found that patients receiving OPUS after implementation (known as OPUS-real world) had about 30% lower odds of a psychiatric hospital admission than the clinical trial participants across the five-year time span. Among patients who were hospitalized, OPUS-real world patients had fewer and shorter hospital stays on average than their clinical trial counterparts. The authors noted this difference might be partially attributed to broader policy shifts seen in Denmark aimed at reducing inpatient stays. “However, it is reassuring that the departure from the constraints of a randomized trial, as well as an increase in caseload, has not led to an apparent increase in psychiatric admissions,” they wrote.

OPUS-real world and clinical trial patients took similar amounts of antipsychotics and other psychotropics during the first four years of the study, but by year five, real-world patients used fewer medications than the clinical trial participants. Likewise, by year five, the OPUS real-world patients were more likely to be employed and/or attend school and more likely to be in a relationship than the clinical trial participants; the real-world cohort was also less likely to have been diagnosed with a substance use disorder.

There were no differences between the groups in terms of suicide, death due to any cause, non-psychiatric hospital visits, or use of outpatient mental health services.

Posselt and colleagues noted that as with psychiatric admissions data, broader changes in Denmark may have contributed to some of the improvements seen among the OPUS-real world patients; for example, employment services may have improved since 1998. But they also suggested that over time, as clinical staff become more experienced with the intervention, they may have found ways to deliver early psychosis services more efficiently and flexibly, which could improve patient outcomes even as caseloads increase.

This study was funded by the Lundbeck Foundation. ■