LAIs vs Usual Care for First Hospitalization in Early Psychosis

Megan Brooks

July 27, 2020

Treatment with a long-acting injectable antipsychotic (LAI) in early-phase schizophrenia can significantly delay time to first hospitalization, new research suggests.

The Prevention of Relapse in Schizophrenia (PRELAPSE) study, which included more than 200 adult patients with schizophrenia, showed that for the group that received an LAI, the average time to first hospitalization was longer and there was a significantly greater reduction in the incidence of first hospitalizations than for those who received usual care.

"We hope that clinicians will consider the use of long-acting formulations of antipsychotic medications earlier in the course of illness so that we can avoid as many preventable hospitalizations as possible," John M. Kane, MD, Zucker Hillside Hospital, Glen Oaks, New York, told Medscape Medical News.

He noted that clinicians are often reluctant to consider this option if the patient has yet to experience a relapse because of poor medication adherence.

"Given very high rates of nonadherence, it seems unfortunate to wait for such a deleterious event before considering a more convenient and effective strategy," Kane said.

The findings were published online July 15 in JAMA Psychiatry.

Longer Time out of Hospital

The PRELAPSE study was a cluster randomized trial conducted in 39 US mental health clinics. It included clinicians at 19 sites who encouraged treatment with once-monthly aripiprazole (Abilify Maintena). Clinicians at the other 20 sites provided treatment as usual.

Treatment as usual was determined by each clinician and could include an LAI.

The analysis included 234 patients enrolled at the once-monthly aripiprazole sites and 255 enrolled at the usual-care sites. Eligibility criteria included being between 18 and 35 years of age, having received a diagnosis of schizophrenia that was confirmed by a structured clinical interview, and having used antipsychotics for less than 5 years.

Fifty-two patients (22%) in the once-monthly aripiprazole group and 91 (36%) in the usual-care group had at least one psychiatric hospitalization during the study period. The average time before first hospitalization was significantly longer in the LAI group than in the usual-care group (613.7 days vs 530.6 days).

The hazard ratio for time to first hospitalization was 0.56 (95% CI, 0.34 – 0.92; P = .02), favoring the LAI.

Use of an LAI in this population with early-phase schizophrenia led to a "significant 44% reduction in the incidence rate of first hospitalization," the investigators report. The number needed to treat to prevent one hospitalization was seven.

The study included only one LAI formulation. However, to the researchers' knowledge, there are no data suggesting differences in efficacy among second-generation LAIs regarding prevention of hospitalization.

They note that two prior studies have reported the superiority of LAIs over oral antipsychotics in first-episode or early-phase schizophrenia.

Experts Weigh In

Commenting on the study for Medscape Medical News, William Carpenter, Jr, MD, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, noted that LAIs have been "underutilized" in the United States.

"So this report is important in adding support to the notion that LAIs can/should be first-line options to consider with patients early in treatment if longer-term continuation treatment is indicated," said Carpenter, who wasn't involved with the research.

He noted that the study may be particularly "influential," inasmuch as the authors are known for careful research and informed thoughts on implications for clinical care. They can also be regarded as "trusted sources of information on treatment of psychosis," Carpenter said.

Also weighing in, Kenneth L. Subotnik, PhD, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles (UCLA), said the study "clearly demonstrates an advantage" with LAIs for delaying psychiatric hospitalization, "which is an important clinical and economic outcome."

However, "the benefits of LAIs in the early course of schizophrenia are potentially far wider than this important goal and may include remediation of impairment in cognition, which in turn can potentially lead to increased occupational and social functioning," Subotnik told Medscape Medical News.

"Potential benefits of LAIs also include improvement in quality of life, preservation of brain myelination, reduction in suicide risk, and reduction in symptoms that might not be reflected in the outcome metric of reduction in hospitalizations," he noted.

Subotnik said another key study finding is that LAIs were readily accepted by patients.

"The common belief among treating clinicians that patients will object to an LAI has less traction now," he said.

Clinicians at UCLA have been "advocating for the use of LAIs early in the course of schizophrenia, when it might channel the disorder into a less turbulent course," he added.

"With the multiple LAI options and the expanding support systems in place for giving the injections, the rationale for a preference for oral antipsychotic medications in the early course of illness is losing validity. It is time for clinicians to consider an LAI option after the first psychotic episode,” said Subotnik.

The study was an investigator-initiated project funded by Lundbeck and Otsuka Pharmaceuticals. Kane reported receiving grants from Otsuka and Lundbeck. In 2019, Carpenter was an advisor to Minerva and sits on a data and safety management board for an ongoing clinical trial by Parexel Pharmaceutical Company. Subotnik has served on the speakers' bureau for Otsuka's Abilify Maintena and has been a CME speaker for Janssen, Inc, Canada, and PeerVoice. He has also served as a consultant to Janssen Scientific Affairs LLC, Alkermes Inc, Medincell Inc, and Teva Pharmaceuticals and has received research support from Alkermes Inc, Genentech Inc, and Janssen Scientific Affairs LLC.

JAMA Psychiatry. Published online July 15, 2020. Abstract

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