Long-Acting Injectables Delay Hospitalization for Schizophrenia

John Kane, MD

It is known that long-acting injectable antipsychotics could potentially reduce the hospitalization risk of schizophrenia patients by enhancing medication adherence. However, this treatment is rarely considered for early-phase schizophrenia treatment.

A team, led by John M. Kane, MD, Departments of Psychiatry and Molecular Medicine, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, compared long-acting formulation of antipsychotic medication to reduce the risk of hospitalization in early-phase schizophrenia with usual care.

In the Prevention of Relapse in Schizophrenia (PRELAPSE) trial with cluster randomization, the investigators examined 489 patients in 39 mental health centers in 19 US states with a two-year follow-up duration.

The study began in December 2014 and concluded in March 2019. The mean age was 25,2 years old and 225 participants had 1 year or less of lifetime antipsychotic use.

The investigators assigned site randomization to 19 clinics to encourage treatment with long-acting aripiprazole monohydrate (aripiprazole once monthly [AOM] condition) and 20 to provide treatment as usual (clinician’s choice [CC] condition).

Included in the study were patients with a schizophrenia diagnosis confirmed by a structured clinical interview, fewer than 5 years of lifetime antipsychotic use, that were between 18-35 years old.

The investigators did not place restrictions on the treatment at CC sites including using long-acting injectables or at AOM sites with the exception that aripiprazole monohydrate had to be prescribed within US Food and Drug Administration-approved guidelines.

The investigators sought primary outcomes of the first psychiatric hospitalization based on participant interviews every 2 months, the service use resource form administered every 4 months, and other sources including health records as available.

There were 52 AOM and 91 CC participants that at least 1 hospitalization. The mean survival time until first hospitalization was 613.7 days (95% CI, 582.3-645.1 days) for AOM participants and 530.6 days (95% CI, 497.3-563.9 days) for CC participants.

For the time to first hospitalization, the hazard ratio was 0.56 (95% CI, 0.34- 0.92; P = .02), which favored the aripiprazole once monthly treatment group.

In addition, survival probabilities were 0.73 (95% CI, 0.65-0.83) for AOM patients and 0.58 (95% CI, 0.50-0.67) for the CC treatment arm.

The number needed to treat to prevent at least 1 additional hospitalization was 7 individuals treated with aripiprazole once monthly compared with clinician’s choice.

“Long-acting injectable antipsychotic use by patients with early-phase schizophrenia can significantly delay time to hospitalization, a personally and economically important outcome,” the authors wrote. “Clinicians should more broadly consider LAI treatment for patients with early-phase illness.”

Recently, investigators discovered the polygenic scores (PGS) of schizophrenia patients could forecast an individual’s cognitive development.

A team, led by Dwight Dickinson, PhD, National Institute of Mental Health, examined whether different cognitive development histories in schizophrenia could reflect variation across dimensions of genetic influence.

Through cluster analyses, the investigators identified 3 cognitive trajectory subgroups in the schizophrenia group—preadolescent cognitive impairment (19%), adolescent disruption of cognitive development (44%), and cognitively stable adolescent development (37%).

The study, “Effect of Long-Acting Injectable Antipsychotics vs Usual Care on Time to First Hospitalization in Early-Phase Schizophrenia,” was published JAMA Psychiatry.