Effect of Long-Acting Injectable Antipsychotics vs Usual Care on Time to First Hospitalization in Early-Phase Schizophrenia: A Randomized Clinical Trial

IMPORTANCE: Long-acting injectable antipsychotics (LAIs) can potentially reduce hospitalization risk by enhancing medication adherence but are rarely considered for early-phase schizophrenia treatment. OBJECTIVE: To determine whether encouraging use of a LAI compared with usual care delays the time to first hospitalization with patients with early-phase illness. DESIGN, SETTING, AND PARTICIPANTS: The Prevention of Relapse in Schizophrenia (PRELAPSE) trial was cluster randomized with a follow-up duration of 2 years. The study began in December 2014, was completed in March 2019, and was conducted in 39 mental health centers in 19 US states. Site randomization assigned 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). Participant eligibility criteria included (1) schizophrenia diagnosis confirmed by a structured clinical interview, (2) fewer than 5 years of lifetime antipsychotic use, and (3) age 18 to 35 years. The AOM sites identified 576 potentially eligible participants, of whom 234 (40.6%) enrolled; CC sites identified 685 potentially eligible participants, of whom 255 (37.2%) enrolled. INTERVENTIONS: There were no restrictions on treatment at CC sites (including using LAIs) or at AOM sites with the exception that aripiprazole monohydrate had to be prescribed within US Food and Drug Administration–approved guidelines. MAIN OUTCOMES AND MEASURES: The primary outcome was time to first psychiatric hospitalization based on participant interviews every 2 months, the service use resource form administered every 4 months, and other sources (eg, health records) as available. Potential events were adjudicated by an independent committee masked to treatment assignment. RESULTS: The 489 participants (368 men [75.3%]) had a mean (SD) age of 25.2 (4.2) years and 225 (46.0%) had 1 year or less lifetime antipsychotic use. Fifty-two AOM (22%) and 91 CC participants (36%) had 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 time to first hospitalization, the hazard ratio was 0.56 (95% CI, 0.34- 0.92; P = .02), favoring AOM. Survival probabilities were 0.73 (95% CI, 0.65-0.83) for AOM participants and 0.58 (95% CI, 0.50-0.67) for CC participants. The number needed to treat