O4.2. THE PREVENTION OF RELAPSE AND HOSPITALIZATION IN FIRST EPISODE AND EARLY PHASE SCHIZOPHRENIA: RESULTS FROM THE PRELAPSE TRIAL

BACKGROUND: Even with early intervention services, a third or more of first-episode patients are hospitalized over the first 2 yrs. of treatment. Non-adherence is a major factor in increasing risk of hospitalization. Long-acting injectable antipsychotics (LAI’s) have shown effectiveness in addressing this concern in both mirror image and cohort studies. However, randomized controlled trials (RCT’s) have reported mixed results. RCT’s can change the ecology of care and do not reflect “real world” conditions, particularly when adherence is a focus of study. The large simple trial (LST) is a design intended to address such concerns. METHODS: The PRELAPSE trial was a LST involving cluster randomization of 39 clinics. 19 sites were randomized to provide LAI treatment-the Aripiprazole Once Monthly (AOM) condition and 20 sites to treatment as usual-Clinician’s Choice (CC). The primary hypothesis was that the opportunity for treatment with AOM would significantly delay time to first hospitalization. Inclusion criteria were: 1) schizophrenia diagnosis confirmed by a Structured Clinical Interview for DSM-5, Research Version (SCID-5); 2) <5 years lifetime antipsychotics, 3) age 18 – 35 yrs; 4) informed consent. Consistent with a LST, rating scale assessments were done (by centralized raters using live, two-way video) only at baseline, 12 and 24 months. Participants were interviewed via phone every other month for data on hospitalizations/ER visits. A key challenge in conducting this study was facilitating the acceptance of LAI’s among early phase patients at the experimental sites. AOM-specific training included information on the role of non-adherence in relapse/hospitalization, the effectiveness of LAIs in this context, the rationale for LAI use and selection of aripiprazole; shared decision-making principles; discussing LAIs with patients/ families; discussion of transition to LAI’s and prescribing guidelines consistent with the package insert for AOM. Training included providing suggested “scripts,” frequently asked questions, role-playing and overcoming logistical barriers to the use of LAIs across different healthcare settings. RESULTS: The 489 participating subjects had a mean age of 25, 75% were male, 44% African-American and 35% Caucasian. 46.0% had <=1 year lifetime antipsychotic exposure. As a result of the staff training at AOM sites only 14% of potential subjects declined participation because of the LAI treatment, and 91% of eligible subjects received at least one LAI treatment within the first three months of study. There were 489 subjects (234 AOM and 255 CC). A total of 52 AOM subjects had at least one hospitalization (22.2%) and 90 CC subjects had a least one (35.3%). For time to first hospitalization, under the proportional hazards assumption, the hazard ratio was HR=0.56 (95% CI = 0.34, 0.92), p=0.02.The estimated survival probabilities and 95% CI’s from the Cox model were 0.73 (0.65, 0.83) for AOM subjects and 0.58 (0.50, 0.67) for CC subjects. This translates to a number needed to treat (NNT) for prevention of one additional hospitalization for every 6.67 subjects treated with AOM relative to CC. DISCUSSION: This study demonstrates the feasibility of engaging the overwhelming majority of early phase patients in the use of LAI’s if clinical staff are well trained. The use of LAI’s in this population produced a significant delay in time to hospitalization and a NNT of 7 for the prevention of hospitalization.