Hospitalization rates in patients switched from oral anti-psychotics to aripiprazole once-monthly: final efficacy analysis

Abstract

Objective: To compare hospitalization rates in patients with schizophrenia treated prospectively with aripiprazole once-monthly 400 mg (AOM 400; an extended-release injectable suspension) vs the same patients’ retrospective rates with their prior oral anti-psychotic therapy. Research design and methods: Multi-center, open-label, mirror-image, naturalistic study in a community setting in North America. Patients who required a change in treatment and/or would benefit from long-acting injectable anti-psychotic therapy were treated prospectively for 6 months with AOM 400. Retrospective data on hospitalization rates were obtained. Clinical trial registration: ClinicalTrials.gov: NCT01432444. Main outcome measures: The proportion of patients with ≥1 psychiatric inpatient hospitalization with oral anti-psychotic therapy examined retrospectively (months –4 to –1 before oral conversion) and after switching to AOM 400 (months 4–6 after initiating AOM 400). Results: Psychiatric hospitalization rates were significantly lower when patients were treated with AOM 400 compared with oral anti-psychotic therapy both in the 3-month primary efficacy sample (2.7% [n = 9/336] vs 27.1% [n = 91/336], respectively; p < 0.0001) and in the total sample (6-month prospective rate: 8.8% [n = 38/433] vs 6-month retrospective rate: 38.1% [n = 165/433]; p < 0.0001). Discontinuations due to adverse events (AEs) during cross-titration were lower in patients cross-titrated on oral aripiprazole for >1 and <4 weeks (2.9% [n = 7/239]) compared with patients cross-titrated for ≤1 week (10.4% [n = 5/48]). The most common treatment-emergent AEs during the prospective treatment phase were insomnia (6.7% [n = 29/431]) and akathisia (6.5% [n = 28/431]). Patient-rated injection-site pain decreased from the first injection to the last visit. Conclusions: In a community setting, patients with schizophrenia demonstrated significantly lower psychiatric hospitalization rates after switching from their prior oral anti-psychotic therapy to AOM 400. Patients served as their own control, and thus an active control group was not included in this study. Confounding factors, such as insurance coverage and availability of hospital beds, were not examined here and deserve further consideration.

Initiation of aripiprazole once-monthly in patients with schizophrenia

“…Information about how to initiate aripiprazole once-monthly 400 mg in patients not currently treated with oral aripiprazole may be found in protocols and results of clinical studies 13,14,21 . Because the 2 pivotal studies were registrational trials, a conservative approach was used, in which patients first converted from their prior antipsychotic to oral aripiprazole monotherapy over 4 to 6 weeks (ie, the oral conversion phase; Figure 3a) and were then stabilized on oral aripiprazole (ie, the oral stabilization J U S T…”

“…Rates of discontinuations due to AEs were numerically higher in patients cross-titrated from other oral antipsychotic therapies to oral aripiprazole for ≤1 week before initiating aripiprazole once-monthly 400 mg compared with patients who cross-titrated for >1 to 4 weeks (10.4% [5/48] Initiating Aripiprazole Once-Monthly for Schizophrenia 8 oral antipsychotics to oral aripiprazole for ≤1 week suggests that cross-titrating for >1 week from other antipsychotics to oral aripiprazole is better tolerated, although clinicians should make treatment decisions based on individual patient profiles. Most patients (n=325) were treated with oral aripiprazole for >1 to 4 weeks, and the majority of them (n=81.5% [265/325]) continued on to treatment with aripiprazole once-monthly 400 mg 21 . These findings suggest that "starting low and going slow" when cross-titrating from other oral antipsychotics to oral aripiprazole before initiating aripiprazole oncemonthly 400 mg may translate to an effective switching strategy in clinical practice (Figure 3a).…”

“…To address this, a post hoc analysis was conducted using data from the multicenter, open-label, mirror-image, naturalistic study of hospitalization rates in patients with schizophrenia in which the more flexible study design was better aligned with clinical practice relative to the pivotal studies 21 . Detailed study design and patient inclusion and exclusion criteria were previously described 21 .…”

“…To address this, a post hoc analysis was conducted using data from the multicenter, open-label, mirror-image, naturalistic study of hospitalization rates in patients with schizophrenia in which the more flexible study design was better aligned with clinical practice relative to the pivotal studies 21 . Detailed study design and patient inclusion and exclusion criteria were previously described 21 . Briefly, adult patients with schizophrenia who were treated with oral antipsychotic therapy in the 7 months before screening and were currently receiving an atypical oral antipsychotic other than aripiprazole were included in the study 21 .…”

“…Detailed study design and patient inclusion and exclusion criteria were previously described 21 . Briefly, adult patients with schizophrenia who were treated with oral antipsychotic therapy in the 7 months before screening and were currently receiving an atypical oral antipsychotic other than aripiprazole were included in the study 21 . For the first 2 weeks after the first injection of aripiprazole once monthly 400 mg, patients who were previously stabilized on oral aripiprazole 10 to 20 mg/d were treated with oral aripiprazole 10 mg/d, and patients who were previously stabilized on oral aripiprazole >20 to 30 mg/d were treated with oral aripiprazole 15 mg/d.…”