Aripiprazole once-monthly as maintenance treatment for bipolar I disorder: a 52-week, multicenter, open-label study

Abstract

Background: The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I.

Methods: This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive ("de novo") patients as well as AOM 400-experienced ("rollover") patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324-331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder-Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified.

Results: Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (< 10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications.

Conclusion: AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709.

Keywords: Aripiprazole once-monthly; Bipolar I disorder; Maintenance treatment; Patient satisfaction; Safety.

Figures

Fig. 1

a Source of patients participating in this clinical trial. de novo = patients who did not participate in the lead-in study and had no prior AOM 400 exposure; Rollover-AOM 400 Arm = rollover patients from the lead-in study who had been randomized to the AOM 400 arm; Rollover-Placebo Arm = rollover patients from the lead-in study who had been randomized to the placebo arm. b Patient disposition across the study. Patients entered the oral aripiprazole cross-titration phase if they were not already receiving oral aripiprazole in their treatment regimen at screening. Those already on aripiprazole therapy at screening entered directly into the oral aripiprazole stabilization phase. AOM 400 aripiprazole once-monthly 400 mg

Fig. 2

TEAEs occurring in ≥ 5% of patients during the AOM 400 maintenance phase, by enrollment source. TEAEs displayed from most common overall at top to least common overall at bottom, displayed as percent incidence in de novo and rollover patients. AOM 400 = aripiprazole once-monthly 400 mg; TEAE treatment-emergent adverse event, URTI upper respiratory tract infection

Fig. 3

Percentage of patients remaining stable throughout the AOM 400 maintenance phase, by enrollment source. Stability defined as (1) outpatient status, (2) Young Mania Rating Scale total score ≤ 12, (3) MADRS total score ≤ 12, and (4) no active suicidality, with active suicidality defined as MADRS item 10 score ≥ 4, or “yes” on question 4 or 5 of the Columbia Suicide Severity Rating Scale. MADRS Montgomery–Asberg Depression Rating Scale, n number evaluable

Fig. 4

Patient evaluation of own satisfaction with AOM 400 (a) and patient assessment of side effects on AOM 400 relative to previous medication (b) using the Patient Satisfaction with Medication Questionnaire-Modified; data collected at last visit of the AOM 400 maintenance phase. AOM 400 aripiprazole once-monthly 400 mg