Frequently Asked Questions

In this post hoc 52-week open-label analysis, aripiprazole once-monthly 400 mg was associated with maintenance of stability in Black/African American adults with bipolar I disorder, with safety outcomes broadly comparable to those in other racial groups. Among patients who were stable at baseline, 90.1% of Black/African American patients remained stable at the last visit, compared with 87.4% of White patients, 91.5% of Asian patients, and 90.9% of patients of other races. The authors also reported functional and quality-of-life outcomes that were similar to or greater than those seen in other racial groups.

About 9 in 10 Black/African American patients remained stable during maintenance treatment. Specifically, 90.1% of Black/African American patients who were stable at the start of the maintenance phase remained stable at the last visit. In this study, stability required outpatient status, a YMRS total score of 12 or lower, a MADRS total score of 12 or lower, and no active suicidality.

No clear signal of worse tolerability was seen in Black/African American patients. Treatment-emergent adverse events occurred in 67.3% of Black/African American patients, compared with 81.2% of White patients, 91.5% of Asian patients, and 100% of patients in the small "other races" group. Rates of serious treatment-emergent adverse events and discontinuations due to treatment-emergent adverse events were reported as similar across racial groups.

The study did not show a higher extrapyramidal symptom burden in Black/African American patients. Changes on clinician-rated extrapyramidal symptom scales were minimal and not clinically meaningful across racial groups. The authors also reported lower or similar rates of akathisia and tremor in Black/African American patients than in patients of other races, and they noted that these lower rates were not explained by lower aripiprazole exposure or greater use of anticholinergics or benzodiazepine derivatives.

A weight increase of at least 7% from baseline occurred in 16.3% of Black/African American patients (17 of 104) at any time point during the study. That rate was similar to Asian patients at 17.0% (16 of 94) and lower than White patients at 21.6% (55 of 255) and patients of other races at 45.5% (5 of 11).

Metabolic conclusions were limited, but this analysis did not show a worse signal in Black/African American patients. Potentially clinically relevant fasting triglyceride values at any time point occurred in 29.2% of Black/African American patients (21 of 72), compared with 40.4% of White patients (69 of 171), 33.0% of Asian patients (29 of 88), and 71.4% of patients of other races (5 of 7). However, HbA1c data were available for only 6.9% of the overall study population, and the numbers for glucose and most lipid measures were too small for meaningful race-based analysis.

Yes. Functioning improved, and the improvement was greater than in some comparison groups. The least squares mean change in FAST total score from baseline to week 52 was -5.97 (95% CI, -8.82 to -3.13) in Black/African American patients, compared with -1.89 (95% CI, -3.24 to -0.53) in White patients (P=.0113; Cohen d=0.30), -1.93 (95% CI, -3.97 to 0.12) in Asian patients (P=.0241; Cohen d=0.33), and 0.15 (95% CI, -5.81 to 6.10) in patients of other races (P=.0679; Cohen d=0.61). The authors noted that the 5.97-point improvement approached the estimated minimal clinically important difference of 8 points.

Yes. Improvement in functioning was significantly correlated with improvement in mood scores at week 52. In Black/African American patients, the correlation between FAST total score change and YMRS total score change was 0.22 (P=.0010), and the correlation between FAST total score change and MADRS total score change was 0.34 (P<.0001). These findings suggest that better mood control was associated with better functioning in this subgroup.

Overall quality-of-life change was generally similar to that seen in other racial groups. The least squares mean change in Brief QoL.BD total score from baseline to week 52 was 2.50 (95% CI, -0.15 to 5.15) in Black/African American patients, compared with 1.93 (95% CI, 0.60 to 3.26) in White patients, -1.02 (95% CI, -3.10 to 1.06) in Asian patients, and 2.96 (95% CI, -2.53 to 8.45) in patients of other races. Some individual quality-of-life items improved more in Black/African American patients, including "Felt Physically Well" and "Woken Up Feeling Refreshed."

Overall discontinuation was higher in Black/African American patients, largely because more patients met protocol-specified withdrawal criteria, often after a positive drug test. All-cause discontinuation was 51.0% in Black/African American patients versus 37.6% in White patients, 23.4% in Asian patients, and 18.2% in patients of other races. Of the 18 Black/African American patients who met predefined withdrawal criteria, 15 did so because of a positive drug test. The authors also reported that, after adjustment for region and baseline BMI with multiplicity control, there were no statistically significant differences in time to treatment discontinuation between Black/African American patients and patients of other races.

These findings are most applicable to maintenance treatment in Black/African American patients who have already been stabilized on aripiprazole, not to acute de novo treatment. The study population entered the maintenance phase after oral aripiprazole stabilization or after completing the lead-in study without mood recurrence, which likely enriched the sample with aripiprazole responders and tolerators. The authors conclude that the findings support use of maintenance AOM 400 in this population, while emphasizing that efficacy and safety findings require confirmation in adequately powered prospective studies.

The main limitations are that this was an exploratory post hoc analysis of an open-label study in patients already stabilized on aripiprazole, with limited power for some outcomes and incomplete metabolic data. The inferential statistics were exploratory and nominal, with no adjustment for multiple comparisons. Prior stabilization likely limited generalizability by enriching the cohort for responders and tolerators, regional confounding was possible because most Black/African American participants were enrolled in North America, and small sample sizes for some laboratory measures, especially HbA1c, prevented meaningful race-based metabolic analysis.