Clinical Summary: Effects of Brexpiprazole on Functioning in Patients With Schizophrenia Who Have Hostility and Agitation Symptoms: Post Hoc Analysis of Short- and Long-Term Trials
Hostility and agitation in schizophrenia can quickly undermine daily functioning and escalate into aggressive behavior, making them high-stakes symptoms to manage. This analysis asks a practical question clinicians face every day: whether brexpiprazole can improve functioning even in patients whose illness includes hostility or agitation.
Key Findings
- In participants with agitation at baseline, functioning improved more over 6 weeks with brexpiprazole than placebo on the modified (3-domain) PSP: least squares (LS) mean difference, 4.05 (95% confidence interval [CI], 2.01–6.10); P < .001; Cohen d, 0.29 (95% CI, 0.14–0.43).
- In participants with hostility at baseline, functioning improved more over 6 weeks with brexpiprazole than placebo on the modified (3-domain) PSP: least squares (LS) mean difference, 2.82 (95% confidence interval [CI], 0.58–5.07); P=.014; Cohen d, 0.19 (95% CI, 0.04–0.35).
- Short-term hostility response occurred in 218/300 participants (72.7%) on brexpiprazole versus 105/170 (61.8%) on placebo, with a relative risk of 1.18 (95% CI, 1.03–1.36); P = .019.
- In participants without hostility, functioning also improved more with brexpiprazole than placebo over 6 weeks: least squares (LS) mean difference, 3.42 (95% CI, 1.37–5.48); P=.001; Cohen d, 0.26 (95% CI, 0.10–0.41).
- Agitation response numerically favored brexpiprazole but was not statistically significant at Week 6: 143/345 participants (41.4%) versus 68/200 (34.0%), with a relative risk of 1.21 (95% CI, 0.95–1.53); P = .12.
In this post hoc analysis, brexpiprazole was associated with greater 6-week functional improvement than placebo in adults with schizophrenia who had hostility and agitation symptoms, and hostility response was higher with brexpiprazole than placebo. The largest short-term functional difference was in participants with agitation at baseline, while participants without agitation showed nonsignificant improvement: LS mean difference, 2.09 (95% CI, −0.18 to 4.36); P = .071.
Practice Implications
- When schizophrenia presents with hostility or agitation, brexpiprazole was associated with significant 6-week improvement on the modified PSP in both subgroups: LS mean difference, 2.82 (95% CI, 0.58–5.07); P=.014 for hostility, and 4.05 (95% CI, 2.01–6.10); P < .001 for agitation.
- Set expectations differently by symptom profile: the largest short-term functional benefit was seen with baseline agitation, while patients without agitation had a nonsignificant PSP advantage at Week 6 (P = .071).
- Monitor hostility directly during early treatment, since remission below the predefined PANSS P7 threshold occurred in 72.7% on brexpiprazole versus 61.8% on placebo by Week 6.
- For patients who remain on treatment, discuss that gains can continue over time: with long-term brexpiprazole, hostility response reached 90.6% at Week 58 and agitation response reached 77.5% at Week 58.
