How-To Guides

Yes. In the 6-week pooled analysis, participants with schizophrenia and baseline hostility had greater improvement in functioning with brexpiprazole than with placebo on the modified 3-domain Personal and Social Performance (PSP) scale: least squares mean difference 2.82 points (95% CI, 0.5875.07; P=.014), with a Cohen d effect size of 0.19 (95% CI, 0.0470.35).

Participants without hostility also improved more with brexpiprazole than placebo, with an LS mean difference of 3.42 points (95% CI, 1.3775.48; P=.001).

Yes. In participants with baseline agitation, brexpiprazole was associated with greater 6-week improvement in functioning than placebo on the modified 3-domain PSP: least squares mean difference 4.05 points (95% CI, 2.0176.10; P<.001), with a Cohen d of 0.29 (95% CI, 0.1470.43).

In participants without agitation, the functional difference versus placebo was not statistically significant: LS mean difference 2.09 points (95% CI, 20.18 to 4.36; P=.071).

Hostility improved more often with brexpiprazole than placebo over 6 weeks. Among participants who had hostility at baseline, 218/300 (72.7%) on brexpiprazole met the predefined hostility response threshold by Week 6, compared with 105/170 (61.8%) on placebo; the relative risk was 1.18 (95% CI, 1.0371.36; P=.019).

In the long-term brexpiprazole analysis, hostility response was observed in 95/115 participants (82.6%) at Week 32 and 77/85 (90.6%) at Week 58.

Agitation response numerically favored brexpiprazole, but the 6-week difference versus placebo was not statistically significant. Among participants with agitation at baseline, 143/345 (41.4%) on brexpiprazole met the predefined agitation response threshold by Week 6, compared with 68/200 (34.0%) on placebo; the relative risk was 1.21 (95% CI, 0.9571.53; P=.12).

With long-term brexpiprazole treatment, agitation response was observed in 95/146 participants (65.1%) at Week 32 and 86/111 (77.5%) at Week 58.

Yes, in the long-term descriptive analysis, functioning improved and then stabilized over up to 58 weeks of continuous brexpiprazole treatment in participants with and without hostility, and in participants with and without agitation.

The long-term analysis included 408 participants, and 177 (43.4%) completed 58 weeks of brexpiprazole treatment.

The main analysis used a modified version of the Personal and Social Performance scale that removed domain D, the disturbing and aggressive behaviors domain, so functioning was assessed only from socially useful activities, personal and social relationships, and self-care.

This approach was developed for the post hoc analysis because standard PSP scores are partly driven by hostility and agitation behaviors. The standard 4-domain PSP was also analyzed as a sensitivity analysis, and the results were similar to the modified 3-domain PSP findings.

Hostility was defined as a baseline PANSS hostility item (P7) score of 3, which corresponds to mild severity or worse, and hostility response was defined as a shift to a P7 score <3.

Agitation was defined as a baseline PANSS-Excited Component score of 14 plus at least 1 of its 5 items rated 4, and agitation response was defined as a 40% improvement in PANSS-EC.

This was a post hoc pooled analysis of five phase 3 brexpiprazole trials: three 6-week randomized, double-blind, placebo-controlled studies and two open-label extension studies allowing up to 58 weeks of treatment.

The authors describe the analyses as exploratory and hypothesis-generating. They also note that P values were nominal, there was no adjustment for multiple comparisons, and the original trials were not designed specifically to study hostility and agitation symptoms.

The short-term trials enrolled adults aged 1865 years who were inpatients with an acute exacerbation of schizophrenia diagnosed by DSM-IV-TR criteria. Participants had to have responded to antipsychotic treatment in the past and be judged by investigators to benefit from hospitalization or continued hospitalization.

People with a first episode of schizophrenia, other DSM-IV-TR mental health diagnoses, or substance use disorders were excluded. The 6-week analysis sample included 1,385 participants with baseline and postbaseline PANSS data.

• It was a post hoc, exploratory analysis of trials not designed to study hostility and agitation specifically.
• There was no adjustment for multiple comparisons, so the findings need replication in a prespecified analysis.
• People with substance use disorders were excluded, which limits generalizability.
• There was no active comparator.
• Benzodiazepine rescue medication was allowed in the original trials, although not before efficacy assessments.
• Hostility was measured with a single PANSS item rather than a dedicated hostility inventory.
• The modified 3-domain PSP was a novel informal approach that used category midpoints, had reduced variability, and requires further validation.