Brexpiprazole Reduces Agitation in Patients With Dementia Due to Alzheimer Disease

Treatment with brexpiprazole led to a significant improvement in agitation for patients with dementia due to Alzheimer disease, according to results from a randomized clinical trial published in JAMA Neurology. The findings support the US Food and Drug Administration approval of brexpiprazole for this indication.

In total, 345 patients were randomized to brexpiprazole, 2 or 3 mg, daily (n=228) or placebo (n=117). Completion rates at 12 weeks were 86.8% and 88.9% for brexpiprazole and placebo, respectively. The primary end point was change in the Cohen-Mansfield Agitation Inventory (CMAI) total score from baseline to week 12. The secondary end point was change in the Clinical Global Impression Severity of Illness (CGI-S) and Improvement (CGI-I) scales, specifically applied to agitation, and the Neuropsychiatric Inventory–Nursing Home (NPI-NH) Agitation/Aggression domain score.

Overall, the group receiving brexpiprazole demonstrated a statistically significant improvement in CMAI scores compared with the placebo group. Baseline scores were 80.6 in the brexpiprazole arm and 79.2 in the placebo arm, with a mean change of –22.6 and –17.3, respectively (least-squares mean difference, −5.32; 95% CI, −8.77 to −1.87; P=.003). “CMAI total score changes indicated an overall reduction in the frequency of agitated behaviors,” the authors explained.

Changes in the CGI-S score were also significantly greater in the brexpiprazole group at week 12 (least-squares mean difference, –0.27; 95% CI, –0.47 to –0.07; P=.008). The intervention group also showed nominally significant greater improvement in NPI-NH total scores (P=.001). “At the individual patient level, responder analyses … suggested that brexpiprazole treatment may be clinically meaningful,” the authors noted. “A greater proportion of patients receiving brexpiprazole than placebo achieved a CGI-I score of 1, very much improved, or 2, much improved (52.4% vs 40.5%), which are widely regarded as clinically meaningful outcomes.”

Regarding safety outcomes, 92 patients (40.7%) reported a treatment-emergent adverse event (TEAE) related to brexpiprazole, compared with 31.0% of the placebo group. Headache was the only brexpiprazole-related TEAE with an incidence rate of 5.0% or greater (6.6%). The majority of TEAEs were mild or moderate in severity. One patient in the intervention group died of cardiac failure during the study period after withdrawing from the trial after 28 days due to the adverse event of hallucinations. They also had serious adverse events (pneumonia and cachexia). The death was considered unrelated to brexpiprazole. No patients reported TEAEs of suicidal ideation or behavior during the study.

“In this 12-week clinical trial, brexpiprazole, 2 or 3 mg, showed a statistically significant improvement [versus] placebo on agitation in patients with Alzheimer dementia. Brexpiprazole was generally well tolerated over 12 weeks in this vulnerable patient population,” the authors summarized. “Overall, brexpiprazole, 2 or 3 mg, appears to have a favorable benefit/risk profile in the treatment of agitation in Alzheimer dementia.”