A Post Hoc Analysis Evaluating the Impact of a Reduction in Psychosis on the Severity of Agitation and Aggression in Patients With Alzheimer’s Disease

This post hoc analysis evaluates whether improvement in hallucinations and delusions during pimavanserin (PIM) treatment among Alzheimer’s dementia (AD) patients with psychosis leads to improvement in symptoms of agitation and aggression. This was a 12 week, randomized, double-blind, placebo-controlled efficacy and safety study (NCT02035553) to assess the severity of hallucinations and delusions in patients with AD psychosis during treatment with PIM 34 mg/day or placebo. The primary endpoint was the change from Baseline to the 6-week Efficacy-Phase endpoint in the Neuropsychiatric Inventory–Nursing Home Version Psychosis Score (NPI-NH-PS) [Domain A (delusions) plus Domain B (hallucinations)]. Agitation/aggression severity was measured from NPI-NH Domain C (NPI-NH-C, agitation/aggression) and Cohen-Mansfield Agitation Inventory Short Form (CMAI-SF) scores. Treatment-group differences in 6-week changes in agitation/aggression were not significantly different between PIM (n=87) and placebo (n=91) (CMAI-SF: P=0.8031; NPI-NH-C: P=0.254). However, patients responsive to PIM (≥30% reduction in 6-week NPI-NH-PS, n=48) showed greater reductions than nonresponders (n=28) on both NPI-NH-C (–2.75, P=0.0021) and CMAI-SF (–3.74, P=0.0550). Defining responses as ≥50% reduction in NPI-NH-PS at Week 6 led to greater differences in improvement of agitation/aggression between responders (n=44) and nonresponders (n=32) (NPI-NH-C: –3.64, P < .0001; CMAI-SF: –3.714, P=0.0483). Likewise, among patients with baseline agitation/aggression (NPI-NH-C ≥6) PIM responders showed significantly greater improvement in agitation/aggression on the NPI-NH-C than nonresponders. In this post-hoc analysis, AD patients whose hallucinations and delusions responded to PIM experienced improvement in symptoms of agitation and aggression. These results suggest an association between reductions of hallucinations/delusions and agitation/aggression in AD patients with psychosis.

This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.