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PIMAVANSERIN IN ALZHEIMER’S DISEASE PSYCHOSIS: EFFICACY IN PATIENTS WITH MORE PRONOUNCED PSYCHOTIC SYMPTOMS

C. Ballard, J.M. Youakim, B. Coate, S. Stankovic

J Prev Alz Dis 2019;6(1):27-33

Background: Pimavanserin is a 5-HT2A receptor inverse agonist/antagonist and is approved in the United States for the treatment of hallucinations and delusions associated with Parkinson’s disease psychosis. Objective: Evaluate the efficacy of pimavanserin on symptoms of psychosis in patients with Alzheimer’s disease (AD). Design: Randomized, double-blind, placebo-controlled trial Setting: Nursing home residents Participants: Patients with AD psychosis Interventions: Pimavanserin 34 mg or placebo daily for 12 weeks Measurements: The primary endpoint was mean change from baseline at Week 6 on the Neuropsychiatric Inventory-Nursing Home Version psychosis score (NPI-NH-PS). In the prespecified subgroup analysis, the mean change in NPI-NH-PS and the responder rates among those with baseline NPI-NH-PS ≥12 were evaluated. Results: Of 181 patients randomized (n=90 pimavanserin; n=91 placebo), 57 had baseline NPI-NH-PS ≥12 (n=27 pimavanserin; n=30 placebo). In this severe subgroup, large treatment effects were observed (delta=-4.43, Cohen’s d=-0.73, p=0.011), and ≥30% improvement was 88.9% vs. 43.3% (p<0.001) and ≥50% improvement was 77.8% vs. 43.3% (p=0.008) for pimavanserin and placebo, respectively. The rate of adverse events (AEs) in the severe subgroup was similar between treatment groups, and urinary tract infection, fall, and agitation were most frequent. Serious AEs was similar with pimavanserin (17.9%) and placebo (16.7%) with fewer discontinuations due to AEs with pimavanserin (7.1%) compared to placebo (10.0%). Minimal change from baseline occurred for the mean MMSE score over 12 weeks. Conclusions: Pimavanserin demonstrated significant efficacy in AD psychosis in patients with higher baseline severity of psychotic symptoms (NPI-NH-PS ≥12). Treatment with pimavanserin showed an acceptable tolerability profile.

CITATION:
C. Ballard ; J.M. Youakim ; B. Coate ; S. Stankovic (2018): Pimavanserin in Alzheimer’s Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2018.30

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