Pimavanserin Effective for Dementia-Related Psychosis 

As published in The New England Journal of Medicine, pimavanserin (Acadia Pharmaceuticals; San Diego, CA) treatment made relapse of dementia related psychosis (DRP) almost 3 times less likely. Results of the phase 3 HARMONY study (NCT03325556) of pimavanserin for DRP were so clearly showed efficacy that the trial was stopped early so that all participants could receive treatment. 

In this trial, all individuals were treated with pimavanserin 34 mg/day for a 12-week stabilization phase. After this phase, participants who responded to pimavanserin (61.8%; 217/351) were randomly assigned to have it continued or substituted with placebo. Among those who had pimavanserin continued, the hazard ratio (HR) for DRP relapse was 0.35 (2-sided P=.005, 1-sided P=.002) compared with those who had placebo substituted. Individuals who had continuation of pimavanserin were more than twice as likely to remain in the study (HR=0.45, 2-sided P=.005; 1-sided P=.002). 

Hallucinations and delusions are among the most difficult to manage symptoms in late-stage dementias, including Alzheimer disease, dementia with Lewy bodies, Parkinson disease dementia, frontotemporal dementia, and vascular dementia. There are no currently approved treatments for psychotic symptoms in dementia, which are often among the reasons for referral to long-term care facilities. For patients and caregivers alike, this marks a potentially substantial improvement in quality of life. 

“This landmark trial showed that when patients responded to pimavanserin and then continued treatment, they were almost 3 times less likely to develop recurrence of their hallucinations and delusions than those patients who discontinued pimavanserin treatment,” said Pierre N. Tariot, MD, director, Banner Alzheimer’s Institute. “This is a substantial finding and a significant advance for a critical public health need in our field. There is no FDA-approved treatment for DRP, and the majority of antipsychotics currently used off-label have equivocal efficacy and may accelerate cognitive decline.”

Unlike the drugs that are often used off label for DRP, pimavanserin had no effect on participants cognitive function as measured by Mini-Mental State Examination (MMSE). No onset or worsening of motor symptoms as measured by Extrapyramidal Symptom Rating Scale A (ESRS-A) was seen. Adverse events with pimavanserin included headache, urinary tract infection, constipation, and asymptomatic QT prolongation. The rate of adverse events was 41% (43/105) in the pimavanserin group and 37% (41/112) of the placebo group.

Participants enrolled in the study had ADD, DLB, PDD, FTD or vascular dementia. Participants were mean age 74.5 years with mean MMSE score 16.7.