Pimavanserin may cut symptoms of dementia-related psychosis

Use of the antipsychotic drug pimavanserin led to a substantial reduction in psychosis symptoms in individuals with dementia regardless of severity or subtype, according to the results of the HARMONY trial presented at AAIC 2020.

“Psychosis is a common and extremely disturbing symptom, which has a severe impact on the lives of people affected by dementia,” said co-author Prof Clive Ballard from the University of Exeter Medical School in Devon, UK, in a press release.

The co-occurrence of neuropsychiatric symptoms with neurodegenerative conditions entails an increased caregiver burden, impairs quality of life, and could lead to earlier progression to severe dementia, nursing home care, and death, hence the need for immediate attention. [Am J Psychiatry 2015;172:460-465; J Am Geriatr Soc 2000;48:938-942]

“Current guidelines and real-world practice involve a trial of off-label antipsychotics when other interventions fail, with [individual] assessment of response [and drug tapering] within 4 months in patients who have responded,” noted Ballard and colleagues. However, the sedative effects of the most widely used antipsychotics may trigger physical injuries (eg, falls) in patients with dementia (ie, elderly) and hasten the deterioration of neurologic function, the researchers pointed out.

Pimavanserin, an inverse agonist/antagonist of the 5-HT_2A receptor, has been approved in the US for the treatment of delusions and hallucinations associated with Parkinson’s disease (PD) psychosis. As such, the team sought to evaluate the potential of pimavanserin in dementia-related psychosis.

A relapse-prevention study was conducted among individuals diagnosed with dementia (based on the National Institute on Aging/Alzheimer’s Association criteria) and moderate-to-severe psychosis (presenting with hallucinations and delusions). Participants who failed brief psychosocial therapy at screening (n=392) entered a 12-week open-label phase wherein they were given pimavanserin 34 mg QD. [AAIC 2020, abstract ODO3-06-02]

Sustained response was observed in nearly two-thirds (62 percent) of participants regardless of dementia subtype (60 percent [Alzheimer’s disease], 71 percent [PD dementia], 46 percent [dementia with Lewy bodies], 50 percent [frontotemporal dementia], and 71 percent [vascular dementia]).

“The response rate was similar regardless of age, dementia severity, or previous drug therapy, with >50 percent of patients meeting response criteria at week 4 across most factors,” said the researchers.

The findings add to the growing evidence supporting the potential of pimavanserin in the management of other neurodegenerative diseases (ie, PD and Alzheimer’s disease psychosis). [Lancet 2014;383:533-540; Lancet Neurol 2018;17:213-222; J Prev Alzheimers Dis 2019;6:27-33]

“[Given the lack of approved effective and safe treatments in this setting,] we urgently need treatments that work … [I am] excited by the potential of pimavanserin to make a real difference,” expressed Ballard.