1. Pimavanserin was shown to lead to a lower risk of relapse of psychosis in patients who had an initial response to pimavanserin for dementia-related psychosis.
2. The trial was stopped early for efficacy.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Dementia-related psychosis results in behavioral disturbances, decreased quality of life, and more rapid cognitive decline. Typical and atypical antipsychotics have been used to manage the psychosis symptoms; however, side effects such as worsening parkinsonism, extrapyramidal side effects, and metabolic abnormalities minimize their use. Pimavanserin, a serotonin-receptor modulator, has been effective in reducing psychotic symptoms in patients with Alzheimer’s disease. As such, this study determined the safety and efficacy of pimavanserin in the treatment of delusions and hallucinations associated with common forms of dementia. The study was designed as a discontinuation trial to determine whether pimavanserin treatment could confer sustained benefits. The study determined pimavanserin led to a lower risk of relapse in patients with an initial response to the therapy. Additionally, adverse effects attributed to pimavanserin included urinary tract infection, asymptomatic QT prolongation, and headache. The randomized control trial was limited by a short study period since the study was stopped early due to efficacy. Nonetheless, this study’s results are significant, and its findings highlight an alternative medication that can be used to treat psychotic symptoms in patients with dementia.
In-Depth [randomized controlled trial]: This randomized control trial study enrolled 392 participants across 101 clinical sites in North America, Europe, and South America. Participants included in the study were between 50 to 90 years of age and met clinical criteria for at least one of the following: Parkinson’s disease dementia, dementia with Lewy bodies, Alzheimer’s disease, frontotemporal dementia, or vascular dementia. Participants who received antipsychotics within two weeks of enrollment were excluded from this study. For the double-blind phase study, the participants were randomized in a 1:1 ratio to receive pimavanserin or placebo, respectively for 26 weeks. The primary endpoint was the time from randomization to relapse. The frequency of relapse was 13% in the pimavanserin group compared to 28% in the control group (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17 to 0.73; P = 0.005). Since the significance level for the Cox regression analysis was below 0.0066 – the prespecified stopping boundary – the study was stopped. Between the open-label phase and double-blind phase studies, a total of five participants had a prolonged QT interval as an adverse event (open-label phase, 0.5% [2 participants]; double-blind trial, 2.9% [3 participants]). Taken together, discontinuation of pimavanserin led to a higher rate of relapse than continuing the treatment in patients for psychosis related to several types of neurodegenerative disease.
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