For the millions of patients with Parkinson disease psychosis, the first agent in a new class of drugs may offer some relief from hallucinations and delusions while easing the challenges that caregivers face.
More than half of the 7 million to 10 million patients with Parkinson disease worldwide have psychosis at some point in their illness. The condition leads to high rates of emergency department visits and nursing home admissions, but safe, effective treatment is lacking.
Data published online today in The Lancet show that pimavanserin, a selective serotonin 5-HT2A inverse agonist, provided significant antipsychotic benefit to 199 patients with Parkinson disease psychosis treated at 54 clinical trial sites in the United States and Canada.
Serotonin 5-HT2A receptors are located in the brain’s neocortex, which is responsible for sensory perceptions, conscious thought, and language. They’re associated with visual hallucinations and delusions. Pimavanserin is an inverse agonist, a type of drug that blocks 5-HT2A receptors more effectively than antagonists.
Patients in the trial randomly received 40 mg of pimavanserin daily or a placebo for 6 weeks. Researchers evaluated their symptoms every 2 weeks with a 9-item scale adapted for Parkinson disease. At day 43 of the study, the primary analysis showed that symptoms improved by 37% in patients who received pimavanserin compared with 14% in the placebo group.
Additional analysis indicated that caregivers for patients taking pimavanserin reported a reduced burden of care compared with the placebo group’s caregivers. Also, patients taking the drug had improved nighttime sleep and daytime wakefulness compared with patients taking a placebo.
In the pimavanserin group, 14% of patients developed urinary tract infections compared with 12% in the placebo group. Falls affected 11% of patients taking the drug compared with 9% who took placebo. Ten patients discontinued pimavanserin because of adverse effects compared with 4 taking a placebo.
The investigators said their study “suggests that pimavanserin is efficacious compared with placebo in Parkinson’s disease psychosis, showing clinically meaningful improvements.”
In an accompanying editorial, Susan Fox, MD, PhD, of the University of Toronto, said further studies will be needed to compare pimavanserin’s efficacy with clozapine and quetiapine, atypical antipsychotic drugs that can worsen motor symptoms and speed up cognitive decline.
But Fox said the study also “opens up a new therapeutic avenue in treatment of Parkinson’s disease psychosis,” and may be useful in treating psychosis in other disorders such as Alzheimer disease.