November 13, 2013
New Drug Shows Promise in Treating Parkinson’s Psychosis

London—A new drug is showing promise in treating psychosis in Parkinson’s disease, a condition that affects about half of the 10 million patients suffering the degenerative disease worldwide.

Published online by The Lancet, the industry-funded phase 3 randomized trial assessed the safety and efficacy of pimavanserin, a new nondopaminergic drug for the treatment of psychotic symptoms.

Nearly 200 Parkinson’s disease psychosis patients were randomly allocated to receive pimavanserin or matching placebo, and those patients taking pimavanserin showed improvement in SADS-PD score—a nine-item Parkinson’s disease–adapted scale—compared with those given placebo after 43 days, according to the study funded by Acadia Pharmaceuticals.

“Psychotic symptoms are common and distressing for people with Parkinson’s and those caring for them. Psychosis is a major driving factor for people with Parkinson's disease being admitted to nursing homes and substantially increases the risk of dying. But no safe and effective drug therapies exist,” explained study leader Professor Clive Ballard from King’s College in London. “Currently, the only treatment options are dopamine antagonist antipsychotic drugs such as clozapine and quetiapine which worsen motor symptoms, speed up cognitive decline, increase the risk of stroke, and can be life-threatening even with short-term use.”

Pimavanserin blocks serotonin 5-HT2A receptors in the neocortex that are associated with visual hallucinations and delusions.

In this study, Ballard and colleagues recruited 199 patients with Parkinson’s disease psychosis, aged 40 years or older, from 54 centers across the United States and Canada. Participants were randomly assigned to receive 40 mg of pimavanserin orally once daily or matching placebo for 6 weeks. The SAPS-PD assessment was used to assess positive symptoms of psychosis at the start of the study and at regular intervals up to Day 43.

After 43 days, patients taking pimavanserin showed a significant, 37%, improvement in SADS-PD score compared with those given placebo, 14%. The pimavanserin users also demonstrated improvement in nighttime sleep, daytime wakefulness, and caregiver burden without worsening of motor symptoms, compared with placebo.

Ballard pointed out that “the clinical benefits of pimavanserin were seen by patients, those caring for them, and independent blinded raters alike.”

The study found that pimavanserin was generally well tolerated, with treatment-related adverse events mild to moderate and similar between the two groups. The most common were urinary tract infections (12% placebo vs. 14% pimavanserin) and falls (9% placebo vs. 11% pimavanserin). Overall, 10 patients discontinued taking pimavanserin because of an adverse event compared with four in the placebo group.

Researchers suggested that, based on these results, pimavanserin could be beneficial in treating Alzheimer’s and other dementias.

Writing in a linked comment, Susan Fox, MD, PhD, an associate professor of neurology at the University of Toronto in Canada, suggests, “Further studies will be needed to determine relative efficacy of pimavanserin and clozapine or quetiapine… [but] Overall, the study opens up a new therapeutic avenue in treatment of Parkinson’s disease psychosis. With a potentially improved safety profile, pimavanserin might be useful for treatment of patients with Parkinson’s disease and mild symptoms of psychosis and help prevent progression to more bothersome symptoms as well as targeting psychosis in other disorders such as Alzheimer’s disease.”

U.S. Pharmacist Social Connect