‘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’, explains Senior Author, Professor Clive Ballard from King’s College 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 works by blocking serotonin 5-HT2A receptors in the neocortex (the part of the brain responsible for sensory perceptions, conscious thought, and language) 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 centres across the USA and Canada. Participants were randomly assigned to receive 40mg of pimavanserin orally once daily or matching placebo for 6 weeks. A nine-item Parkinson’s disease-adapted scale was used to assess positive symptoms (SAPS-PD) at the start of the study and at regular intervals up to day 43.
The researchers used a brief run-in phase of psychosocial interaction to reduce the common placebo effect noted in Parkinson’s disease clinical trials when treatment starts.
After 43 days, patients taking pimavanserin showed a significant improvement in SADS-PD score (psychotic symptoms) compared with those given placebo (37 per cent improvement vs 14 per cent). Additionally, improvements in night-time sleep, daytime wakefulness, and caregiver burden were also noted compared with placebo. No worsening of motor symptoms was reported in patients given pimavanserin.
Importantly, says Professor Ballard, ‘The clinical benefits of pimavanserin were seen by patients, those caring for them, and independent blinded raters alike.’
Pimavanserin was generally well tolerated, and treatment-related adverse events were mild to moderate and similar between the two groups. The most common were urinary tract infections (12 per cent placebo vs 14 per cent pimavanserin) and falls (9 per cent vs 11 per cent). Ten patients discontinued taking pimavanserin because of an adverse event compared with four in the placebo group.
Based on these results the researchers suggest that pimavanserin also has the potential to be used to treat psychotic symptoms common in Alzheimer’s and other dementias. Professor Ballard added: ‘The results of this study are so promising that we are preparing for a phase II trial with ACADIA Pharmaceuticals to look at the efficacy and safety of pimavanserin for treating psychosis in patients with Alzheimer’s disease. Psychotic symptoms are commonly associated with Parkinson’s disease, Alzheimer’s disease and other neurodegenerative conditions and can cause significant distress to patients and their families and caregivers, so a treatment that can safely and effectively reduce these symptoms has the potential to really improve people’s lives.’
Writing in a linked Lancet Comment, Susan Fox an Associate Professor of Neurology at the University of Toronto in Canada says, ‘Overall this study opens up a new therapeutic avenue in treating Parkinson’s disease psychosis. With a potentially better safety profile, treating Parkinson’s disease patients with mild symptoms may be a potential therapeutic benefit to prevent progression to more bothersome symptoms as well as targeting psychosis in other disorders such as Alzheimer’s disease…Further studies will be required to determine the relative efficacy compared with clozapine and quetiapine.’
Notes to editors
Read the research paper.
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