The FDA recently approved pimavanserin (Nuplazid) as the first drug therapy for hallucinations and delusions associated with Parkinson's disease psychosis.
The FDA recently approved pimavanserin (Nuplazid) as the first drug therapy for hallucinations and delusions associated with Parkinson’s disease psychosis, for which it had previously been given priority review and granted breakthrough therapy designation.
Parkinson’s disease psychosis is a serious condition that can occur in up to 50% of patients. According to the National Institutes of Health, about 1 million Americans have Parkinson’s disease, and approximately 50,000 new patients are diagnosed each year.1
Pimavanserin is an atypical antipsychotic speculated to work through a combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors. Although the drug has no contraindications, it does have a black box warning of increased risk of death in elderly patients with dementia-related psychosis. The most common related adverse reactions are peripheral edema and confusional state.2
Pimavanserin was studied in a phase 3, randomized, double-blind, placebo-controlled trial of 199 patients. Eligible patients had to be aged 40 years or older and meet predefined diagnostic criteria for Parkinson’s disease psychosis, such as showing psychotic symptoms for at least 1 month or experiencing symptoms severe enough to warrant treatment with antipsychotics.3
The primary outcome was change in total Parkinson’s disease-adapted scale for assessment of positive symptoms (SAPS-PD) score from baseline to day 43. This measure specifically showed symptoms that occur frequently and are sensitive to change in Parkinson’s disease psychosis. Secondary outcomes included change by day 43 in clinical global impression-severity (CGI-S) and clinical global impression-improvement (CGI-I) scale scores.3
The trial results showed significant improvements in SAPS-PD scores with pimavanserin treatment compared with placebo. Patients who received pimavanserin had a mean change equating to a 37% improvement from baseline, compared with 14% for placebo (p=0·0006). The secondary outcomes showed that patients in the pimavanserin group had greater improvements in investigator-assessed measures of antipsychotic benefit, including CGI-S and CGI-I, compared with placebo.3
Ten patients in the pimavanserin group discontinued therapy because of an adverse event, compared with 2 in the placebo group.3
The study authors concluded that pimavanserin is a viable alternative for the treatment of psychosis in Parkinson’s disease. Previously, the only available option was the off-label use of atypical antipsychotics with unknown efficacy and safety profiles.3
Nuplazid is expected to launch in June 2016.
1. FDA. Nuplazid FDA news release. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm498442.htm. Accessed May 2016.
2. Nuplazid [package insert]. San Diego, CA: ACADIA Pharmaceuticals Inc.; April 2016.
3. Cummings J, Isaacson S, Mills R, et al. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014 Feb 8;383(9916):533-540. doi:10.1016/S0140-6736(13)62106-6.