Mechanistic Complications With Atypical Antipsychotics for Parkinson Disease Psychosis: Dilesh Doshi, PharmD


The vice president of Health Economics and Outcomes Research at Acadia Pharmaceuticals provided perspective on the mechanistic advantages of pimavanserin over atypical antipsychotics to treat Parkinson disease psychosis. [WATCH TIME: 2 minutes]

WATCH TIME: 2 minutes

"Unlike pimavanserin, these antipsychotics that are used off-label work by blocking the dopamine receptor as well as serotonin receptor."

Psychosis is common in Parkinson disease (PD), with an overall prevalence ranging from 26% to 60%, depending on which symptoms are included. Prior to the FDA approval of pimavanserin (Nuplazid; Acadia Pharmaceuticals) in 2016, PD psychosis was typically managed through other atypical antipsychotic medications. These off-label therapeutics can result in worsened motor symptoms, cognitive decline, metabolic disturbance, and in the case of clozapine, need for specialized monitoring of absolute neurotrophil counts.

Earlier this year, a systematic review and network meta-analysis was published assessing the efficacy, safety, and acceptability of pimavanserin vs other atypical antipsychotics such as quetiapine, olanzapine, clozapine, ziprasidone, and risperidone. Across 19 studies, using Clinical Global Impression Scale for Severity, pimavanserin (standardized mean differences, –4.81; 95% CI, –5.39 to –4.24) and clozapine (SMD, –4.25; 95% CI, –5.24 to –3.26) significantly improved symptoms relative to placebo. Notably, quetiapine was associated with a significant decline in cognition without affecting motor function.

Following the analysis, NeurologyLive® sat down with Dilesh Doshi, PharmD, vice president of Health Economics and Outcomes Research at Acadia Pharmaceuticals, to discuss the significance of the findings. Doshi talked specifically on the mechanisms of action of these therapies, and why pimavanserin offers patients with PD psychosis greater advantages.

1. Yunusa I, Rashid N, Rajagopalan K, et al. Comparative efficacy, safety, and acceptability of pimavanserin and other atypical antipsychotics for Parkinson’s disease psychosis: systematic review and network meta-analysis. J Geriatr Psychiatry Neurol. Published online January 31, 2023. doi:10.1177/08919887231154933
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