Systematic Reviews
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Jul 19, 2020; 10(7): 162-174
Published online Jul 19, 2020. doi: 10.5498/wjp.v10.i7.162
Pimavanserin for the treatment of psychosis in Alzheimer’s disease: A literature review
Shilpa Srinivasan, Rajesh R Tampi, Kripa Balaram, Arushi Kapoor
Shilpa Srinivasan, Department of Neuropsychiatry and Behavioral Science, Palmetto Health USC Medical Group, University of South Carolina School of Medicine, Columbia, SC 29203, United States
Rajesh R Tampi, Department of Psychiatry and Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH 44307, United States
Rajesh R Tampi, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, United States
Kripa Balaram, MD, Department of Psychiatry, MetroHealth, Cleveland, OH 44109, United States
Arushi Kapoor, Penn Memory Center at the Penn Neuroscience Center, Perelman Center for Advanced Medicine, Philadelphia, PA 19104, United States
Author contributions: All authors contributed to this work.
Conflict-of-interest statement: All the authors declare that they have no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Shilpa Srinivasan, MD, Doctor, Professor, Department of Neuropsychiatry and Behavioral Science, Palmetto Health USC Medical Group, University of South Carolina School of Medicine, 3555 Harden Street Extension, Suite 301, Columbia, SC 29203, United States.
Received: February 13, 2020
Peer-review started: February 13, 2020
First decision: April 3, 2020
Revised: May 25, 2020
Accepted: June 10, 2020
Article in press: June 10, 2020
Published online: July 19, 2020

Alzheimer’s disease (AD) is among the most prevalent forms of dementia in the world and neuropathological studies suggest similar high prevalence of mixed (AD + vascular) dementias. Approximately 25%-50% of individuals with AD develop psychosis sometime during their illness. The presence of psychosis in AD worsens outcomes. Currently there are no United States Food and Drug Administration (FDA) approved medications for the treatment of psychosis in AD. Pimavanserin, a novel atypical antipsychotic medication, was approved by the FDA for the treatment of hallucinations and delusions associated with Parkinson disease psychosis and is currently in clinical trials for the treatment of psychosis in AD.


To evaluate the existing literature regarding the use of pimavanserin for treating psychosis among individuals with AD.


A literature review of clinical studies of pimavanserin treatment for psychosis in individuals with AD was performed using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Trials were identified by systematically searching PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2019. The 5-point Jadad scoring system was used to assess the methodologic quality of the randomized placebo-controlled trials.


A total of 499 citations were retrieved and pooled in EndNote and de-duplicated to 258 citations. This set was uploaded to Covidence for screening. Two separate screeners (Srinivasan S and Tampi RR) evaluated the titles, abstracts, and full text of eligible articles. Of the identified 258 abstracts, 98 articles underwent full text review and 2 publications from 1 randomized controlled trial (RCT) were included in the final analysis. The quality of evidence was assessed to be of good methodologic quality, scoring 4 out of 5 using the 5-point Jadad questionnaire with the Jadad Scoring calculation. This systematic review found only one RCT that evaluated the use of pimavanserin for the treatment of psychosis among individuals with AD. This phase 2 trial resulted in two publications, the second of which was a subgroup analysis from the original study. The evidence from these two publications showed that pimavanserin improves psychotic symptoms among individuals with AD when compared to placebo at week 6.


Pimavanserin may be a pharmacologic consideration for the treatment for psychosis in AD. Additional RCTs are needed to assess the evidence of effectiveness before pimavanserin is considered a standard treatment.

Keywords: Pimavanserin, Alzheimer’s disease, Psychosis, Psychotic disorders, Antipsychotic agents

Core tip: This systematic review was conducted to evaluate the evidence from randomized controlled clinical trials of pimavanserin for the treatment of psychosis in individuals with Alzheimer’s disease (AD). Behavioral disturbances including psychosis are prevalent in AD, and have a significant impact on management and outcomes. There are currently no United States Food and Drug Administration approved medications for the management of behavioral disturbance in AD. Based on the findings of our systematic review, pimavanserin, a novel atypical antipsychotic, may be a new pharmacologic consideration for treating psychosis in individuals with AD.