Pimavanserin for the treatment of psychosis in Alzheimer’s disease: A literature review

Background 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. Aim To evaluate the existing literature regarding the use of pimavanserin for treating psychosis among individuals with AD. Methods 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. Results 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. Conclusion 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.