Literature Review Underscores the Need for Appropriate Treatments for Dementia-Related Psychosis

There currently are no FDA-approved treatments for dementia-related psychosis; however, antipsychotics are often used to treat its symptoms. Atypical antipsychotics (AAPs) have significant safety risks, including Boxed Warnings about increased risk of mortality in older patients with dementia.

A systematic literature review presented at the 13th Clinical Trials on Alzheimer’s Disease Congress 2020 suggested that currently used AAPs may confer only marginal benefits in treating hallucinations and delusions but carry a high risk of significant adverse events (AEs), accelerated cognitive decline, and potentially higher mortality among patients with dementia-related psychosis.

Researchers combed PubMed/Medline, PsycInfo, Embase, Cochrane central register of controlled trials, and conference proceedings from Jan. 2000 to April 2020, as well as reference lists from selected publications for English-language articles. Studies of interest reported on psychosis among patients with dementia (aged ≥40 years, those living at home or nursing home, gender, ethnicity) with Alzheimer’s disease (AD), frontotemporal dementia, vascular dementia (VaD), dementia with Lewy bodies (DLB), and Parkinson’s disease (PD) dementia. Double-blind, active-comparator, or placebo-controlled randomized, controlled trials (RCTs), open-label trials, and observational studies were included.

A total of 61 publications were selected, encompassing a total of 43 blinded RCTs, 16 open-label trials, and two observational studies, with a study duration ranging from four to 52 weeks (average, 12 weeks). Of these, 23 articles were from studies in the United States, 32 were conducted in institutionalized settings (e.g., nursing home or long-term care facilities), and 59 included patients with dementia, mostly of AD type, while two studies had PD dementia-related psychosis as their primary inclusion criteria. Of the 49 parallel group studies, 26 were placebo-controlled studies, and 23 had active controls.

There were 31 trials of risperidone, 16 of quetiapine, 15 of olanzapine, three of aripiprazole, and one study each of ziprasidone, tiapride, and brexpiprazole. A total of 15,419 patients were included in the studies, with a mean age of 80 years (range, 66-87 years); approximately 67% were female.

The review showed that risperidone, olanzapine, quetiapine, and aripiprazole demonstrated modest psychotic symptom improvements among patients with dementia-related psychosis, while risperidone was reported to have consistent symptom improvements. Both quetiapine and aripiprazole had mixed results, and lower-dose olanzapine showed greater symptom improvements than higher doses.

Somnolence was the most common AE associated with the major antipsychotics, with weight gain and tardive dyskinesia being more commonly reported for olanzapine and risperidone, respectively. Other AEs reported for all AAPs were falls and extrapyramidal signs, although these did not occur with brexpiprazole.

Studies also show that these antipsychotics may be associated with greater cognitive declines and potentially increased mortality in patients. Compared with placebo, odds of all-cause discontinuations were lower with aripiprazole, while olanzapine, quetiapine, risperidone, and brexpiprazole resulted in no differences. Aripiprazole and olanzapine had lower discontinuation rates due to lack of efficacy; olanzapine had higher discontinuation rates due to safety concerns.

The study is limited by heterogeneity and potential bias.

These results underscore the need for new treatment options with a favorable benefit-risk profile for the treatment of dementia-related psychosis,” the researchers concluded.

Presentation: P071: Comparative efficacy, safety, tolerability, and effectiveness of antipsychotics in the treatment of dementia related psychosis (DRP): A systematic literature review. Presented at the 13th Clinical Trials on Alzheimer’s Disease Congress 2020, Nov. 4-7, 2020.