Dementia-Related Psychosis and Off-Label Use of Atypical Antipsychotics

different pills
different pills
With atypical antipsychotics (AAPs) being prescribed off-label for treating dementia-related psychosis, the study authors evaluated the comparative efficacy, safety, and effectiveness of AAPS by conducting a network meta-analysis.

The following article is a part of conference coverage from the American Psychiatric Association Annual Meeting 2021, held virtually from May 1 to 3, 2021. The team at Psychiatry Advisor will be reporting on the latest news and research conducted by leading experts in psychiatry. Check back for more from the APA 2021.


A recent network meta-analysis showed no improvement in dementia-related psychosis (DRP) with quetiapine and limited, nonsignificant improvement with olanzapine and aripiprazole, which also confer considerable risk for adverse events and increased mortality, according to results presented at the American Psychiatric Association annual meeting, held virtually from May 1 to May 3, 2021.

Characterized by delusions and hallucinations, DRP can increase dementia’s debilitating effects. Presenters conducted a network meta-analysis that evaluated the comparative safety, effectiveness, and efficacy of off-label atypical antipsychotics (AAPs) commonly used to treat patients with DRP. Pooled data from 22 observational studies and clinical trials found via a systematic literature review of studies of DRP treated with AAPs (aripiprazole, brexpiprazole, olanzapine, quetiapine, and risperidone) were analyzed.

Outcomes included efficacy based on neuropsychiatric inventory-nursing home version (NPI-NH psychosis subscale effectiveness (all-cause discontinuations, lack of efficacy, and adverse events [AEs]), and safety (mortality, cerebrovascular events [CVAEs], and others [falls, fractures, injuries, somnolence, etc.]).

When compared with placebo, a small, numerical improvement in DRP symptoms was seen with aripiprazole (standardized mean differences [SMD] -0.12; 95% CI, -0.31 to 0.06) and olanzapine (SMD -0.17; 95% CI, -0.04 to 0.02; 5 studies; n=1891), while psychosis was not improved with use of quetiapine (SMD 0.04; 95% CI, -0.23 to 0.32). Compared with placebo, significantly lower odds of all-cause discontinuation were shown by aripiprazole (SMD 0.71; 95% CI, 0.51-0.98; 20 studies; n=5744), and significantly lower odds of discontinuation due to lack of efficacy were seen with aripiprazole (SMD 0.5; 95% CI, 0.31-0.82) and olanzapine (SMD 0.48; 95% CI, 0.31-0.74; 12 studies; n=4382), while results for risperidone and quetiapine were not significant.

Odds of discontinuation due to AEs (19 studies, n=5445) were higher for olanzapine (SMD 2.62; 95% CI, 1.75-3.92), brexpiprazole (SMD 1.80; 95% CI, 0.80-4.07), quetiapine (SMD 1.25; 95% CI, 0.82-1.91), aripiprazole (SMD 1.38; 95% CI, 0.90-2.13), and risperidone (SMD 1.41; 95% CI, 1.02-1.94). Furthermore, compared with placebo, risperidone (SMD 3.68; 95% CI, 1.68-8.95) and olanzapine (SMD 4.47; 95% CI, 1.36-14.69) demonstrated significantly greater odds of CVAEs, and the odds of mortality (15 studies, n=4989) were higher for aripiprazole (SMD 1.58; 95% CI, 0.62-4.04), brexpiprazole (SMD 2.22; 95% CI, 0.30-16.56), olanzapine (SMD 2.21; 95% CI, 0.84-5.85), quetiapine (SMD 1.68; 95% CI, 0.70-4.03), and risperidone (SMD 1.63; 95% CI, 0.93-2.85). Similar patterns were observed between medications for other safety outcomes.

“Overall, the results demonstrate that quetiapine exhibited no DRP [dementia-related psychosis] symptom improvement, while olanzapine and aripiprazole have limited, nonsignificant improvements. These off-label AAPs had greater odds of mortality, CVAEs, and discontinuations due to adverse events,” the study investigators concluded. They also indicated there is an unmet need for safer and efficacious treatment options in patients with DRP.

Visit Psychiatry Advisor’s meetings section for complete coverage of APA 2021.


Yunusa I, Rashid N, Demos G, Abler V, Rajagopalan K. Comparative effectiveness of commonly used off-label atypical antipsychotics in the treatment of dementia-related psychosis: a network meta-analysis. Presented at: APA 2021; May 1-3, 2021. Abstract/Poster 5464.