OBJECTIVES : Acetylcholinesterase inhibitors (AChEIs) offer modest effect size for managing dementia symptoms; this may lead to exacerbation including behavioral and psychological symptoms of dementia (BPSD) thereby necessitating treatment with antipsychotics. This study evaluated the extent of prescribing cascade involving AChEIs and antipsychotics in older dementia patients.

METHODS : Using 2005-2018 TriNetX Electronic Medical Records (EMR), a nested case-control study was conducted in a cohort of AChEI users. The base cohort included patients aged ≥ 65 years with dementia, no use of AChEIs and antipsychotics between January – June 2005. Cases were those who initiated treatment with antipsychotics between July 2005 – December 2018. Incidence density sampling was used to match each case with 4 controls based on age and sex. Date of the first antipsychotic prescription formed the event date for cases. Primary exposure was incident prescription of AChEIs within 6 months before the event date. Conditional logistic regression model was used to evaluate the association between AChEI use and antipsychotic prescribing cascade after controlling for other risk factors.

RESULTS : There were 16,413 cases and 65,609 matched controls. Cases were significantly more likely than controls to have incident AChEI exposure within 6 months preceding the event date (7.39% vs 0.43 %; p-value <.0001). Multivariable analyses revealed that incident AChEI exposure was significantly associated with higher odds of antipsychotic prescribing cascade, compared to non-use (OR =69.74; 95% CI, 54.48 - 89.28). Depression (OR =1.13; 95% CI, 1.08 -1.18), falls (OR =1.23; 95% CI, 1.15- 1.30), psychoses (OR =2.88; 95% CI, 2.66 -3.12), fluid and electrolyte disorders (OR =1.25; 95% CI, 1.19 - 1.31) and other neurological disorders (OR =1.08; 95% CI, 1.01- 1.16) were significantly associated with antipsychotic cascade.

CONCLUSIONS : The finding of strong association between AChEI initiation and antipsychotic cascade suggests the need to focus on studying the impact of these cascades in the vulnerable dementia patients.