Psychotropic Polypharmacy in Alzheimer's Disease: A Potentially Inappropriate Medication Perspective in Older Adults

Neuropsychiatric symptoms (NPS) are highly prevalent in Alzheimer's disease (AD). Consequently, potentially inappropriate medication (PIM) use is particularly common among older adults with AD. Psychotropic polypharmacy may increase the risk of various adverse outcomes beyond cognitive decline. Although geriatric prescribing criteria and dementia-care guidelines offer important safety recommendations, a clinically integrated framework for potentially inappropriate psychotropic medication use in older adults with AD remains insufficiently developed. This article is a narrative review rather than a systematic review or meta-analysis. The authors searched the literature in PubMed, Embase, and the Cochrane Library, focusing on studies, guidelines, consensus statements, regulatory safety warnings, and medication-safety criteria published between January 2015 and June 2026. This review specifically examines anticholinergic drugs, antipsychotics, benzodiazepines and Z-drugs, tricyclic antidepressants, and select newer antidepressants-including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine, trazodone, and paroxetine-guided by the 2023 American Geriatrics Society (AGS) Beers Criteria®. Current evidence indicates that these medications may contribute to cognitive decline through anticholinergic burden, sedation, and pharmacodynamic interactions with cholinesterase inhibitors, such as donepezil and memantine. However, the strength of evidence varies considerably across drug classes and study designs, ranging from randomized controlled trials to observational studies and expert consensus. This study also summarizes current nonpharmacological strategies and proposes a structured clinical medication review framework. Overall, this review highlights the importance of minimizing inappropriate psychotropic use in AD, prioritizing non-pharmacological interventions, and conducting individualized risk-benefit assessments in clinical practice.