Psychotropic Medication and Cognitive, Functional, and Neuropsychiatric Outcomes in Alzheimer's Disease (AD)

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BACKGROUND/OBJECTIVES: There are growing concerns about the safety and efficacy of psychotropic medications in Alzheimer's disease (AD). We sought to examine associations between psychotropic medication exposure and longitudinal change in cognitive, functional, and neuropsychiatric outcomes in a large clinical AD cohort. DESIGN: Longitudinal observational study. SETTING: National Alzheimer's Disease Coordinating Center combining data from 39 Alzheimer's disease centers. PARTICIPANTS: 8,034 participants with AD dementia. MEASUREMENTS: Mini-Mental State Exam (MMSE), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), and Neuropsychiatric Inventory Questionnaire (NPI-Q) Total. Probability of exposure to medication (the propensity score, PS) calculated via logistic regression. Medication classes included all antipsychotics (atypical vs conventional), antidepressants (Selective Serotonin Reuptake Inhibitor [SSRI] vs non-SSRI), and benzodiazepines. Participants treated with a medication class were matched with participants not treated with that class with the closest-matched PS. The effect of medication treatment was assessed using linear mixed-effects models. RESULTS: Participants had a mean (SD) age of 75.5 (9.8) years, and mean (SD) scores of MMSE 21.3 (5.7), CDR-SB 5.5 (3.4), and NPI-Q Total 4.5 (4.4). Mean duration of follow-up was 2.9–3.3 years depending on medication class. Non-SSRI antidepressant use was associated with better CDR-SB (2-year difference in change-DIC: −0.38 [−0.61, −0.15], P =.001). Atypical antipsychotic use was associated with greater decline on MMSE (DIC: −0.91 [−1.54, −0.28] P =.005) and CDR-SB scores (DIC: 0.50 [0.14, 0.86], P =.006). Notably, no drug class was associated with better NPI-Q scores. CONCLUSIONS: Use of atypical antipsychotics was associated with poorer cognition and function, and no drug class was associated with improvement in neuropsychiatric symptoms.

Original languageEnglish (US)
Pages (from-to)955-963
Number of pages9
JournalJournal of the American Geriatrics Society
Issue number4
StatePublished - Apr 2021


  • Alzheimer's disease
  • antidepressants
  • antipsychotics
  • benzodiazepines
  • outcomes

ASJC Scopus subject areas

  • Geriatrics and Gerontology


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