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Background <p>Agitation affects up to 80% of individuals with dementia and is particularly common among nursing home residents. Second-generation antipsychotics (SGAs) are frequently used to manage agitation but are associated with serious safety risks. Selective serotonin reuptake inhibitors (SSRIs) have been proposed as safer alternatives, though real-world comparative evidence is limited.</p> Objective <p>To compare the real-world effectiveness of SSRIs versus SGAs for agitation among nursing home residents with dementia.</p> Design <p>National active comparator new user cohort study.</p> Participants <p>Long-stay US nursing home residents aged ≥ 65&#xa0;years with dementia and agitation who newly initiated an SSRI or SGA from 2011 to 2018, based on Medicare claims and the Minimum Data Sets 3.0.</p> Main Measures <p>Outcomes included change in Agitated and Reactive Behavior Scale score (continuous; range 0–12, higher = worse) and achieving minimal clinically important improvement (binary; ≥ 1-point decline) from baseline to 60–120&#xa0;days. Weighted linear models incorporating overlap propensity score and inverse probability of censoring weights within generalized estimating equation&#xa0;models estimated adjusted treatment effects in intention-to-treat and as-treated analyses.</p> Key Results <p>Among 19,508 SSRI and 21,541 SGA new users, baseline characteristics were well balanced after weighting. In as-treated analyses, SSRI new users experienced greater mean reductions in Agitated and Reactive Behavior Scale score (difference: − 0.14 [95% CI, − 0.19 to − 0.09]) and a higher probability of achieving minimal improvement (difference: 3.6% [95% CI, 2.7 to 4.6]) compared with SGA new users. These differences were most pronounced among residents with mild-to-moderate agitation and mild-to-moderate cognitive impairment.</p> Conclusion <p>Initiation of SSRIs was associated with modest improvements in agitation compared with SGAs among US nursing home residents with dementia. These findings support SSRIs as potential pharmacologic alternatives to antipsychotics and provide real-world evidence relevant to dementia care, particularly given FDA black box warnings for antipsychotics.</p>

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Comparative Effectiveness of Antidepressants and Second-Generation Antipsychotics for Agitation Among Nursing Home Residents with Dementia

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Shiwei Liang,
  • Kate L. Lapane,
  • Brian R. Ott,
  • Jennifer Tjia,
  • Jonggyu Baek,
  • Yiyang Yuan,
  • Matthew Alcusky

摘要

Background

Agitation affects up to 80% of individuals with dementia and is particularly common among nursing home residents. Second-generation antipsychotics (SGAs) are frequently used to manage agitation but are associated with serious safety risks. Selective serotonin reuptake inhibitors (SSRIs) have been proposed as safer alternatives, though real-world comparative evidence is limited.

Objective

To compare the real-world effectiveness of SSRIs versus SGAs for agitation among nursing home residents with dementia.

Design

National active comparator new user cohort study.

Participants

Long-stay US nursing home residents aged ≥ 65 years with dementia and agitation who newly initiated an SSRI or SGA from 2011 to 2018, based on Medicare claims and the Minimum Data Sets 3.0.

Main Measures

Outcomes included change in Agitated and Reactive Behavior Scale score (continuous; range 0–12, higher = worse) and achieving minimal clinically important improvement (binary; ≥ 1-point decline) from baseline to 60–120 days. Weighted linear models incorporating overlap propensity score and inverse probability of censoring weights within generalized estimating equation models estimated adjusted treatment effects in intention-to-treat and as-treated analyses.

Key Results

Among 19,508 SSRI and 21,541 SGA new users, baseline characteristics were well balanced after weighting. In as-treated analyses, SSRI new users experienced greater mean reductions in Agitated and Reactive Behavior Scale score (difference: − 0.14 [95% CI, − 0.19 to − 0.09]) and a higher probability of achieving minimal improvement (difference: 3.6% [95% CI, 2.7 to 4.6]) compared with SGA new users. These differences were most pronounced among residents with mild-to-moderate agitation and mild-to-moderate cognitive impairment.

Conclusion

Initiation of SSRIs was associated with modest improvements in agitation compared with SGAs among US nursing home residents with dementia. These findings support SSRIs as potential pharmacologic alternatives to antipsychotics and provide real-world evidence relevant to dementia care, particularly given FDA black box warnings for antipsychotics.