抗うつ薬が認知症患者の認知機能低下を加速 (Antidepressants linked to faster cognitive decline in dementia)

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2025-02-25 カロリンスカ研究所(KI)

カロリンスカ研究所とサールグレンスカ大学病院の研究者たちは、抗うつ薬が認知症患者の認知機能低下を加速させる可能性があることを示す新たな研究結果を発表しました。この観察研究では、スウェーデン認知症登録(SveDem)のデータを用いて、18,740人の患者を対象に分析が行われ、そのうち約23%が抗うつ薬を処方されていました。研究の結果、抗うつ薬を使用している患者は、使用していない患者と比較して、認知機能の低下がより速く進行することが明らかになりました。特に、選択的セロトニン再取り込み阻害薬(SSRI)のエスシタロプラムが最も速い認知機能低下と関連しており、次いでシタロプラムやセルトラリンが続きました。一方、異なる作用機序を持つミルタザピンは、エスシタロプラムよりも認知機能への悪影響が少ないことが示されました。研究者たちは、特定の認知症タイプやバイオマーカーを持つ患者が、異なる抗うつ薬に対してより良い、または悪い反応を示すかどうかを今後調査する予定です。

<関連情報>

認知症患者における抗うつ薬の使用と認知機能の低下:全国コホート研究 Antidepressant use and cognitive decline in patients with dementia: a national cohort study

Minjia Mo,Tamar Abzhandadze,Minh Tuan Hoang,Simona Sacuiu,Pol Grau Jurado,Joana B. Pereira,Luana Naia,Julianna Kele,Silvia Maioli,Hong Xu,Maria Eriksdotter & Sara Garcia-Ptacek
BMC Medicine  Published:25 February 2025
DOI:https://doi.org/10.1186/s12916-025-03851-3

抗うつ薬が認知症患者の認知機能低下を加速 (Antidepressants linked to faster cognitive decline in dementia)

Abstract

Background
Dementia is associated with psychiatric symptoms but the effects of antidepressants on cognitive function in dementia are understudied. We aimed to investigate the association between antidepressants and cognitive decline in patients with dementia, and the risk of severe dementia, fractures and death, depending on antidepressant class, drug, and dose.

Methods
This is a national cohort study. Patients with dementia registered in the Swedish Registry for Cognitive/Dementia Disorders-SveDem from May 1, 2007, until October 16, 2018, with at least one follow-up after dementia diagnosis, and who were new users of antidepressants, were included. Antidepressant use as a time varying exposure defined during the 6 months leading up to dementia diagnosis or each subsequent follow-up. We used linear mixed models to examine the association between antidepressant use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores. We used Cox proportional hazards models to calculate the hazard ratios for severe dementia (MMSE score < 10), fracture, and death. We compared antidepressant classes and drugs, and analyzed dose–response.

Results
We included 18740 patients (10 205 women [54.5%]; mean [SD] age, 78.2[7.4] years), of which 4271 (22.8%) received at least one prescription for an antidepressant. During follow-up, a total of 11912 prescriptions for antidepressants were issued, with selective serotonin reuptake inhibitors (SSRI) being the most common (64.8%). Antidepressant use was associated with faster cognitive decline (β (95% CI) = - 0.30(- 0.39, - 0.21) points/year), in particular sertraline (- 0.25(- 0.43, - 0.06) points/year), citalopram (- 0.41(- 0.55, - 0.27) points/year), escitalopram (- 0.76(- 1.09, - 0.44) points/year), and mirtazapine (- 0.19(- 0.34, - 0.04) points/year) compared with non-use. The association was stronger in patients with severe dementia (initial MMSE scores 0–9). Escitalopram showed a greater decline rate than sertraline. Compared with non-use, dose response of SSRIs on greater cognitive decline and higher risks of severe dementia, all-cause mortality, and fracture were observed.

Conclusions
In this cohort study, current antidepressant use was associated with faster cognitive decline; furthermore, higher dispensed doses of SSRIs were associated with higher risk for severe dementia, fractures, and all-cause mortality. These findings highlight the significance of careful and regular monitoring to assess the risks and benefits of different antidepressants use in patients with dementia.

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