Background To investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. Methods An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10 months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults aged 60 years or older with major depressive disorder (MDD) or persistent depressive disorder and a 24-item Hamilton Rating Scale for Depression (HRSD) ≥16 were enrolled. Primary measures assessed serially over 12 months include response (50% reduction from baseline HRSD score), remission (HRSD score <10), and frailty (non/intermediate frail [0–2 deficits] vs frail [≥3 deficits]); latent class analysis was used to classify longitudinal frailty trajectories. Results A 2-class model best fit the data, identifying a consistently low frailty risk (63% of the sample) and consistently high frailty risk (37% of the sample) trajectory. Response and remission rates (ps ≤ .002) for adults in the high-risk frailty class were at least 21 percentage points worse than those in the low-risk class over 12 months. Furthermore, subsequent frailty was associated with previous frailty (ps ≤ .01) but not previous response or remission (ps ≥ .10). Conclusions Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.

中文翻译：

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晚年的虚弱和抑郁：一种具有独特临床表现和抗抑郁反应差的高危合并症

背景 调查身体虚弱、加速生物衰老的临床表现和患有抑郁症的老年人的抗抑郁药物反应之间的纵向关系。方法 在门诊研究诊所进行为期 8 周的随机安慰剂对照试验（艾司西酞普兰或度洛西汀），然后进行 10 个月的开放式抗抑郁药物治疗（增强、转换策略）。121 名 60 岁或以上患有重度抑郁症 (MDD) 或持续性抑郁症且 24 项汉密尔顿抑郁量表 (HRSD) ≥16 的成年人被纳入研究。在 12 个月内连续评估的主要指标包括反应（从基线 HRSD 评分减少 50%）、缓解（HRSD 评分 <10）和虚弱（非/中间虚弱 [0-2 缺陷] 对比虚弱 [≥3 缺陷]）；潜在类别分析用于对纵向脆弱轨迹进行分类。结果 2 类模型最适合数据，确定了持续低虚弱风险（样本的 63%）和持续高虚弱风险（样本的 37%）轨迹。在 12 个月的时间里，高风险虚弱类别的成年人的反应率和缓解率 (ps ≤ .002) 比低风险类别的成年人至少低 21 个百分点。此外，随后的虚弱与之前的虚弱相关 (ps ≤ .01)，但与之前的反应或缓解无关 (ps ≥ .10)。结论 抗抑郁药物对老年人虚弱背景下发生的 MDD 效果不佳。此外，即使实现了抗抑郁反应，这种反应也无助于改善他们的脆弱性。