Abstract：
BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research.
METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities.
RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes.
CONCLUSIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively.
CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.
METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities.
RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes.
CONCLUSIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively.
CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.
摘要：
背景：难治性抑郁症（TRD）是重度抑郁症（MDD）的一个子集，其症状对一线治疗无反应。在老年人中,TRD的评估和治疗由于该人群特有的心理社会风险因素而变得复杂，以及相对缺乏研究。
方法：叙事综述旨在（1）定义临床实践和研究的TRLLD；（2）描述心理社会危险因素；（3）回顾心理和非药物治疗；（4）讨论临床表型在个性化治疗中的作用；（5）概述研究重点。
结果：我们对TRLLD的定义集中在原发性抑郁症患者对药物和神经调节的反应上。心理社会风险因素包括创伤和早期生活逆境，慢性身体疾病,社会孤立,个性,和护理障碍。有希望的非药物治疗包括认知训练，心理治疗,和生活方式干预。通过检查合并症的影响的研究，突出了临床表型的效用，症状维度(例如，冷漠)，和大脑结构/功能的变化。
结论：TRLLD研究相对缺乏。这限制了从中得出可靠模式的经验数据的范围，并使定量评估文献的工作复杂化。
结论：TRLLD是一种复杂的疾病，鉴于我们的人口老龄化，需要进一步调查。虽然这篇综述强调了迄今为止TRLLD研究的有希望的广度，需要更多的研究来帮助阐明，例如,实施风险缓解策略的最佳时机，协作护理方法的价值，与更强大的反应相关的特定治疗成分，和表型分析，以帮助告知治疗决策。
方法：叙事综述旨在（1）定义临床实践和研究的TRLLD；（2）描述心理社会危险因素；（3）回顾心理和非药物治疗；（4）讨论临床表型在个性化治疗中的作用；（5）概述研究重点。
结果：我们对TRLLD的定义集中在原发性抑郁症患者对药物和神经调节的反应上。心理社会风险因素包括创伤和早期生活逆境，慢性身体疾病,社会孤立,个性,和护理障碍。有希望的非药物治疗包括认知训练，心理治疗,和生活方式干预。通过检查合并症的影响的研究，突出了临床表型的效用，症状维度(例如，冷漠)，和大脑结构/功能的变化。
结论：TRLLD研究相对缺乏。这限制了从中得出可靠模式的经验数据的范围，并使定量评估文献的工作复杂化。
结论：TRLLD是一种复杂的疾病，鉴于我们的人口老龄化，需要进一步调查。虽然这篇综述强调了迄今为止TRLLD研究的有希望的广度，需要更多的研究来帮助阐明，例如,实施风险缓解策略的最佳时机，协作护理方法的价值，与更强大的反应相关的特定治疗成分，和表型分析，以帮助告知治疗决策。
