Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.
Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.
复制标题
抗抑郁药物增强与转换治疗难治性老年抑郁症。
DOI：
10.1056/nejmoa2204462
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Nicol,Ginger
中科院分区：
文献类型：
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作者：
Lenze,EricJ;Mulsant,BenoitH;Roose,StevenP;Lavretsky,Helen;Reynolds3rd,CharlesF;Blumberger,DanielM;Brown,PatrickJ;Cristancho,Pilar;Flint,AlastairJ;Gebara,MarieA;Gettinger,TorieR;Lenard,Emily;Miller,JPhilip;Nicol,Ginger
BackgroundThe benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been widely studied.MethodsWe conducted a two-step，open-label trial involving adults 60 years old or older with treatment-resistant depression.在第1步中，患者以1：1：1的比例随机分配至阿立哌唑增加现有抗抑郁药物、安非他酮增加或从现有抗抑郁药物转换为安非他酮。没有从第1步获益或不符合第2步条件的患者在第2步中以1：1的比例随机分配至锂盐增强治疗或改用去甲替林治疗。每一步大约持续10周。主要结果是心理幸福感较基线的变化，采用美国国立卫生研究院的积极影响和一般生活满意度子量表进行评估（人群平均值为50;得分越高表示幸福感越高）。次要结果是缓解depress.ResultsIn第1步，共619例患者入组; 211人被分配到阿立哌唑增强，206安非他酮增强，和202开关安非他酮。幸福感得分分别提高了4.83分、4.33分和2.04分。阿立哌唑强化组和转换为安非他酮组之间的差异为2.79分（95% CI，0.56至5.02; P=0.014，预先设定的阈值P值为0.017）;阿立哌唑强化与安非他酮强化或安非他酮强化与转换为安非他酮的组间差异不显著。阿立哌唑强化组中28.9%的患者缓解，安非他酮强化组中28.2%的患者缓解，转换为安非他酮组中19.3%的患者缓解。福尔斯率最高的安非他酮增量。在第2步中，共入组248例患者; 127例被分配接受锂强化治疗，121例转换为去甲替林治疗。幸福感得分分别提高了3.17分和2.18分（差异为0.99; 95%CI为-1.92至3.91）。缓解发生在18.9%的患者在锂增强组和21.5%的开关去甲替林组;率下降在两个groups.ConclusionsIn老年人难治性抑郁症，增强现有的抗抑郁药阿立哌唑改善福祉显着超过10周比开关安非他酮，并与一个数字较高的发病率缓解。在增加或改用安非他酮治疗失败的患者中，增加锂盐或改用去甲替林治疗后的幸福感变化和缓解发生率相似。（由以患者为中心的结局研究所资助; OPTIMUM ClinicalTrials.gov编号，NCT 02960763。
BackgroundThe benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied.MethodsWe conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression.ResultsIn step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P=0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, −1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups.ConclusionsIn older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.)