2023年3月23日 |《新英格兰医学杂志》英文音频和中英文摘要

难治性老年期抑郁症的治疗：抗抑郁药增效 vs. 换药

背景

难治性老年抑郁症患者抗抑郁药增效或换药的获益和风险尚未经过广泛研究。

方法

我们开展了一项两阶段、开放标签试验，该试验纳入年龄≥60岁的难治性抑郁症患者。在第1阶段，患者按1:1:1比例随机分组，分别使用阿立哌唑将现有抗抑郁药增效，使用安非他酮将现有抗抑郁药增效或将现有抗抑郁药改用安非他酮。第1阶段未获益或不符合第1阶段纳入标准的患者在第2阶段按1:1比例随机分组，分别使用锂剂增效或改用去甲替林。每个阶段持续约10周。主要结局是心理幸福感相对于基线的变化，使用美国国立卫生研究院（National Institutes of Health）积极情绪和总体生活满意度分量表（Toolbox Positive Affect and General Life Satisfaction subscales）进行评估（人群的平均值，50；评分较高表示幸福感较强）。次要结局是抑郁症缓解。

结果

第1阶段共纳入619例患者；211例被分配使用阿立哌唑增效，206例使用安非他酮增效，202例改用安非他酮。幸福感评分分别提高了4.83分、4.33分和2.04分。阿立哌唑增效组与改用安非他酮组之间的差异为2.79分（95% CI，0.56~5.02；P=0.014，预设阈值P值为0.017）；阿立哌唑增效组与安非他酮增效组之间无显著差异，安非他酮增效组与改用安非他酮组之间也无显著差异。阿立哌唑增效组28.9%的患者出现缓解，安非他酮增效组为28.2%，而改用安非他酮组为19.3%。安非他酮增效组的跌倒发生率最高。第2阶段共纳入248例患者；127例被分配使用锂剂增效，121例改用去甲替林。幸福感评分分别提高了3.17分和2.18分（差异，0.99；95% CI，−1.92~3.91）。增效组18.9%的患者出现缓解，改用去甲替林组为21.5%；两组患者的跌倒发生率相似。

Result

In 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.

结论

在难治性老年抑郁症患者中，使用阿立哌唑将现有抗抑郁药增效后，10周期间的幸福感改善幅度显著超过改用安非他酮，而且抑郁缓解率在数值上较高。在增效或改用安非他酮后治疗失败的患者中，使用锂剂增效或改用去甲替林后的幸福感变化和抑郁缓解率相似。(由以患者为中心的结局研究所[Patient-Centered Outcomes Research Institute]资助；OPTIMUM在ClinicalTrials.gov注册号为NCT02960763）。

Conclusions

In 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; OPTIMUM ClinicalTrials.gov number, NCT02960763.)

lebrikizumab治疗中重度特应性皮炎的两项3期试验

Two Phase 3 Trials of Lebrikizumab for Moderate-to-Severe Atopic Dermatitis

背景

lebrikizumab是靶向白介素-13的高亲和力IgG4单克隆抗体，可阻止白介素-4Rα-白介素-13Rα1异二聚体受体信号复合物的形成。

我们开展了两项设计完全相同、为期52周的随机、双盲、安慰剂对照3期试验；两项试验均包括16周诱导期和36周维持期。我们以2∶1的比例将符合条件的中重度特应性皮炎患者（成人[≥18岁]和青少年[12~<18岁，体重≥40 kg]）随机分组，两组分别接受250 mg lebrikizumab（在基线时和第2周时的负荷剂量为500 mg）或安慰剂，每2周1次皮下给药。我们评估了截至第16周的诱导期结局，并在本文中报告。主要结局是研究者总体评估（Investigator’s Global Assessment，IGA）评分为0或1分（表示皮肤无病变或几乎无病变；范围，0~4分[重度疾病]），第16周时相对于基线降低（表示改善）至少2分。次要结局包括湿疹面积和严重程度指数（Eczema Area and Severity Index）评分（EASI-75应答）改善75%，以及瘙痒和瘙痒对睡眠的干扰评估。本试验还评估了安全性。

We conducted two identically designed, 52-week, randomized, double-blind, placebo-controlled, phase 3 trials; both trials included a 16-week induction period and a 36-week maintenance period. Eligible patients with moderate-to-severe atopic dermatitis (adults [≥18 years of age] and adolescents [12 to <18 years of age, weighing ≥40 kg]) were randomly assigned in a 2:1 ratio to receive either lebrikizumab at a dose of 250 mg (loading dose of 500 mg at baseline and week 2) or placebo, administered subcutaneously every 2 weeks. Outcomes for the induction period were assessed up to 16 weeks and are included in this report. The primary outcome was an Investigator’s Global Assessment (IGA) score of 0 or 1 (indicating clear or almost clear skin; range, 0 to 4 [severe disease]) with a reduction (indicating improvement) of at least 2 points from baseline at week 16. Secondary outcomes included a 75% improvement in the Eczema Area and Severity Index score (EASI-75 response) and assessments of itch and of itch interference with sleep. Safety was also assessed.

在试验1中，lebrikizumab组283例患者中的43.1%和安慰剂组141例患者中的12.7%达到了主要结局（P<0.001）；EASI-75应答率分别为58.8%和16.2%（P<0.001）。在试验2中，lebrikizumab组281例患者中的33.2%和安慰剂组146例患者中的10.8%达到了主要结局（P<0.001）；EASI-75应答率分别为52.1%和18.1%（P<0.001）。lebrikizumab治疗后，瘙痒和瘙痒对睡眠的干扰指标有改善。lebrikizumab组患者的结膜炎发生率高于安慰剂组患者。诱导期的大多数不良事件为轻度或中度，未导致试验终止。

Result

结论

在两项3期试验的诱导期， lebrikizumab治疗16周对中重度特应性皮炎青少年和成人患者有效。（由Dermira资助；ADvocate1和ADvocate2在ClinicalTrials.gov注册号分别为NCT04146363和NCT04178967）。

Conclusions

饮用咖啡对非卧床成人健康状况的急性效应

Acute Effects of Coffee Consumption on Health among Ambulatory Adults

背景

咖啡是全球范围内人们最常饮用的饮料之一，但饮用咖啡对健康状况的急性效应尚不明确。

结果

参与者平均（±SD）年龄为39±13岁；51%为女性，51%为非西班牙语裔白种人。评估结果表明，参与者对随机分配方案的依从性高。饮用含咖啡因咖啡与每日58次房性期前收缩相关，而在避免摄入咖啡因的日子，每日发生53次房性期前收缩（率比，1.09；95%置信区间[CI]，0.98~1.20；P=0.10）。饮用含咖啡因咖啡与不摄入咖啡因分别与以下情况相关：每日154次和102次室性期前收缩（率比，1.51；95% CI，1.18~1.94），每日10,646步和9665步（平均差，1058；95% CI，441~1675），每晚睡眠时间397分钟和432分钟（平均差，36；95% CI，25~47）；血糖水平95 mg/dL和96 mg/dL（平均差，－0.41；95% CI，－5.42~4.60）。

Result

The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P=0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, −0.41; 95% CI, −5.42 to 4.60).

结论

在此项随机试验中，与避免摄入咖啡因相比，饮用含咖啡因咖啡未显著增加每日房性期前收缩次数。（由美国加州大学旧金山分校[University of California，San Francisco]和美国国立卫生研究院资助；CRAVE在ClinicalTrials.gov注册号为NCT03671759）。

Conclusions