Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial.
Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial.
复制标题
DOI：
10.1097/jgp.0b013e318227f4da
复制
发表时间：
2012-06
期刊：
影响因子：
--
通讯作者：
ADAPT Research Group
中科院分区：
文献类型：
--
作者：
Fields C;Drye L;Vaidya V;Lyketsos C;ADAPT Research Group
一些证据表明，炎症机制可能与抑郁症的严重程度和进展有关。其中一个途径是通过环氧合酶(COX)产生前列腺素。虽然晚年抑郁症尤其与炎症有关，但我们不知道在这一人群中使用COX抑制剂，如非类固醇抗炎药(NSAIDs)来治疗抑郁综合征的已发表研究。目的：评价非甾体抗炎药塞来昔布和萘普生对老年人抑郁症状的影响。阿尔茨海默病抗炎预防试验(Adapt)是一项在美国六家记忆诊所进行的随机、安慰剂对照、双掩蔽临床试验。认知正常的志愿者年龄在70岁及以上，有阿尔茨海默病家族史，他们被随机分配给塞来昔布200 mg，每日2次，萘普生钠220 mg，每日2次，或安慰剂。包括30个条目的老年抑郁量表(GDS)在登记时和每年的随访中对所有参与者进行测试。基线时GDS评分为5分的参与者被归类为抑郁。在2528名登记的参与者中，有2312人至少返回进行了一次后续访问。在基线时，大约五分之一的人有明显的抑郁症状。在所有三个治疗组中，随着时间的推移，平均GDS评分和有明显抑郁症状的百分比保持相似。此外，在基线有明显抑郁症状的受试者中，随着时间的推移，GDS评分没有治疗效果。在使用广义估计方程(GEE)回归的纵向分析中，较高的基线GDS评分、既往精神病史、年龄较大、在研究中的时间、与时间交互作用的认知较低，但不是治疗分配，随着时间的推移与显著较高的GDS评分相关。与安慰剂相比，随着时间的推移，塞来昔布或萘普生治疗并不能改善抑郁症状。虽然炎症与老年抑郁症有关，但这些结果并不支持这样的假设，即在这些剂量的NSAIDs中抑制环氧合酶途径可以缓解老年人的抑郁症状。
Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression. One pathway implicated is the production of prostaglandins via the enzyme cyclooxygenase (COX). Although late life depression in particular has been associated with inflammation, we know of no published studies using COX inhibitors, such as nonsteroidal anti-inflammatory drugs (NSAIDs), in the treatment of depressive syndromes in this population. To evaluate the effect of the NSAIDs celecoxib and naproxen on depressive symptoms in older adults. The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) was a randomized, placebo-controlled, double-masked clinical trial conducted at six U.S. memory clinics. Cognitively normal volunteers aged 70 and over with a family history of Alzheimer-like dementia were randomly assigned to receive celecoxib 200mg BID, naproxen sodium 220mg BID, or placebo. The 30-item version of the Geriatric Depression Scale (GDS) was administered to all participants at enrollment and at yearly follow-up visits. Participants with a GDS score >5 at baseline were classified as depressed. Of 2,528 participants enrolled 2,312 returned for at least one follow-up visit. Approximately one-fifth had significant depressive symptoms at baseline. Mean GDS score, and the percentage with significant depressive symptoms, remained similar over time across all three treatment groups. Furthermore, there was no treatment effect on GDS scores over time in the subgroup of participants with significant depressive symptoms at baseline. In longitudinal analysis using Generalized Estimating Equations (GEE) regression, higher baseline GDS scores, a prior psychiatric history, older age, time in the study, and lower cognition interacting with time, but not treatment assignment, were associated with significantly higher GDS scores over time. Treatment with celecoxib or naproxen did not improve depressive symptoms over time compared with placebo. While inflammation has been implicated in late life depression, these results do not support the hypothesis that inhibition of the cyclooxygenase pathway with these NSAIDs at these doses alleviates depressive symptoms in older adults.