Department of Psychiatry, Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD, USA.
Am J Geriatr Psychiatry. 2012 Jun;20(6):505-13. doi: 10.1097/JGP.0b013e318227f4da.
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 was a randomized, placebo-controlled, double-masked clinical trial conducted at six U.S. memory clinics. Cognitively normal volunteers age 70 and older with a family history of Alzheimer-like dementia were randomly assigned to receive celecoxib 200 mg twice daily, naproxen sodium 220 mg twice daily, 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 greater than 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 COX pathway with these NSAIDs at these doses alleviates depressive symptoms in older adults.
有几条证据表明，炎症机制可能与抑郁的严重程度和发展有关。一个被牵连的途径是通过环氧化酶（COX）产生前列腺素。尽管特别是老年抑郁症与炎症有关，但我们不知道有任何已发表的研究使用 COX 抑制剂（如非甾体抗炎药（NSAIDs））来治疗该人群的抑郁综合征。
评估 NSAIDs 塞来昔布和萘普生对老年患者抑郁症状的影响。
阿尔茨海默病抗炎预防试验是一项在美国六家记忆诊所进行的随机、安慰剂对照、双盲临床试验。认知正常的 70 岁及以上、有阿尔茨海默病样痴呆家族史的志愿者被随机分配接受塞来昔布 200mg 每日两次、萘普生钠 220mg 每日两次或安慰剂。所有参与者在入组时和每年的随访访问时都接受了 30 项老年抑郁量表（GDS）的评估。基线时 GDS 评分大于 5 的参与者被归类为抑郁。
在 2528 名入组的参与者中，有 2312 名至少随访了一次。大约五分之一的人在基线时有明显的抑郁症状。所有三组治疗的平均 GDS 评分和有明显抑郁症状的百分比随时间推移保持相似。此外，在基线时有明显抑郁症状的参与者亚组中，GDS 评分随时间的治疗效果没有差异。使用广义估计方程（GEE）回归的纵向分析表明，较高的基线 GDS 评分、既往精神病史、年龄较大、研究时间和随时间变化的认知功能较低，但与治疗分配无关，与随时间推移 GDS 评分显著升高相关。
与安慰剂相比，塞来昔布或萘普生治疗并没有改善抑郁症状随时间的变化。虽然炎症与老年抑郁症有关，但这些结果并不支持 COX 途径的抑制用这些 NSAIDs 在这些剂量下减轻老年患者抑郁症状的假说。
