title: Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older:  findings from a randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To evaluate the effect of the NSAIDs celecoxib and naproxen on depressive symptoms in older adults.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychiatry, Johns Hopkins Bayview and Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fields
authors.forename: Lea
authors.initials: L
authors.lastname: Drye
authors.forename: Vijay
authors.initials: V
authors.lastname: Vaidya
authors.forename: Constantine
authors.initials: C
authors.lastname: Lyketsos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009288:Naproxen / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D009288:Naproxen; D000068579:Celecoxib