Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial

Topic: Risk, prevention and care in population studies

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. Conclusion 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.

Key findings

• Background Several lines of evidence suggest that inflammatory mechanisms may be involved in the severity and progression of depression.
• 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.
• 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.

Why it matters

In this randomized, placebo-controlled trial of 2,528 cognitively normal volunteers aged 70 and older with a family history of Alzheimer-like dementia, celecoxib and naproxen did not benefit depressive symptoms. The study addresses depressive symptoms in this population, not the treatment, cure, or prevention of Alzheimer's disease itself.

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Study details

• Study designlongitudinal study
• Participants2,528
• Evidence strengthHigh

Read the original

• DOI: 10.1097/jgp.0b013e318227f4da
• PubMed: 21775876
• Original source →
• Free full text: PubMed Central →

Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).

@article{fields2012-21775876,
  author  = {Fields, C. and Drye, L. and Vaidya, V. and Lyketsos, C. and {ADAPT Research Group}},
  title   = {{Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older: findings from a randomized controlled trial}},
  journal = {The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry},
  year    = {2012},
  doi     = {10.1097/jgp.0b013e318227f4da},
  pmid    = {21775876},
  url     = {https://doi.org/10.1097/jgp.0b013e318227f4da}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial Neurology · 2007-04-25 · usefulness score 71/100 · Treatments
• Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib Archives of neurology · 2008-05-12 · usefulness score 69/100 · Treatments
• Development and validation of a geriatric depression screening scale: A preliminary report Journal of Psychiatric Research · 1982-01-01 · usefulness score 54/100 · Cognitive tests and assessment

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