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

Cynthia Fields, Lea Drye, Vijay Vaidya, Constantine G Lyketsos

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)505-513
Number of pages9
JournalAmerican Journal of Geriatric Psychiatry
Volume20
Issue number6
DOIs
StatePublished - Jun 2012

Fingerprint

Celecoxib
Naproxen
Randomized Controlled Trials
Depression
Geriatrics
Therapeutics
Anti-Inflammatory Agents
Placebos
Prostaglandin-Endoperoxide Synthases

Keywords

  • Anti-inflammatory treatment
  • celecoxib
  • late-life depression
  • naproxen

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology

Cite this

@article{7956de433f6f4fa29fad7c1cdb1dcfb1,
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. 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.",
keywords = "Anti-inflammatory treatment, celecoxib, late-life depression, naproxen",
author = "Cynthia Fields and Lea Drye and Vijay Vaidya and Lyketsos, {Constantine G}",
year = "2012",
month = "6",
doi = "10.1097/JGP.0b013e318227f4da",
language = "English (US)",
volume = "20",
pages = "505--513",
journal = "American Journal of Geriatric Psychiatry",
issn = "1064-7481",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

TY - JOUR

T1 - Celecoxib or naproxen treatment does not benefit depressive symptoms in persons age 70 and older

T2 - Findings from a randomized controlled trial

AU - Fields, Cynthia

AU - Drye, Lea

AU - Vaidya, Vijay

AU - Lyketsos, Constantine G

PY - 2012/6

Y1 - 2012/6

N2 - 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.

AB - 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.

KW - Anti-inflammatory treatment

KW - celecoxib

KW - late-life depression

KW - naproxen

UR - http://www.scopus.com/inward/record.url?scp=84861460724&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861460724&partnerID=8YFLogxK

U2 - 10.1097/JGP.0b013e318227f4da

DO - 10.1097/JGP.0b013e318227f4da

M3 - Article

C2 - 21775876

AN - SCOPUS:84861460724

VL - 20

SP - 505

EP - 513

JO - American Journal of Geriatric Psychiatry

JF - American Journal of Geriatric Psychiatry

SN - 1064-7481

IS - 6

ER -