Research

Use of non-steroidal anti-inflammatory drugs and risk of Parkinson’s disease: nested case-control study

BMJ 2011; 342 doi: 10.1136/bmj.d198 (Published 20 January 2011)
Cite this as: BMJ 2011;342:d198
  1. Jane A Driver, assistant professor of medicine123,
  2. Giancarlo Logroscino, associate professor of neurology4,
  3. Linda Lu, instructor of medicine2,
  4. J Michael Gaziano, professor of medicine1235,
  5. Tobias Kurth, director of research56
  1. 1Geriatric Research, Education and Clinical Center, VA Boston Healthcare System; Boston MA, USA
  2. 2Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston
  3. 3Massachusetts Veterans Epidemiology Research Information Center, VA Boston Healthcare System
  4. 4Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy
  5. 5Division of Preventive Medicine, Brigham and Women’s Hospital
  6. 6INSERM Unit 708—Neuroepidemiology and UPMC University Paris 06, Paris, France
  1. Correspondence to: J A Driver, Division of Aging, Brigham and Women’s Hospital, 1620 Tremont Street, Boston, MA 02120, USA jdriver{at}partners.org
  • Accepted 19 October 2010

Abstract

Objective To evaluate the relation between Parkinson’s disease and prior use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large cohort of men.

Design Case-control analysis nested in the Physicians’ Health Study.

Participants 22 007 male physicians aged 40–84 years without indications for or contraindications to regular NSAID use and free of Parkinson’s disease at baseline. Cases and controls were matched by age alone or by age and scores for confounders (comorbidity and indicators of NSAID use). Up to five controls were matched to each of 616 cases by age and 565 cases by age and confounder scores.

Setting United States.

Main outcome measures Odds of having been exposed to prior non-aspirin NSAID or aspirin use by participants with Parkinson’s disease and by their controls in each case-control set.

Results Participants who had ever used non-aspirin NSAIDs had an increased risk of Parkinson’s disease (odds ratio 1.28 (95% CI 1.05 to 1.56) in the age matched group but not in the group also matched on confounder scores (odds ratio 1.17 (0.94 to 1.46)). There was an increased risk of Parkinson’s disease in men who had 1–2 years of regular non-aspirin NSAID use (odds ratio 1.35 (1.07 to 1.70)), a finding that remained significant after matching for confounder scores as well (odds ratio 1.35 (1.05 to 1.75)). In contrast, the significant association of use of non-aspirin NSAIDs for ≥5 years (odds ratio 1.48 (1.05 to 2.09)) in the age matched group was entirely attenuated in the group also matched on confounder scores (1.03 (0.70 to 1.53)). There was also a suggestion that men who regularly used aspirin had an increased risk of Parkinson’s disease. Positive associations between non-aspirin NSAID or aspirin and risk of Parkinson’s disease tended to disappear when analyses were limited to drug use ≥5 years before the disease diagnosis.

Conclusions This case-control study did not find evidence that NSAID use reduces Parkinson’s disease risk. The positive associations observed between NSAID use and Parkinson’s disease might have been due to confounding by indication as the use was clustered in the few years before disease diagnosis.

Footnotes

  • We thank the staff of the Physician’s Health Study and the 22 071 dedicated physicians who have made this project possible.

  • Contributors: JAD conceived and designed the study, performed the data analyses, wrote the first draft of the article, and is guarantor for the study. LL helped with the research and drafting of the manuscript. JMG, GL, and TK gave detailed advice at all stages of the analyses. All authors contributed to the writing of the paper and gave substantial advice and input into the study. All authors had full access to the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

  • Funding: This research is funded by a grant from the Parkinson’s Disease Foundation. The Physicians’ Health Study is supported by grants CA-34944, CA-40360, and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the National Heart, Lung, and Blood Institute, Bethesda, MD. The study sponsor had no role in study design; data collection, analysis, or interpretation; writing the article; or the decision to submit it for publication. The researchers are independent from funders and sponsors.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: JAD has support from the Parkinson’s Disease Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • We report a full disclosure for the past five years for each of the authors. JAD has a research grant from the Parkinson’s Disease Foundation, the Hartford Foundation, Harvard Medical School, and a Career Development Award from the Veteran’s Administration. LL has nothing to disclose. GL has received research funding from the Amyotrophic Lateral Sclerosis Association, Italian Ministry of Health, the Apulia Region, and special funding from the Italian Ministry of Universities and has received honorariums from Pfizer, Novartis, Glaxo, and Lilly Pharmaceutical for speaking engagements. JMG has received investigator initiated research funding and support as principal investigator from National Institutes of Health, BASF, DSM Pharmaceuticals, Wyeth Pharmaceuticals, McNeil Consumer Products, and Pliva; received honoraria from Bayer and Pfizer for speaking engagements; and is a consultant for Bayer, McNeil Consumer Products, Wyeth Pharmaceuticals, Merck, Nutraquest, and GlaxoSmithKline. TK has received investigator initiated research funding from the French National Research Agency, the US National Institutes of Health, Merck, the Migraine Research Foundation, and the Parkinson’s Research Foundation; is a consultant to i3 Drug Safety and World Health Information Science Consultants, LLC; and has received honoraria from the American Academy of Neurology, Genzyme, Merck, and Pfizer for educational lectures.

  • Ethical approval: All participants in the Physician’s Health Study provided written informed consent, and the trial was approved by the institutional review board of the Brigham and Women’s Hospital. This study, which used analysis of existing data, was also approved by the institutional review board of the Brigham and Women’s Hospital.

  • Data sharing: No additional data available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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