Benefits and harms of doxycycline treatment for Gulf War Veterans' illnesses: A randomized, double-blind, placebo-controlled trial

Sam T. Donta, Charles C. Engel, Joseph F. Collins, Joel B. Baseman, Lisa L. Dever, Thomas Taylor, Kathy D. Boardman, Lewis E. Kazis, Suzanne E. Martin, Rebecca A. Horney, Annette L. Wiseman, Douglas S. Kernodle, Raymond P. Smith, Aldona L. Baltch, Christine Handanos, Brian Catto, Luis Montalvo, Michael Everson, Warren Blackburn, Manisha ThakoreSheldon T. Brown, Larry Lutwick, Dorothy Norwood, Jack Bernstein, Catherine Bacheller, Bruce Ribner, L. W.Preston Church, Kenneth H. Wilson, Prabhakar Guduru, Robert Cooper, Joseph Lentino, Richard J. Hamill, Arnold B. Gorin, Victor Gordan, David Wagner, Cliff Robinson, Pierre DeJace, Ronald Greenfield, Lisa Beck, Marvin Bittner, H. Ralph Schumacher, Fredric Silverblatt, James Schmitt, Edward Wong, Margaret A.K. Ryan, Javier Figueroa, Christopher Nice, John R. Feussner

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Background: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. Objective: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. Design: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. Setting: 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. Participants: 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. Intervention: Doxycycline, 200 mg, or matching placebo daily for 12 months. Measurements: The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. Results: No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. Limitations: Adherence to treatment after 6 months was poor. Conclusion: Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.

Original languageEnglish (US)
Pages (from-to)85-94+I-12
JournalAnnals of internal medicine
Issue number2
StatePublished - Jul 20 2004

All Science Journal Classification (ASJC) codes

  • Internal Medicine


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