title: Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a randomized, double-blind, placebo-controlled trial.
abstract: 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.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up.
  
  
  METHODS
  26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers.
  
  
  METHODS
  491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood.
  
  
  METHODS
  Doxycycline, 200 mg, or matching placebo daily for 12 months.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Adherence to treatment after 6 months was poor.
  
  
  CONCLUSIONS
  Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.
authors.affiliation: Veterans Affairs Medical Center, Boston, MA 02130, USA
authors.forename: Sam T
authors.initials: ST
authors.lastname: Donta
authors.forename: Charles C
authors.initials: CC
authors.lastname: Engel
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Collins
authors.forename: Joel B
authors.initials: JB
authors.lastname: Baseman
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Dever
authors.forename: Thomas
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authors.lastname: Taylor
authors.forename: Kathy D
authors.initials: KD
authors.lastname: Boardman
authors.forename: Lewis E
authors.initials: LE
authors.lastname: Kazis
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Martin
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Horney
authors.forename: Annette L
authors.initials: AL
authors.lastname: Wiseman
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Kernodle
authors.forename: Raymond P
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authors.forename: Aldona L
authors.initials: AL
authors.lastname: Baltch
authors.forename: Christine
authors.initials: C
authors.lastname: Handanos
authors.forename: Brian
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authors.lastname: Catto
authors.forename: Luis
authors.initials: L
authors.lastname: Montalvo
authors.forename: Michael
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authors.lastname: Everson
authors.forename: Warren
authors.initials: W
authors.lastname: Blackburn
authors.forename: Manisha
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authors.lastname: Thakore
authors.forename: Sheldon T
authors.initials: ST
authors.lastname: Brown
authors.forename: Larry
authors.initials: L
authors.lastname: Lutwick
authors.forename: Dorothy
authors.initials: D
authors.lastname: Norwood
authors.forename: Jack
authors.initials: J
authors.lastname: Bernstein
authors.forename: Catherine
authors.initials: C
authors.lastname: Bacheller
authors.forename: Bruce
authors.initials: B
authors.lastname: Ribner
authors.forename: L W Preston
authors.initials: LW
authors.lastname: Church
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Wilson
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Guduru
authors.forename: Robert
authors.initials: R
authors.lastname: Cooper
authors.forename: Joseph
authors.initials: J
authors.lastname: Lentino
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hamill
authors.forename: Arnold B
authors.initials: AB
authors.lastname: Gorin
authors.forename: Victor
authors.initials: V
authors.lastname: Gordan
authors.forename: David
authors.initials: D
authors.lastname: Wagner
authors.forename: Cliff
authors.initials: C
authors.lastname: Robinson
authors.forename: Pierre
authors.initials: P
authors.lastname: DeJace
authors.forename: Ronald
authors.initials: R
authors.lastname: Greenfield
authors.forename: Lisa
authors.initials: L
authors.lastname: Beck
authors.forename: Marvin
authors.initials: M
authors.lastname: Bittner
authors.forename: H Ralph
authors.initials: HR
authors.lastname: Schumacher
authors.forename: Fredric
authors.initials: F
authors.lastname: Silverblatt
authors.forename: James
authors.initials: J
authors.lastname: Schmitt
authors.forename: Edward
authors.initials: E
authors.lastname: Wong
authors.forename: Margaret A K
authors.initials: MA
authors.lastname: Ryan
authors.forename: Javier
authors.initials: J
authors.lastname: Figueroa
authors.forename: Christopher
authors.initials: C
authors.lastname: Nice
authors.forename: John R
authors.initials: JR
authors.lastname: Feussner
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004269:DNA, Bacterial / Q000097:blood; D004311:Double-Blind Method; D004318:Doxycycline / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009174:Mycoplasma / Q000302:isolation & purification; D009175:Mycoplasma Infections / Q000188:drug therapy*; D009325:Nausea / Q000139:chemically induced; D010349:Patient Compliance; D018923:Persian Gulf Syndrome / Q000188:drug therapy* / Q000382:microbiology; D010787:Photosensitivity Disorders / Q000139:chemically induced; D016896:Treatment Outcome; D014728:Veterans
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004318:Doxycycline