Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a randomized, double-blind, placebo-controlled trial.
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.
Donta
Sam T
ST
Veterans Affairs Medical Center, Boston, MA 02130, USA
Engel
Charles C
CC
Collins
Joseph F
JF
Baseman
Joel B
JB
Dever
Lisa L
LL
Taylor
Thomas
T
Boardman
Kathy D
KD
Kazis
Lewis E
LE
Martin
Suzanne E
SE
Horney
Rebecca A
RA
Wiseman
Annette L
AL
Kernodle
Douglas S
DS
Smith
Raymond P
RP
Baltch
Aldona L
AL
Handanos
Christine
C
Catto
Brian
B
Montalvo
Luis
L
Everson
Michael
M
Blackburn
Warren
W
Thakore
Manisha
M
Brown
Sheldon T
ST
Lutwick
Larry
L
Norwood
Dorothy
D
Bernstein
Jack
J
Bacheller
Catherine
C
Ribner
Bruce
B
Church
L W Preston
LW
Wilson
Kenneth H
KH
Guduru
Prabhakar
P
Cooper
Robert
R
Lentino
Joseph
J
Hamill
Richard J
RJ
Gorin
Arnold B
AB
Gordan
Victor
V
Wagner
David
D
Robinson
Cliff
C
DeJace
Pierre
P
Greenfield
Ronald
R
Beck
Lisa
L
Bittner
Marvin
M
Schumacher
H Ralph
HR
Silverblatt
Fredric
F
Schmitt
James
J
Wong
Edward
E
Ryan
Margaret A K
MA
Figueroa
Javier
J
Nice
Christopher
C
Feussner
John R
JR
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
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004318:Doxycycline