ORIGINAL CONTRIBUTION Cognitive Behavioral Therapy and Aerobic Exercise for Gulf War Veterans’ Illnesses A Randomized Controlled Trial Sam T. Donta, MD; Daniel J. Clauw, MD; Charles C. Engel, Jr, MD, MPH; Peter Guarino, MPH; Peter Peduzzi, PhD; David A. Williams, PhD; James S. Skinner, PhD; Andre ´ Barkhuizen, MD; Thomas Taylor, MD; Lewis E. Kazis, ScD; Stephanie Sogg, PhD; Stephen C. Hunt, MD; Cynthia M. Dougherty, PhD; Ralph D. Richardson, PhD; Charles Kunkel, MD; William Rodriguez, MD; Edwin Alicea, MD; Philippe Chiliade, MD; Margaret Ryan, MD, MPH; Gregory C. Gray, MD, MPH; Larry Lutwick, MD; Dorothy Norwood, MD; Samantha Smith, PhD; Michael Everson, PhD; Warren Blackburn, MD; Wade Martin, MD; J. McLeod Griffiss, MD; Robert Cooper, MD; Ed Renner, PhD, MPH; James Schmitt, MD; Cynthia McMurtry, MD; Manisha Thakore, MD; Deanna Mori, PhD; Robert Kerns, PhD; Maryann Park, MD; Sally Pullman-Mooar, MD; Jack Bernstein, MD; Paul Hershberger, PhD; Don C. Salisbury, DO; John R. Feussner, MD, MPH; for the VA Cooperative Study #470 Study Group I N 1990 AND 1991, 700000 US troops were deployed to the Per- sian Gulf in what became known as the Gulf War. Upon their return, many Gulf War veterans from both the US and other allied forces began to re- port chronic, unexplained fatigue, pain, Author Affiliations are listed at the end of this article. Members of the VA Cooperative Study #470 Study Group and the data and safety monitoring board are listed in reference 14 of this article. Corresponding Author and Reprints: Peter Peduzzi, PhD, Cooperative Studies Program Coordinating Cen- ter (151A), VA Connecticut Healthcare System, 950 Campbell Ave, West Haven, CT 06516 (e-mail: peterp5 @mindspring.com). Context Gulf War veterans’ illnesses (GWVI), multisymptom illnesses characterized by persistent pain, fatigue, and cognitive symptoms, have been reported by many Gulf War veterans. There are currently no effective therapies available to treat GWVI. Objective To compare the effectiveness of cognitive behavioral therapy (CBT), ex- ercise, and the combination of both for improving physical functioning and reducing the symptoms of GWVI. Design, Setting, and Patients Randomized controlled 2  2 factorial trial con- ducted from April 1999 to September 2001 among 1092 Gulf War veterans who re- ported at least 2 of 3 symptom types (fatigue, pain, and cognitive) for more than 6 months and at the time of screening. Treatment assignment was unmasked except for a masked assessor of study outcomes at each clinical site (18 Department of Vet- erans Affairs [VA] and 2 Department of Defense [DOD] medical centers). Interventions Veterans were randomly assigned to receive usual care (n = 271), con- sisting of any and all care received from inside or outside the VA or DOD health care systems; CBT plus usual care (n=286); exercise plus usual care (n=269); or CBT plus exercise plus usual care (n = 266). Exercise sessions were 60 minutes and CBT sessions were 60 to 90 minutes; both met weekly for 12 weeks. Main Outcome Measures The primary end point was a 7-point or greater in- crease (improvement) on the Physical Component Summary scale of the Veterans Short Form 36-Item Health Survey at 12 months. Secondary outcomes were standardized measures of pain, fatigue, cognitive symptoms, distress, and mental health function- ing. Participants were evaluated at baseline and at 3, 6, and 12 months. Results The percentage of veterans with improvement in physical function at 1 year was 11.5% for usual care, 11.7% for exercise alone, 18.4% for CBT plus exercise, and 18.5% for CBT alone. The adjusted odds ratios (OR) for improvement in exercise, CBT, and exercise plus CBT vs usual care were 1.07 (95% confidence interval [CI], 0.63-1.82), 1.72 (95% CI, 0.91-3.23), and 1.84 (95% CI, 0.95-3.55), respectively. The OR for the overall (marginal) effect of receiving CBT (n = 552) vs no CBT (n = 535) was 1.71 (95% CI, 1.15-2.53) and for exercise (n=531) vs no exercise (n=556) was 1.07 (95% CI, 0.76-1.50). For secondary outcomes, exercise alone or in combination with CBT significantly improved fatigue, distress, cognitive symptoms, and mental health functioning, while CBT alone significantly improved cognitive symptoms and mental health functioning. Neither treatment had a significant impact on pain. Conclusion Our results suggest that CBT and/or exercise can provide modest relief for some of the symptoms of chronic multisymptom illnesses such as GWVI. JAMA. 2003;289:1396-1404 www.jama.com For editorial comment see p 1436. 1396 JAMA, March 19, 2003—Vol 289, No. 11 (Reprinted) ©2003 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ on 02/25/2013