Gulf War Illness: A Systematic Review of Therapeutic Interventions and Management Strategies [Internet]

Aim We conducted a systematic review of therapeutic interventions for Gulf War Illness (GWI) to evaluate effectiveness and harms and identify potentially promising treatments. Methods We searched electronic databases, trial registries, and reference lists through September 2019 for randomized and non-randomized controlled trials and cohort studies directly comparing interventions for Veterans with GWI to each other, placebo, or usual care. We abstracted data on study design, demographics, interventions, and outcomes. Two reviewers independently assessed studies for inclusion, quality, and strength of evidence using pre-specified criteria. We resolved discordant ratings by discussion and consensus. Results We identified 12 RCTs, each of which examined a different intervention for GWI. We found moderate-strength evidence that cognitive behavioral therapy (CBT) and exercise, separately and in combination, were associated with improvements in several GWI symptom domains. There was low-strength evidence of benefit from 2 mindfulness-based interventions and Continuous Positive Airway Pressure (CPAP). Mindfulness-based stress reduction improved pain, cognitive functioning, fatigue, depression, and posttraumatic stress disorder (PTSD), while mind-body bridging improved fatigue, depression, PTSD, and sleep, although pain and other outcomes did not improve. CPAP improved overall physical health, pain, cognitive functioning, fatigue, mental health, and sleep quality in a small study of Veterans with sleep-disordered breathing and GWI. We found moderate-strength evidence that doxycycline is ineffective for GWI in mycoplasma DNA-positive Veterans and increases the risk of adverse effects compared with placebo. We also found 33 ongoing, single-arm pilot, or unpublished studies examining a variety of interventions. Conclusion There is moderate-strength evidence of benefit from CBT and exercise, and low-strength evidence of benefit from 2 distinct mindfulness-based interventions as well as CPAP. Doxycycline was ineffective and associated with harms (moderate-strength evidence). Emerging evidence examines a wide array of treatments. Larger, more rigorous studies are needed to reproduce and characterize positive findings.