included nontraditional interventions (for example, complementary medicine and alternative medicine) in addition to traditional interventions (for example, pharmaceuticals). A summary of the search strategy can be found in Chapter 3.

Three studies of interventions for the symptoms associated with CMI were conducted in the 1991 Gulf War veteran population. Those studies were included in the assessment with studies conducted in different populations that had a similar constellation of symptoms. The generalizability of studies on nonveterans to veterans is not known.

As described in Chapter 4, the strength of the evidence on each type of intervention was graded as insufficient, low, moderate, or high. Strength of evidence is not equivalent to efficacy or effectiveness of a treatment. Strength of evidence is a measure of confidence in the body of evidence. Efficacy or effectiveness of treatment takes into account the strength of evidence and the net benefit of the treatment to the patients.

Several studies showing high and moderate strength of evidence were conducted in the 1991 Gulf War veteran population (Donta et al., 2003, 2004; Guarino et al., 2001; Mori et al., 2006). Although the study of doxycycline was found to have high strength of evidence and was conducted in a group of 1991 Gulf War veterans who had CMI, it did not demonstrate efficacy; that is, doxycycline did not reduce or eliminate the symptoms of CMI in the study population (Donta et al., 2004). Of the studies found to have moderate strength of evidence were studies of exercise and group cognitive behavioral therapy (CBT) that were conducted in 1991 Gulf War veterans who had CMI and demonstrated a net benefit in reducing the symptoms associated with CMI (Donta et al., 2003; Guarino et al., 2001; Mori et al., 2006). Those studies evaluated the effects of exercise and CBT in combination and individually. The therapeutic benefit of exercise was unclear in those studies. Group CBT rather than exercise may confer the main therapeutic benefit with respect to physical symptoms. Additional studies, not conducted in 1991 Gulf War veterans, also reported a net benefit of exercise or group CBT in reducing symptoms associated with CMI (Bleichhardt et al., 2004; Lidbeck, 2003; Martin et al., 2007; Peters et al., 2002; Rief et al., 2002; Zaby et al., 2008).

Studies of individual CBT (high strength of evidence) and St. John’s wort (SJW; moderate strength of evidence) did not include 1991 Gulf War veterans who had CMI. Studies of individual CBT showed a consistent pattern of symptom improvement in people who had unexplained symptoms (Allen et al., 2006; Escobar et al., 2007; Sharpe et al., 2011; Sumathipala et al., 2000, 2008). Studies of SJW in people who had somatoform disorders also demonstrated symptom improvement (Muller et al., 2004; Volz et al., 2002).



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