Peterson et al1 propose a number of factors that could explain the different outcomes in their trial and those of Bou-Holaigah et al,2 who found fludrocortisone acetate to benefit patients with chronic fatigue syndrome. However, Peterson et al fail to mention an additional factor that should not be overlooked, namely, the different forms in which fludrocortisone was administered. Bou-Holaigah et al gave their patients the drug in the form of tablets, whereas Peterson et al gave their subjects tablets hidden in capsules. This masking may have biased their results. In fact, the dissolution times of tablets extemporaneously converted to capsules are strikingly prolonged.3 Therefore, it is appropriate to point out that "[s]lowing down the dissolution rate of a commercial drug used as a control in a clinical trial could severely bias the results of such trials."3
Baschetti R. Treatment for Chronic Fatigue Syndrome. Arch Intern Med. 1998;158(20):2266. doi:
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