Ampligen is a synthetic nucleic acid product that was designed to stimulate the production of interferons, a family of immune response modifiers that are also known to have antiviral activity. Although it may not directly induce interferon, reports of double-blinded, placebo-controlled studies of CFS patients documented modest improvements in cognition and performance among Ampligen recipients compared with the placebo group. These preliminary results will need to be confirmed by further study. The Food and Drug Administration (FDA) does not approve Ampligen for widespread use, and the administration of this drug in CFS patients should be considered experimental. Ampligen is not widely available, is costly, and is generally not reimbursable through insurance programs. Finally, although most recipients of Ampligen tolerated the drug well, adverse reactions, such as liver damage, were reported and are still incompletely characterized.

Gamma globulin is pooled human immune globulin and contains antibody molecules directed against a broad range of common infectious agents. Gamma globulin is ordinarily used as a means for passively immunizing persons whose immune system has been compromised, or who have been exposed to an agent that might cause more serious disease in the absence of immune globulin. Gamma globulin is not effective in the treatment of CFS. Serious adverse reactions are uncommon, although in rare instances gamma globulin may initiate anaphylactic shock .

Corticosteroids. Controlled studies of corticosteroids have been conducted because some patients with CFS had a slight decrease in urinary cortisol levels. Some benefits were noted in patients treated with low dose hydrocortisone but the effects disappeared after one month. High dose replacement therapy had some benefit but was complicated by attendant adrenal suppression.

Dehydroepiandrosterone (DHEA) was reported in preliminary studies to improve symptoms in some patients. However, in subsequent studies, this finding has not been confirmed and the use of DHEA in patients should be regarded as experimental. Its use should be limited to patients with documented abnormalities in DHEA levels and function.

High colonic enemas have no demonstrated value in the treatment of CFS. The procedure can promote intestinal disease.

Kutapressin is a crude extract from pig's liver. It is not readily available and there is no scientific evidence that it has any value in the treatment of CFS patients. Kutapressin can elicit allergic reactions.

Neurosurgery. Unpublished reports of malformations at the base of the skull (Chiari malformations) as being causative of CFS have been circulated, and surgical intervention has been suggested in some of those unsubstantiated reports. Surgical intervention is not recommended at this time.