Theodore Henderson, MD, PhD

From: 'The Role of Antiviral Therapy in Chronic Fatigue Treatment' <a href="http://www.psychiatryadvisor.com/opinion/the-role-of-antiviral-therapy-in-chronic-fatigue-treatment/article/405424/2/">http://www.psychiatryadvisor.com/opinion/the-role-of-antiviral-therapy-in-chronic-fatigue-treatment/article/405424/2/</a>

A recent consensus review on Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME)1 concluded that CFS/ME is significantly underdiagnosed and that the condition is likely caused, in part, by viruses. These findings are in line with my clinical work. Together, these two sources of data point to a pathway which may help the 2.5 million sufferers of this disease in the United States.
In February, the Institute of Medicine (IOM) completed its <a href="http://www.iom.edu/Reports/2015/ME-CFS.aspx">committee review</a> on CFS/ME. This study was sponsored by the Department of Health and Human Services, the National Institutes of Health, and the Centers for Disease Control, among others.1

A comprehensive literature <a href="http://www.effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productid=2005">review and critique</a> was completed by the Agency for Healthcare Research and Quality in December  as part of this process.2 Many important advancements in the medical conceptualization of CFS/ME are included in this 282 page document.
Perhaps the most important evolutionary step was the clear message delivered on page 15 of the introduction: CFS/ME is underdiagnosed and misunderstood. More than 80% of patients go undiagnosed, while 65% of patients spend more than a year seeking the correct diagnosis. A lack of understanding of this disorder has contributed to many patients feeling maligned, blamed, and undertreated.
Some patients told the committee that they felt belittled, dismissed, and ignored by their health care professionals. Patients also have reported that some treatment strategies, including the oft-cited graded exercise regimen, exacerbated their symptoms.3
Equally striking in this report was the clear assertion that CFS/ME likely has an infectious etiology and that viruses, in particular Epstein-Barr virus (EBV), are high on the list of suspected agents.1
My clinical work has focused on the viral and immunological pathogenesis of CFS/ME. In my clinic, I have treated over 200 adults and over 30 adolescents with what the IOM now says should be called Systemic Exertion Intolerance Disease (SEID). While I have not published my adult cases, a case series of adolescents was published last year.4 What has emerged from my work is that over 85% of patients with SEID (diagnosed by Fukuda criteria5) respond to antiviral therapy. Among adolescents, the outcome is better with 92% responding.
A critical second conclusion of my work is that a subset of patients diagnosed with depression — particularly treatment-resistant depression — actually had SEID. The adolescents in the case series were all referred for evaluation of depression or mood disorder. They all presented with marked fatigue, exertion induced malaise, brain fog, and impaired academic performance.

Patients were treated with the antiviral, <a href="http://www.psychiatryadvisor.com/valtrex/drug/1931/">valacyclovir</a> (Valtrex), at a dose of 1000 mg twice a day. Only one patient experienced nausea and discontinued the antiviral. Improvement occurred over the course of 3-5 months. Eighty-six percent of the patients responded by 3 months, and 92% responded by 5 months. Symptoms of fatigue, exertion induced malaise, excessive sleep, napping, unrefreshing sleep, headaches, cognitive symptoms, and emotional symptoms all resolved.

Fatigue was specifically measured with the Fatigue Severity Scale,9 the Fatigue Symptom Inventory,10 and the Multidimensional Fatigue Symptom Inventory-Short Version (MFSI),11 which also allows assessment of cognitive symptoms, emotional symptoms, pain, and vigor. The general score on the MFSI dropped from 23.31 (+1.11) to 1.1 (+1.37) and the vigor score rose from 4.54 (+2.40) to 16.50 (+3.37). All changes were statistically significant.4 All of the responders had improved school performance, and five of seven who had previously dropped out of school had re-enrolled.

Laboratory data which I consistently find to be abnormal include: Decreased NK cell numbers, decreased NK cell function, elevated EBV antibody titers, elevated HHV6 antibody titers, and, to a lesser extent, elevated cytomegalovirus antibody titers. Some patients have obtained perfusion Single Photon Emission Computed Tomography (SPECT) scans which show diffuse hypoperfusion consistent with findings in the literature.13,14
Response to valacyclovir is slow, as often an interval of 3 months or more is necessary. Duration of treatment is variable, ranging from 8 months to years. Cessation of antiviral treatment can sometimes precipitate a relapse of symptoms.
Laboratory data which I consistently find to be abnormal include: Decreased NK cell numbers, decreased NK cell function, elevated EBV antibody titers, elevated HHV6 antibody titers, and, to a lesser extent, elevated cytomegalovirus antibody titers. Some patients have obtained perfusion Single Photon Emission Computed Tomography (SPECT) scans which show diffuse hypoperfusion consistent with findings in the literature.13,14
Response to valacyclovir is slow, as often an interval of 3 months or more is necessary. Duration of treatment is variable, ranging from 8 months to years. Cessation of antiviral treatment can sometimes precipitate a relapse of symptoms.