An outsider's view of chronic fatigue syndrome may provide clues to how we perceive

Lee Nyberg of the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) pointed out a very interesting manuscript by Mark Demitrack of Neuronetics, Inc. that recently appeared in the literature.

In it, he looks at clinical methodology and its implications for the study of therapeutic interventions for chronic fatigue syndrome (CFS). His comments might just as easily apply to PBS/IC, and are worth noting.

He points out that CFS is best conceptualized as a final common pathway illness. There is ample room for improvement of methods for case ascertainment and symptom measurement in treatment studies. He could be discussing PBS/IC, when he states that "Another aspect of the interpretation of clinical outcome in treatment studies is a thorough characterization of the degree of treatment resistance of the sample." As with PBS/IC, patients are often seen after a long lead time in tertiary centers where treatment studies are suggested to those refractory to standard therapy. These are probably not representative of the more typical patients who may be early in their illness. This is an area that has received a lot of attention in psychiatry where one of the best validated methodologies to ascertain the presence and degree of treatment resistance is the Antidepressant Treatment History Form (ATHF). This issue has been recognized by NIDDK and is behind the latest ongoing trial of the Interstitial Cystitis Clinical Research Network studying amitriptyline in treatment naïve patients.

A standard treatment resistance questionnaire might be a useful addition to clinical PBS/IC studies wherein the therapeutic outcomes may reveal more about the problem of treatment resistance rather than an understanding of the intervention itself.

The author concludes that pragmatic therapeutic studies can be done, despite an absence of clear understanding of CFS pathophysiology. These studies should aim to improve the identification of less chronic, more treatment responsive patient samples and focus on the development of a more sophisticated array of disease-specific observer and self-administered symptom rating scales sensitive to clinical change. I recommend this article to all of those interested in PBS/IC as the parallels can be vividly drawn by the reader.

By Philip M Hanno MD, MPH

Pharmacogenomics 7:521-528, 2006

Demitrack MA

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