Subgroup of FM patients more likely respond to placebo

Janis Kelly

December 15, 2005

December 15, 2005

Ann Arbor, MI - Fibromyalgia (FM) patients with larger pain fluctuations are more likely to respond to placebo, and those responses might be enough to cloud the results of placebo-controlled clinical trials, Dr Richard E Harris (University of Michigan, Ann Arbor) reports in the November 2005 issue of Arthritis & Rheumatism [ 1 ] .

These results have direct implications for drug trials in FM and perhaps broader implications for other pain syndromes .

"These results have direct implications for drug trials in FM and perhaps broader implications for other pain syndromes," Harris writes." To counteract or control for this effect, one could either stratify participants based on baseline pain-variability index [PVI] or even remove individuals with high pain variability prior to randomization."

Great pain variability among subjects

Harris studied 125 patients with FM who used electronic diaries to capture pain intensity levels in real time. The patients were enrolled in a randomized, placebo-controlled trial of the new norepinephrine serotonin reuptake inhibitor (NSRI) milnacipran (Ixel, Cypress Bioscience Inc). This analysis, which was supported by Cypress Bioscience and the US National Institutes of Health, assessed variability in pain according to the PVI (standard deviation of pain entries over time) in patients with FM.

Pain variability varied greatly among subjects, with some patients reporting large variations in pain intensity but others reporting smaller fluctuations. The fluctuations in pain intensity reported by an individual were relatively stable over time, and this enabled the investigators to examine the associations of PVI with response to drug or placebo.

"We observed that pain variability predicts drug responsiveness. Individuals with a greater PVI at baseline were more likely to be responders; this effect was seen almost exclusively in those randomized to placebo as compared with those receiving milnacipran, suggesting that high pain variability may be a predictor of a placebo response," Harris writes.

High pain variability may be a predictor of a placebo response .

"Difference in real-time pain variability is a relatively unstudied area," Harris says . "It looks like FM patients display a wide range in variability (ie, some have constant pain whereas others have fluctuating pain)." He adds that the fact that FM patients with greater pain variability were also more likely to be placebo responders was "an unexpected finding, but one that may be very relevant if replicated by others."

The fact that pain is not constant for some FM patients has implications both for how pain should be measured in FM and for treatment.

"If placebo responders can be excluded from trials, it would be easier to show specific drug effects," Harris says. He also tells rheuma wire that he would like to see this study repeated in other chronic pain syndromes, most notably idiopathic chronic low back pain.



1. Harris RE, Williams DA, McLean SA, et al. Characterization and consequences of pain variability in individuals with fibromyalgia. Arthritis Rheum 2005; 52:3670-3674.


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