Four days later, a leading arthritis journal devoted more than half its pages to reports that FMS is a genuine medical condition (Semin Arthritis Rheum, 2007; 36: 335-379).
A coincidence? After all, as recently as three years ago, FMS was put in the same diagnostic box as the chronic fatigue (CFS/ME) and Gulf War syndromes-conditions that had "no clearly demonstrated pathophysiolog-ical origin" and were associated with "psychiatric problems" (J Clin Exp Neuropsychol, 2004; 26: 369-92). In fact, for decades, doctors tended to diagnose anyone with pain not linked to a physical problem as a psychosomatic-and prescribed an antidepressant.
That's all changed now. The recent review of the clinical evidence for FMS proposes the theory that it is caused by neuroendocrine aberrations leading to 'central sensitization', where the nerves in certain parts of the body become extremely sensitive, with the result that even mild pressure or the slightest touch can cause pain.
The author of the theory is professor of rheumatology Dr Muhammad Yunus, of the University of Illinois. "FMS is based on real neurochemical pathol-ogy," he says. "In some patients, stress and depression may contribute to the symptoms, but they are all based on objective changes in the central nervous system" (Semin Arthritis Rheum, 2007; 36: 339-56).
So, as a further confirmation that FMS is a genuine medical condition, there's now a drug for it-Lyrica-described by Pfizer, the company that makes it, as "a breakthrough for the more than six million Americans who suffer from this debilitating condition, who previously had no FDA-approved treatment options". It's likely that Pfizer is already lobbying the European regulatory authorities, too.
How does pregabalin work? Pfizer claims it "reduces overfiring of nerve signals" by binding to the calcium channels of cells in the central nervous system. "However, the exact mech-anism of action is unknown," says the drug company. That's no criticism, of course, as we don't really know how aspirin works. But, is Lyrica really the breakthrough it's cracked up to be?
Lyrica facts so far
The drug has been through only two clinical trials, both funded by Pfizer. The first involved doctors who had financial links to the drug industry. This eight-week, multicentre, double-blind, placebo-controlled trial used a range of doses of pregabalin and involved more than 500 FMS patients.
The results were less than ideal. They found that only the highest dose (450 mg/day) had any significant effect-and that effect was not much better than with a placebo: only 48 per cent of patients taking the drug experienced any "clinically meaning-ful" pain reduction compared with 27 per cent with a placebo. Overall, across all the dosages, there was a mere 10 per cent reduction in pain (Arthritis Rheum, 2005; 52: 1264-73).
In the second clinical trial, a higher dose of pregabalin (600 mg/day) was used for 14 days in an effort to boost its performance. But even that dosage didn't significantly reduce pain in more than two-thirds of the 745 patients (presented at a meeting of the American Academy of Neurology in Boston, 2007).
Although Pfizer is touting Lyrica as a new drug for FMS, pregabalin was first marketed three years ago as an anticonvulsant drug for epilepsy. However, as it turned out to have only a modest effect in preventing seizures, Pfizer was on the look-out for other conditions the agent might treat. To date, Lyrica has been tested in patients suffering from alcohol withdrawal symptoms, generalized anxiety dis-order, restless legs syndrome, diabetic neuropathy and essential tremor-but none with any major success.
Pfizer claims that Lyrica is well tolerated but, in fact, about a third of trial patients dropped out because they couldn't handle the effects of the drug, which included dizziness, sleepiness, dry mouth, swelling of the hands and feet, blurred vision, weight gain and difficulty in concentrating.
Pfizer admits, albeit in the small print of the adverse-events data, to the drug's bearing a litany of unpleasant conditions-no doubt dismal reading for the patients using Lyrica. Up to one in 10 patients experiences ataxia (movement incoordination), dysarthria (speech disorders), tremor, lethargy, memory impairment, euphoria, constipation, decreased libido and/or erectile dysfunction. Moreover, up to one in 100 suffers depression, confusion, agitation, hallucinations, myoclonus, hypo-/hyperaesthesia (under-/over-sensitivity to touch), tachycardia, excessive salivation, sweating, flushing, rash, muscle cramps, myalgia (muscle pain), arthralgia (joint pain), urinary incontinence, pain or discomfort on urinating, thrombocytopenia and/or kidney stones.
Pregabalin is also a schedule V controlled substance because of its "potential for abuse and dependence" (Am J Health Syst Pharm, 2007; 64: 1475-82).
Whatever Lyrica's performance, you can be sure that other Big Pharma players are already lining up their own drugs for the still almost virgin fibromyalgia market.
See also WDDTY vol 18 no 1 for alternative treatments for FMS.