Reprinted from
The Journal of Myofascial Therapy, 1(4):3, 4 April 1995


RELIABLE SCIENTIFIC REPORTING

Editorial by Dr. John C. Lowe

I was recently in the office of an M.D. who has a busy family practice. When he told me he's just started treating a few fibromyalgia patients, I asked how he does so. He told me cyclobenzaprine (Flexeril) and sometimes amitriptyline (Elavil). His reason for using these, when I asked, was "Because studies show they work."

I asked whether he'd read the study by Dr. Simon Carette and colleagues on amitriptyline and cyclobenzaprine, the only long-term trial to date. The preliminary data appeared in a 1992 issue of Arthritis and Rheumatism[1] and the complete study in a 1994 issue of the same journal.[2] The study did not show either amitriptyline or cyclobenzaprine to be more effective than a placebo, except short-term only for a very small percentage of patients.

He admitted he hadn't read Carette's findings, but he had read a 1994 article by I. John Russell, M.D., Ph.D.,[3] published in the Journal of Musculoskeletal Pain (IMP). Dr. Russell wrote, "Several investigators have demonstrated that amitriptyline is helpful in very low doses ... ," and "Another drug with demonstrated efficacy is cyclobenzaprine." Dr. Russell, a rheumatologist, fibromyalgia researcher, and Editor of JMP, provided three references for amitriptyline and three for cyclobenzaprine. He didn't include among them the 1992 or 1994 Carette articles.

The majority of patients in Carette's study did not improve. Of the placebo patients, 100% failed to benefit. Of amitriptyline patients, 79%, and of cyclobenzaprine patients, 88% didn't benefit. Put another way, 21 % of amitriptyline patients and 12% of cyclobenzaprine patients improved. The superiority of the drugs over the placebo, slight as it was, was only evident during the first month of the study. At three and six months, placebo patients had improved as much as the drug patients.

Carette speculated that more subjects in his study groups might have shown a real superiority of the drugs over the placebo. The main point at this time, however, is this: in the only long-term study, the results showed the drugs did not work any better than a placebo after one month. And during that first month, only a smidgen of the patients had improved somewhat. Moreover, 98% of patients taking cyclobenzaprine had adverse effects, and 13% of the patients stopped the drug because of adverse effects. This means more patients had bad side effects than improved: 13% to 12%. 

To me, use of these drugs is nothing to get excited over. Maybe in the future, another long-term study will show the drugs work better than a placebo. On the other hand, maybe one will show they don't. But at this point, anyone who writes that investigators have shown the efficacy of these drugs makes a highly misleading statement. An appeal to scientific accuracy demands a single statement: The only long-'term study of the effects of these drugs shows that they slightly benefit a very small percentage of patients for only a month or so.

In the article in JMP, Dr. Russell mentioned the "efficacy" of amitriptyline and cyclobenzaprine while discussing a hypothesis of the pathology of fibromyalgia. He wasn't discussing the percentage of patients who benefited from drugs or how long the benefits lasted. Nonetheless, he is an authority who has the potential for influencing the treatment choices of clinicians who don't read the original journal reports of drug studies. Because of this, I feel he and other fibromyalgia authorities must be precise in their statements in their articles, papers, and lectures. His statements in his paper about the efficacy of cyclobenzaprine and amitriptyline, however, are not precise. Many clinicians will simply accept without question his treatment endorsements and those of other sometimes-imprecise researchers. I know this to be true because I've talked with many who have. These clinicians prescribe these two drugs and similar ones. After all, "Several investigations have demonstrated that amitriptyline is helpful in very low doses. .. " and "Another drug with demonstrated efficacy is cyclobenzaprine." Clinicians assume these drugs are effective because of sweeping endorsements of effectiveness, not careful and accurate statements that reflect what the scientific evidence shows.

Busy practitioners who don't read most original journal papers on treatment studies are dependant on the statements fibromyalgia authorities make in journals and lectures Because of this, these authorities have an obligation to report precisely and accurately what science has told us. This isn't up to the authorities' discretion. It's a scientific and journalistic responsibility, and it has everything to do with the question of credibility. —JCL

References

1. Carette, S., Bell, MJ., et al.: A controlled trial of amitriptyline, cyclobenzaprine, and placebo in fibromyalgia. Arthritis & Rheum., 35(suppl.9):112, 1992.

2. Carette, S., Bell, MJ., et al.: Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. Arthritis & Rheum., 37(1):32-40, 1994.

3. Russell, LJ.: Pathogenesis of fibromyalgia: the neurohormonal hypothesis. J. Musculoskel. Pain, 2(1):73-86, 1994.