Fibromyalgia update
Bandolier
has only dipped a toe into these waters, agitated as they are by disagreement
over whether the condition exists, diagnosis, and whether any treatments, of
whatever sort, work. Readers press for a less insipid approach, so a quick
traipse through some recent(ish) reviews and trials.
A
word of caution, though, is needed. Fibromyalgia trials come with different
inclusion criteria, suggestions of differences between women and men, and
different outcomes (pain, sleep, trigger point numbers or tenderness, as a few
examples). There is no comprehensive whizzo treatment that does what it says on
the tin, so we are always looking for small gains, not cures.
Antidepressants
A
systematic review published in 2000 [1] included nine randomised trials, only
some of which were double blind. It included three cyclobenzaprine studies,
even though cyclobenzaprine is classified as a muscle relaxant. The remaining
studies were small, and we are given only effect sizes, which showed a moderate
effect for a variety of outcomes, including global assessment and pain.
Newer antidepressant studies
Since
this review we have at least three more small studies involving amitriptyline,
and three more large randomised trials, two on duloxetine and one on
milnacipran.
As
duloxetine is available it is worth looking at the studies [2,3]. Both enrolled
patients with fibromyalgia using ACR (American College of Rheumatology)
criteria, and with at least moderate pain, and had sensible exclusions. One was
exclusively, and one predominantly in women. In the 532 randomised women, 38%
had at least 50% improvement in pain over 12 weeks with 60 mg duloxetine (once
or twice a day), compared with 21% with placebo. The NNT was 5.8 (4.0 to 10).
There were improvements in quality of life, and more adverse events with
duloxetine, especially nausea and dry mouth.
Cyclobenzaprine
Five
randomised trials were included in a meta-analysis [4], but neither trials nor
review appear to be of a particularly high standard. The best that can be said
is that there may be an NNT of about 5 for symptom improvement.
Pregabalin
We
found only a single study [5] looking at an anticonvulsant. Here, pregabalin
at three dose levels was compared with placebo over eight weeks in 529 patients
(90% women) with ACR-defined fibromyalgia, with at least moderate initial pain.
There
was a strong dose-response, with only the top dose of 450 mg/day pregabalin
being significantly different from placebo. At least 50% reduction in pain was
achieved by 29% of patients on pregabalin 450 mg, compared with 13% on placebo.
The NNT over eight weeks was 6.3 (3.9 to 16). Adverse events included
dizziness, somnolence, and dry mouth.
Comment
The
results are summarised in Table 1. On the whole, not a body of evidence to be
comfortable about. There is a crying need for a robust, evidence-based
approach, applying criteria of quality, validity, and size, to help get a grip.
Table 1: Summary of evidence for drug interventions in fibromyalgia
| Intervention | How good is the evidence | Efficacy |
| Older antidepressants | A mixed bag of a small number of small trials, never really evaluated for quality or validity. | Indication of moderate effect size, but probability of some bias |
| Duloxetine | Two good, modern, randomised double blind trials, using ACR criteria, largely on women | NNT about 6 for ≥50% pain reduction |
| Cyclobenzaprine | No confidence that this evidence can be trusted because of possible deficiencies in trials and review | NNT of about 5 for some symptom improvement, but residual bias likely |
| Pregabalin | One trial, with only one arm effective, so efficacy data limited to about 260 patients. Good randomised, double blind trial using ACR criteria, largely on women | NNT about 6 for ≥50% pain reduction |
It
is also important to acknowledge that fibromyalgia attracts many other
interventions, including exercise, lifestyle modification, and some rather more
peculiar ones. It is clear that there is no quick fix, which makes a sensible
approach even more imperative to avoid chasing after ephemera.
References:
- LM Arnold et al. Antidepressant treatment of fibromyalgia: a meta-analysis and review. Psychosomatics 2000 41: 104-113.
- LM Arnold et al. A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis & Rheumatism 2004 50: 2974-2984.
- LM Arnold et al. A randomized, double-blind, placebo-controlled trial of duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder. Pain 2005 119: 5-15.
- JK Tofferi et al. Treatment of fibromyalgia with cyclobenzaprine: a meta-analysis. Arthritis & Rheumatism 2004 51: 9-13.
- LJ Crofford et al. Pregabalin for the treatment of fibromyalgia syndrome. Arthritis & Rheumatism 2005 52: 1264-1273.