February 9, 2012 — Even small changes in pain intensity may greatly affect quality of life for patients with rheumatoid arthritis (RA). Muscle relaxants and neuromodulators have been tried as agents for improving RA pain control, but 2 Cochrane systematic reviews by Bethan Richards, MBBS, MMed, M Sports Med, and colleagues, published online January 18, conclude that only topical capsaicin merits consideration as add-on therapy.
Dr. Richards, who is medical superintendent and staff specialist in rheumatology at the Royal Prince Alfred Hospital Institute of Rheumatology and Orthopedics, Camperdown, Australia, told Medscape Medical News, "It should be stressed that the current evidence available is weak, based on small numbers of patients, and was carried out in a prebiologic era. We found weak evidence (6 trials, 126 participants) in the muscle relaxant paper that neither the benzodiazepine agents (diazepam and triazolam) nor the non-benzodiazepine agent (zopiclone) reduce pain when taken for 1 to 14 days. However, even this short use was associated for both agents with drowsiness and dizziness.
"In the neuromodulator paper," Dr. Richards continued, "we found that there was weak evidence (4 trials, 141 participants) that using oral nefopam, topical capsaicin, and oromucosal cannabis for 1 to 7 days can reduce pain in patients with rheumatoid arthritis better than placebo. Each of these agents was associated with a significant side effect profile, which for oral nefopam and cannabis seemed to outweigh the benefits. These agents are also difficult to access. Nefopam is not widely available, and cannabis is illegal in many parts of the world. However, given the relatively mild nature of the adverse events (local burning), capsaicin could be considered as an add-on therapy for patients with persistent local pain and an inadequate response or intolerance to other treatments."
The reviewers analyzed randomized controlled trials that compared a muscle relaxant with another therapy (active, including nonpharmacological therapies, or placebo) in adult patients with RA and that reported at least 1 clinically relevant outcome. This included benzodiazepines (diazepam, triazolam) and zopiclone.
They also analyzed randomized controlled trials that compared any neuromodulator with another therapy (active or placebo, including nonpharmacological therapies) in adult patients with RA who had at least 1 clinically relevant outcome measure. This included anticonvulsants, ketamine, bupropion, methylphenidate, nefopam, capsaicin, and the cannabinoids.
"From a clinician's point of view, the evidence presented in the analysis is very weak and not reflective of current-day patients with rheumatoid arthritis. Hence we are currently forced to extrapolate from the better-quality data available on these agents in other patient populations (knowing patients with RA may not respond the same way) and use our own clinical judgment. This is obviously not ideal, but the best we have until better quality trials in patients with RA become available," Dr. Richards said.
The researchers were surprised at the lack of high-quality trials in patients with RA, in whom pain control is a high priority. "The trials that were available were small and of low quality. In particular, there were no studies on neuromodulators such as pregabalin and gabapentin, which are often used in clinical practice," Dr. Richards said.
The researchers also warn that the populations included in this review are not reflective of current-day patients with RA. They write, "More than half the included trial participants were inpatients who were hospitalised with poorly controlled disease. Many were only receiving [nonsteroidal anti-inflammatory drugs], or occasionally low dose corticosteroids or [disease-modifying antirheumatic drugs], reflective of practice at the time. The patients selected for inclusion were predominantly women and had various degrees of RA disease severity. It was unclear what other analgesics they were taking at the time of the studies and whether the patients had any co-morbidities. It also remains unclear as to what type of pain these agents were being used for."
The authors have disclosed no relevant financial relationships.
Dr. Richards, who is medical superintendent and staff specialist in rheumatology at the Royal Prince Alfred Hospital Institute of Rheumatology and Orthopedics, Camperdown, Australia, told Medscape Medical News, "It should be stressed that the current evidence available is weak, based on small numbers of patients, and was carried out in a prebiologic era. We found weak evidence (6 trials, 126 participants) in the muscle relaxant paper that neither the benzodiazepine agents (diazepam and triazolam) nor the non-benzodiazepine agent (zopiclone) reduce pain when taken for 1 to 14 days. However, even this short use was associated for both agents with drowsiness and dizziness.
"In the neuromodulator paper," Dr. Richards continued, "we found that there was weak evidence (4 trials, 141 participants) that using oral nefopam, topical capsaicin, and oromucosal cannabis for 1 to 7 days can reduce pain in patients with rheumatoid arthritis better than placebo. Each of these agents was associated with a significant side effect profile, which for oral nefopam and cannabis seemed to outweigh the benefits. These agents are also difficult to access. Nefopam is not widely available, and cannabis is illegal in many parts of the world. However, given the relatively mild nature of the adverse events (local burning), capsaicin could be considered as an add-on therapy for patients with persistent local pain and an inadequate response or intolerance to other treatments."
The reviewers analyzed randomized controlled trials that compared a muscle relaxant with another therapy (active, including nonpharmacological therapies, or placebo) in adult patients with RA and that reported at least 1 clinically relevant outcome. This included benzodiazepines (diazepam, triazolam) and zopiclone.
They also analyzed randomized controlled trials that compared any neuromodulator with another therapy (active or placebo, including nonpharmacological therapies) in adult patients with RA who had at least 1 clinically relevant outcome measure. This included anticonvulsants, ketamine, bupropion, methylphenidate, nefopam, capsaicin, and the cannabinoids.
"From a clinician's point of view, the evidence presented in the analysis is very weak and not reflective of current-day patients with rheumatoid arthritis. Hence we are currently forced to extrapolate from the better-quality data available on these agents in other patient populations (knowing patients with RA may not respond the same way) and use our own clinical judgment. This is obviously not ideal, but the best we have until better quality trials in patients with RA become available," Dr. Richards said.
The researchers were surprised at the lack of high-quality trials in patients with RA, in whom pain control is a high priority. "The trials that were available were small and of low quality. In particular, there were no studies on neuromodulators such as pregabalin and gabapentin, which are often used in clinical practice," Dr. Richards said.
The researchers also warn that the populations included in this review are not reflective of current-day patients with RA. They write, "More than half the included trial participants were inpatients who were hospitalised with poorly controlled disease. Many were only receiving [nonsteroidal anti-inflammatory drugs], or occasionally low dose corticosteroids or [disease-modifying antirheumatic drugs], reflective of practice at the time. The patients selected for inclusion were predominantly women and had various degrees of RA disease severity. It was unclear what other analgesics they were taking at the time of the studies and whether the patients had any co-morbidities. It also remains unclear as to what type of pain these agents were being used for."
The authors have disclosed no relevant financial relationships.
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