Pain management is a high priority for patients with rheumatoid arthritis. Despite deficiencies in research data, neuromodulators have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain.
The aim of this review was to determine the efficacy and safety of neuromodulators in pain management in patients with rheumatoid arthritis. Neuromodulators included in this review were anticonvulsants ( Gabapentin, Pregabalin, Phenytoin, sodium Valproate [ Acid Valproic ], Lamotrigine, Carbamazepine, Levetiracetam, Oxcarbazepine, Tiagabine and Topiramate ), Ketamine, Bupropion, Methylphenidate, Nefopam, Capsaicin and the cannabinoids.
Four trials with high risk of bias were included in this review. Two trials evaluated oral Nefopam ( 52 participants ) and one trial each evaluated topical Capsaicin ( 31 participants ) and oromucosal Cannabis ( 58 participants ).
The pooled analyses identified a significant reduction in pain levels favouring Nefopam over placebo ( weighted mean difference [ WMD ] -21.16, 95% CI -35.61 to -6.71; number needed to treat, NNT=2, 95% CI 1.4 to 9.5 ) after two weeks.
There were insufficient data to assess withdrawals due to adverse events.
Nefopam was associated with significantly more adverse events ( RR=4.11, 95% CI 1.58 to 10.69; NNH=9, 95% CI 2 to 367 ), which were predominantly nausea and sweating.
In a mixed population trial, qualitative analysis of patients with rheumatoid arthritis showed a significantly greater reduction in pain favouring topical Capsaicin over placebo at one and two weeks ( MD -23.80, 95% CI -44.81 to -2.79; NNT 3, 95% CI 2 to 47; MD -34.40, 95% CI -54.66 to -14.14; NNT 2, 95% CI 1.4 to 6 respectively ).
No separate safety data were available for patients with rheumatoid arthritis, however 44% of patients developed burning at the site of application and 2% withdrew because of this.
One small, low quality trial assessed oromucosal Cannabis against placebo and found a small, significant difference favouring Cannabis in the verbal rating score pain at present ( MD -0.72, 95% CI -1.31 to -0.13 ) after five weeks.
Patients receiving Cannabis were significantly more likely to suffer an adverse event ( risk ratio, RR=1.82, 95% CI 1.10 to 3.00; NNH=3, 95% CI 3 to 13 ). These were most commonly dizziness ( 26% ), dry mouth ( 13% ) and light headedness ( 10% ).
According to authors, there is currently weak evidence that oral Nefopam, topical Capsaicin and oromucosal Cannabis are all superior to placebo in reducing pain in patients with rheumatoid arthritis. However, each agent is associated with a significant side effect profile.
The confidence in the estimates is not strong given the difficulties with blinding, the small numbers of participants evaluated and the lack of adverse event data. In some patients, however, even a small degree of pain relief may be considered worthwhile.
Until further research is available, given the relatively mild nature of the adverse events, Capsaicin could be considered as an add-on therapy for patients with persistent local pain and inadequate response or intolerance to other treatments.
Oral Nefopam and oromucosal Cannabis have more significant side effect profiles however and the potential harms seem to outweigh any modest benefit achieved. ( Xagena )
Richards BL et al, Cochrane Database of Systematic Reviews 2012, Issue 1. Art. No.: CD008921