Neuromodulators for pain management in rheumatoid arthritis

Background Pain management is a high priority for patients with rheumatoid arthritis (RA). Despite deficiencies in research data, neuromodulators have gained widespread clinical acceptance as adjuvants in the management of patients with chronic musculoskeletal pain. Objectives The aim of this review was to determine the efficacy and safety of neuromodulators in pain management in patients with RA. Neuromodulators included in this review were anticonvulsants (gabapentin, pregabalin, phenytoin, sodium valproate, lamotrigine, carbamazepine, levetiracetam, oxcarbazepine, tiagabine and topiramate), ketamine, bupropion, methylphenidate, nefopam, capsaicin and the cannabinoids. Search methods We performed a computer‐assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44, 2010) and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 and 2009 American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) conference s and performed a handsearch of reference lists of articles. Selection criteria We included randomised controlled trials which compared any neuromodulator to another therapy (active or placebo, including non‐pharmacological therapies) in adult patients with RA that had at least one clinically relevant outcome measure. Data collection and analysis Two blinded review authors independently extracted data and assessed the risk of bias in the trials. Meta‐analyses were used to examine the efficacy of a neuromodulator on pain, depression and function as well as their safety. Main results 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; NNTH 9, 95% CI 2 to 367), which were predominantly nausea and sweating. In a mixed population trial, qualitative analysis of patients with RA showed a significantly greater reduction in pain favouring top