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Meta-Analysis
. 2012 Jan 18;1(1):CD008922.
doi: 10.1002/14651858.CD008922.pub2.

Muscle relaxants for pain management in rheumatoid arthritis

Bethan L Richards  1 , Samuel L Whittle, Rachelle Buchbinder
Affiliations
Meta-Analysis

Muscle relaxants for pain management in rheumatoid arthritis

Bethan L Richards et al. Cochrane Database Syst Rev. .

Abstract

Background: Pain management is a high priority for patients with rheumatoid arthritis (RA). Muscle relaxants include drugs that reduce muscle spasm (for example benzodiazepines such as diazepam (Valium), alprazolam (Xanax), lorazepam (Ativan) and non-benzodiazepines such as metaxalone (Skelaxin) or a combination of paracetamol and orphenadrine (Muscol)) and drugs that prevent increased muscle tone (baclofen and dantrolene). Despite a paucity of evidence supporting their use, antispasmodic and antispasticity muscle relaxants 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 muscle relaxants in pain management in patients with RA. The muscle relaxants that were included in this review are the antispasmodic benzodiazepines (alprazolam, bromazepam, chlordiazepoxide,cinolazepam, clonazepam, cloxazolam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, flutoprazepam, halazepam, ketazolam, loprazolam, lorazepam, lormetazepam, medazepam, midazolam, nimetazepam, nitrazepam, nordazepam, oxazepam, pinazepam, prazepam, quazepam, temazepam, tetrazepam, triazolam), antispasmodic non-benzodiazepines (cyclobenzaprine, carisoprodol, chlorzoxazone, meprobamate, methocarbamol, metaxalone, orphenadrine, tizanidine and zopiclone), and antispasticity drugs (baclofen and dantrolene sodium).

Search methods: We performed a search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 4th quarter 2010), MEDLINE (1950 to week 1 November 2010), EMBASE (Week 44 2010), and PsycINFO (1806 to week 2 November 2010). We also searched the 2008 to 2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of relevant articles.

Selection criteria: We included randomised controlled trials which compared a muscle relaxant to another therapy (active, including non-pharmacological therapies, or placebo) in adult patients with RA and that reported at least one clinically relevant outcome.

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 muscle relaxants on pain, depression, sleep and function, as well as their safety.

Main results: Six trials (126 participants) were included in this review. All trials were rated at high risk of bias. Five cross-over trials evaluated a benzodiazepine, four assessed diazepam (n = 71) and one assessed triazolam (n = 15). The sixth trial assessed zopiclone (a non-benzodiazepine) (n = 40) and was a parallel group study. No trial duration was longer than two weeks while three single dose trials assessed outcomes at 24 hours only. Overall the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo, alone (at 24 hrs, 1 or 2 weeks) or in addition to non-steroidal anti-inflammatory drugs (NSAIDs) (at 24 hrs), on pain intensity, function, or quality of life. Data from two trials of longer than 24 hours duration (n = 74) (diazepam and zopiclone) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo (number needed to harm (NNTH) 3, 95% CI 2 to 7). These were predominantly central nervous system side effects, including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11).

Authors' conclusions: Based upon the currently available evidence in patients with RA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or one week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over two weeks. However, even short term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.

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Conflict of interest statement

None known

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Muscle relaxant versus control, outcome: 1.1 Pain 24 hrs.
4
4
Forest plot of comparison: 1 Muscle relaxant versus control, outcome: 1.2 Pain 1‐2 weeks.
5
5
Forest plot of comparison: 5 Muscle relaxant versus control ‐ safety, outcome: 5.1 Withdrawal due to adverse events.
6
6
Forest plot of comparison: 5 Muscle relaxant versus control ‐ safety, outcome: 5.2 Total adverse events.
7
7
Forest plot of comparison: 5 Muscle relaxant versus control ‐ safety, outcome: 5.3 Total adverse events ‐ trials greater than 24hrs duration.
8
8
Forest plot of comparison: 5 Muscle relaxant versus control ‐ safety, outcome: 5.5 Subgroups adverse events.
1.1
1.1. Analysis
Comparison 1 Muscle relaxant versus control, Outcome 1 Pain 24hrs.
1.2
1.2. Analysis
Comparison 1 Muscle relaxant versus control, Outcome 2 Pain 1‐2 weeks.
2.1
2.1. Analysis
Comparison 2 Benzodiazepine versus placebo, Outcome 1 Pain 24hrs.
2.2
2.2. Analysis
Comparison 2 Benzodiazepine versus placebo, Outcome 2 Pain 1 week.
2.3
2.3. Analysis
Comparison 2 Benzodiazepine versus placebo, Outcome 3 Sleep (MSLT).
2.4
2.4. Analysis
Comparison 2 Benzodiazepine versus placebo, Outcome 4 Sleep (Polysomnography).
2.5
2.5. Analysis
Comparison 2 Benzodiazepine versus placebo, Outcome 5 Sleep (Patient reported outcome measures).
2.6
2.6. Analysis
Comparison 2 Benzodiazepine versus placebo, Outcome 6 Depression.
3.1
3.1. Analysis
Comparison 3 Benzodiazepine + NSAID versus NSAID ‐ pain, Outcome 1 Pain 24hrs.
3.2
3.2. Analysis
Comparison 3 Benzodiazepine + NSAID versus NSAID ‐ pain, Outcome 2 Sleep (Wolff Sleep Score).
4.1
4.1. Analysis
Comparison 4 Non‐benzodiazepine versus placebo, Outcome 1 Pain.
4.2
4.2. Analysis
Comparison 4 Non‐benzodiazepine versus placebo, Outcome 2 Functional Status.
4.3
4.3. Analysis
Comparison 4 Non‐benzodiazepine versus placebo, Outcome 3 Sleep (Polysomnography).
4.4
4.4. Analysis
Comparison 4 Non‐benzodiazepine versus placebo, Outcome 4 Sleep (Patient reported outcomes) Spiegel Sleep Questionnaire.
4.5
4.5. Analysis
Comparison 4 Non‐benzodiazepine versus placebo, Outcome 5 Sleep (Patient reported outcomes) Leeds Sleep Evaluation.
5.1
5.1. Analysis
Comparison 5 Muscle relaxant versus control ‐ safety, Outcome 1 Withdrawal due to adverse events.
5.2
5.2. Analysis
Comparison 5 Muscle relaxant versus control ‐ safety, Outcome 2 Total Adverse Events.
5.3
5.3. Analysis
Comparison 5 Muscle relaxant versus control ‐ safety, Outcome 3 Total Adverse events ‐ trials greater than 24hrs duration.
5.4
5.4. Analysis
Comparison 5 Muscle relaxant versus control ‐ safety, Outcome 4 Total adverse events ‐ trials 24hr duration only.
5.5
5.5. Analysis
Comparison 5 Muscle relaxant versus control ‐ safety, Outcome 5 Subgroups Adverse Events.
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