Muscle Relaxants for Nonspecific Low Back Pain: A Systematic Review Within the Framework of the Cochrane Collaboration

Maurits W. van Tulder, PhD, Tony Touray, MD, Andrea D. Furlan, MD, Sherra Solway, MSc, BSc (PT), Lex M. Bouter, PhD

Disclosures

Spine. 2003;28(17) 

In This Article

Abstract and Introduction

Abstract

Study Design: A systematic review of randomized and/or double-blinded controlled trials.
Summary of Background Data: The use of muscle relaxants in the management of nonspecific low back pain is controversial. It is not clear if they are effective, and concerns have been raised about the potential adverse effects involved.
Objectives: The aim of this review was to determine if muscle relaxants are effective in the treatment of nonspecific low back pain.
Methods: A computer-assisted search of the Cochrane Library (Issue 2, 2002), MEDLINE (1966 up to October 2001), and EMBASE (1988 up to October 2001) was carried out. These databases were searched using the algorithm recommended by the Cochrane Back Review Group. References cited in the identified articles and other relevant literature were screened. Randomized and/or double-blinded controlled trials, involving patients diagnosed with nonspecific low back pain, treated with muscle relaxants as monotherapy or in combination with other therapeutic methods, were included for review. Two reviewers independently carried out the methodologic quality assessment and data extraction of the trials. The analysis comprised not only a quantitative analysis (statistical pooling) but also a qualitative analysis ("best evidence synthesis"). This involved the appraisal of the strength of evidence for various conclusions using a rating system based on the quality and outcomes of the studies included. Evidence was classified as "strong," "moderate," "limited," "conflicting," or "no" evidence.
Results: Thirty trials met the inclusion criteria. Twenty-three trials (77%) were of high quality; 24 trials (80%) were on acute low back pain. Four trials studied benzodiazepines, 11 nonbenzodiazepines, and 2 antispasticity muscle relaxants in comparison with placebo. Results showedthat there is strong evidence that any of these muscle relaxants are more effective than placebo for patients with acute low back pain on short-term pain relief. The pooled relative risk for nonbenzodiazepines versus placebo after 2 to 4 days was 0.80 (95% confidence interval: 0.71 to 0.89) for pain relief and 0.49 (95% confidence interval: 0.25 to 0.95) for global efficacy. Adverse events, however, with a relative risk of 1.50 (95% confidence interval: 1.14 to 1.98) were significantly more prevalent in patients receiving muscle relaxants and especially the central nervous system adverse effects (relative risk 2.04; 95% confidence interval: 1.23 to 3.37). The various muscle relaxants were found to be similar in performance.
Conclusions: Muscle relaxants are effective in the management of nonspecific low back pain, but the adverse effects require that they be used with caution. Trials are needed that evaluate if muscle relaxants are more effective than analgesics or nonsteroidal anti-inflammatory drugs.

Introduction

Muscle relaxants are one of the many treatments currently employed in the management of nonspecific low back pain (LBP). Thirty-five percent of patients visiting a primary care physician for LBP are prescribed muscle relaxants.[1] The term "muscle relaxants" is very broad and includes a wide range of drugs with different indications and mechanisms of action. Muscle relaxants can be divided into two main categories: antispasmodic and antispasticity medications.

Antispasmodics are used to decrease muscle spasm associated with painful conditions such as LBP. Antispasmodics can be subclassified into benzodiazepines and nonbenzodiazepines.

Benzodiazepines (e.g., diazepam, tetrazepam) are used as anxiolytics, sedatives, hypnotics, anticonvulsants, and/or skeletal muscle relaxants.[2] In general, there is no evidence that any one benzodiazepine is more effective than another if adequate dosage is given; however, pharmacokinetic differences between the drugs may be important considerations in prescription choice.

Nonbenzodiazepines include a variety of drugs that can act at the brain stem or spinal cord level.[2] The mechanisms of action with the central nervous system are still not completely understood. Cyclobenzaprine is structurally similar to the tricyclic antidepressants; however, it has strong side effects such as sedation.[3] It is currently believed that cyclobenzaprine acts in the brain stem rather than at the spinal cord level. Carisoprodol and metaxalone have moderate antispasmodic effects and are mildly sedative. Carisoprodol blocks interneuronal activity in the descending reticular formation and spinal cord. Carisoprodol is metabolized to meprobamate. Meprobamate was introduced as an antianxiety agent in 1955 and is prescribed primarily to treat anxiety, tension, and associated muscle spasms. Its onset and duration of action are similar to the intermediate-acting barbiturates; however, therapeutic doses of meprobamate produce less sedation and toxicity than barbiturates. Excessive use can result in psychological and physical dependence. Chlorzoxazone acts at the spinal cord and subcortical levels, inhibiting multisynaptic reflex arcs. The mechanism of action of methocarbamol in humans has not been established, but may be due to central nervous system depression. It has no direct action on the contractile mechanism of striated muscle, the motor endplate, or the nerve fiber. Cyclobenzaprine and orphenadrine have anticholinergic activity (which is responsible for some side effects such as dry mouth). Tolperisone has a lidocaine-like activity and stabilizes nerve membranes. It blocks in a dose-dependent manner mono- and polysynaptic reflexes at the spinal level. Tolperisone is supposed to mediate muscle relaxation without concomitant sedation or withdrawal phenomena.[4] Some antispasmodic drugs (e.g., Tizanidine) have showed in animal studies that in addition to muscle relaxant and antinociceptive effect they have also gastroprotective effects which may favor the combination of antispasmodics with nonsteroidal anti-inflammatory drugs (NSAIDs).[5]

Antispasticity medications are used to reduce spasticity that interferes with therapy or function, such as in cerebral palsy, multiple sclerosis, and spinal cord injuries.[6] The mechanism of action of the antispasticity drugs with the peripheral nervous system (e.g., dantrolene sodium) is the blockade of the sarcoplasmic reticulum calcium channel. This reduces calcium concentration and diminishes actin-myosin interaction. Baclofen is a gamma aminobutyric acid (GABA) derivative with central nervous system action. It inhibits transmission at spinal level and also depresses the central nervous system.[7]

The use of muscle relaxants for low back pain continues to be a source of controversy among physicians, mainly because of their side effects. In addition to sedation, potential adverse effects include drowsiness, headache, blurred vision, nausea, and vomiting. Potential for abuse and dependency has also been reported.[8] The controversy is evident in the recommendations found in national clinical guidelines for the management of low back pain in primary care. Some guidelines recommend muscle relaxants alone or in combination with NSAIDs as optional, others clearly do not recommended using them.[9] Despite this, 91% of physicians report using muscle relaxants even if they are conditionally discouraged by guidelines.[10]

The role of muscle spasm in the pathophysiology of LBP is also controversial. Low back pain is generally considered to be the result of a self-perpetuating cycle of pain and spasm. Some physicians have questioned this model and thus, the efficacy of muscle relaxants.[11] Others view muscle spasm as a protective physiologic response that should not be inhibited by muscle relaxants.[12] Muscle spasm secondary to a pathologic lesion in the lumbosacral region (e.g., facet joints, discs, muscles, or ligaments) will immobilize the back and therefore contribute to the healing process.

Controversies surrounding muscle relaxants have resulted in some resistance to their use in patient care. Studies have been published which suggest a potential role for muscle relaxants in clinical practice[13]; however, there is a lack of good quality research on the clinical application of these drugs.[14]

Objectives

The aim of this systematic review was to determine if muscle relaxants are effective in the treatment of nonspecific LBP. The following comparisons were investigated:

  1. Muscle relaxants versus placebo

  2. Muscle relaxants versus paracetamol/acetaminophen

  3. Muscle relaxants versus NSAIDs

  4. Muscle relaxants versus mscle relaxants

  5. Muscle relaxants + analgesics/NSAIDs versus placebo + analgesics/NSAIDs

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