Skeletal Muscle Relaxants

Health care providers prescribe skeletal muscle relaxants for a variety of indications. However, the comparative efficacy of these drugs is not well known. Skeletal muscle relaxants consist of both antispasticity and antispasmodic agents, a distinction that prescribers often overlook. The antispasticity agents - baclofen, tizanidine, dantrolene, and diazepam -aid in improving muscle hypertonicity and involuntary jerks. Antispasmodic agents, such as cyclobenzaprine, are primarily used to treat musculoskeletal conditions. Much of the evidence from clinical trials regarding skeletal muscle relaxants is limited because of poor methodological design, insensitive assessment methods, and small numbers of patients. Although trial results seem to support the use of these agents for their respective indications, efficacy data from comparator trials did not particularly favor one skeletal muscle relaxant over another. Therefore, the choice of a skeletal muscle relaxant should be based on its adverse-effect profile, tolerability, and cost (See and Ginzburg 2008).

Spasm is defined as an involuntary and abnormal muscle contraction and therefore encompasses multiple different subtypes of involuntary muscle activity. After acute muscu-loskeletal injury, the most common type of involuntary muscle activity found is spasm from segmental reflex activity resulting in increased muscle contraction in an effort to splint and protect injured tissues (Clawson 2001). Antispasticity and antispasmodic agents are often used in conjunction with the other nonopioid analgesics and with opioids for pain with a component of muscle spasm.

As reviewed by Chou et al., skeletal muscle relaxants are a heterogeneous group of medications used to treat two different types of underlying conditions: spasticity from upper motor neuron syndromes and muscular pain or spasms from peripheral musculoskeletal conditions (Chou et al. 2004). Although widely used for these indications, there appear to be gaps in our understanding of the comparative efficacy and safety of different skeletal muscle relaxants.

Chou et al. systematically reviewed the evidence for the comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions (Chou et al. 2004). They used randomized trials, observational studies, electronic databases, reference lists, and pharmaceutical company submissions. Searches were performed through January 2003. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 101 randomized trials were included in this review. No randomized trial was rated good quality, and there was little evidence of rigorous adverse event assessment in included trials or observational studies (Chou et al. 2004). They concluded that there was fair evidence that baclofen, tizanidine, and dantrolene were effective compared to placebo in patients with spasticity (primarily multiple sclerosis). There was fair evidence that baclofen and tizanidine were roughly equivalent for efficacy in patients with spasticity, but insufficient evidence to determine the efficacy of dantrolene compared to baclofen or tizanidine. There was fair evidence that although the overall rate of adverse effects between tizanidine and baclofen was similar, tizanidine was associated with more dry mouth and baclofen with more weakness (Chou et al. 2004).

There was fair evidence that cyclobenzaprine, carisoprodol, orphenadrine, and tizanidine were effective compared to placebo in patients with musculoskeletal conditions (primarily acute back or neck pain). Cyclobenzaprine has been evaluated in most clinical trials and has consistently been found to be effective. There are very limited or inconsistent data regarding the effectiveness of metaxalone, methocarbamol, chlorzoxazone, baclofen, or dantrolene compared to placebo in patients with musculoskeletal conditions. There was insufficient evidence to determine the relative efficacy or safety of cyclobenzaprine, carisoprodol, orphenadrine, tizanidine, metaxalone, methocarbamol, and chlorzoxazone. Dantrolene and, to a lesser degree chlorzoxazone, have been associated with rare serious hepatotoxicity (Chou et al. 2004).

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