Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review

Abstract

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. 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. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions. Randomized trials (for comparative efficacy and adverse events) and observational studies (for adverse events only) that included oral medications classified as skeletal muscle relaxants by the FDA were sought using 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. There is fair evidence that baclofen, tizanidine, and dantrolene are effective compared to placebo in patients with spasticity (primarily multiple sclerosis). There is fair evidence that baclofen and tizanidine are roughly equivalent for efficacy in patients with spasticity, but insufficient evidence to determine the efficacy of dantrolene compared to baclofen or tizanidine. There is fair evidence that although the overall rate of adverse effects between tizanidine and baclofen is similar, tizanidine is associated with more dry mouth and baclofen with more weakness. There is fair evidence that cyclobenzaprine, carisoprodol, orphenadrine, and tizanidine are effective compared to placebo in patients with musculoskeletal conditions (primarily acute back or neck pain). Cyclobenzaprine has been evaluated in the most clinical trials and has consistently been found to be effective. There is very limited or inconsistent data regarding the effectiveness of metaxalone, methocarbamol, chlorzoxazone, baclofen, or dantrolene compared to placebo in patients with musculoskeletal conditions. There is 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.

Modified Ashworth scale reliability for measurement of lower extremity spasticity among patients with SCI

“…13,14 A prior systematic review of the comparative and efficacy and safety of skeletal muscle relaxants for treatment of spasticity among patients with diverse neurologic impairments revealed equivalent efficacy of baclofen and tizanidine with a higher frequency of dry mouth with tizanidine and more weakness with baclofen. 15 A recent systematic review of stretching efficacy indicated inconclusive evidence regarding its efficacy for spasticity reduction. 16 Quantitative assessment of spasticity (both relative and absolute) is vital to the detection of spasticity among individuals with SCI and determination of treatment efficacy in a clinical trial setting or effectiveness in the clinic setting.…”

Análise dos medicamentos relaxantes musculares de ação central comercializados no Brasil na perspectiva do Cuidado ao Idoso

“…Os relaxantes musculares comercializados no país são de diferentes classes químicas do nível 4 da ATC, mas considerando o emprego terapêutico abrangem dois grupos, o do baclofeno, tizanidina, tiocolchicosídeo empregados em condições espásticas como esclerose múltipla, lesão de medula espinhal e paralisia cerebral; o outro grupo de fármacos é representado pelo carisoprodol, ciclobenzaprina, clorzoxazona e orfenadrina, empregados em condições musculoesqueléticas como lombalgias 12,35,36 .…”

“…As indicações clínicas dos relaxantes musculares são fundamentadas em evidências científicas limitadas por causa de delineamentos metodológicos de baixa qualidade, métodos de avaliação insensíveis e inclusão de número reduzido de pacientes nos ensaios clínicos 12,35,37 . É preocupante a ausência de estudos clínicos avaliando a eficácia de relaxantes musculares nos diferentes grupos etários 35 , principalmente considerando que nos Estados Unidos estima-se que aproximadamente 2 milhões de pessoas por ano usam relaxantes musculares, principalmente para lombalgia, sendo que cerca de 300.000 dos usuários são idosos 12 .…”

“…É preocupante a ausência de estudos clínicos avaliando a eficácia de relaxantes musculares nos diferentes grupos etários 35 , principalmente considerando que nos Estados Unidos estima-se que aproximadamente 2 milhões de pessoas por ano usam relaxantes musculares, principalmente para lombalgia, sendo que cerca de 300.000 dos usuários são idosos 12 .…”

“…RESULTS: We identified 18 drugs from group M03B, of which 7 (38.9%) are registered in Brazil. Of the 67 specialties registered, 35 12 . Entretanto, esses medicamentos podem induzir efeitos anticolinérgicos e sedação, o que potencialmente pode trazer riscos aos idosos.…”