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Journal of Pain and Symptom Management Aug 2004Skeletal muscle relaxants are a heterogeneous group of medications used to treat two different types of underlying conditions: spasticity from upper motor neuron... (Comparative Study)
Comparative Study Meta-Analysis Review
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.
Topics: Clinical Trials as Topic; Comorbidity; Evidence-Based Medicine; Humans; Motor Neuron Disease; Muscle Spasticity; Musculoskeletal Diseases; Neuromuscular Agents; Peripheral Nervous System Diseases; Treatment Outcome
PubMed: 15276195
DOI: 10.1016/j.jpainsymman.2004.05.002 -
Anesthesiology Jan 2019Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia...
BACKGROUND
Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality.
METHODS
The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given.
RESULTS
Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities.
CONCLUSIONS
Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.
Topics: Humans; Dantrolene; Databases, Factual; Malignant Hyperthermia; Muscle Relaxants, Central; Neuromuscular Depolarizing Agents; Succinylcholine
PubMed: 30550426
DOI: 10.1097/ALN.0000000000002490 -
Orphanet Journal of Rare Diseases Jun 2019Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea,... (Review)
Review
BACKGROUND
Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. Clinical course without treatment may result in serious disability or death. A review of treatment and its response is still pending.
RESULTS
Sixty-four cases of Satoyoshi syndrome were published between 1967 and 2018. 47 cases described the treatment administered. Drugs used can be divided into two main groups of treatment: muscle relaxants/anticonvulsants, and corticosteroids/immunosuppressants. Dantrolene improved muscle symptoms in 13 out of 15 cases, but not any other symptoms of the disease. Other muscle relaxants or anticonvulsant drugs showed little or no effect. 28 out of 30 cases responded to a regimen that included costicosteroids. Other immunosuppressive drugs including cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus and cyclophosphamide were used to decrease corticosteroid dose or improve efficacy. Immunoglobulin therapy was used in nine patients and four of them obtained a favorable response.
CONCLUSION
Corticosteroids was the most widely treatment employed with the best results in Satoyoshi syndrome. Further studies are needed to determine optimal dose and duration of corticosteroids as well as the role of other immunosuppressants and immunoglobulin therapy. Genetic or autoimmune markers will be useful to guide future therapies.
Topics: Adrenal Cortex Hormones; Alopecia; Animals; Anticonvulsants; Bone and Bones; Dantrolene; Diarrhea; Female; Humans; Immunization, Passive; Immunosuppressive Agents; Male; Rare Diseases; Spasm
PubMed: 31217029
DOI: 10.1186/s13023-019-1120-7 -
The Cochrane Database of Systematic... Nov 2014Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis... (Meta-Analysis)
Meta-Analysis Review
Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis and acute renal failure. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events.Data collection and analysis Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with: D-ribose,glucagon, verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high-dose creatine. Minimal subjective benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/Dangiotens in converting enzyme(ACE) phenotype. A carbohydrate-rich diet resulted in better exercise performance compared with a protein-rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance. Four studies reported adverse effects. Oral ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including light-headedness and hunger. In one study, branched chain amino acids caused a deterioration of functional outcomes. Dantrolene was reported to cause a number of adverse effects including tiredness, somnolence, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of myalgia.Authors' conclusions Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit.
Topics: Creatine; Dietary Carbohydrates; Dietary Proteins; Dietary Supplements; Glycogen Storage Disease Type V; Humans; Physical Endurance; Ramipril; Randomized Controlled Trials as Topic; Sucrose
PubMed: 25391139
DOI: 10.1002/14651858.CD003458.pub5 -
Health Technology Assessment... 2003To identify the drug treatments currently available for the management of spasticity and pain in multiple sclerosis (MS), and to evaluate their clinical and... (Comparative Study)
Comparative Study Review
OBJECTIVES
To identify the drug treatments currently available for the management of spasticity and pain in multiple sclerosis (MS), and to evaluate their clinical and cost-effectiveness.
DATA SOURCES
Electronic bibliographic databases, National Research Register, MRC Clinical Trials Register and the US National Institutes of Health Clinical Trials Register.
REVIEW METHODS
Systematic searches identified 15 interventions for the treatment of spasticity and 15 interventions for treatment of pain. The quality and outcomes of the studies were evaluated. Reviews of the treatment of spasticity and pain when due to other aetiologies were also sought.
RESULTS
There is limited evidence of the effectiveness of four oral drugs for spasticity: baclofen, dantrolene, diazepam and tizanidine. Tizanidine appears to be no more effective than comparator drugs such as baclofen and has a slightly different side-effects profile. Despite claims that it causes less muscle weakness, there was very little evidence that tizanidine performed any better in this respect than other drugs, although it is more expensive. The findings of this review are consistent with reviews of the same treatments for spasticity derived from other aetiologies. There is good evidence that both botulinum toxin (BT) and intrathecal baclofen are effective in reducing spasticity, and both are associated with functional benefit. However, they are invasive, and substantially more expensive. None of the studies included in the review of pain were designed specifically to evaluate the alleviation of pain in patients with MS and there was no consistency regarding the use of validated outcome measures. It was suggested that, although expensive, the use of intrathecal baclofen may be associated with significant savings in hospitalisation costs in relation to bed-bound patients who are at risk of developing pressure sores, thus enhancing its cost-effectiveness. No studies of cost-effectiveness were identified in the review of pain. There is evidence, albeit limited, of the clinical effectiveness of baclofen, dantrolene, diazepam, tizanidine, intrathecal baclofen and BT and of the potential cost-effectiveness of intrathecal baclofen in the treatment of spasticity in MS.
CONCLUSIONS
Many of the interventions identified are not licensed for the alleviation of pain or spasticity in MS and the lack of evidence relating to their effectiveness may also limit their widespread use. Indeed, forthcoming information relating to the use of cannabinoids in MS may result in there being better evidence of the effectiveness of new treatments than of any of the currently used drugs. It may therefore be of value to carry out double-blind randomised controlled trials of interventions used in current practice, where outcomes could include functional benefit and impact on quality of life. Further research into the development and validation of outcomes measures for pain and spasticity may also be useful, as perhaps would cost-utility studies.
Topics: Adolescent; Adult; Clinical Trials as Topic; Cost-Benefit Analysis; Evidence-Based Medicine; Humans; Middle Aged; Multiple Sclerosis; Muscle Relaxants, Central; Muscle Spasticity; Pain; Treatment Outcome; United Kingdom
PubMed: 14636486
DOI: 10.3310/hta7400 -
Developmental Medicine and Child... Dec 2017To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP). (Review)
Review
AIM
To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP).
METHOD
A systematic review was performed according to the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Articles were searched for in PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, Database of Reviews of Effectiveness, OTSeeker, Physiotherapy Evidence Database, REHABDATA, and ClinicalTrials.gov.
RESULTS
Sixteen articles met the eligibility criteria. Eight studies on trihexyphenidyl and two on levodopa showed contradictory results. Low efficacy was reported for diazepam, dantrolene sodium, perphenazine, and etybenzatropine. Tetrabenazine, gabapentin and levetiracetam should be studied in more detail. The updated available evidence does not support any therapeutic algorithm for the management of dyskinetic CP.
INTERPRETATION
This lack of evidence is partially owing to the inconsistency of classifications of patients and of outcome measures used in the reviewed studies. Further randomized, double-blind, placebo-controlled pharmacological trials, optimized for different age groups, based on valid, reliable, and disease-specific rating scales are strongly needed. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health.
WHAT THIS PAPER ADDS
Evidence to prove (or disprove) the efficacy of oral drugs in dyskinetic cerebral palsy is low. The most investigated drugs, trihexyphenidyl and levodopa, show contradictory results. Tetrabenazine, levetiracetam, and gabapentin efficacy should be studied in more detail. Lack of evidence is partially due to the inconsistency of classifications and outcome measures used. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health in next clinical trials.
Topics: Anticonvulsants; Cerebral Palsy; Dyskinesias; Humans; Neurotransmitter Agents; Outcome Assessment, Health Care
PubMed: 28872668
DOI: 10.1111/dmcn.13532 -
The Cochrane Database of Systematic... 2000Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are... (Review)
Review
BACKGROUND
Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available.
OBJECTIVES
To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients.
SEARCH STRATEGY
Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies.
SELECTION CRITERIA
Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration.
DATA COLLECTION AND ANALYSIS
Two independent reviewers extracted data and the findings of the trials were summarised. Missing data were collected by correspondence with principal investigators. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed.
MAIN RESULTS
Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria. Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive.
REVIEWER'S CONCLUSIONS
The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing. The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.
Topics: Anti-Dyskinesia Agents; Botulinum Toxins; Humans; Multiple Sclerosis; Muscle Relaxants, Central; Muscle Spasticity; Randomized Controlled Trials as Topic
PubMed: 11034714
DOI: 10.1002/14651858.CD001332 -
The Cochrane Database of Systematic... 2000Spasticity is a major health problem for patients with a spinal cord injury (SCI) that limits patients' mobility and affects independence in activities of daily living... (Review)
Review
BACKGROUND
Spasticity is a major health problem for patients with a spinal cord injury (SCI) that limits patients' mobility and affects independence in activities of daily living and work. Spasticity may also cause pain, loss of range of motion, contractures, sleep disorders and impair ambulation in patients with an incomplete lesion. The effectiveness of available drugs is still uncertain and they may cause adverse effects. Assessing what works in this area is complicated by the lack of valid and reliable measurement tools. The aim of this systematic review is to critically appraise and summarise existing information of the effectiveness of available treatments and to identify areas where further research is needed.
OBJECTIVES
To assess the effectiveness and safety of Baclofen, Dantrolene, Tizanidine and any other drugs for the treatment of long term spasticity in SCI patients as well as the effectiveness and safety of different routes of administration of Baclofen.
SEARCH STRATEGY
We searched the Injuries Group specialised register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINHALH up to 1998. Drug companies and experts active in the area were also contacted.
SELECTION CRITERIA
All parallel and crossover RCTs including spinal cord injury patients complaining of "severe spasticity". Studies where less than 50% of patients had a spinal cord injury were excluded.
DATA COLLECTION AND ANALYSIS
Methodological quality of studies (allocation concealment, blinding, patients characteristics, inclusion and exclusion criteria; interventions; outcomes; lost to follow up) was independently assessed by two investigators. The heterogeneity among studies did not allow quantitative combination of results.
MAIN RESULTS
Nine out of 53 studies met the inclusion criteria. Study design was: 8 cross over, 1 parallel-group trial. Two studies (14 SCI patients), showed a significant effect of intrathecal baclofen in reducing spasticity (Ashworth Score and ADL performances), compared to placebo, without any side effect. The study comparing tizanidine to placebo (118 SCI patients) showed a significant effect of tizanidine in improving Ashworth Score but not in ADL performances. Tizanidine group reported significant rates of adverse effects (drowsiness, xerostomia). For the other drugs (Gabapentine, Clonidine, Diazepam, Amytal and oral Baclofen ) the results do not provide evidence for a clinical significant effectiveness.
REVIEWER'S CONCLUSIONS
There is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.
Topics: Baclofen; Clonidine; Dantrolene; Humans; Muscle Relaxants, Central; Parasympatholytics; Spasm; Spinal Cord Injuries
PubMed: 10796750
DOI: 10.1002/14651858.CD001131 -
Critical Care (London, England) 2007Although rapid cooling and management of circulatory failure are crucial to the prevention of irreversible tissue damage and death in heatstroke, the evidence supporting... (Review)
Review
INTRODUCTION
Although rapid cooling and management of circulatory failure are crucial to the prevention of irreversible tissue damage and death in heatstroke, the evidence supporting the optimal cooling method and hemodynamic management has yet to be established.
METHODS
A systematic review of all clinical studies published in Medline (1966 to 2006), CINAHL (Cumulative Index to Nursing & Allied Health Literature) (1982 to 2006), and Cochrane Database was performed using the OVID interface without language restriction. Search terms included heatstroke, sunstroke, and heat stress disorders.
RESULTS
Fourteen articles reported populations subjected to cooling treatment for classic or exertional heatstroke and included data on cooling time, neurologic morbidity, or mortality. Five additional articles described invasive monitoring with central venous or pulmonary artery catheters. The four clinical trials and 15 observational studies covered a total of 556 patients. A careful analysis of the results obtained indicated that the cooling method based on conduction, namely immersion in iced water, was effective among young people, military personnel, and athletes with exertional heatstroke. There was no evidence to support the superiority of any one cooling technique in classic heatstroke. The effects of non-invasive, evaporative, or conductive-based cooling techniques, singly or combined, appeared to be comparable. No evidence of a specific endpoint temperature for safe cessation of cooling was found. The circulatory alterations in heatstroke were due mostly to a form of distributive shock associated with relative or absolute hypovolemia. Myocardial failure was found to be rare.
CONCLUSION
A systematic review of the literature failed to identify reliable clinical data on the optimum treatment of heatstroke. Nonetheless, the findings of this study could serve as a framework for preliminary recommendations in cooling and hemodynamic management of heatstroke until more evidence-based data are generated.
Topics: Adult; Aged; Aged, 80 and over; Dantrolene; Heat Stroke; Hemodynamics; Humans; Hydrotherapy; Hypothermia, Induced; Middle Aged; Muscle Relaxants, Central; Treatment Outcome
PubMed: 17498312
DOI: 10.1186/cc5910 -
Europa Medicophysica Mar 2006The aim of this paper was to assess the effectiveness and safety of baclofen, dantrolene, tizanidine and any other drugs for the treatment of long-term spasticity in... (Review)
Review
UNLABELLED
The aim of this paper was to assess the effectiveness and safety of baclofen, dantrolene, tizanidine and any other drugs for the treatment of long-term spasticity in spinal cord injury (SCI) patients, as well as the effectiveness and safety of different routes of administration of baclofen. A systematic review of randomised controlled trials (RCTs), within the Cochrane Collaboration Injuries Group, was carried out. The Cochrane Injuries Group Specialised Register, the Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL were searched up to July 2006 without language restriction. Drug companies and experts active in the area were also contacted to find other relevant studies. Two investigators independently identified relevant studies, extracted data and assessed methodological quality of studies resolving disagreement by consensus. Nine out of 55 studies met the inclusion criteria. The heterogeneity among studies did not allow quantitative combination of
RESULTS
Study designs were: 8 crossover, 1 parallel-group trial. Two studies (14 SCI patients) showed a significant effect of intrathecal baclofen in reducing spasticity (Ashworth score and activities of daily living [ADL] performances), compared to placebo, without any adverse effect. The study comparing tizanidine to placebo (118 SCI patients) showed a significant effect of tizanidine in improving Ashworth score but not in ADL performances. The tizanidine group reported significant rates of adverse effects (drowsiness, xerostomia). For the other drugs (gabapentine, clonidine, diazepam, amytal and oral baclofen) the results do not provide evidence for a clinical significant effectiveness. This systematic review indicates that there is insufficient evidence to assist clinicians in a rational approach to antispastic treatment for SCI. Further research is urgently needed to improve the scientific basis of patient care.
Topics: Baclofen; Clonidine; Dantrolene; Humans; Muscle Relaxants, Central; Muscle Spasticity; Randomized Controlled Trials as Topic; Spinal Cord Injuries
PubMed: 16565680
DOI: No ID Found