Amivet.org2

Choosing a Skeletal Muscle Relaxant
Sharon See, PharmD, BCPS, and regina ginzBurg, PharmD
St. John’s University College of Pharmacy and Allied Health Professions, Jamaica, New York
Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However,
evidence of their effectiveness consists mainly of studies with poor methodologic design. In
addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal
anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support
using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal
anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies
have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the
most heavily studied and has been shown to be effective for various musculoskeletal conditions.
The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia
caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although
effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are
consistently reported with all skeletal muscle relaxants. The potential adverse effects should be
communicated clearly to the patient. Because of limited comparable effectiveness data, choice
of agent should be based on side-effect profile, patient preference, abuse potential, and possible
drug interactions. (Am Fam Physician. 2008;78(3):365-370. Copyright 2008 American Acad-
emy of Family Physicians.)
Skeletal muscle relaxants are often conditions. The american Pain Society and the american College of Physicians recom- ditions including low back pain, neck mend using acetaminophen and nonsteroi-pain, fibromyalgia, tension head- dal anti-inflammatory drugs (nSaiDs) as aches, and myofascial pain syndrome. The first-line agents for acute low back pain and goals of treatment include managing muscle reserving skeletal muscle relaxants as an pain and improving functional status so the alternative treatment option.12 This recom-patient can return to work or resume previ- mendation is based on available literature, which shows skeletal muscle relaxants are Skeletal muscle relaxants are divided into better than placebo, but not more effective two categories: antispastic (for conditions than nSaiDs in patients with acute back such as cerebral palsy and multiple sclero- pain. Similar recommendations exist in sis) and antispasmodic agents (for muscu- treating tension headaches.13 a meta-analysis loskeletal conditions). antispastic agents evaluating the use of cyclobenzaprine showed (e.g., baclofen [Lioresal], dantrolene [Dant- that, although this drug was better than pla- rium]) should not be prescribed for muscu- cebo for the treatment of fibromyalgia, it loskeletal conditions because there is sparse was considered inferior to antidepressants.14 evidence to support their use. rather, an additionally, recent guidelines on fibromy-antispasmodic agent may be more appropri- algia recommend using a comprehensive approach that utilizes tramadol (ultram), antidepressants, and/or a heated pool (with prodol (Soma), cyclobenzaprine (Flexeril), or without exercise).15metaxalone (Skelaxin), and methocarba- Prescription rates for nonspecific back mol (robaxin) were among the top 200 pain revealed that skeletal muscle relaxants drugs dispensed in the united States in accounted for 18.5 percent of prescriptions 2006.10,11 Despite their popularity, skeletal compared with 16.3 percent for nSaiDs and muscle relaxants should not be the primary 10 percent for cyclooxygenase-2 inhibitors.16 drug class of choice for musculoskeletal Because of the high rate of prescribing skeletal Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright 2008 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests.
Skeletal Muscle Relaxants
Table 1. Skeletal Muscle Relaxants (Antispasmodic Agents)
Physical or psychological dependence may occur; withdrawal symptoms may occur with Rare idiosyncratic reactions (mental status changes, transient quadriplegia, and temporary loss of vision) after first dose; may Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Al ergy-type reactions may occur after the first to fourth dose; Contraindicated in acute intermittent porphyria may be mild (e.g., cutaneous rash) or more severe (e.g., asthma attack, angioneurotic edema, hypotension, or anaphylactic shock); antihistamines, epinephrine, or corticosteroids may be needed Avoid use in patients with hepatic impairment Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Hepatoxicity (rare); discontinue with elevated liver function test Anticholinergic effect (drowsiness, dry mouth, urinary retention, Rare but serious adverse effects are arrhythmias, seizures, 5-mg dose as effective as 10-mg, with fewer adverse effects Avoid in older patients and in patients with glaucomaPossible drug interaction with CYP450 inhibitorsSeizures reported with concomitant use of tramadol (Ultram); combination should be avoided in patients with medical conditions that may induce seizures Contraindicated in patients with arrhythmias, recent myocardial infarction, or congestive heart failureFDA pregnancy category B Long elimination half-life; avoid in older patients and in patients with hepatic impairment Possible drug interaction with CYP450 inhibitors Complete blood count and liver function tests indicated for prolonged useFDA pregnancy category D; avoid especial y in the first trimester Drowsiness, dizziness, headache, nervousness Use with caution in patients with liver failure Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Less dizziness and drowsiness than other skeletal muscle relaxants Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Possible exacerbation of myasthenia gravis symptoms FDA pregnancy category C; reports of fetal abnormalities Anticholinergic effect (drowsiness, dry mouth, urinary retention, Avoid in patients with glaucoma, cardiospasm, or myasthenia gravis Decreases effect of phenothiazines (e.g., chlorpromazine [Thorazine†], promethazine [Phenergan]) Confusion, tachycardia, hypersensitivity reaction (with high doses) Dose-related hypotension, sedation, and dry mouth Hepatotoxicity; monitor liver function tests at baseline and one, Do not use with CYP1A2 inhibitors, ciprofloxacin (Cipro) or fluvoxamine (Luvox CR) Caution with CYP1A2 inhibitors, central nervous system depressants, or alcohol Withdrawal and rebound hypertension may occur in patients Decreased effectiveness with oral contraceptives discontinuing therapy after receiving high doses for long period NOTE: The table contains only selected highlights about these medications. All of these drugs may cause increased drowsiness with central nervous *—For the recommended adult dosage. Estimated cost to the pharmacist based on average wholesale prices (rounded to the nearest dol ar) in Red Book. system depressants. Caution is advised when prescribing skeletal muscle relaxants in older patients. Montvale, N.J.: Medical Economics Data, 2007. Cost to the patient will be higher, depending on prescription fil ing fee. CYP = cytochrome P; FDA = U.S. Food and Drug Administration; GI = gastrointestinal. †—Brand not available in the United States. Information from references 1 through 9. Skeletal Muscle Relaxants
Table 1. Skeletal Muscle Relaxants (Antispasmodic Agents)
Physical or psychological dependence may occur; withdrawal symptoms may occur with Rare idiosyncratic reactions (mental status changes, transient quadriplegia, and temporary loss of vision) after first dose; may Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Al ergy-type reactions may occur after the first to fourth dose; Contraindicated in acute intermittent porphyria may be mild (e.g., cutaneous rash) or more severe (e.g., asthma attack, angioneurotic edema, hypotension, or anaphylactic shock); antihistamines, epinephrine, or corticosteroids may be needed Avoid use in patients with hepatic impairment Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Hepatoxicity (rare); discontinue with elevated liver function test Anticholinergic effect (drowsiness, dry mouth, urinary retention, Rare but serious adverse effects are arrhythmias, seizures, 5-mg dose as effective as 10-mg, with fewer adverse effects Avoid in older patients and in patients with glaucomaPossible drug interaction with CYP450 inhibitorsSeizures reported with concomitant use of tramadol (Ultram); combination should be avoided in patients with medical conditions that may induce seizures Contraindicated in patients with arrhythmias, recent myocardial infarction, or congestive heart failureFDA pregnancy category B Long elimination half-life; avoid in older patients and in patients with hepatic impairment Possible drug interaction with CYP450 inhibitors Complete blood count and liver function tests indicated for prolonged useFDA pregnancy category D; avoid especial y in the first trimester Drowsiness, dizziness, headache, nervousness Use with caution in patients with liver failure Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Less dizziness and drowsiness than other skeletal muscle relaxants Possible respiratory depression when combined with benzodiazepines, barbiturates, codeine or its derivatives, or other muscle relaxants Possible exacerbation of myasthenia gravis symptoms FDA pregnancy category C; reports of fetal abnormalities Anticholinergic effect (drowsiness, dry mouth, urinary retention, Avoid in patients with glaucoma, cardiospasm, or myasthenia gravis Decreases effect of phenothiazines (e.g., chlorpromazine [Thorazine†], promethazine [Phenergan]) Confusion, tachycardia, hypersensitivity reaction (with high doses) Dose-related hypotension, sedation, and dry mouth Hepatotoxicity; monitor liver function tests at baseline and one, Do not use with CYP1A2 inhibitors, ciprofloxacin (Cipro) or fluvoxamine (Luvox CR) Caution with CYP1A2 inhibitors, central nervous system depressants, or alcohol Withdrawal and rebound hypertension may occur in patients Decreased effectiveness with oral contraceptives discontinuing therapy after receiving high doses for long period NOTE: The table contains only selected highlights about these medications. All of these drugs may cause increased drowsiness with central nervous *—For the recommended adult dosage. Estimated cost to the pharmacist based on average wholesale prices (rounded to the nearest dol ar) in Red Book. system depressants. Caution is advised when prescribing skeletal muscle relaxants in older patients. Montvale, N.J.: Medical Economics Data, 2007. Cost to the patient will be higher, depending on prescription fil ing fee. CYP = cytochrome P; FDA = U.S. Food and Drug Administration; GI = gastrointestinal. †—Brand not available in the United States. Information from references 1 through 9. Skeletal Muscle Relaxants
SORT: kEY REcOMMEndATiOnS FOR PRAcTicE
Skeletal muscle relaxants are not considered first-line therapy for musculoskeletal conditions.
Skeletal muscle relaxants may be used as adjunctive therapy for acute low back pain.
Antispasmodic agents should be used short-term (two weeks) for acute low back pain. There is no clear evidence that one skeletal muscle relaxant is superior to another for Choice of skeletal muscle relaxant should be based on individual drug characteristics and A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, see http://www.aafp.
org/afpsort.xml. muscle relaxants, an understanding of the risks and benefits shown to improve pain, muscle spasm, functional status, of this class of drugs is vital. This article presents evidence and global evaluation versus diazepam (Valium) in two regarding the use of antispasmodic skeletal muscle relax- fair-quality studies.23,24 Conversely, two other fair- and ants for various musculoskeletal conditions, and appropri- poor-quality studies did not reveal any significant dif- ate drug selection if a skeletal muscle relaxant is required. ference between cyclobenzaprine and diazepam.25,26 one highlights of contraindications, adverse effects, and drug meta-analysis evaluated 14 studies comparing cycloben-interactions for these drugs are listed in Table 1.1-9 zaprine with placebo for back and neck pain.27 The trials included were of less than 14 days’ duration. Cycloben- Evidence of Effectiveness
zaprine was found to be moderately more effective than Many of the studies evaluating the effectiveness of skel- placebo, but had more central nervous system adverse etal muscle relaxants are hampered by poor methodologic effects. The authors also described several limitations of design, including incomplete reporting of compliance, the meta-analysis including inadequate blinding, hetero-improper or no mention of allocation concealment, not geneity among studies, and the presence of publication utilizing intention-to-treat methods, and inadequate ran- bias.27 overall, studies appear to be consistent, with cyclo- domization.17,18 nonetheless, skeletal muscle relaxants have benzaprine having greatest benefit within the first few been evaluated in systematic reviews and meta-analyses.
days of treatment rather than at one or two weeks.18,27 Skeletal muscle relaxants have also been studied as BAck And nEck PAin
adjunctive therapy to analgesics in treating acute low back Some evidence appears to support nonbenzodiazepine pain. in one open-label study (20 patients), the addition of skeletal muscle relaxants, such as carisoprodol, cyclo- cyclobenzaprine to naproxen (naprosyn) resulted in a sta- benzaprine, orphenadrine (norflex), and tizanidine tistically significant decrease in muscle spasm and tender-(zanaflex), for acute low back pain.17,18 These agents ness compared with naproxen alone.28 a Cochrane review have been shown to be moderately effective for short- analyzed three high-quality trials (560 total patients) that term relief (two weeks) compared with placebo.17,18 ran- showed tizanidine plus analgesics was more effective in domized controlled trials involving metaxalone have providing pain relief and decreasing muscle spasm than not been conducted since the 1970s. one fair-quality analgesics alone.17 Conversely, one low-quality open-label study showed no difference between metaxalone and study (867 patients) comparing cyclobenzaprine alone placebo.19 Limited evidence exists to support the use of (5 mg three times daily) versus combination with ibuprofen skeletal muscle relaxants in chronic low back pain.17,20 (Motrin; either 400 or 800 mg three times daily) showed Benzodiazepines have been effective for short-term use that, although all groups improved at seven days, there was compared with placebo, but the basis of this recommen- no statistical difference in outcomes among the groups.29 dation stemmed from trials involving tetrazepam, which nonetheless, the use of combination therapy has been is not available in the united States.21,22 supported in quickening recovery,17 with minimal Cyclobenzaprine has been the most heavily studied overall risk of adverse effects (relative risk [rr] = 1.34; drug, with consistently proven effectiveness.17,18 it was 95% confidence interval [Ci], 0.67 to 2.67].20 368  American Family Physician
Volume 78, Number 3 ◆ August 1, 2008 Skeletal Muscle Relaxants
FiBROMYAlgiA
short-term use; therefore, multiple modalities (e.g., phys- Cyclobenzaprine has also been studied in treating fibro- ical therapy, adjunctive analgesics) may be warranted to myalgia. a meta-analysis of five trials ranging from six prevent chronic use of these medications.
to 24 weeks’ duration included a total of 312 patients Selection of a skeletal muscle relaxant should be with fibromyalgia. The authors reported that, although individualized to the patient. if there are tender spots cyclobenzaprine moderately improved sleep and pain, over the muscle or trigger points on physical examina-the long-term benefits were unknown. This meta- tion, a skeletal muscle relaxant is a reasonable adjunct analysis was limited by a high drop-out rate, short trial to analgesic treatment of low back pain. Skeletal muscle duration, few studies having an intention-to-treat design, relaxants may also be used as an alternative to nSaiDs and inadequate blinding.14 in patients who are at risk of gastrointestinal or renal complications. cOMPARiSOn dATA
Patients with low back pain or fibromyalgia may bene- Strong data comparing skeletal muscle relaxants to each fit from treatment with cyclobenzaprine. recent evidence other are scarce. a systematic review evaluated 46 tri- showed similar effectiveness at half of its manufacturer rec- als (head-to-head and placebo-controlled) comprising ommended dose (5 mg), but with fewer adverse effects.33 it mostly of studies on low back pain or neck syndromes. may optimally be used in younger patients with limited or The placebo-controlled trials included 17 on cyclobenza- no medical conditions. higher doses of cyclobenzaprine prine, six on tizanidine, four on carisoprodol, and four or tizanidine would be appropriate to promote sedation on orphenadrine, and were mostly conducted more than in cases of more severe discomfort or perceived muscu-15 years ago. The average patient enrollment was less than lar spasm. although there appears to be insufficient data 150 patients (range 12 to 400 patients). in general, all of the on metaxalone and methocarbamol, these may be useful drugs were shown to have some benefit.18 The limitations in patients who cannot tolerate the sedative properties of of published comparison trials include using unvalidated cyclobenzaprine or tizanidine. of note, methocarbamol scales to measure outcomes, involving small numbers of costs substantially less than metaxalone.
participants, and often not reporting adverse effects of Carisoprodol is metabolized to meprobamate (a class studied medications. one fair-quality study showed cari- iii controlled substance) and has been shown to produce soprodol was better than diazepam at improving muscle psychological and physical dependence.34 Carisoprodol spasm and global and functional status in patients with and diazepam should be reserved for last-line therapy low back pain.30 another fair-quality study comparing because of their abuse potential and lack of superiority tizanidine with chlorzoxazone (Parafon Forte) for back to other skeletal muscle relaxants. although all skeletal spasms did not show any significant difference.31 muscle relaxants should be used with caution in older a different systematic review did include some studies patients, diazepam especially should be avoided in older which were considered to be high quality.17 These studies patients or in patients with significant cognitive or revealed no difference in outcomes (e.g., muscle spasms, hepatic impairment. muscle pain, tension, tenderness, functional status) This is one in a series of “Clinical Pharmacology” articles coordinated by among cyclobenzaprine versus carisoprodol; chlorzoxa- Al en F. Shaugnessy, PharmD, Tufts University Family Medicine Residency zone versus tizanidine; or diazepam versus tizanidine.17 at Cambridge Health Al iance, Malden, Mass.
Place in Therapy
The Authors
although the evidence for effectiveness of skeletal mus-cle relaxants in musculoskeletal conditions is limited, SHARon See, PharmD, BCPS, is an associate clinical professor at St. John’s strong evidence does exist in terms of toxicity. in acute University College of Pharmacy and Al ied Health Professions in Jamaica, nY, and a faculty member at the Beth Israel Residency Program in Urban low back pain trials, skeletal muscle relaxants increased Family Practice in new York, nY. She received her doctor of pharmacy overall adverse effects (rr = 1.50; 95% Ci, 1.14 to 1.98) degree from Rutgers University College of Pharmacy in new Brunswick, nJ, and central nervous system adverse effects (rr = 2.04; and completed an inpatient family medicine pharmacy specialty residency at 95% Ci, 1.23 to 3.37) such as dizziness and drowsiness.17 Deaconess Hospital and the St. Louis College of Pharmacy in St. Louis, Mo. Because of the weak evidence for comparable effective- ReGInA GInzBURG, PharmD, is an assistant clinical professor at St. John’s ness, selection of an agent should be based on side-effect University Col ege of Pharmacy and Al ied Health Professions and a faculty profile, patient preference, abuse potential, drug interac- member at the Beth Israel Residency Program in Urban Family Practice. She received her doctor of pharmacy degree from St. John’s University Col- tion potential, and other characteristics of the individ- lege of Pharmacy and Al ied Health Professions, and completed a general ual drugs.32 Skeletal muscle relaxants are indicated for practice residency at Albert einstein Medical Center in Philadelphia, Pa. August 1, 2008 ◆ Volume 78, Number 3 American Family Physician  369
Skeletal Muscle Relaxants
Address correspondence to Sharon See, PharmD, BCPS, St. John’s Uni- 15. Carvil e SF, Arendt-Nielsen S, Bliddal H, et al. EULAR evidence-based versity College of Pharmacy and Allied Health Professions, 8000 Utopia recommendations for the management of fibromyalgia syndrome. Ann Parkway, Jamaica, NY 11439 (e-mail: [email protected]). Reprints are Rheum Dis. 2008;67(4):536-541.
16. Luo X, Pietrobon R, Curtis LH, Hey LA. Prescription of nonsteroidal anti- inflammatory drugs and muscle relaxants for back pain in the United Author disclosure: nothing to disclose.
States. Spine. 2004;29(23):E531-E537.
17. van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM. Muscle REFEREncES
relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003;(2):CD004252.
1. Carisoprodol (carisoprodol) tablet [package insert]. Philadelphia, Pa.: 18. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of Mutual Pharmaceutical Company, Inc.; 2006. http://dailymed.nlm.nih.
skeletal muscle relaxants for spasticity and musculoskeletal conditions: gov/dailymed/fdaDrugXsl.cfm?id=2774&type=display. Accessed Janu- a systematic review. J Pain Symptom Manage. 2004;28(2):140-175.
19. Diamond S. Double-blind study of metaxalone; use as a skeletal-muscle 2. Chlorzoxazone (chlorzoxazone) tablet [package insert]. Sellersville, Pa.: relaxant. JAMA. 1966;195(6):479-480.
Teva Pharmaceuticals USA; 2003. http://dailymed.nlm.nih.gov/dailymed/ 20. Chou R, Huffman LH. Medications for acute and chronic low back fdaDrugXsl.cfm?id=2402&type=display. Accessed January 14, 2008.
pain: a review of the evidence for an American Pain Society/Ameri- 3. Cyclobenzaprine hydrochloride (cyclobenzaprine hydrochloride) tab- can Col ege of Physicians clinical practice guideline. Ann Intern Med. let [package insert]. Corona, Calif.: Watson Laboratories, Inc.; 2005. http://dailymed.nlm.nih.gov/dailymed/fdaDrugXsl.cfm?id=2794&type 21. Arbus L, Fajadet B, Aubert D, Morre M, Goldfinger E. Activity of tetraz- =display. Accessed January 14, 2008.
epam in low back pain. Clin Trials J. 1990;27(4):258-267.
4. Diazepam (diazepam) tablet [package insert]. Miami, Fla.: IVAX 22. Salzmann E, Pforringer W, Paal G, Gierend M. Treatment of chronic low- Pharmaceuticals, Inc.; 2004. http://dailymed.nlm.nih.gov/dailymed/ back syndrome with tetrazepam in a placebo control ed double-blind fdaDrugXsl.cfm?id=3430&type=display. Accessed January 14, 2008.
trial. J Drug Dev. 1992;4:219-228.
5. Skelaxin (metaxalone) [package insert]. Briston, Tenn.: King Phar- 23. Scheiner JJ. Cyclobenzaprine in the treatment of local muscle spasm. In: maceuticals; 2007. http://dailymed.nlm.nih.gov/dailymed/drugInfo.
Clinical Evaluation of Flexeril (Cyclobenzaprine HCI/MSD). Minneapolis, cfm?id=4505. Accessed January 14, 2008.
Minn.: Postgraduate Medicine Communications;1978:39-48.
6. Methocarbamol (methocarbamol) tablet [package insert]. Eatontown, 24. Aiken DW. A comparative study of the effects of cyclobenzaprine, diaz- NJ: West-ward Pharmaceutical Corp.; 2003. http://dailymed.nlm. epam, and placebo on acute skeletal muscle spasm of local origin. In: nih.gov/dailymed/fdaDrugXsl.cfm?id=2833&type=display. January 14, Clinical Evaluation of Flexeril (Cyclobenzaprine HCI/MSD). Minneapolis, Minn.: Postgraduate Medicine Communications;1978:34-38.
7. Orphenadrine citrate extended-release (orphenadrine citrate) tablet 25. Brown BR jr, Womble J. Cyclobenzaprine in intractable pain syndrome [package insert]. Princeton, NJ: Sandoz, Inc.; 2006. http://dailymed.nlm.
with muscle spasms. JAMA. 1978;240(11):1151-1152.
nih.gov/dailymed/drugInfo.cfm?id=3665. Accessed January 14, 2008.
26. Basmajian JV. Cyclobenzaprine hydrochloride effect on skeletal muscle 8. Tizanidine hydrochloride (tizanidine hydrochloride) tablet [package spasm in the lumbar region and neck: two double-blind control ed clini- insert]. Pomona, NY: Barr Laboratories.; 2006.http://dailymed.nlm.
cal laboratory studies. Arch Phys Med Rehabil. 1978;59(2):58-63.
nih.gov/dailymed/fdaDrugXsl.cfm?id=1147&type=display. 27. Browning R, Jackson JL, O’Mal ey PG. Cyclobenzaprine and back pain: a meta-analysis. Arch Intern Med. 2001;161(13):1613-1620.
9. United States Food and Drug Administration. 2007 safety alerts for drugs, biologics, medical devices, and dietary supplements. Zanaflex (tizanidine 28. Borenstein DG, Lacks S, Wiesel SW. Cyclobenzaprine and naproxen ver- hydrochloride) tablets and capsules. http://www.fda.gov/medwatch/ sus naproxen alone in the treatment of acute low back pain and muscle safety/2007/safety07.htm#Zanaflex. Accessed January 14, 2008.
spasm. Clin Ther. 1990;12(2):125-131.
10. DrugTopics.com. Top 200 brand-name drugs by units in 2006. http:// 29. Childers MK, Borenstein D, Brown RL, et al. Low-dose cyclobenza- www.drugtopics.com/drugtopics/data/articlestandard//drugtopics/ prine versus combination therapy with ibuprofen for acute neck or 092007/407649/article.pdf. Accessed January 14, 2008.
back pain with muscle spasm: a randomized trial. Curr Med Res Opin. 2005;21(9):1485-1493.
11. DrugTopics.com. Top 200 generic drugs by units in 2006. http:// www.drugtopics.com/drugtopics/data/articlestandard//drugtopics/ 30. Boyles W, Glassman J, Soyka J. Management of acute musculoskel- 092007/407652/article.pdf. Accessed January 14, 2008.
etal conditions: thoracolumbar strain or sprain. Double-blind evalua-tion comparing the efficacy and safety of carisoprodol with diazepam. 12. Chou R, Qaseem A, Snow V, et al., for the Clinical Efficacy Assess- Today’s Ther Trends. 1983;1:1-16.
ment Subcommittee of the American Col ege of Physicians; American Col ege of Physicians; American Pain Society Low Back Pain Guideline 31. Bragstad A, Blikra G. Evaluation of a new skeletal muscle relaxant in Panel. Diagnosis and treatment of low back pain: a joint clinical prac- the treatment of lower back pain (a comparison of DS 103-282 with tice guideline from the American Col ege of Physicians and the Ameri- chlorzoxazone). Curr Ther Res Clin Exp. 1979;26(1):39-43.
can Pain Society [published correction appears in Ann Intern Med. 32. Beebe FA, Barkin RL, Barkin S. A clinical and pharmacologic review of 2008;148(3):247-248]. Ann Intern Med. 2007;147(7):478-491.
skeletal muscle relaxants for musculoskeletal conditions. Am J Ther. 13. National Headache Foundation. National Headache Foundation stan- dards of care for headache diagnosis and treatment. Chicago, Il .: 33. Borenstein DG, Korn S. Efficacy of a low-dose regimen of cycloben- National Headache Foundation; 2007. http://www.headaches.org/ zaprine hydrochloride in acute skeletal muscle spasm: results of two consumer/press%20releases/51507/FINAL_NHF%20Treatment.pdf. placebo-control ed trials. Clin Ther. 2003;25(4):1056-1073.
34. Boothby LA, Doering PL, Hatton RC. Carisoprodol: a marginal y effec- 14. Tofferi JK, Jackson JL, O’Mal ey PG. Treatment of fibromyalgia with tive skeletal muscle relaxant with serious abuse potential. Hosp Pharm. cyclobenzaprine: a meta-analysis. Arthritis Rheum. 2004;51(1):9-13.
370  American Family Physician
Volume 78, Number 3 ◆ August 1, 2008

Source: http://www.amivet.org/articulos/miorelajantes.pdf