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Research · Medication

Muscle relaxants

Pooled trials found muscle relaxants lowered acute low back pain by about 8 points of 100 in the first 2 weeks, with no gain in disability, and two trials found nothing added to an NSAID. Drowsiness is frequent, reported by 29% to 38% on cyclobenzaprine against 10% on placebo.

Add to Bio HackChecked 2026-11-13
Status
Prescription drugs in the US. Cyclobenzaprine and methocarbamol are FDA-approved as adjuncts to rest and physical therapy for acute, painful musculoskeletal conditions. Tizanidine is approved for spasticity in adults, and oral baclofen for spasticity from multiple sclerosis.
Also called
cyclobenzaprine, Flexeril, Amrix, Fexmid, tizanidine, Zanaflex, methocarbamol, Robaxin, baclofen, Lioresal, Ozobax, skeletal muscle relaxants, antispasmodics, antispasticity drugs
Taken for
back pain, neck pain, muscle spasm, muscle strain, spasticity in multiple sclerosis, fibromyalgia, chronic headache, alcohol use disorder

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help5

Reported risks12

What people take it for, and what was found

Shown to help5

Strong

Acute low back pain

Shown to lower acute low back pain by about 8 points on a 100-point scale within 2 weeks, with no gain in disability and more side effects.

The numbers and sources
Effect
In acute low back pain, non-benzodiazepine muscle relaxants lowered pain intensity at 2 weeks or less by 7.7 points on a 0 to 100 scale against control (95% CI 3.3 to 12.1), with no significant change in disability (-3.3, 95% CI -7.3 to 0.7). Adverse events were more frequent (RR 1.6, 95% CI 1.2 to 2.0) [1]. An earlier Cochrane review found non-benzodiazepine relaxants better than placebo for pain relief after 2 to 4 days (RR 0.80, 95% CI 0.71 to 0.89) and global efficacy (RR 0.49, 95% CI 0.25 to 0.95), with more adverse events (RR 1.50, 95% CI 1.14 to 1.98) [2]. For cyclobenzaprine, people were more likely to report improvement by day 14 than on placebo (OR 4.7, 95% CI 2.7 to 8.1), a number needed to treat of 2.7, with effect sizes of 0.38 to 0.58 that were largest in the first 4 days [3].
Population
6,505 adults with non-specific low back pain in 31 pooled trials, from 49 reviewed [1]; 30 trials, 24 of them in acute low back pain [2]; randomized placebo-controlled trials of cyclobenzaprine in adults with back pain [3].
Sources
[1], [2], [3]
Caveats
The most recent review rated its evidence very low certainty and described the pain reduction as not clinically important, with most trials at high risk of bias [1]. A separate review found fair evidence for cyclobenzaprine and tizanidine in acute back or neck pain and very limited or inconsistent data for methocarbamol and baclofen [4].
Limited

Methocarbamol for acute low back pain

One trial found 44% on methocarbamol stopped treatment early with complete pain relief, against 18% on placebo, in acute low back pain with spasm.

The numbers and sources
Effect
Over up to 8 days, 44% on methocarbamol and 18% on placebo ended treatment early because pain was gone, and 19% against 52% stopped because treatment was judged not to be helping. At the final visit 67% on methocarbamol and 35% on placebo rated the treatment as having helped. Adverse events were reported by 5 patients [7].
Population
202 adults with acute low back pain for at least 24 hours with spasm and restricted movement, 98 on methocarbamol and 104 on placebo [7].
Sources
[7]
Caveats
One trial, run in 2002 and analyzed after the fact for publication in 2015 [7]. A systematic review found very limited or inconsistent data for methocarbamol against placebo [4].
Moderate

Fibromyalgia

Shown to improve overall fibromyalgia symptoms with cyclobenzaprine, with about 5 treated for one extra person improved, and no change in fatigue or tender points.

The numbers and sources
Effect
Across 5 placebo-controlled trials, people on cyclobenzaprine were more likely to report overall improvement (OR 3.0, 95% CI 1.6 to 5.6), a risk difference of 0.21 (95% CI 0.09 to 0.34) and a number needed to treat of 4.8 (95% CI 3.0 to 11). Pain improved early in treatment and sleep improved. Fatigue and tender points did not improve at any time [9].
Population
People with fibromyalgia in 5 randomized, placebo-controlled trials of cyclobenzaprine [9].
Sources
[9]
Caveats
One meta-analysis of 5 trials, of cyclobenzaprine only. Not an FDA-approved use [10].
Limited

Chronic daily headache

One trial found tizanidine lowered a headache index by 54% against 19% on placebo over 12 weeks in adults with chronic daily headache.

The numbers and sources
Effect
In the last 4 weeks of treatment, the headache index improved 54% on tizanidine and 19% on placebo, severe headache days 55% against 21%, and headache duration 35% against 19%. Total headache days improved 30% against 22%, which was not significant. Sleepiness was reported by 47% on tizanidine, dizziness by 24% and dry mouth by 23% [11].
Population
134 adults randomized after a placebo run-in, 77% with migraine, of whom 85 completed 12 weeks [11].
Sources
[11]
Caveats
One trial with many dropouts, at a mean dose of 18 mg a day. Not an FDA-approved use [12].
Moderate

Baclofen for alcohol dependence

Shown to raise days abstinent by about 9 percentage points and lower relapse slightly in alcohol dependence, with no change in heavy drinking days.

The numbers and sources
Effect
Against placebo, baclofen raised the percentage of days abstinent (mean difference 9.07, 95% CI 3.30 to 14.85) and lowered the risk of relapse (RR 0.87, 95% CI 0.77 to 0.99). Heavy drinking days, drinks per drinking day, craving, anxiety and depression did not differ. Fatigue, dizziness, sleepiness, dry mouth, tingling and muscle spasms were more frequent on baclofen [13].
Population
1,818 adults with alcohol dependence in 17 trials, 70% men, mean age 46.5, most treated for 12 weeks at 30 to 300 mg a day [13].
Sources
[13]
Caveats
The lower relapse risk held in people who had been detoxified first and not in other subgroups. Not an FDA-approved use [14].

Mixed results1

Moderate

Spasticity in multiple sclerosis

Mixed results: one review found fair evidence that baclofen and tizanidine reduce spasticity against placebo, and a Cochrane review called the evidence in multiple sclerosis poorly documented.

The numbers and sources
Effect
A systematic review of 101 randomized trials found fair evidence that baclofen and tizanidine reduce spasticity against placebo, mainly in multiple sclerosis, and that the two are roughly equivalent, with more dry mouth on tizanidine and more weakness on baclofen. None of the trials met its top quality rating [4]. A Cochrane review of 26 placebo-controlled and 13 comparative studies in multiple sclerosis found that of the 8 placebo-controlled trials using the Ashworth scale of muscle tone, 3 showed a significant difference, and that spasms and function were assessed with unvalidated scores [8].
Population
People with spasticity, mostly from multiple sclerosis, in 101 randomized trials of muscle relaxants [4]; people with multiple sclerosis in 39 studies of anti-spasticity drugs [8].
Sources
[4], [8]
Caveats
Both reviews date from 2003 and 2004. Neither pooled an effect size.

Not shown to help1

Moderate

Added to an NSAID for acute low back pain

Not shown to improve function or pain at 1 week when added to naproxen or ibuprofen for acute low back pain in two emergency department trials.

The numbers and sources
Effect
In people sent home from an emergency department with naproxen, function at 1 week improved 10.1 points on a 24-point scale with cyclobenzaprine added and 9.8 points with placebo added (difference 0.3, 98.3% CI -2.6 to 3.2) [5]. In people sent home with ibuprofen, function improved 11.1 points with placebo added, 10.6 with baclofen, 10.1 with metaxalone and 11.2 with tizanidine. Moderate to severe pain at 1 week was reported by 30% on placebo, 33% on baclofen and 33% on tizanidine [6].
Population
323 adults with acute low back pain of 2 weeks or less, 108 assigned cyclobenzaprine 5 mg [5]; 320 adults with acute low back pain of 2 weeks or less in 4 groups [6].
Sources
[5], [6]
Caveats
Both trials came from emergency departments in one city and followed people for 1 week as the main outcome.

Doses studied

The label's cyclobenzaprine trials compared 5 mg and 10 mg tablets with placebo, and the label states it is for short periods of up to 2 or 3 weeks [10]. One emergency department trial gave cyclobenzaprine 5 mg tablets with naproxen [5]. The other gave baclofen 10 mg or tizanidine 2 mg, as 1 or 2 capsules 3 times a day as needed, with ibuprofen [6]. The methocarbamol trial treated for up to 8 days [7].

The tizanidine label reports single doses of 8 mg and 16 mg in its spasticity studies, and describes withdrawal reactions after 20 to 28 mg a day for 9 weeks or more [12]. The headache trial raised tizanidine over 4 weeks to as much as 24 mg a day, with a mean of 18 mg [11]. The alcohol dependence trials used baclofen at 30 to 300 mg a day [13].

Risks

Reported risks12

StrongVery common

Drowsiness, dry mouth and dizziness

Shown to raise drowsiness, reported by 29% to 38% on cyclobenzaprine against 10% on placebo and by 48% on tizanidine against 10%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In the label's controlled trials, drowsiness was reported by 29% on cyclobenzaprine 5 mg, 38% on 10 mg and 10% on placebo, and dry mouth by 21%, 32% and 7% [10]. On tizanidine, sleepiness was reported by 48% against 10% on placebo, dry mouth by 49% against 10%, weakness or tiredness by 41% against 16% and dizziness by 16% against 4% [12]. In one controlled study of baclofen, drowsiness was reported by 63% against 36% on placebo, and the label gives dizziness and weakness at 5% to 15% each [14]. Pooled across low back pain trials, adverse events were about 1.5 to 1.6 times as frequent as on control, and central nervous system effects twice as frequent (RR 2.04, 95% CI 1.23 to 3.37) [1][2].
Population
713 people on cyclobenzaprine and 469 on placebo [10]; 264 on tizanidine and 261 on placebo [12]; 175 people in the baclofen study [14]; pooled low back pain trials [1][2].
Sources
[10], [12], [14], [1], [2]
Caveats
The methocarbamol label lists drowsiness and dizziness and gives no rates [15]. The cyclobenzaprine label states that adverse events are more frequent and more severe in older adults [10].
LimitedVery common

Tizanidine: low blood pressure

One label study found hypotension in 16% after 8 mg of tizanidine and 33% after 16 mg, against none on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In the label's single-dose study, hypotension was reported by 16% after 8 mg and 33% after 16 mg, against 0% on placebo, and a slow heart rate by 2% and 10% against 0%. The label states that fainting has been reported after marketing and calls for monitoring when tizanidine is taken with blood pressure medication [12].
Population
45 people given 8 mg, 49 given 16 mg and 48 given placebo [12].
Sources
[12]
Caveats
Single doses in people with spasticity from multiple sclerosis, from one label study.
ModerateCommon

Tizanidine: liver test abnormalities

Shown to raise liver test abnormalities, reported in 6% on tizanidine against 2% on placebo. The label warns of liver cell injury.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In the label's multiple-dose controlled studies, a liver test abnormality was reported in 6% on tizanidine and 2% on placebo. The label states that tizanidine may cause hepatocellular liver injury and calls for aminotransferase monitoring at baseline and 1 month after the maximum dose is reached [12].
Population
264 people on tizanidine and 261 on placebo in the label's multiple-dose studies [12].
Sources
[12]
Caveats
The label table does not say which liver tests were abnormal or by how much.
LimitedCommon

Tizanidine: hallucinations

The label reports formed visual hallucinations or delusions in 5 of 170 people, 3%, in two controlled studies of tizanidine.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Formed, visual hallucinations or delusions were reported in 5 of 170 patients (3%) in two North American controlled studies. Most knew the events were not real. One developed psychosis, and one had problems for at least 2 weeks after stopping [12].
Population
170 people on tizanidine in two controlled studies [12].
Sources
[12]
Caveats
The label gives no placebo rate.
LimitedCommon

Baclofen in kidney disease: confusion

Linked to hospital admission with confusion within 30 days in older adults with kidney disease, in 1.11% at 20 mg a day or more against 0.42% at lower doses.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Among older adults with chronic kidney disease newly prescribed baclofen, admission with encephalopathy within 30 days occurred in 1.11% of those started at 20 mg a day or more and 0.42% of those started lower (weighted RR 3.54, 95% CI 2.24 to 5.59). The excess rose as kidney function fell, to 2.90 percentage points at an eGFR below 30. Against non-users, risk was higher at both doses (RR 5.90 and 19.8) [17]. The baclofen label states that the drug is mainly excreted unchanged by the kidneys [14].
Population
15,942 adults aged 66 or older in Ontario with an eGFR below 60 and not on dialysis, and 284,263 non-users [17].
Sources
[17], [14]
Caveats
Observational, in older adults from one province.
LimitedHow often is not known

Tizanidine with ciprofloxacin, fluvoxamine and oral contraceptives

One small study found ciprofloxacin raised tizanidine blood levels 10-fold and deepened its fall in blood pressure. The label contraindicates the combination.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In healthy volunteers, ciprofloxacin 500 mg twice a day raised tizanidine exposure 10-fold (range 6 to 24) and its peak level 7-fold. Systolic pressure fell 35 mm Hg against 15 mm Hg on placebo and diastolic 24 against 11, with more drowsiness [16]. The label lists strong CYP1A2 inhibitors, naming fluvoxamine and ciprofloxacin, as contraindicated, and says use with oral contraceptives and other weaker inhibitors such as cimetidine, famotidine, acyclovir and some heart rhythm drugs is to be avoided [12].
Population
10 healthy volunteers in a crossover study, each given one 4 mg dose of tizanidine [16].
Sources
[16], [12]
Caveats
A drug-level study in 10 people, with one dose of tizanidine.
LimitedHow often is not known

Stopping suddenly

The labels warn that stopping baclofen abruptly has caused hallucinations and seizures, and stopping tizanidine can cause rebound high blood pressure and a fast heart rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The baclofen label states that hallucinations and seizures have occurred on abrupt withdrawal [14]. The tizanidine label states that withdrawal reactions include rebound hypertension, tachycardia and increased muscle tone, particularly after 20 to 28 mg a day for 9 weeks or more or with concurrent narcotics [12].
Population
People stopping baclofen or tizanidine, as described in the labels [14][12].
Sources
[14], [12]
Caveats
The labels give no rate.
LimitedHow often is not known

Cyclobenzaprine: serotonin syndrome

The label warns that serotonin syndrome has been reported when cyclobenzaprine is combined with antidepressants, tramadol or MAO inhibitors, and contraindicates MAO inhibitors.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The cyclobenzaprine label states that potentially life-threatening serotonin syndrome has been reported with SSRIs, SNRIs, tricyclic antidepressants, tramadol, bupropion, meperidine, verapamil or MAO inhibitors. Use with an MAO inhibitor or within 14 days of one is contraindicated, and the label reports hyperpyretic crisis, seizures and deaths with that combination [10].
Population
People taking cyclobenzaprine with these drugs, as described in the label [10].
Sources
[10]
Caveats
Postmarketing reports with no rate.
LimitedHow often is not known

With opioids

Linked to slightly more opioid overdose when a muscle relaxant was taken with an opioid, more so with baclofen and beyond 60 days of use.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Against opioid use alone, concurrent use of a skeletal muscle relaxant was associated with opioid overdose (combined HR 1.21, 95% CI 1.00 to 1.48). The hazard ratio was 0.91 for 14 days or less and 1.80 (95% CI 1.30 to 2.48) beyond 60 days. It was 1.83 for baclofen (95% CI 1.11 to 3.04), 1.84 for carisoprodol, and 1.39 when a benzodiazepine was also used [18].
Population
Incident and prevalent opioid user cohorts in a population-based study [18].
Sources
[18]
Caveats
Observational, and the main estimate's interval reaches 1.00.
LimitedHow often is not known

With alcohol and other sedating drugs

The labels warn that cyclobenzaprine and methocarbamol may add to the effects of alcohol and other central nervous system depressants.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The cyclobenzaprine label states that the drug, especially with alcohol or other central nervous system depressants, may impair the mental and physical abilities needed for driving or operating machinery [10]. The methocarbamol label states that the drug may have a general depressant effect on the central nervous system and cautions about combined effects with alcohol and other depressants [15].
Population
People taking these drugs, as described in the labels [10][15].
Sources
[10], [15]
Caveats
The labels cite no study and give no rate.
LimitedHow often is not known

Injuries in older adults

Linked to more injuries in older adults, with 32% higher odds among recent users of a muscle relaxant in one case-control study.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Among older adults, 1.30% of those with an injury and 0.77% of matched controls had used a muscle relaxant in the prior 60 days (adjusted OR 1.32, 95% CI 1.16 to 1.50). The odds ratio was 1.42 for methocarbamol (95% CI 1.16 to 1.75) and 1.22 for cyclobenzaprine (95% CI 1.02 to 1.45) [19].
Population
27,974 older adults with an injury and 104,303 matched controls, from a base population of 322,806 [19].
Sources
[19]
Caveats
Observational. The shares are of people with an injury who had used the drug, not of users who were injured.
LimitedStudied in pregnancyHow often is not known

Use in pregnancy

The labels report withdrawal symptoms in newborns after baclofen through pregnancy and fetal abnormalities after methocarbamol, with no controlled studies in pregnant women.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The baclofen label states that withdrawal symptoms, including increased muscle tone, tremor, jitteriness and seizure, have been reported in newborns whose mothers took oral baclofen throughout pregnancy [14]. The methocarbamol label states that there have been reports of fetal and congenital abnormalities after exposure in the womb [15]. The tizanidine label states that, based on animal data, it may cause fetal harm [12]. The cyclobenzaprine label reports no harm in animal studies and no adequate studies in pregnant women [10].
Population
Pregnant women and newborns, as described in the labels [14][15][12][10].
Sources
[14], [15], [12], [10]
Caveats
Case reports and animal data with no rate.

Claims tested and not found

  1. That adding a muscle relaxant to an NSAID helps acute low back pain more than the NSAID alone. With naproxen, function at 1 week improved 10.1 points with cyclobenzaprine added and 9.8 with placebo added [5]. With ibuprofen, it improved 11.1 points with placebo added, 10.6 with baclofen and 11.2 with tizanidine [6].

Related

NSAIDs

Sources

  1. Cashin AG, Folly T, Bagg MK, et al. Efficacy, acceptability, and safety of muscle relaxants for adults with non-specific low back pain: systematic review and meta-analysis. BMJ. 2021. https://doi.org/10.1136/bmj.n1446
  2. van Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM. Muscle relaxants for non-specific low-back pain. Cochrane Database of Systematic Reviews. 2003. https://doi.org/10.1002/14651858.CD004252
  3. Browning R, Jackson JL, O'Malley PG. Cyclobenzaprine and back pain: a meta-analysis. Archives of Internal Medicine. 2001. https://doi.org/10.1001/archinte.161.13.1613
  4. Chou R, Peterson K, Helfand M. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. Journal of Pain and Symptom Management. 2004. https://doi.org/10.1016/j.jpainsymman.2004.05.002
  5. Friedman BW, Dym AA, Davitt M, et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015. https://doi.org/10.1001/jama.2015.13043
  6. Friedman BW, Irizarry E, Solorzano C, et al. A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain. Annals of Emergency Medicine. 2019. https://doi.org/10.1016/j.annemergmed.2019.02.017
  7. Emrich OM, Milachowski KA, Strohmeier M. Methocarbamol bei akuten Rückenschmerzen (Methocarbamol in acute low back pain. A randomized double-blind controlled study). MMW Fortschritte der Medizin. 2015. https://doi.org/10.1007/s15006-015-3307-x
  8. Shakespeare D, Boggild M, Young CA. Anti-spasticity agents for multiple sclerosis. Cochrane Database of Systematic Reviews. 2003. https://doi.org/10.1002/14651858.CD001332
  9. Tofferi JK, Jackson JL, O'Malley PG. Treatment of fibromyalgia with cyclobenzaprine: A meta-analysis. Arthritis Care & Research. 2004. https://doi.org/10.1002/art.20076
  10. Cyclobenzaprine hydrochloride tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=85128989-bfa3-4b82-94c1-f90b14ccd2f9
  11. Saper JR, Lake AE, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache. 2002. https://doi.org/10.1046/j.1526-4610.2002.02122.x
  12. Zanaflex (tizanidine hydrochloride) capsules and tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60c27d35-7349-4fc6-86ad-70fffdbe3e08
  13. Agabio R, Saulle R, Rösner S, Minozzi S. Baclofen for alcohol use disorder. Cochrane Database of Systematic Reviews. 2023. https://doi.org/10.1002/14651858.CD012557.pub3
  14. Baclofen tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1b0f50c8-62e3-414d-96d3-5fd16e8043ab
  15. Methocarbamol tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2e38ac9-1cf3-14ca-e053-2a95a90a8522
  16. Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clinical Pharmacology & Therapeutics. 2004. https://doi.org/10.1016/j.clpt.2004.08.018
  17. Muanda FT, Weir MA, Bathini L, et al. Association of Baclofen With Encephalopathy in Patients With Chronic Kidney Disease. JAMA. 2019. https://doi.org/10.1001/jama.2019.17725
  18. Li Y, Delcher C, Wei YJ, et al. Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population-Based Cohort Study. Clinical Pharmacology & Therapeutics. 2020. https://doi.org/10.1002/cpt.1807
  19. Spence MM, Shin PJ, Lee EA, Gibbs NE. Risk of injury associated with skeletal muscle relaxant use in older adults. Annals of Pharmacotherapy. 2013. https://doi.org/10.1345/aph.1R735

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