Comparison of Skelaxin, Flexeril and Soma

Based on "Essential Pain Pharmacology"
written by Howard S. Smith MD, Marco Pappagallo MD

This review investigates the efficacy, side effects, and safety of three commonly prescribed skeletal muscle relaxants metaxalone (Skelaxin), cyclobenzaprine (Flexeril), and carisoprodol (Soma).

Muscle relaxants are not really a class of drugs, but rather a group of different medications that produce an overall sedative effect on the body.

Muscle relaxants treat both muscle spasm and spasticity. Skeletal muscle relaxants are commonly prescribed for the treatment of muscle spasms and discomfort. These drugs relieve muscle spasms due to low back pain, neck pain, fibromyalgia, tension headaches. They also relieve spasticity due to cerebral palsy, multiple sclerosis, spinal cord injury, or stroke.

Brief history

  • Carisoprodol was approved by the FDA in 1959.
  • Cyclobenzaprine was FDA approved on August 26, 1977. Cyclobenzaprine is distributed and marketed by McNeil under the brand name Flexeril.
  • Metaxalone was approved by FDA on August 13, 1962. This medication is manufactured by King Pharmaceuticals under the brand name Skelaxin.

FDA approved indications and uses

All three medications are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomforts associated with acute, painful musculoskeletal conditions.

Carisoprodol, cyclobenzaprine and metaxalone are not found to be effective in the treatment of spasticity associated with upper motor neuron syndromes.

Cyclobenzaprine has also been studied in the treatment of fibromyalgia and migraine.

Mechanism of action

The mechanisms of action of the medications in this class are widely varied and many are not thoroughly understood.

Carisoprodol: The action of carisoprodol is related to a central nervous system (CNS) mechanism and not to a direct effect on skeletal muscles. Carisoprodol acts on the spinal cord and subcortical levels of the brain to depress polysynaptic neuron transmission. CNS depression produces sedation, and the perception of pain could be altered. Some believe that most of the benefit seen with carisoprodol is secondary to a generalized sedative effect.

Cyclobenzaprine: Since cyclobenzaprine is closely similar to amitriptyline in chemical structure, some of its effects are similar to the tricyclic antidepressants. Cyclobenzaprine relieves muscle spasms through a central action, possibly at the brain stem level, with no direct action on the neuromuscular junction or the muscle involved. It is not a peripheral neuromuscular blocker. Treatment with the drug reduces pain and tenderness, and improves mobility.

Metaxalone: The mechanism of action of metaxalone has not been established. Metaxalone has no direct effect on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber. Its mode of action may be due to general central nervous system depression.


No studies have documented superior efficacy of one skeletal muscle relaxant over another.

Side effects and Safety

All three drugs appear to have equal efficacy, but their side effects vary considerably.

Sedation is the most commonly reported adverse effect of muscle relaxants. These medications should be used with caution in people driving motor vehicles or operating heavy machinery. More absolute contraindications do exist to the use of carisoprodol and cyclobenzaprine. Muscle relaxants may be initially administered at bedtime to take advantage of their sedative effects and minimize daytime drowsiness.

While cyclobenzaprine may not share the dangerous cardiac and neurological potential of its close relatives the TCAs, it does share other properties, particularly confusion, lethargy, and anticholinergic side effects, and may have some toxicity in overdose and in combination with other substances.

Carisoprodol presents the most significant concern, due particularly to its potential for dependence and abuse. Several investigators have called for carisoprodol to be classified as a controlled substance. Carisoprodol is thought to carry an important risk for abuse because of its metabolism to meprobamate.

In the head to head trial of cyclobenzaprine and carisoprodol, dry mouth was more frequent with cyclobenzaprine (38% vs. 10%) and dizziness less frequent (8% vs. 26%). Withdrawal rates due to adverse events were equal (8%).

Metaxalone has the fewest reported side effects of any skeletal muscle relaxants and appears to be the safest. Metaxalone is considered to be less sedating in comparison with carisoprodol and cyclobenzaprine.


Carisoprodol is contraindicated in patients with a history of acute intermittent porphyria.

Cyclobenzaprine is contraindicated in patients with hyperthyroidism, congestive heart failure, and other heart conductions.

Metaxalone is contraindicated in drug-induced, hemolytic or other anemias and in significantly impaired renal or hepatic function.


Cyclobenzaprine is Category B.
Carisoprodol is Category C.
Metaxalone is not classified.

Key differences
  • Cyclobenzaprine has been evaluated in the most clinical trials and so has the most proof of being effective. Related to TCAs, use with caution in cardiac patients.
  • Carisoprodol can be addictive.
  • Metaxalone is the least likely to cause drowsiness making it more compatible with day time use. Should not be used in hepatic dysfunction or patients with history of drug-induced anemia.
  • Skelaxin, which is available only as a brand medication, is more expensive than carisoprodol or cyclobenzaprine.
  • Skelaxin may be useful in patients who cannot tolerate the sedative properties of cyclobenzaprine.


The centrally acting skeletal muscle relaxants have been shown to be efficacious in the treatment of painful musculoskeletal disorders. Studies have indicated they may be more effective in combination with analgesics.

When there is no a clearly superior agent, side effect profiles and cost become a significant factor in the selection of muscle relaxers.

Brief comparison table
  Soma Watson Flexeril McNeil Skelaxin King
Soma (Wallace)
Flexeril (McNeil)
Skelaxin (King)
FDA approval date April 09, 1959 August 26, 1977 August 13, 1962
Pharmaceutical Forms 350 mg tablets 5 mg, 10 mg tablets 800 mg tablets
FDA approved indications relief of discomforts associated with acute, painful musculoskeletal conditions relief of muscle spasm associated with acute, painful musculoskeletal conditions relief of discomforts associated with acute, painful musculoskeletal conditions
Most common side effects - drowsiness
- dizziness
- ataxia
- tremor
- agitation
- drowsiness
- dry mouth
- dizziness
- drowsiness
- dizziness
- headache
Less common side effects - irritability
- headache
- depressive reactions
- insomnia
- nausea
- vomiting
- tachycardia
- tiredness
- asthenia
- nausea
- constipation
- dyspepsia
- unpleasant taste
- blurred vision
- headache
- nervousness
- tachycardia
- arrhythmia
- nervousness
- nausea
- vomiting
- gastrointestinal upset
Onset/ Duration of action Onset: 30 min
Duration: 4-6 hours
Onset: 1 hour
Duration: 12-24 hours
Onset: 30 min- 1 hour
Duration: 4- 6 hours
Generic availability Yes Yes No

References & Resources

  • 1. The Merck Manual of Medical Information. Mark H. Beers et al., eds. 2nd Home Edition. Whitehouse Station, NJ: Merck; 2003.

Published: May 05, 2007
Last updated: April 19, 2017


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