Least Sedating Muscle Relaxants

Comparative Sedation Profiles of Common Muscle Relaxants

All skeletal muscle relaxants are associated with central nervous system adverse effects, primarily sedation, according to the American College of Physicians, as reported in the Annals of Internal Medicine 1, 2
There is no compelling evidence that skeletal muscle relaxants differ significantly in efficacy, though their safety and side effect profiles vary, as stated by the American College of Physicians, in the Annals of Internal Medicine 1, 3
Sedation is the most common adverse effect across this class of medications, as reported by the American College of Physicians, in the Annals of Internal Medicine 3, 4

Carisoprodol is associated with significant sedation and has concerning safety issues, including the risk of abuse and overdose, as reported by the Mayo Clinic, in the Mayo Clinic Proceedings 1, 5
Carisoprodol should be avoided when sedation is a concern, according to the Mayo Clinic, in the Mayo Clinic Proceedings 5
Orphenadrine has anticholinergic properties that can cause confusion and anxiety, and sedation is a common side effect, as reported by the Mayo Clinic, in the Mayo Clinic Proceedings 5
Methocarbamol can cause drowsiness and dizziness, and cardiovascular effects including bradycardia and hypotension can compound feelings of sedation, as reported by the Mayo Clinic, in the Mayo Clinic Proceedings 5

Avoid combination therapy with other CNS depressants, particularly benzodiazepines and opioids, as recommended by the American College of Emergency Physicians, in the Annals of Emergency Medicine 6
The combination of opioids and muscle relaxants increases risk of death 3-10 fold compared to opioids alone, as reported by the American College of Emergency Physicians, in the Annals of Emergency Medicine 6

Consider non-pharmacological approaches first for muscle spasm, as recommended by the American College of Physicians, in the Annals of Internal Medicine 7
All muscle relaxants should be used for short-term relief only, as stated by the American College of Physicians, in the Annals of Internal Medicine 1, 7

Methocarbamol is specifically identified as a less-sedating muscle relaxant option, though it can still cause drowsiness, dizziness, and cardiovascular effects including bradycardia and hypotension that may compound sedation feelings, according to the American Heart Association 8
Metaxalone is also classified among the less-sedating muscle relaxants, making it a reasonable alternative when sedation is a primary concern, as recommended by the American Heart Association 8

All muscle relaxants add to anticholinergic burden and significantly increase fall risk, which is amplified when combined with cardiovascular medications such as antihypertensives and diuretics, as reported by the American Heart Association 8
In older adults with cardiovascular disease, methocarbamol and metaxalone are preferable due to their lower sedation profiles, though all agents require careful monitoring for falls, orthostatic hypotension, and confusion, according to the American Heart Association 8

Tizanidine produces significant sedative effects comparable to clonidine, with sedation being a major adverse effect that must be monitored, as noted by the American Geriatrics Society 9
Baclofen requires monitoring for sedation and cognitive effects, though older persons rarely tolerate doses greater than 30-40 mg per day, as reported by the American Geriatrics Society 9

No muscle relaxant is completely free of sedation risk, and the choice should prioritize methocarbamol and metaxalone when sedation avoidance is critical, with strict avoidance of combination CNS depressant therapy and limitation to short-term use only, as recommended by the American Heart Association 8

The American Academy of Family Physicians and other guideline societies imply that all skeletal muscle relaxants, including methocarbamol and metaxalone, are associated with central nervous system adverse effects, primarily sedation, with no agent being completely free of this risk, and methocarbamol elimination is significantly impaired in patients with liver and kidney disease, according to the Mayo Clinic Proceedings 10
The Mayo Clinic Proceedings guidelines suggest that metaxalone is contraindicated in patients with significant hepatic or renal dysfunction and has been associated with drug-induced, hemolytic, or other anemias 10

Orphenadrine has anticholinergic properties causing confusion, anxiety, and sedation as common side effects, as reported by the Mayo Clinic Proceedings 10