What are the recommended muscle relaxers for patients with muscle spasms, considering factors such as impaired renal (kidney) function, liver dysfunction, and elderly patients with a history of dementia?

Comprehensive List of Muscle Relaxants with Clinical Recommendations

For acute muscle spasm in general adult populations, cyclobenzaprine 5 mg three times daily is the preferred first-line muscle relaxant, but this agent must be avoided entirely in elderly patients, those with dementia, and patients with hepatic impairment. 1, 2

First-Line Muscle Relaxants for General Adult Population

Cyclobenzaprine

• Cyclobenzaprine 5 mg three times daily for 7-14 days is the preferred alternative for acute neck or back pain with muscle spasm due to moderate superiority over placebo 1
• The 5 mg dose is as effective as 10 mg three times daily but associated with lower incidence of sedation 3
• Onset of relief is apparent within 3-4 doses of the 5 mg regimen 3
• Adding cyclobenzaprine to NSAIDs or acetaminophen provides greater short-term pain relief than analgesic monotherapy, though this increases CNS adverse events 1
• Cyclobenzaprine should be used with caution in mild hepatic impairment starting with 5 mg dose and titrating slowly upward; it is not recommended in moderate to severe hepatic impairment 4

Methocarbamol

• Methocarbamol is an alternative option for acute muscle spasm 1
• Methocarbamol elimination is significantly impaired in patients with liver and kidney disease and causes drowsiness, dizziness, and cardiovascular effects including bradycardia and hypotension 5, 2
• Should be avoided in patients with renal or hepatic impairment 1, 5

Metaxalone

• Metaxalone is available for acute musculoskeletal conditions 6
• Metaxalone is contraindicated in patients with significant hepatic or renal dysfunction 5, 2
• Has multiple CNS adverse effects including drowsiness, dizziness, and irritability 5, 2
• Should be avoided in patients with renal or hepatic impairment 1

Carisoprodol

• Carisoprodol has fair evidence of effectiveness compared to placebo in musculoskeletal conditions 6
• Carisoprodol should be completely avoided in elderly patients due to high risk of sedation and falls 2
• Has substantial abuse and addiction potential and is classified as a controlled substance 5
• Raises the greatest concern for physical and psychological dependence and has perhaps the greatest toxicity among muscle relaxants 7

Orphenadrine

• Orphenadrine has fair evidence of effectiveness compared to placebo in musculoskeletal conditions 6
• Orphenadrine has anticholinergic properties that can cause confusion, anxiety, tremors, urinary retention, and cardiovascular instability 5
• Listed in the Beers Criteria as potentially inappropriate for older adults due to strong anticholinergic properties 2
• Should be used with caution in patients with cardiac issues and in the elderly 5

Chlorzoxazone

• Chlorzoxazone has very limited or inconsistent data regarding effectiveness compared to placebo 6
• Has been associated with rare serious hepatotoxicity 6

Muscle Relaxants for Spasticity (CNS-Related Conditions)

Baclofen

• Baclofen is the preferred muscle relaxant for elderly patients requiring muscle relaxant therapy, starting at 5 mg up to three times daily with maximum tolerated doses of 30-40 mg per day 1, 5, 2
• Baclofen is a GABA-B agonist with documented efficacy for muscle spasm and spasticity, particularly in CNS injury and neuromuscular disorders 5, 2
• There is fair evidence that baclofen is effective compared to placebo in patients with spasticity (primarily multiple sclerosis) 6
• Starting with low doses (5 mg three times daily) and gradual titration minimizes common side effects of dizziness, somnolence, and gastrointestinal symptoms 5
• Baclofen should never be discontinued abruptly; slow tapering is required after prolonged use to avoid withdrawal symptoms including delirium, seizures, and CNS irritability 1, 5, 2
• Baclofen should be used with caution in patients with renal or hepatic impairment, starting at the lowest effective dose 1

Tizanidine

• Tizanidine is an alternative option for elderly patients, starting at 2 mg up to three times daily 1, 2
• Requires monitoring for orthostatic hypotension and sedation 1
• There is fair evidence that tizanidine is effective compared to placebo in patients with spasticity 6
• Fair evidence suggests baclofen and tizanidine are roughly equivalent for efficacy in spasticity, but tizanidine is associated with more dry mouth and baclofen with more weakness 6
• Tizanidine is an α2-adrenergic agonist that can produce hypotension; two-thirds of patients treated with 8 mg had a 20% reduction in either diastolic or systolic BP 8
• The hypotensive effect is dose related and has been measured following single doses ≥2 mg 8
• Tizanidine occasionally causes liver injury; approximately 5% of patients had elevations of liver function tests to greater than 3 times the upper limit of normal 8
• Monitoring of aminotransferase levels is recommended during the first 6 months of treatment (baseline, 1,3, and 6 months) and periodically thereafter 8
• 48% of patients receiving any dose of tizanidine reported sedation as an adverse event; in 10% of cases, sedation was rated as severe 8
• Tizanidine use has been associated with formed visual hallucinations or delusions in 3% of patients in controlled clinical studies 8
• Should be used with caution in renally impaired patients 1, 2
• Should be avoided in older adults due to significant sedation and hypotension per some guidelines 5

Dantrolene

• There is fair evidence that dantrolene is effective compared to placebo in patients with spasticity 6
• Insufficient evidence to determine the efficacy of dantrolene compared to baclofen or tizanidine 6
• Dantrolene has been associated with rare serious hepatotoxicity 6
• Very limited or inconsistent data regarding effectiveness in musculoskeletal conditions 6

Muscle Relaxants for Anesthesia (Neuromuscular Blocking Agents)

Rocuronium

• Rocuronium is a non-depolarizing muscle relaxant used in anesthesia 9
• Rocuronium is mainly eliminated in urine and bile; clearance is reduced in renal failure and cirrhotic patients 9
• In neuromuscular disease with primary muscle damage, there is very significant increase in sensitivity to rocuronium (reduced dose requirement) 9
• Can be reversed with sugammadex at doses of 2-8 mg/kg depending on depth of blockade 9

Atracurium

• Atracurium is probably recommended in cases of renal/hepatic failure 9
• Roughly half is eliminated by organ-independent reactions (Hofmann reaction and ester hydrolysis) and half by metabolism or excretion 9
• Pharmacokinetics and pharmacodynamics are similar in subjects with and without kidney and liver failure 9
• A 50-75% reduction in recommended dose is common in myasthenia patients 9

Cisatracurium

• Cisatracurium is probably recommended in cases of renal/hepatic failure 9
• One of ten isomers of atracurium with overwhelmingly non-enzymatic elimination 9
• Has similar pharmacokinetic and pharmacodynamic profiles in patients with and without renal and hepatic failure 9
• More potent than atracurium 9

Suxamethonium (Succinylcholine)

• Suxamethonium is probably recommended for electroconvulsive therapy as a short-acting muscle relaxant 9
• Remains the gold standard for electroconvulsive therapy in the vast majority of cases 9
• For obese patients, administer at 1.0 mg/kg based on actual body weight 9
• In myasthenia, resistance is observed (decreased potency and need to increase dose) 9

Special Population Considerations

Elderly Patients

• All muscle relaxants are listed in the American Geriatrics Society Beers Criteria as potentially inappropriate medications for older adults due to anticholinergic effects, sedation, and increased risk of falls 5, 2
• Cyclobenzaprine should be avoided in elderly patients as it is structurally identical to amitriptyline with comparable adverse effect profiles including CNS impairment, delirium, slowed comprehension, and falling 1, 2
• Baclofen is the preferred agent for elderly patients requiring muscle relaxant therapy 1, 5, 2
• Tizanidine is an alternative for elderly patients 1, 2
• Start with the lowest possible effective dose and use for the shortest duration necessary 1, 2
• Avoid prescribing muscle relaxants with other medications that have anticholinergic properties 2
• Muscle relaxants should be avoided in frail patients with mobility deficits, weight loss, weakness, or cognitive deficits 5

Patients with Dementia

• Cyclobenzaprine should be avoided in patients with dementia due to anticholinergic effects 1, 2
• Carisoprodol should be avoided due to high risk of sedation and falls 2
• Orphenadrine should be avoided due to strong anticholinergic properties 2

Patients with Renal Impairment

• Benzylisoquinoline muscle relaxants (atracurium/cisatracurium) are probably recommended in cases of renal failure 9
• Methocarbamol should be avoided 1, 5
• Metaxalone is contraindicated 5, 2
• Baclofen or tizanidine should be used with caution, starting at the lowest effective dose 1
• Efficacy of sugammadex is decreased in patients with severe renal failure (creatinine clearance <30 mL/min) 9

Patients with Hepatic Impairment

• Benzylisoquinoline muscle relaxants (atracurium/cisatracurium) are probably recommended in cases of hepatic failure 9
• Cyclobenzaprine should be used with caution in mild hepatic impairment starting with 5 mg dose; not recommended in moderate to severe impairment 4
• Methocarbamol should be avoided 1, 5
• Metaxalone is contraindicated 5, 2
• Baclofen or tizanidine should be used with caution, starting at the lowest effective dose 1

Patients with Neuromuscular Disease

• Neuromuscular blockade monitoring is probably recommended following muscle relaxant use 9
• Sugammadex is probably recommended for reversal of residual neuromuscular blockade following steroidal muscle relaxants 9
• In myasthenia, non-depolarizing muscle relaxants show increased sensitivity and duration of action with 50-75% reduction in recommended dose 9

Critical Safety Warnings and Pitfalls

Duration of Use

• Never prescribe muscle relaxants for chronic pain conditions; there is no evidence of benefit beyond 2-3 weeks 1
• Most muscle relaxants have no evidence of efficacy in chronic pain 5, 2

Adverse Events

• All muscle relaxants are associated with 50% higher total adverse events and double the CNS adverse events compared to placebo 1
• Common effects include somnolence, dizziness, dry mouth, and increased fall risk 1
• Cyclobenzaprine exhibits low nanomolar affinity for histamine H1 receptors and blocks them in a noncompetitive manner, facilitating significant sedative effects 10

Drug Interactions

• Cyclobenzaprine is contraindicated with MAO inhibitors due to risk of potentially life-threatening serotonin syndrome 4
• Serotonin syndrome has been reported with cyclobenzaprine when combined with SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, or verapamil 4
• Cyclobenzaprine may enhance effects of alcohol, barbiturates, and other CNS depressants 4
• Tizanidine should not be used with other α2-adrenergic agonists 8

Withdrawal Risks

• Abrupt discontinuation of baclofen must be avoided; slow tapering is required to prevent withdrawal symptoms including delirium, seizures, and CNS irritability 1, 5, 2

Non-Pharmacological Alternatives

• Consider non-pharmacological approaches for muscle spasm management first, including rest and physical therapy 1, 2
• For elderly patients, topical analgesics may provide relief with fewer systemic side effects 1, 5
• Scheduled acetaminophen may be effective for mild to moderate musculoskeletal pain in elderly patients 1, 5
• If the condition is primarily neuropathic pain rather than true spasticity, consider gabapentinoids (pregabalin, gabapentin) or duloxetine instead 5