Which muscle relaxant is safer to try first, cyclobenzaprine or baclofen?

Cyclobenzaprine is Safer to Try First

Cyclobenzaprine should be tried before baclofen for musculoskeletal pain, as baclofen carries significantly higher risks of encephalopathy, delirium, falls, and injury in this indication and is primarily an antispasticity agent for upper motor neuron syndromes rather than a first-line muscle relaxant for musculoskeletal conditions. 1

Evidence Against Using Baclofen First

Sparse Evidence for Musculoskeletal Pain

• Baclofen has only sparse evidence supporting its use for low back pain and musculoskeletal conditions, as it is primarily designed as an antispasticity agent for upper motor neuron syndromes 1
• The American College of Physicians does not recommend baclofen as a first-line or even first-alternative muscle relaxant for acute musculoskeletal pain 1

Significantly Higher Risk of Serious Adverse Events

• Baclofen carries a 2.29-fold higher risk of encephalopathy at 30 days compared to tizanidine (subdistribution hazard ratio 2.29,95% CI 1.43-3.67), with this elevated risk persisting through one year of treatment 2
• Baclofen is associated with a 2.35-fold higher risk of encephalopathy compared to cyclobenzaprine at 30 days (SHR 2.35,95% CI 1.59-3.48), with risk remaining elevated through the first year (SHR 1.94,95% CI 1.56-2.40) 2
• In older adults specifically, baclofen carries a 3.33-fold higher risk of delirium (HR 3.33,95% CI 2.11-5.26) and a 1.54-fold higher risk of injury (HR 1.54,95% CI 1.21-1.96) compared to tizanidine 3
• Baclofen is associated with a 68% higher risk of falls compared to tizanidine in older adults (SHR 1.68,95% CI 1.20-2.36) 4

Evidence Supporting Cyclobenzaprine First

Strong Efficacy Evidence

• Cyclobenzaprine has the most robust evidence base for acute musculoskeletal pain, with multiple high-quality trials demonstrating efficacy for muscle spasm, local pain reduction, and increased range of motion 5
• Both 5 mg and 10 mg three times daily regimens show significantly higher efficacy scores compared to placebo, with the 5 mg dose providing similar effectiveness to 10 mg but with lower sedation rates 5
• Onset of relief occurs within 3-4 doses of the 5 mg regimen, providing rapid symptom control 5

More Favorable Safety Profile

• The most common adverse effects with cyclobenzaprine are mild, dose-related sedation and dry mouth 5
• While cyclobenzaprine does carry anticholinergic risks and sedation concerns (particularly in older adults per the American Geriatrics Society Beers Criteria 6, 7), these risks are substantially lower than baclofen's risk of encephalopathy and delirium
• Efficacy appears independent of sedation, as meaningful treatment effects were observed even in patients who did not report somnolence 5

Clinical Algorithm for Muscle Relaxant Selection

First-Line Choice

• Start with cyclobenzaprine 5 mg three times daily for acute musculoskeletal pain, as this provides optimal balance of efficacy and tolerability 5
• Use for short-term only (≤2 weeks), as all muscle relaxant trials were limited to this duration 1

If Cyclobenzaprine Fails or Is Not Tolerated

• Switch to tizanidine as the first alternative, which has the strongest evidence base among alternatives (8 trials for acute low back pain) and works through a different mechanism (alpha-2 adrenergic agonism) 1
• Tizanidine has a similar adverse effect profile to cyclobenzaprine but may work when cyclobenzaprine fails due to its distinct mechanism 1

Avoid Baclofen for Musculoskeletal Pain

• Reserve baclofen exclusively for spasticity from upper motor neuron conditions (multiple sclerosis, spinal cord injury, cerebral palsy) where it has established efficacy 1, 8
• Do not use baclofen for routine musculoskeletal pain given the lack of supporting evidence and substantially elevated risks 1, 3, 2

Critical Safety Considerations

Special Populations Requiring Extra Caution

• Older adults face particularly high risks with both agents but especially baclofen, including falls, delirium, anticholinergic effects, and cognitive decline 6, 3, 4
• If muscle relaxants are necessary in older adults, cyclobenzaprine at the lowest effective dose (2.5-5 mg) is preferable to baclofen, though close monitoring remains essential 6, 5

Duration Limitations

• There is insufficient evidence for chronic use of any muscle relaxant for musculoskeletal pain 1
• When discontinuing after prolonged use, taper cyclobenzaprine gradually over 2-3 weeks to prevent withdrawal symptoms (malaise, nausea, headache) 7

Monitoring Requirements

• Monitor all patients on cyclobenzaprine for anticholinergic effects (dry mouth, constipation, urinary retention) and sedation 7
• Hold cyclobenzaprine on the day of surgery due to potential interactions with anesthetics 6, 7