Flexeril (Cyclobenzaprine) for Muscle Spasms
For acute muscle spasms, start cyclobenzaprine 5 mg three times daily for 2-3 weeks maximum, as this dose provides equivalent efficacy to 10 mg with significantly less sedation. 1, 2
Recommended Dosing Algorithm
Standard dosing:
- Start with 5 mg three times daily (preferred initial dose) 1, 2
- May increase to 10 mg three times daily based on individual response if 5 mg is insufficient 1
- Duration: Limit use to 2-3 weeks maximum 1
Special populations requiring dose adjustment:
- Elderly patients: Start with 5 mg once daily, titrate slowly 1
- Hepatic impairment (mild): Start with 5 mg and titrate slowly upward 1
- Hepatic impairment (moderate to severe): Do not use 1
Mechanism and Clinical Effects
Cyclobenzaprine is a centrally acting 5-HT2 receptor antagonist structurally related to amitriptyline, not a direct skeletal muscle relaxant 3. The drug works through central nervous system mechanisms rather than peripheral muscle effects 3.
Onset and duration:
- Duration of action: 4-6 hours 3
- Clinical improvement apparent within 3-4 doses of the 5 mg regimen 2
- Efficacy is independent of sedation—patients who don't experience drowsiness still achieve meaningful pain relief 2
Evidence for Efficacy
The 5 mg dose is as effective as 10 mg but better tolerated:
- Two large trials (n=1405) demonstrated 5 mg three times daily was statistically superior to placebo for all primary endpoints (global impression of change, medication helpfulness, relief from starting backache) 1, 2
- The 5 mg dose showed equivalent efficacy to 10 mg with lower sedation rates 2
- Efficacy demonstrated in both low back pain (two-thirds of patients) and neck pain (one-third of patients) 2
Critical Safety Considerations
Anticholinergic effects (similar to tricyclic antidepressants):
- Dry mouth, drowsiness, confusion, constipation, urinary retention 3
- Hallucinations and confusion possible 3
- Particularly problematic in elderly patients 3
Drug interactions requiring caution:
- Contraindicated with MAO inhibitors due to serotonin syndrome risk 3
- Potential for serotonin syndrome when combined with SSRIs or SNRIs 4
- Interactions with sedatives and anesthetic agents 3
Perioperative management:
- Hold on day of surgery due to interactions with sedatives and anesthetics 3
Discontinuation Protocol
After long-term use, taper over 2-3 weeks to prevent withdrawal:
- Withdrawal symptoms include malaise, nausea, and headache lasting 2-4 days 3, 4
- These symptoms are uncomfortable but not life-threatening 3
- Do not stop abruptly after prolonged use 4
When Cyclobenzaprine Fails: Alternative Agents
First alternative: Tizanidine
- Strongest evidence-based alternative with efficacy in 8 trials for acute low back pain 5, 4
- Different mechanism (alpha-2 adrenergic agonism) may provide benefit when cyclobenzaprine fails 5, 4
- Recommended by American College of Physicians as first alternative 5, 4
Agents to avoid:
- Diazepam: Inappropriate for older adults due to fall risk, sedation, and anticholinergic effects 3, 5, 4
- Baclofen: Only for upper motor neuron spasticity, not routine musculoskeletal pain 3, 5, 4
- Carisoprodol: Controlled substance with abuse potential, requires slow taper over 4-9 days if discontinuing 3
Common Pitfalls to Avoid
Duration of therapy:
- All muscle relaxant trials were ≤2 weeks duration 5, 4
- No evidence supports chronic use for musculoskeletal pain 5, 4
- Prescribing beyond 2-3 weeks increases risk without proven benefit 1
Combination therapy:
- Adding ibuprofen to cyclobenzaprine 5 mg provides no additional benefit over cyclobenzaprine alone 6
- Combination with NSAIDs increases side effects (primarily drowsiness) without improving efficacy 1, 6
Misconceptions about mechanism: