Tolerance to Cyclobenzaprine
Tolerance to cyclobenzaprine is not a clinically significant concern, as the available evidence does not document tolerance development with this medication. Unlike carisoprodol, which has documented tolerance and abuse potential, cyclobenzaprine lacks evidence of pharmacological tolerance even with prolonged use 1.
Key Evidence on Tolerance
No documented tolerance in clinical trials: Multiple systematic reviews and clinical trials spanning 2-24 weeks found no evidence of tolerance development with cyclobenzaprine 1.
Withdrawal symptoms are distinct from tolerance: While cyclobenzaprine can cause withdrawal symptoms (malaise, nausea, headache) lasting 2-4 days after discontinuation with long-term use, these are uncomfortable but not life-threatening and do not indicate tolerance 1, 2.
Contrast with carisoprodol: The Mayo Clinic Proceedings specifically notes that carisoprodol "can lead to tolerance, dependence, and withdrawal symptoms" with prolonged abuse at high dosage, but makes no such statement about cyclobenzaprine 1.
Clinical Implications
Short-term use is standard: All muscle relaxant trials were limited to 2 weeks or less, indicating these agents should only be used short-term regardless of tolerance concerns 3.
Efficacy maintained throughout treatment: Studies of cyclobenzaprine 5-10 mg TID for 7-14 days showed sustained efficacy without evidence of diminishing effect over the treatment period 4, 5, 6.
Tapering is for withdrawal prevention, not tolerance: The recommended 2-3 week taper is to prevent withdrawal symptoms, not because of tolerance development 2.
Important Caveats
Anticholinergic effects persist: The anticholinergic side effects (dry mouth, drowsiness, constipation) do not diminish with continued use, which actually argues against tolerance to the drug's primary mechanisms 1, 7.
No abuse potential documented: Unlike controlled substances, cyclobenzaprine is not classified as having abuse or addiction potential 1.