What is the comparison between Orphenadrine citrate, Cyclobenzaprine (Flexeril), and Gabapentin?

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Last updated: March 11, 2025View editorial policy

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From the Guidelines

Orphenadrine citrate, Flexeril (cyclobenzaprine), and gabapentin are distinct medications with different applications, and the choice between them depends on the specific condition being treated, with gabapentin being more suitable for chronic nerve pain conditions and Flexeril for acute muscle spasms. When considering the treatment of acute muscle spasms, Flexeril (cyclobenzaprine) is often preferred due to its effectiveness and fewer anticholinergic side effects compared to orphenadrine citrate, as noted in studies 1.

  • For acute muscle spasms from injury, Flexeril is typically prescribed at 5-10mg up to three times daily, usually for short-term use (2-3 weeks).
  • Gabapentin, an anticonvulsant medication, is typically started at 300mg once daily, gradually increasing to 300-600mg three times daily as needed, and can be used long-term for chronic conditions such as diabetic neuropathy or postherpetic neuralgia.
  • Side effects differ between these medications: muscle relaxants commonly cause drowsiness and dry mouth, while gabapentin may cause dizziness, fatigue, and peripheral edema.
  • It is essential to use these medications with caution in elderly patients and those with impaired kidney function, and patients should avoid alcohol and be aware of potential driving impairment while taking any of these medications, as highlighted in 1. The most recent and highest quality study 1 provides guidance on the use of nonopioid analgesics, including skeletal muscle relaxants and anticonvulsants, for the treatment of chronic pain, emphasizing the importance of considering the specific condition being treated and the potential side effects of each medication.

From the Research

Comparison of Orphenadrine Citrate, Cyclobenzaprine, and Gabapentin

  • The comparison between Orphenadrine citrate, Cyclobenzaprine (Flexeril), and Gabapentin can be made based on their efficacy and safety in treating various conditions.
  • Efficacy:
    • Gabapentin is effective in treating neuropathic pain conditions, such as postherpetic neuralgia and painful diabetic neuropathy, with a number needed to treat to benefit (NNT) of 8.0 and 5.9, respectively 2.
    • Cyclobenzaprine is effective in treating muscle spasm associated with low back and neck pain, with significant improvements in patient's rating of medication helpfulness and relief from local pain 3.
    • Orphenadrine citrate is effective in treating musculoskeletal conditions, such as acute back or neck pain, with fair evidence of efficacy compared to placebo 4.
  • Safety:
    • Gabapentin is associated with adverse events, such as dizziness, somnolence, and peripheral oedema, with a number needed to treat for harm (NNH) of 3.8 for dizziness and 6.3 for somnolence 2.
    • Cyclobenzaprine is associated with adverse events, such as daytime drowsiness and somnolence, with more frequent reports of drowsiness in the cyclobenzaprine immediate release group compared to the extended release group 3.
    • Orphenadrine citrate has been associated with rare serious hepatotoxicity, although the evidence is limited 4.
  • Clinical Use:
    • Gabapentin is recommended as a first-line treatment for central neuropathic pain, along with duloxetine and tricyclic antidepressants 5.
    • Cyclobenzaprine is recommended for the treatment of muscle spasm associated with acute, painful musculoskeletal conditions 3.
    • Orphenadrine citrate is used to treat musculoskeletal conditions, although its efficacy and safety compared to other skeletal muscle relaxants are not well established 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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