Is baclofen (GABA receptor agonist) the same as cyclobenzaprine (muscle relaxant)?

No, Baclofen and Cyclobenzaprine Are Fundamentally Different Drugs

Baclofen is a GABA-B receptor agonist primarily used for spasticity from upper motor neuron syndromes, while cyclobenzaprine is structurally identical to amitriptyline and used for acute musculoskeletal pain—they have completely different mechanisms of action, indications, and should not be considered interchangeable. 1

Key Mechanistic Differences

Baclofen (GABA-B Agonist)

• Baclofen activates GABA-B receptors on primary afferent terminals, reducing calcium influx and decreasing release of excitatory neurotransmitters 2
• Works by inhibiting both monosynaptic and polysynaptic reflexes at the spinal level through hyperpolarization of afferent terminals 3
• Primarily indicated for severe spasticity from central nervous system injury, demyelinating conditions, and other neuromuscular disorders 1

Cyclobenzaprine (Tricyclic Structure)

• Cyclobenzaprine is essentially identical to amitriptyline with similar anticholinergic adverse effects including dry mouth, drowsiness, confusion, urinary retention, and constipation 4
• Does not directly relax skeletal muscle despite its classification—effects are nonspecific and not related to actual muscle relaxation 1
• Approved for acute musculoskeletal pain, not for spasticity 1

Clinical Indications Where They Differ

When Baclofen May Be Appropriate

• Baclofen has documented efficacy as a second-line drug for paroxysmal neuropathic pain, particularly trigeminal neuralgia 1, 5
• Consider baclofen when true muscle spasm from upper motor neuron pathology is suspected, not for routine musculoskeletal pain 1
• Baclofen is not recommended for routine musculoskeletal pain—it is primarily an antispasticity agent 4

When Cyclobenzaprine May Be Appropriate

• Cyclobenzaprine has the most consistent evidence for acute musculoskeletal conditions, particularly acute back or neck pain 6
• All muscle relaxant trials were 2 weeks or less in duration—cyclobenzaprine should only be used short-term 7, 4
• No evidence supports chronic use of cyclobenzaprine for musculoskeletal pain 1

Critical Safety Distinctions

Baclofen-Specific Risks

• Baclofen requires slow tapering when discontinuing after prolonged use to avoid potential delirium and seizures 1, 4
• Baclofen was associated with higher risk of falls compared to tizanidine in older adults (subdistribution hazard ratio 1.68,95% CI 1.20-2.36) 8
• Common side effects include dizziness, somnolence, and gastrointestinal symptoms—start with low dose and gradually increase 1

Cyclobenzaprine-Specific Risks

• Abrupt discontinuation after long-term use can cause withdrawal symptoms including malaise, nausea, and headache—taper over 2-3 weeks 4
• Monitor for serotonin syndrome when combining with SSRIs or SNRIs 4
• Contraindicated with monoamine oxidase inhibitors 4

When True Muscle Spasm Requires Treatment

If muscle spasm from upper motor neuron pathology is suspected, consider benzodiazepines or baclofen rather than cyclobenzaprine, which does not actually relieve muscle spasm 1

Important Caveats

• Given minimal data and risks of adverse effects, baclofen is only rarely considered for trials when neuropathic pain has been refractory to other therapies 1
• Both drugs carry significant fall risk in older adults and should be used with extreme caution in this population 1, 8
• Neither drug should be prescribed under the mistaken belief that they work through the same mechanism or are interchangeable alternatives 1