How do baclofen and tizanidine (Flexiril) compare in mechanism, dosing, side‑effect profile, contraindications, and suitability for treating spasticity?

Comparison of Baclofen and Tizanidine (Flexeril)

Critical Clarification

Note: Flexeril is cyclobenzaprine, not tizanidine. However, based on the context provided, this comparison addresses baclofen versus tizanidine, as tizanidine is the muscle relaxant most commonly compared to baclofen for spasticity management. 1

Direct Recommendation

Both baclofen and tizanidine demonstrate roughly equivalent efficacy for reducing spasticity in multiple sclerosis and stroke, but tizanidine causes less muscle weakness while baclofen causes less dry mouth and sedation; choose tizanidine when preserving muscle strength is critical, and baclofen when dry mouth or sedation would be poorly tolerated. 2, 3

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Mechanism of Action

Baclofen

• Acts as a GABA-B receptor agonist in the central nervous system, enhancing inhibitory neurotransmission to reduce spasticity 4

Tizanidine

• Functions as a centrally acting alpha-2 adrenergic receptor agonist that reduces spasticity through presynaptic inhibition of motor neurons 5

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Comparative Efficacy

Overall Spasticity Reduction

• Fair evidence demonstrates that baclofen and tizanidine are roughly equivalent in reducing overall spasticity, spasms, and clonus in multiple sclerosis patients 2, 3
• Both medications reduce spasticity and pain without producing significant functional gains in the majority of controlled trials 1

Functional Outcomes

• Tizanidine demonstrates superior preservation of muscle strength, bladder function, and activities of daily living compared to baclofen 6
• In one double-blind trial, muscle strength and daily activities improved more with tizanidine (8-36 mg/day) than baclofen (10-80 mg/day) 6

Clinical Preference

• Neurologists and physiotherapists rated baclofen as superior based on perceived efficacy and tolerance in one Canadian trial, though patient-reported efficacy differences were not statistically significant (39% vs 24% rating good-to-excellent) 3

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Dosing Protocols

Baclofen

• Typical dose range: 10-80 mg daily in divided doses 6, 3
• Requires gradual titration over several weeks 3

Tizanidine

• Start with 2 mg up to three times daily, particularly in older adults or those with renal impairment 7
• Optimal dose range: 8-36 mg daily 6
• Older adults rarely tolerate doses greater than 30-40 mg per day 7
• Titrate gradually while monitoring for muscle weakness, urinary dysfunction, cognitive effects, sedation, and orthostasis 7

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Side Effect Profile

Baclofen

• Most common adverse effect: muscle weakness (significantly more troublesome than with tizanidine) 3
• May cause significant sedation, particularly in stroke patients 1
• Less dry mouth compared to tizanidine 2

Tizanidine

• Most common adverse effects: dry mouth (xerostomia), somnolence, and tiredness 6, 3
• Can cause significant hypotension requiring monitoring 7, 5
• Less muscle weakness compared to baclofen 2, 3
• Overall rate of adverse effects is similar between tizanidine and baclofen, but the specific side effect profiles differ 2

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Contraindications and Safety Warnings

Baclofen

• Abrupt discontinuation can precipitate life-threatening withdrawal with seizures, visual and auditory hallucinations, hyperthermia, and potentially fatal outcomes 8
• Withdrawal symptoms include anxiety, agitation, delirium, fever, tremor, tachycardia, and seizures 8
• Must be tapered slowly in all long-term users 8
• Intrathecal baclofen withdrawal is especially hazardous, producing high fever, altered mental status, rebound spasticity, muscle rigidity, rhabdomyolysis, multiorgan failure, and death 8

Tizanidine

• Absolutely contraindicated with ciprofloxacin or fluvoxamine due to marked reduction in tizanidine clearance and risk of severe toxicity 8
• Concomitant use with CYP1A2 inhibitors (oral contraceptives, acyclovir, amiodarone, verapamil, mexiletine, propafenone, cimetidine, famotidine) can produce significant hypotension, bradycardia, and enhanced sedation 8
• Use with extreme caution or avoid entirely in hepatic dysfunction due to hepatotoxicity risk and reduced clearance 8
• Requires dose reduction and careful monitoring in renal impairment 8
• Avoid abrupt discontinuation in long-term users; taper slowly to prevent withdrawal symptoms including tachycardia, hypertension, and rebound hypertonia 7
• Should be avoided in elderly patients with significant cardiovascular disease due to heightened risk of hypotension and sedation 8

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Monitoring Requirements

Tizanidine-Specific Monitoring

• Perform baseline heart rate and blood pressure assessment, followed by weekly heart rate checks (by pulse, event recorder, or office ECG) throughout the first month of treatment to detect early bradycardia 8
• Monitor blood pressure regularly due to hypotensive effects 7, 5

Baclofen-Specific Monitoring

• During any baclofen taper, vigilantly monitor for withdrawal signs—fever, tachycardia, increased spasticity, and mental status changes—and be prepared to reinstitute baclofen promptly if these occur 8

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Clinical Suitability by Condition

Spasticity of Spinal Origin (Spinal Cord Injury, Multiple Sclerosis)

• Both baclofen and tizanidine are preferred centrally acting agents for spasticity of spinal origin 4
• The American Heart Association recommends tizanidine for chronic stroke patients with spasticity causing pain, poor skin hygiene, or decreased function 7, 5

Spasticity of Cerebral Origin (Stroke, Traumatic Brain Injury)

• Dantrolene may be preferable in spasticity of cerebral origin where sensitivity to sedating effects is generally higher 4
• However, tizanidine is not contraindicated during stroke recovery, unlike diazepam 7, 5
• Baclofen may cause significant sedation and have less impact on spasticity in stroke victims compared to other conditions 1

Preservation of Muscle Strength

• Choose tizanidine when preserving muscle strength is a clinical priority, as it causes significantly less weakness than baclofen 6, 2, 3

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Treatment Algorithm

Step 1: Conservative Management

• Begin with positioning, passive stretching, and range-of-motion exercises several times daily 1

Step 2: Oral Pharmacotherapy

• For spasticity of spinal origin (MS, SCI): Choose either baclofen or tizanidine based on side effect tolerance
  • Select tizanidine if muscle weakness must be avoided 6, 2
  • Select baclofen if dry mouth or sedation would be poorly tolerated 2, 3
• For spasticity of cerebral origin (stroke, TBI): Consider tizanidine over baclofen due to lower sedation risk in this population 4

Step 3: Invasive Options

• If oral agents fail to achieve adequate control, escalate to botulinum toxin injections, phenol/alcohol nerve blocks, intrathecal baclofen, or neurosurgical procedures (selective dorsal rhizotomy or dorsal root entry zone lesion) 5

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Critical Pitfalls to Avoid

• Never abruptly discontinue baclofen, even when the patient appears clinically stable on tizanidine during cross-titration 8
• Do not use tizanidine in patients with hypotonia (reduced muscle tone); it is specifically for spasticity (increased muscle tone) 7, 5
• Never co-prescribe tizanidine with ciprofloxacin or fluvoxamine 8
• Do not confuse Flexeril (cyclobenzaprine) with tizanidine; they are different medications with different indications 2
• Distinguish true spasticity (velocity-dependent hyperactivity of stretch reflexes) from general muscle weakness before initiating treatment 5