What is the recommended dosing regimen for Baclofen (Lioresal) in a patient with muscle spasticity, considering factors such as renal function and potential side effects?

Baclofen Dosing for Muscle Spasticity

Start oral baclofen at 5 mg three times daily and titrate upward by 5 mg per dose every 3 days until achieving adequate spasticity control or reaching a maximum of 80 mg/day, while monitoring closely for dose-limiting sedation and weakness that commonly occur above 60 mg/day. 1

Initial Dosing Strategy

Oral baclofen should be initiated at low doses with gradual upward titration to minimize central nervous system adverse effects. 2, 1

• Begin with 5 mg three times daily (15 mg total daily dose) 1
• Increase by 5 mg per dose (15 mg total daily) every 3 days based on response 1
• Target the lowest effective dose that provides meaningful spasticity reduction 2

Maximum Dosing and Dose-Limiting Factors

Adverse effects become prominent at doses exceeding 60 mg/day, with sedation, confusion, and excessive weakness being the primary concerns. 1

• Maximum recommended daily dose is 80 mg/day (divided into 3-4 doses) 1
• Adverse effects occur in 25-75% of patients, with severity increasing dose-dependently 3, 1
• Treatment discontinuation due to intolerable side effects occurs in 4-27% of patients 3
• Common dose-limiting effects include sedation, dizziness, mental confusion, somnolence, muscle weakness, nausea, and paresthesia 3, 1

Clinical Effectiveness Considerations

Oral baclofen is FDA-approved for spasticity but has limited evidence for functional improvement, particularly in stroke patients where it may cause significant sedation with less impact on spasticity compared to other conditions. 2

• Effective in reducing spasticity of spinal origin in approximately 80% of patients 4
• Reduces frequency and severity of muscle spasms in 87% of patients 4
• In stroke patients specifically, oral baclofen may reduce spasticity and pain but produces no significant functional gains 2
• Most effective when administered early in disease progression, before permanent disabilities develop 5
• Provides little benefit for spasticity of cerebral origin 4

Renal Function Adjustments

Baclofen is primarily renally excreted, requiring dose reduction in patients with impaired kidney function to prevent drug accumulation and increased toxicity. 1

• Reduce both initial and maintenance doses in patients with renal impairment 1
• Monitor more closely for adverse effects in patients with decreased renal clearance 1

When to Consider Intrathecal Baclofen

Intrathecal baclofen should be considered for patients who fail to respond to maximum oral doses (80 mg/day) or experience intolerable side effects, as it delivers drug directly to cerebrospinal fluid at 1/100th the oral dose while minimizing systemic adverse effects. 2, 3, 1

• Consider as early as 3-6 months after stroke in patients refractory to oral therapy 2
• Appropriate for chronic stroke patients (>6 months post-stroke) with spasticity causing pain, poor hygiene, or decreased function 2
• Provides higher CSF drug concentrations than achievable orally while reducing central side effects like drowsiness and confusion 3
• Allows programmable dosing that can be adjusted throughout the day (lower during ambulation, higher at night for sleep) 3

Critical Safety Warnings

Baclofen may worsen obstructive sleep apnea by promoting upper airway collapse during sleep, requiring careful assessment in patients with pre-existing sleep disorders. 6, 7

• Screen for sleep-disordered breathing before initiating therapy 6, 7
• Avoid abrupt discontinuation, which can cause withdrawal symptoms 1
• Use with caution in patients with seizure disorders 1

Stepwise Treatment Algorithm

Spasticity should be treated using a stepwise approach, beginning with the least invasive modalities before progressing to pharmacologic interventions. 2

1. First-line non-pharmacologic: Positioning, passive stretching, range of motion exercises (several times daily), splinting, or serial casting 2
2. Second-line oral medications: Baclofen, tizanidine, or dantrolene for spasticity causing pain, poor hygiene, or decreased function 2
3. Third-line focal injections: Botulinum toxin for localized spasticity (Class I recommendation for upper limb) 2
4. Fourth-line intrathecal therapy: Intrathecal baclofen for severe, refractory cases 2, 3