What is the recommended starting dose, titration schedule, maximum dose, side effects, contraindications, and tapering plan for baclofen in an adult without significant renal impairment being treated for spasticity?

Baclofen for Spasticity in Adults

Starting Dose and Titration Schedule

Start baclofen at 5 mg three times daily (15 mg/day total) and increase by 5 mg per dose every 3 days until optimal effect is achieved, typically between 40-80 mg daily. 1

The FDA-approved titration schedule is: 1

• Days 1-3: 5 mg three times daily (15 mg/day)
• Days 4-6: 10 mg three times daily (30 mg/day)
• Days 7-9: 15 mg three times daily (45 mg/day)
• Days 10-12: 20 mg three times daily (60 mg/day)
• Beyond day 12: Further increases may be necessary based on response

The typical therapeutic dosing range is 30-80 mg/day divided into 3-4 doses. 2, 3

Important Titration Considerations

• Allow 4-8 weeks at maximum tolerated dose before declaring treatment failure. 2
• The lowest dose compatible with optimal response should be targeted to minimize CNS adverse effects including sedation, dizziness, and mental confusion. 2, 3
• Slower titration (every 2-5 weeks instead of every 3 days) may be warranted in medically frail patients or those at higher risk for adverse effects. 2

Maximum Dose

The maximum daily dose should not exceed 80 mg (20 mg four times daily). 1

While the FDA label caps the dose at 80 mg/day, some guidelines note that doses can be raised above this in select circumstances with adequate patient education and close monitoring for toxicity. 2 However, for standard practice in adults without renal impairment, 80 mg/day remains the recommended maximum. 1

Side Effects

The main adverse effects of oral baclofen include: 2, 4

• Sedation and somnolence (most common)
• Excessive weakness (particularly problematic compared to alternatives like tizanidine)
• Dizziness and vertigo
• Mental confusion and psychological disturbances
• Gastrointestinal symptoms 2

The incidence of adverse effects ranges from 10-75%, with most being dose-related, transient, and reversible. 4 Adverse effects typically appear at doses >60 mg/day. 2 The rate of treatment discontinuation due to intolerable adverse effects ranges from 4-27%. 2

Special Safety Concerns

• Baclofen may worsen obstructive sleep apnea by promoting upper airway collapse during sleep. 2, 3 Patients with sleep-disordered breathing should be carefully assessed before initiating therapy. 3
• Respiratory depression can occur as a manifestation of CNS toxicity, particularly in overdose situations. 2
• Use extreme caution with other CNS depressants due to additive sedation. 2

Contraindications

Absolute Contraindications

For intrathecal administration (not oral): 2

• Anticoagulant therapy
• Coagulopathy
• Local or systemic infection
• Anatomical abnormality of the spine

Relative Contraindications and High-Risk Conditions

• Significant hepatic dysfunction: Baclofen should be avoided or used with extreme caution due to potential for increased CNS effects and toxicity risk. 2
• Compromised respiratory function: Use with extreme caution due to risk of respiratory depression. 2
• Elderly patients: More susceptible to adverse effects due to altered pharmacokinetics; require more cautious application and sometimes reduced dosages. 2

Note: The question specifies adults WITHOUT significant renal impairment, but for completeness: patients with moderate or greater renal impairment should start with the lowest dose (5 mg/day) due to renal clearance, with mandatory dose reduction. 2

Tapering Plan

Baclofen must NEVER be abruptly discontinued in long-term users—it must be tapered slowly over weeks to avoid life-threatening withdrawal syndrome. 2

Withdrawal Syndrome Characteristics

Abrupt cessation can lead to: 2, 4

• Seizures
• Hallucinations and delirium
• High fever and hyperthermia
• Tachycardia
• Rebound spasticity and muscle rigidity
• Potentially death

These withdrawal symptoms can evolve over 1-3 days and may become fulminant if not recognized and treated promptly. 2 The best management is resuming baclofen as soon as possible. 2

Tapering Protocol

When discontinuation is necessary, taper slowly over several weeks by gradually reducing the dose. 2 The exact tapering schedule should mirror the titration schedule in reverse, decreasing by approximately 5-10 mg every 3-7 days, though slower tapers may be needed for patients on higher doses or longer duration of therapy.

Continue baclofen preoperatively, including the day of surgery, to avoid withdrawal. 2

Clinical Context and Treatment Algorithm

When to Use Baclofen

Baclofen is indicated for generalized spasticity, NOT focal spasticity. 2, 5 The treatment algorithm recommended by the American Heart Association is: 2, 5

1. First-line: Non-pharmacological approaches including antispastic positioning, range of motion exercises, stretching, splinting, and serial casting 2, 5
2. For focal spasticity: Botulinum toxin is preferred over baclofen 2, 5
3. For generalized spasticity: Oral baclofen, tizanidine, or dantrolene 2, 5
4. For severe refractory spasticity: Intrathecal baclofen 2, 5

Important Limitations

Oral baclofen may reduce spasticity and pain but produces no significant functional gains in stroke patients. 3 This is a critical consideration when setting treatment expectations.

Tizanidine has equivalent efficacy to baclofen for spasticity but better tolerability, particularly less weakness. 2 Consider tizanidine as an alternative, especially in patients who need to maintain strength for ambulation or transfers.

Medications to Avoid

Benzodiazepines (such as diazepam) should be avoided during stroke recovery due to deleterious effects on recovery. 2, 5