Introduction
Baclofen is a centrally-acting skeletal muscle relaxant used primarily for the management of spasticity. It is a gamma-aminobutyric acid (GABA) derivative that acts as a GABA-B receptor agonist. First introduced in the 1970s, baclofen has become a cornerstone therapy for spasticity associated with multiple sclerosis, spinal cord injuries, and other neurological conditions.
Mechanism of Action
Baclofen exerts its therapeutic effects by activating GABA-B receptors at the spinal cord level. It hyperpolarizes primary afferent terminals, reducing the release of excitatory neurotransmitters such as glutamate and aspartate. This action inhibits monosynaptic and polysynaptic reflexes at the spinal level, leading to reduced muscle spasticity. Unlike other muscle relaxants, baclofen acts primarily on the central nervous system rather than directly on skeletal muscle.
Indications
- Management of spasticity resulting from multiple sclerosis, spinal cord injuries, or other spinal cord diseases
- Treatment of muscle spasms and rigidity in cerebral palsy
- Off-label uses: Treatment of intractable hiccups, trigeminal neuralgia, alcohol withdrawal syndrome, and neuropathic pain (with varying evidence support)
Dosage and Administration
Oral administration:- Initial dose: 5 mg three times daily
- May increase by 15 mg daily every 3 days
- Maintenance dose: 40-80 mg daily in divided doses
- Maximum dose: 80 mg daily (some sources recommend up to 100 mg daily)
- Reserved for severe spasticity unresponsive to oral therapy
- Requires implantation of a programmable pump
- Initial test dose: 50-100 mcg
- Maintenance infusion: 300-800 mcg/day
- Renal impairment: Requires dose reduction (CrCl <30 mL/min: reduce dose by 25-50%)
- Hepatic impairment: Use with caution
- Elderly: Start with lower doses due to increased sensitivity
- Pediatrics: Safety and effectiveness not established for children under 12 years
Pharmacokinetics
- Absorption: Rapidly absorbed from GI tract; bioavailability approximately 70%
- Distribution: Widely distributed throughout the body; crosses blood-brain barrier and placenta
- Protein binding: Approximately 30%
- Metabolism: Minimal hepatic metabolism (15%)
- Elimination: Primarily renal excretion (70-80% unchanged)
- Half-life: 2.5-4 hours
- Time to peak concentration: 2-3 hours
Contraindications
- Hypersensitivity to baclofen or any component of the formulation
- Intrathecal administration in patients with infection at the injection site
- Intravenous administration (causes CNS depression and cardiovascular collapse)
Warnings and Precautions
- Abrupt discontinuation: May cause withdrawal symptoms including hallucinations, seizures, and rebound spasticity
- CNS depression: May impair mental and/or physical abilities; caution when operating machinery
- Renal impairment: Requires dose adjustment due to primarily renal excretion
- Psychiatric effects: May cause confusion, hallucinations, or mood changes
- Autonomic dysreflexia: Risk in spinal cord injury patients
- Pregnancy: Category C - use only if potential benefit justifies potential risk
- Breastfeeding: Excreted in human milk; use with caution
Drug Interactions
- CNS depressants: Enhanced sedative effects with alcohol, benzodiazepines, opioids, and other sedating medications
- MAO inhibitors: May increase CNS depressant effects
- Antihypertensives: Additive hypotensive effects
- Levodopa: May increase risk of hallucinations
- Tricyclic antidepressants: May increase muscle relaxant effects
Adverse Effects
Common (≥10%):- Drowsiness
- Dizziness
- Weakness
- Fatigue
- Nausea
- Headache
- Insomnia
- Constipation
- Hypotension
- Confusion
- Seizures
- Hallucinations
- Respiratory depression
- Rhabdomyolysis
- Severe hypersensitivity reactions
Monitoring Parameters
- Spasticity reduction and functional improvement
- CNS effects (sedation, dizziness, cognitive function)
- Renal function (serum creatinine, BUN)
- Blood pressure (especially during dose titration)
- Signs of withdrawal upon discontinuation
- For intrathecal therapy: pump function and catheter integrity
Patient Education
- Take exactly as prescribed; do not stop abruptly
- Avoid alcohol and other CNS depressants
- May cause drowsiness - avoid driving or operating machinery until effects are known
- Rise slowly from sitting/lying position to prevent dizziness
- Report any signs of infection if receiving intrathecal therapy
- Keep all follow-up appointments for dose adjustments
- Notify healthcare provider if pregnancy is planned or suspected
References
1. FDA Prescribing Information: Lioresal (baclofen) 2. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th edition 3. Lexicomp Online: Baclofen monograph 4. Clinical Pharmacokinetics of Baclofen. Eur J Clin Pharmacol. 1992;42(3):279-82 5. Management of Spasticity in Multiple Sclerosis. Neurology. 2018;91(20):e1-e10 6. Intrathecal Baclofen Therapy: An Update. PM R. 2009;1(9):852-8 7. Baclofen Withdrawal: A Comprehensive Review. J Pain Symptom Manage. 2020;59(4):925-936
This monograph is intended for educational purposes only and should not replace clinical judgment. Always consult appropriate references and clinical guidelines for specific patient care decisions.