What is the role of Baclofen (GABA receptor agonist) in the treatment of spasticity?

From the Guidelines

Baclofen is a recommended treatment for spasticity, particularly for patients with severe chronic lower extremity spasticity that cannot be effectively managed by other interventions, as suggested by the 2024 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines 1.

Treatment Approach

The treatment approach for spasticity typically involves a stepwise approach, beginning with the least-invasive modalities and progressing to more invasive ones.

• Positioning, passive stretching, and range of motion exercise may provide relief, and should be done several times daily in persons with spasticity.
• Corrective measures for contractures that interfere with function include splinting, serial casting, or surgical correction.
• Oral antispasticity agents, such as baclofen, can be useful for generalized spastic dystonia but may result in dose-limiting sedation or other side effects 2.

Baclofen Therapy

Baclofen works by activating GABA-B receptors in the spinal cord, inhibiting the release of excitatory neurotransmitters and reducing muscle tone and spasms.

• The typical starting dose is 5 mg three times daily, gradually increasing by 5 mg every 3 days until the desired effect is achieved, usually between 40-80 mg per day (maximum 100 mg daily).
• Treatment should begin with oral administration, with potential progression to intrathecal baclofen therapy via an implanted pump for severe cases unresponsive to oral treatment.
• Common side effects include drowsiness, dizziness, and weakness, which often improve with continued use.
• Patients should be warned against abrupt discontinuation, which can cause serious withdrawal symptoms including hallucinations, seizures, and rebound spasticity.

Special Considerations

Baclofen should be used cautiously in elderly patients and those with renal impairment, and dosage should be reduced in these populations.

• Regular follow-up is essential to assess efficacy and manage side effects.
• Other treatment options, such as botulinum toxin injections and physical modalities like NMES or vibration, may be considered as adjuncts to rehabilitation therapy 2.

From the FDA Drug Label

Indications and Usage Baclofen tablets are useful for the alleviation of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. Baclofen is indicated for the treatment of spasticity, specifically for:

• Relief of flexor spasms
• Concomitant pain
• Clonus
• Muscular rigidity Key conditions where baclofen may be useful include:
• Multiple sclerosis
• Spinal cord injuries
• Other spinal cord diseases 3

From the Research

Baclofen for Treatment of Spasticity

• Baclofen is a commonly used medication for the treatment of spasticity, which is a common and disabling symptom for many patients with upper motor neuron dysfunction 4.
• The medication works as an agonist at gamma-aminobutyric acid (GABA) receptors, acting as a neuroinhibitor to decrease spasticity 5.
• Oral baclofen has been shown to be effective in many patients with spasticity, regardless of the underlying disease or severity, and is at least comparable with other antispasmodic agents 6.
• However, oral baclofen can have adverse effects, such as muscle weakness, nausea, somnolence, and paraesthesia, which can affect between 25% and 75% of patients and limit its usefulness 6.

Intrathecal Baclofen

• Intrathecal baclofen, which is administered directly into the cerebrospinal fluid, may be an effective alternative for patients who experience intolerable side effects or who fail to respond to the maximum recommended dose of oral baclofen 6.
• This method of administration allows for higher concentrations of baclofen to be delivered directly to the site of action, while minimizing drug-related side effects 7.
• Studies have shown that intrathecal baclofen can be effective in reducing severe spasticity in patients who are unresponsive or cannot tolerate oral baclofen, with level 2 evidence supporting its short-term effectiveness and level 3 evidence supporting its long-term effectiveness 7.

Comparison with Other Treatments

• Baclofen has been compared to other treatments for spasticity, including botulinum toxin type A, which has been shown to be an effective therapeutic option for spasticity caused by spinal cord injury 8.
• While baclofen had a more strongly improved disability assessment scale score than botulinum toxin type A at 4 and 6 weeks, both treatments had consistently improved Barthel Index scores, which measure functional ability 8.
• The choice of treatment for spasticity will depend on individual patient needs and circumstances, and may involve a combination of pharmacotherapy, physical therapy, and other interventions 4.