Mechanism of action
Baclofen (Lioresal) is a structural analog of GABA and inhibits monosynaptic and polysynaptic spinal reflexes. It binds the GABA(B) receptor, which is coupled to calcium and potassium channels and occurs both pre- and postsynaptically:20
Activation of GABA(B) receptors may also inhibit gamma motor neuron activity and decrease muscle spindle sensitivity.22,23
Studies in people with multiple sclerosis have found that baclofen effectively reduces spasticity, decreasing frequency and severity of sudden painful spasms and improving range of joint movement.24–26 Increased weakness was commonly reported, however.
In patients with spinal cord lesions, baclofen is very helpful in reducing flexor spasms.
For stroke patients, baclofen is less beneficial.27,28 Such patients often had a modest decrease in that was interpreted subjectively as slightly reduced stiffness. No effect was noted on hyperreflexia or clonus.23,28
Diazepam is often used as an to baclofen in treating spasticity.
Pharmacokinetics and dosage
Baclofen is rapidly absorbed after oral administration, but central nervous system penetration is relatively limited. The mean is short, averaging 3.5 hours. Because it is partially metabolized by the liver (15%) and excreted by the kidney, the dose should be decreased in patients with hepatic or renal impairment.
Doses often are initiated at 5 mg daily, increasing to three times daily as tolerated. Thereafter, doses can be increased slowly at increments of 5 mg per day as needed. It may be helpful to initiate doses and increases at night to minimize side effects. The highest recommended dosage is 80 mg daily in divided doses. For some patients, this dose may be insufficient to relieve symptoms. Higher doses may be attempted cautiously, as side effects are likely to be more prominent.23
Side effects are related mainly to central nervous system depression and include:
Early clinical studies suggested that baclofen might be a proconvulsant and could exacerbate epilepsy. However, two prospective studies found that baclofen neither increased seizure frequency in epilepsy patients109 nor provoked paroxysmal activity on electroencephalography.110 Therefore baclofen is not contraindicated in epilepsy patients, but it should be tapered gradually. Baclofen may suppress activity in the hippocampus at concentrations below those that suppress normal synaptic transmission. Several reports suggest that baclofen may reduce myoclonus in epilepsy patients.111–113
Abrupt cessation of sustained treatment should be avoided, because sudden withdrawal of baclofen may cause hallucinations, psychosis, visual disturbances, and seizures.29,30
Paients with severe limitations who are not helped by other therapies may respond to baclofen infused directly into the intrathecal space. (See Another option: Intrathecal baclofen.)
Adapted from: Bassi V, Kita M, Feldman DS, and Devinsky O. Spasticity. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;231–247. With permission from Elsevier (www.elsevier.com).
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