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Antiepileptic drugs
In therapeutic doses, antiepileptic drugs (AEDs) do not worsen spasticity. Several (in addition to gabapentin, covered elsewhere) have been shown to reduce spasticity, sometimes in combination with other medications: PhenytoinPhenytoin (Dilantin, Phenytek) and chlorpromazine (Thorazine) were preliminarily investigated in open and controlled studies to treat spasticity. In both types of studies, most patients exhibited both objective and subjective improvement with each drug.114 Tone was reduced in spastic muscles, and functional status was improved. (Phenytoin toxicity can worsen spasticity, however.115) The combination of phenytoin and chlorpromazine was most effective. Lethargy and somnolence were the most common side effects. These drugs may exert their action by suppressing fusimotor efferent and afferent discharges from muscle spindles.113 TiagabineTiagabine (Gabitril), a GABA uptake inhibitor developed as an AED, may reduce spasticity. In an open-label study, 14 children with congenital or acquired spastic quadriplegia and intractable epilepsy were treated with tiagabine. The dosage gradually was titrated upward until seizures ceased, adverse effects supervened, or the maximum dose of 1.1 mg/kg daily was reached. The mean improvement in motor function was approximately 50%. Other findings included improved muscle tone, strength, coordination, range of motion, and relaxation of extremities, with less ataxia and wobbling.116 ValproateIn one patient, baclofen and sodium valproate (Depakote, Depakene) were used successfully to relieve writer’s cramp. Writer’s cramp may result from striatal dopaminergic hyperactivity. Both sodium valproate and baclofen can increase GABA-ergic activity.117 The two drugs may act synergistically to reduce activity in the nigrostriatal dopaminergic pathway and inhibit release of dopamine in the striatum.118 CarbamazepineCombined therapy with baclofen and carbamazepine (Tegretol, Carbatrol) can reduce spasticity and improve muscle tone, range of motion, and coordination in patients with brainstem and other supraspinal injuries.119 OxcarbazepineBittencourt and Silvado120 observed that in several epilepsy patients who also exhibited spasticity, oxcarbazepine (Trileptal) reduced both seizure frequency and spasticity throughout the study. Minor side effects included nausea and dizziness. These authors subsequently assessed two patients with MS and one with transverse myelitis, who had lower-extremity spasticity. The antispastic effect of oxcarbazepine occurred at doses between 600 and 1,200 mg daily, usually below the dose that produced nausea, dizziness, and somnolence.121 ClonazepamClonazepam (Klonopin), alone or in combination with baclofen, may successfully treat spasticity. Cendrowski and Sobzcyk122 studied 25 patients with MS and other spastic disorders, 33 MS patients without other spastic disorders, and 10 control patients, all of whom were given clonazepam, baclofen, or placebo. Both clonazepam and baclofen were significantly more effective than placebo for spasticity. They were equally effective, but trends suggested that clonazepam was more effective in patients with slight muscle hypertonia mainly of cerebral origin and that baclofen was better suited to patients with severe spinal spasticity. The combination of both drugs was most effective in treating some MS patients.122 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. |
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