Spasticity

Oral Medications

A variety of medications are available for the treatment of spasticity. When spasticity is focal rather than diffuse in nature, the sedation and confusion associated with the use of oral medications may limit their effectiveness.

Dantrolene Dantrolene (Dantrium®)has FDA approval for use in controlling the manifestations of chronic spasticity secondary to upper motor neuron disorders in children and adults.55 The mechanism of action of dantrolene is to reduce the release of calcium into the sarcoplasmic reticulum of muscles. This drug, which has a half-life of 8.7 hours, affects fast muscle fibers more than it does slow muscle fibers.56

The initial recommended dose of dantrolene for the treatment of spasticity in adults is 25 mg daily for 7 days. This may be increased to 25 milligrams 3 times daily for 7 days, then to 50 mg 3 times daily for 7 days and then to 100 mg 3 times daily. Before beginning therapy a therapeutic goal should be identified with doses increased accordingly. Therapy should be stopped if benefits are not seen within 45 days. The maximum dose in adults is 100 mg 4 times daily.55

The initial recommended dose of dantrolene for the treatment of spasticity in children is 0.5 milligram/kilogram (mg/kg) once daily for 7 days. This may be increased to 0.5 mg/kg 3 times daily for 7 days, then 1 mg/kg 3 times daily for 7 days, and then 2 mg/kg 3 times daily. Doses higher than 100 mg 4 times daily should not be used. As in adults, a therapeutic goal should be identified before beginning therapy and doses should be increased accordingly. Therapy should be stopped if benefits are not seen within 45 days.55

Although side effects include drowsiness, dizziness, weakness, malaise, fatigue, and diarrhea, dantrolene is less likely to cause problems with confusion or cognition than are the benzodiazepines and oral baclofen. Because of the potential for dantrolene to cause hepatotoxicity, regular monitoring of hepatic function is required with the use of this drug. The typical starting dose of dantrolene is 25 mg by mouth, daily, with titration to efficacy. There are no specific changes recommended for the dosing regimen for the geriatric patient.47,57

Benzodiazepines
Benzodiazepines do not have FDA approval for the treatment of spasticity, although they are widely used for this condition.

Diazepam acts by facilitating the postsynaptic action of GABA, although it has no direct GABA mimetic effect. The half-life of diazepam is 27 to 37 hours. Common side effects include sedation, ataxia, and fatigue. The typical effective dose of diazepam for the treatment of spasticity is 2 to 10 mg, three or four times per day. In the geriatric population, a typical starting dose is 2.0 to 2.5 mg once per day.58

Clonazepam is a sedative-anxiolytic, which decreases nocturnal spasms, hyperreflexia, and resistance to range of motion. Side effects include weakness, hypotension, ataxia, dyscoordination, sedation, depression, and memory impairment. Prolonged use may also increase the risk of addiction. Clonazepam is usually administered at bedtime, in a dose of 0.5 to 1.0 mg.59

Imidazolines Clonidine (Catapres® tablet or transdermal patch) and tizanidine (Zanaflex®) are imidazolines that reduce spasticity through their action on the CNS. These drugs typically cause less muscle weakness than do the benzodiazepines, which may be valuable when it is important for the patient to retain strength. The most common side effect of these drugs is sedation, and they may also cause hypotension, dry mouth, dizziness, renal impairment, and psychosis.

Tizanidine is approved by the FDA for the treatment of spasticity. Tizanidine has a peak effect of 1 to 2 hours and a duration of action of 3 to 6 hours. The usual starting dose of tizanidine is 1 to 2 mg by mouth, which is then gradually increased in 1- to 2-mg increments. The drug may be repeated at 6- to 8-hour intervals as needed, up to 3 doses per 24 hours. However, the daily dose should not exceed 36 mg. The safety and efficacy of tizanidine have not been determined in children. Tizanidine may cause hepatotoxicity, and regular monitoring of hepatic function is required. Dantrolene and tizanidine are usually not prescribed together because they may each cause hepatotoxicity.60 Concomitant use of tizanidine and either fluvoxamine or ciprofloxacin should be avoided.55,61

Clonidine does not carry FDA labeling for the treatment of spasticity. Support for its use is derived from the results of open-label trials and clinical experience.62 The half-life of oral clonidine is 12 to 16 hours. The usual starting dose of oral clonidine is 0.1 mg twice a day, with titration to 0.2 to 0.6 mg twice a day, to a maximum of 2.4 mg per day. The transdermal formulation of clonidine is typically initially administered as one TTS-1 patch (equivalent to 0.1 mg per 24 hours) per week, with titration to two TTS-3 patches (equivalent to 0.6 mg per 24 hours) per week. No dosing recommendations are available for geriatric patients. Clonidine is much more likely than tizanidine to cause hypotension.

Baclofen Orally administered baclofen (Lioresal®) has FDA approval for the treatment of spasticity in children and adults resulting from multiple sclerosis and spinal cord injuries/diseases and intrathecally for spasticity related to cerebral palsy and spinal cord injury.63

Baclofen is an analog of GABA and binds to the GABAB receptors found in the spinal cord, decreasing stretch reflexes, the rate of muscle spasms and clonus, pain, and tightness and improves range of motion.

The initial recommended dose of oral baclofen for the treatment of spasticity in adults is 5 mg 3 times a day. The dose may be increased by 15-mg/day increments every 3 days. Although 80 mg per day (divided into 3 or 4 doses) is a commonly accepted maximum, dosing up to 200 mg per day has been used safely and effectively.

Keeping in mind that the safety and efficacy of oral baclofen have not been established in children younger than 12 years of age, the initial recommended starting dose of oral baclofen for the treatment of spasticity in children aged 2 to 7 years is 10 to 15 mg/day (in 2 to 3 divided doses). The dose may be increased by 5- to 15-mg/day increments every 3 days to a maximum dose of 40 mg/day (in 3 to 4 divided doses). For children older than 8 years, the initial recommended starting dose of baclofen is 10 to 15 mg/day orally (in 2 to 3 divided doses). The dose may be increased by 5- to 15-mg/day increments every 3 days to a maximum dose of 40 mg/day (in 3 to 4 divided doses).

Side effects may include vertigo, urinary frequency, muscle weakness drowsiness, confusion, headache, nausea, seizures, constipation, dyspnea, impaired vision, severe fatigue, urticaria, and edema.63