Tizanidine is used alone or in conjunction with other standard therapies (e.g., baclofen) for the management of spasticity associated with cerebral or spinal injury. In these patients, tizanidine decreases the number and severity of spasms, alleviates clonus, and improves mobility to a greater extent than does placebo. Some evidence from comparative studies suggests that tizanidine may produce muscle weakness less frequently than other antispastic agents (e.g., baclofen, diazepam). The manufacturer states that because of its short duration of effect, tizanidine should be reserved for those daily activities and times when relief of spasticity is most important.
Efficacy for the management of spasticity has been demonstrated in 2 placebo-controlled, randomized studies in patients with multiple sclerosis or spinal cord injury. In these studies, patients 18-75 years of age received initial tizanidine hydrochloride dosages of 2 or 4 mg daily, which were titrated according to response and tolerance to a maximum of 36 mg (in up to 3 divided doses) daily over a 3-week period. Following initial dosage titration, tizanidine hydrochloride dosages averaged 30.7-31.1 mg daily. Based on changes in Ashworth scores (a 5-point rating scale for assessing muscle tone, with 0 representing normal muscle tone and 4 representing immobilization of the muscle by spasticity), reductions in muscle tone were greater with tizanidine than with placebo during dosage titration, plateau, and/or study end point assessments. Mean reductions from baseline in Ashworth scores at the end point assessment were 4.41 and 0.44 for the tizanidine and placebo groups, respectively, in one study and 4.4 and 1.2, respectively, in the other study. However, in the larger of these studies, reductions in muscle tone (primary outcome measure) with tizanidine were not associated with comparable improvements in secondary outcome measures such as muscle strength, the frequency of daytime muscle spasms, pain, or deep tendon reflex activity. Improvement in muscle tone with tizanidine therapy was not consistently associated with improvements in quality of life as determined by activities of daily living (ADL) assessment scores.
In comparative studies in patients with spasticity associated with multiple sclerosis or cerebrovascular disorders, principally stroke, tizanidine's ability to improve muscle tone has been shown to be similar to that of baclofen or diazepam. Combined analysis of data from studies of 4-8 weeks' duration indicated improvements in muscle tone, spasms, and clonus in about 50-67% of patients treated with any of these drugs, while improvement in muscle strength was noted in about 33% of such patients. In these studies, patients receiving tizanidine exhibited better retention of muscle strength than those receiving baclofen or diazepam, and the incidence of somnolence was somewhat lower with tizanidine than with diazepam.
Concomitant therapy with tizanidine and another antispastic agent (e.g., baclofen) reportedly may allow control of spasticity with lower dosages of each agent. However, it should be kept in mind that such concomitant therapy may cause additive sedative effects
(see Drug Interactions: Alcohol and Other CNS Depressants); some clinicians suggest that tizanidine not be given concomitantly with benzodiazepines (e.g., diazepam).