Side effects such as muscle weakness and sedation have often been problematic in patients who take medications for spasticity. This is especially true in the stroke population, who tend to be older and weaker, and who suffer from a number of comorbidities. In 1997, the Food and Drug Administration approved tizanidine to treat increased muscle tone and spasticity in the United States.

Tizanidine is an imidazoline derivative which inhibits spinal reflex transmission by descending facilatory pathways and via supraspinal inhibitory effects. It may also have pain-relieving properties, possibly the result of its inhibition of substance P. Dosing starts at 2mg to 4mg three times a day, which can be slowly titrated to a maximum of 36 mg/day. It is metabolized in the liver, and has an elimination half-life of 4-8 hours, with peak serum levels occurring at 1-2 hours after dosing.

In comparison to baclofen, tizanidine shows similar efficacy for most parameters of spasticity, but appears to have a better profile for clonus and muscle strength. In patients with spasticity associated with cerebral disorders, tizanidine was found to be as effective as either diazepam or baclofen. Improvements were noted in clonus and stretch reflexes, and there was a decrease in the frequency of flexor spasms. In comparison to baclofen, patients taking tizanidine showed more functional improvement in the areas of dressing, general dexterity, pain, and ambulation.

The frequency of sedation is approximately 50% at the higher end of the dosing range. Other side effects such as hallucinations, liver injuries, gastrointestinal disturbances, nervousness, dizziness, and skin rash are less frequently reported than with other spasticity medications, and these side effects are generally reversible with discontinuation of the drug. Because liver function abnormalities have been noted in some patients on the drug, liver enzymes should be monitored.

Tizanidine has been shown to be a safe and effective medication for spasticity in spinal cord injury and multiple sclerosis. As it has little effect on muscle strength, it should also be considered as a first line medication in stoke patients with spasticity. There have not been extensive studies to assess the efficacy of tianidine in the treatment of spasticity due to acquired brain injuries; therefore, tizanidine can be recommended for the treatment of spasticity in TBI patients with the same caution that applies to other anti-spasticity agents, where the incidence of sedation is a particular concern.

For more information: Kaplan, Mark S, M.D. Tizanidine: Another Tool in the Management of Spasticity. J Head Trauma Rehabil 1997: 12(5):93-97.

Gelber, D. M.D., Good, D.M.D. , and Sergay, S. MB, BCh. Stroke and Rehabilitation: Understanding the Impact of Spasticity. Medical Education Resources. pp. 16-2 1.

Lisa Palen Hu, M.D.