Open-Label Dose-Titration Safety and Efficacy Study of Tizanidine Hydrochloride in the Treatment of Spasticity Associated With Chronic Stroke

Abstract

Background and Purpose-Spasticity is a frequently observed motor impairment that develops after stroke; it can cause pain and disability in those affected. The objective of the present study was to evaluate the safety and efficacy of tizanidine, a centrally acting ␣ 2 -adrenergic agonist, in the treatment of stroke-related spasticity. Methods-Forty-seven patients, who were a minimum of 6 months poststroke and had significant spasticity, were studied at 4 centers.Tizanidine was administered in an open-label manner for 16 weeks, beginning at 2 mg/d and slowly titrated to a maximum of 36 mg/d. The Modified Ashworth Scale, muscle strength testing, functional assessments, and Pain and Functional Spasticity Questionnaires were administered at baseline and at 4, 8, 16, and 18 weeks (after 1 week off tizanidine). Results-Spasticity was significantly improved between baseline and week 16, with a decrease in total upper extremity Modified Ashworth Scale score of 2.80Ϯ0.47 (PϽ0.0001). No decline in strength was noted. Treatment with tizanidine resulted in a significant improvement in pain intensity (Pϭ0.0375), quality of life (Pϭ0.0001), and physician assessment of disability (Pϭ0.0001). The most frequent side effects were somnolence (62%) and dizziness (32%). No serious adverse events were considered to be drug related. Ten of 47 patients (21%) were able to reach the maximum daily dosage of 36 mg. Conclusions-Overall, the data suggest that tizanidine is safe and efficacious in the treatment of stroke-related spasticity, preserving muscle strength while reducing muscle tone and painful spasms in affected patients.

Spasticity after stroke: Physiology, assessment and treatment

“…Adapted from [98,108,126]. Tizanidine, an adrenoceptor agonist, is another centralacting drug that increases the pre-synaptic inhibition of motor neurons [101,102]. This pharmacological agent is used less often than other drugs like Baclofen, perhaps because of its novelty or potentially its side-effects (e.g., sedation, hypotension, asthenia, dizziness, hallucination or hepatotoxicity) [103,104].…”

Veterans Affairs/Department of Defense Clinical Practice Guideline for the Management of Adult Stroke Rehabilitation Care

“…Oral drug agents such as tizanidine, 70 dantrolene, 71 and oral baclofen 72 can be used to treat spasticity that results in pain, poor skin hygiene, or decreased function. Tizanidine should be used specifically for chronic stroke patients (Evidence LevelϭB).…”

Management of Spasticity

“…Patients report less muscle weakness from tizanidine than baclofen or diazepam, but side effects include drowsiness, fatiguability, dizziness, dry mouth, and gastrointestinal disturbance [ 37 -39 ]. There is a small incidence of abnormal liver function tests and these should be monitored at intervals during therapy [ 40 ]. Tizanidine may be combined with baclofen, presenting the opportunity to reduce the dosage of both drugs, but additive adverse effects, including sedation, may occur.…”