Prospective assessment of tizanidine for spasticity due to acquired brain injury

Objective: To determine if orally delivered tizanidine will control spastic hypertonia due to acquired brain injury. Design: Randomized, double-blind, placebo-controlled, crossover design, wit h 2 8-week treatment arms separated by a 1-week washout period at baseline. Patients were randomly assigned to receive tizanidine or a matching placeb o. Setting: Tertiary care outpatient and inpatient rehabilitation center attac hed to a university hospital. Participants: Seventeen persons recruited in a consecutive manner, 9 of who m had suffered a stroke and 8 a traumatic brain injury, and had more than 6 months of intractable spastic hypertonia. Intervention: Over a 6-week period, subjects were slowly titrated up to the ir maximum tolerated dose (up to 36mg/d). Following a 1-week drug taper and 1-week period in which no study drug was administered, patients were then crossed over to the other study medication following an identical titration regime. Main Outcome Measures: Subjects were evaluated for dose and effect througho ut the trial as well as for side effects. Data for Ashworth rigidity scores , spasm scores, deep tendon reflex scores, and motor strength were collecte d on the affected upper extremity (UE) and lower extremity (LE). Difference s over time were assessed via descriptive statistics, Friedman's analysis, and Wilcoxon's signed-rank. Data are reported as the mean +/- 1 standard de viation. Results: Following 4 weeks of treatment when subjects reached their maximal tolerated dosage, the average LE Ashworth score on the affected side decre ased from 2.3 +/- 1.4 to 1.7 +/- 1.1 (p < .0001). The spasm score decreased from 1.0 +/- 0.9 to 0.5 +/- 0.8 (p = .0464), while the reflex score was no t statistically significant decreasing from 2.2 +/- 1.0 to 2.0 +/- 1.1 (p = .0883). The average UE Ashworth score on the affected side decreased from 1.9 +/- 1.1 to 1.5 +/- 0.9 (p < .0001). There was no significant change in the UE spasm and reflex scores. While there were positive placebo effects o n motor tone, the active drug was still significantly better than placebo f or decreasing LE tone (p = .0006) and UE tone (p = .0007). With a reduction in motor tone, there was an increase in motor strength (p = .0089). The av erage dosage at 4 weeks was 25.2mg/d. Conclusion: Tizanidine is effective in decreasing the spastic hypertonia as sociated with acquired brain injury, which is dose-dependent. There are lim itations on its use due to side effects related to drowsiness.