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.


METHODS
Randomized, double-blind, placebo-controlled, crossover design, with 2 8-week treatment arms separated by a 1-week washout period at baseline. Patients were randomly assigned to receive tizanidine or a matching placebo.


METHODS
Tertiary care outpatient and inpatient rehabilitation center attached to a university hospital.


METHODS
Seventeen persons recruited in a consecutive manner, 9 of whom had suffered a stroke and 8 a traumatic brain injury, and had more than 6 months of intractable spastic hypertonia.


METHODS
Over a 6-week period, subjects were slowly titrated up to their maximum tolerated dose (up to 36 mg/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.


METHODS
Subjects were evaluated for dose and effect throughout the trial as well as for side effects. Data for Ashworth rigidity scores, spasm scores, deep tendon reflex scores, and motor strength were collected on the affected upper extremity (UE) and lower extremity (LE). Differences over time were assessed via descriptive statistics, Friedman's analysis, and Wilcoxon's signed-rank. Data are reported as the mean +/- 1 standard deviation.


RESULTS
Following 4 weeks of treatment when subjects reached their maximal tolerated dosage, the average LE Ashworth score on the affected side decreased 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 not 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 on motor tone, the active drug was still significantly better than placebo for 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 average dosage at 4 weeks was 25.2mg/d.


CONCLUSIONS
Tizanidine is effective in decreasing the spastic hypertonia associated with acquired brain injury, which is dose-dependent. There are limitations on its use due to side effects related to drowsiness.
Meythaler
J M
JM
Department of Physical Medicine and Rehabilitation, University of Alabama School of Medicine, Birmingham, AL, USA. JMeythal@uab.edu
Guin-Renfroe
S
S
Johnson
A
A
Brunner
R M
RM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000150:complications* / Q000503:physiopathology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009122:Muscle Hypertonia / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D009125:Muscle Relaxants, Central / Q000494:pharmacology / Q000627:therapeutic use*; D009128:Muscle Spasticity / Q000145:classification / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D011446:Prospective Studies; D012021:Reflex, Abnormal / Q000187:drug effects; D012720:Severity of Illness Index; D012894:Sleep Stages / Q000187:drug effects; D016896:Treatment Outcome
D009125:Muscle Relaxants, Central; C023754:tizanidine; D003000:Clonidine