Relationship of the antispasticity effect of tizanidine to plasma concentration in patients with multiple sclerosis
P. W. Nance, W. A. Sheremata, S. G. Lynch, T. Vollmer, S. Hudson, G. S. Francis, P. O'Connor, J. A. Cohen, R. T. Schapiro, R. Whitham, M. K. Mass, J. W. Lindsey and K. Shellenberger
Section of Physical Medicine and Rehabilitation, University of Manitoba, Winnipeg, Canada.
BACKGROUND: Spasticity is a serious problem in multiple sclerosis (MS) and
many patients do not achieve a satisfactory response to currently available
oral antispasticity drugs. Tizanidine hydrochloride, an alpha
2-noradrenergic agonist, has been shown to have an antispasticity effect in
single center trials of patients with MS. OBJECTIVE: To compare plasma
concentrations of tizanidine with objective measures of muscle tone in
patients with MS with moderate to severe spasticity. SETTING: Ten centers,
all tertiary referral centers for the specialized treatment of patients
with MS, in the United States and Canada. DESIGN: A randomized,
double-blind, placebo-controlled, dose-response study of tizanidine
hydrochloride (8 or 16 mg). PATIENTS: One hundred forty-two patients with
spastic MS who were not taking any interfering medication, such as an
antispasticity drug or other alpha-noradrenergic agonist, entered the
trial. RESULTS: Tizanidine treatment reduced muscle tone significantly, as
shown by improved Ashworth scores and increased knee swing amplitude
recorded by the pendulum test, both of which correlated significantly with
plasma concentration. Placebo had no significant effect on muscle tone.
Dizziness, drowsiness, dry mouth, and fatigue were reported most often in
the group treated with tizanidine at peak plasma concentration.
CONCLUSIONS: Tizanidine reduces spasticity in MS, and both therapeutic
effects and side effects are related to the plasma drug levels.
