Background: Approximately 90% of patients with multiple sclerosis (MS) experience spasticity during their lifetime. Tizanidine HCl is an alpha2 adrenergic agonist indicated for treating spasticity due to MS or spinal cord injury.
Objectives: To compare the clinical efficacy and safety of once-nightly sublingual versus oral tizanidine HCl (8 mg) or placebo in MS patients with spasticity requiring treatment.
Methods: A double-blind, double-dummy, randomized, 3-treatment, 2-way crossover, comparative, placebo-controlled study was conducted in a neuroimmunology clinic of a university-affiliated medical center (December 2005 to March 2006). Enrolled patients received placebo once nightly and were then randomized to receive oral tizanidine HCl following sublingual tizanidine HCl or sublingual tizanidine HCl following oral tizanidine HCl, each arm for 7 days. The patients were evaluated for spasticity (Ashworth scale), mobility, Global Assessments of Disease Severity and Change, and safety parameters, including next-day somnolence (Epworth Sleepiness Scale), fatigue, hypotension, and hepatotoxicity.
Results: Sixteen MS patients aged 20 to 65 years with spasticity requiring treatment and Expanded Disability Status Scale score of 6.5 or less were enrolled. There were significant reductions in next-day (12-14 hours after dosing) spasticity following sublingual tizanidine compared with placebo and oral tizanidine, oral versus placebo treatment, and sublingual tizanidine versus placebo treatment. Fatigue, hypotension, or hepatotoxicity levels did not increase.
Conclusions: Overnight sublingual tizanidine provides improvement in next-day spasticity compared with placebo, without increasing next-day somnolence. The Epworth somnolence score improved significantly with sublingual tizanidine treatment. This is contrary to the reported day-dose tizanidine use, in which increased somnolence is the most cited cause for patient dissatisfaction and noncompliance.