Nightly sublingual tizanidine HCl in multiple sclerosis: clinical efficacy and
safety.
Author(s): Vakhapova V, Auriel E, Karni A.
Affiliation(s): Neuroimmunology Clinic, Department of Neurology, Tel Aviv Sourasky Medical Center
and Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Publication date & source: 2010, Clin Neuropharmacol. , 33(3):151-4
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.
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