Nightly sublingual tizanidine HCl in multiple sclerosis: clinical efficacy and safety.
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.


OBJECTIVE
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.
Vakhapova
Veronika
V
Neuroimmunology Clinic, Department of Neurology, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Auriel
Eitan
E
Karni
Arnon
A
D000286:Administration, Sublingual; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000328:Adult; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018592:Cross-Over Studies; D006970:Disorders of Excessive Somnolence / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000503:physiopathology; D009128:Muscle Spasticity / Q000188:drug therapy*; D010352:Patient Dropouts; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; C023754:tizanidine; D003000:Clonidine