TIZANIDINE TREATMENT OF SPASTICITY CAUSED BY MULTIPLE-SCLEROSIS - RESULTS OF A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

This multicenter, stratified, randomized, placebo-controlled, double-b lind trial evaluated tizanidine for use in the United States for spast icity secondary to MS. The 15-week trial was divided into baseline (we eks 6 and 1), titration (2 mg to a maximum of 36 mg/d; weeks 2 to 4), and plateau (weeks 5 to 13) phases, followed by dose tapering (week 14 ) and a final visit (week 15). Primary efficacy parameters were scores on muscle tone (Ashworth Scale) and type and frequency of muscle spas ms (patient diaries). All efficacy parameters were evaluated by the ph ysician/assessor, and the physician/prescriber was responsible for all dosage adjustments. The patient, physician/assessor, and physician/pr escriber made global evaluations of antispastic efficacy. Tizanidine p roduced a significantly greater reduction than placebo in spasms and c lonus (patient diaries) but no significant differences in Ashworth sco res. Patients and physician/prescribers, but not physican/assessors, g ave significantly better scores in the overall assessment of efficacy and tolerability. No significant differences in other secondary effica cy parameters were noted. Adverse events were reported for 66 (61%) of the 109 placebo-treated patients and 101 (91%) of the 111 tizanidine- treated patients; 6 (6%) and 14 (13%) discontinued treatment, respecti vely. Patient and physician perception of improvement demonstrated mor e consistent differences between groups than did the Ashworth Scale, p erhaps because of inexperience with this measure or failure to conside r time between drug administration and assessment.