BOSTON — Botulinum toxin injections are significantly more effective than oral tizanidine in reducing muscle tone and normalizing the appearance of spastic upper limbs in patients who have experienced a stroke or traumatic brain injury.
In fact, Dr. David Simpson reported at the annual meeting of the American Academy of Neurology, tizanidine—a first-line therapy for cerebral spasticity—was significantly less effective than placebo, suggesting it's time for physicians “to reconsider our first-line treatment for these patients, “said Dr. Simpson, professor of neurology at the Mount Sinai School of Medicine, New York.
Allergan Inc. sponsored the trial; Dr. Simpson and some of his coinvestigators have received research support and personal compensation from the company.
He presented the initial results of an 18-week three-way study of botulinum toxin, tizanidine, and placebo in 60 patients with increased upper limb tone secondary to stroke or traumatic brain injury.
Patients were randomized to either botulinum toxin injection plus oral placebo; tizanidine plus placebo injections; or oral placebo-placebo injections. All botulinum toxin patients received a mandatory injection of 50 units in the wrist flexors; providers could also inject additional toxin in other upper limb muscles, at doses deemed therapeutic. The maximum botulinum exposure was 500 units. Dilutions above the elbow were 2 cm
Tizanidine was titrated according to the label indications: 4 mg/day, escalating 4 mg every 3–4 days based on frequent consultation and patient reaction, to a maximum of 36 mg/day. If adverse events occurred, patients were permitted to slow their titration.
At baseline, all patients had a modified Ashworth score of at least 3 (0 indicates normal tone, whereas 5 indicates rigidity). By week 3, patients receiving the toxin showed significantly more wrist flexor relaxation than the other groups (−1.25 vs. −0.25 for tizanidine and −0.67 for placebo). The results were similar at week 6. By week 18, the toxin group was moving back toward its baseline scores.
Finger tone was also significantly more improved in patients in the toxin group than in those in the tizanidine or placebo groups (−1.32 vs. −0.22 and −0.69).
“In fact, the placebo group did significantly better than the tizanidine group in both categories,” he said.
Only limb posture cosmesis was significantly improved in the Disability Assessment Score, he said. The greatest improvement occurred in the botulinum toxin group.