NEW YORK (Reuters Health) – In patients with upper-extremity spasticity due to stroke or traumatic brain injury (TBI), botulinum toxin injections are safer and more effective than oral tizanidine (TZD) in reducing tone and disfigurement, according to results of a randomized multicenter trial.

“Most physicians continue to initiate therapy with oral agents due to their lesser short-term cost or perceived convenience, or in response to payor mandate,” Dr. David Simpson, at New York’s Mount Sinai Medical Center, and his associates note in the April Journal of Neurology, Neurosurgery and Psychiatry. “However, there has been no controlled study that directly compares focal and systemic agents in patients with spasticity.”

The 60 study subjects, ages 18 to 85, had spasticity of the wrist from a stroke or TBI at least 3 months earlier. They were randomized in a double-blind manner to IM botulinum neurotoxin toxin Type A (BoNT) plus oral placebo (n = 20), TZD plus IM placebo (n = 21), or oral and IM placebo (n = 19).

TZD was started at 2 mg/day and increased by 4 mg every 3-4 days up to 36 mg/day, depending on side effects. Treatment continued for 18 weeks. BoNT 50 U/muscle was injected into each of the wrist flexors at the baseline visit.

BoNT was more effective in reducing tone in wrist flexors at week 3 (p < 0.001 vs TZD; p < 0.02 vs placebo) and at week 6 (p = 0.002 vs TZD; p = 0.08 vs placebo). At week 6, tone had improved by at least one grade in 84% of subjects in the BoNT group, 28% in the TZD group, and 63% in the placebo group. Similar findings were documented for finger flexor tone. At no point during the 18-week treatment period was TZD superior to placebo. BoNT also produced significantly greater improvement in patient perception of limb position at week 6. The incidence of adverse events related to treatment, primarily somnolence, was significantly greater in the oral therapy group. According to the researchers, “The systemic side effects in the TZD group are concerning in a population that may already be compromised due to neurological disability.” They conclude: “The results of this study suggest that injections of BoNT alone to treat focal or multifocal spasticity decrease muscle tone with few systemic effects and should be considered as the primary treatment before oral medications.” In an editorial, Dr. Geoffrey Sheean at the University of California, San Diego writes that this paper “deals a final blow to the notion that oral antispasticity medications should be tried first…for focal upper-limb poststroke spasticity….Furthermore, the greater risk of side-effects, especially somnolence…means that the insistence upon using such medications before BoNT could be ethically compromised.” Reference:
J Neurol Neurosurg Psychiatry 2009;80:359,380-385.