Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study

J Neurol Neurosurg Psychiatry. 2009 Apr;80(4):380-5. doi: 10.1136/jnnp.2008.159657. Epub 2008 Oct 31.

Abstract

Background: While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared.

Methods: This study performed a randomised, double-blind, placebo-controlled trial to compare injection of BoNT-Type A into spastic upper limb muscles versus oral tizanidine (TZD), or placebo, in 60 subjects with upper-limb spasticity due to stroke or traumatic brain injury (TBI). Wrist flexors were systematically injected, while other upper limb muscles were injected as per investigator judgement. Participants were randomised into three groups: (1) intramuscular BoNT plus oral placebo; (2) oral TZD plus intramuscular placebo; (3) intramuscular placebo plus oral placebo. The primary outcome was the difference in change in wrist flexor modified Ashworth score (MAS) between groups. Other outcome measures included MAS at elbow and finger joints, Disability Assessment Scale (DAS) and adverse events (AE).

Results: BoNT produced greater tone reduction than TZD or placebo in finger and wrist flexors at week 3 (p<0.001 vs TZD; p<0.02 vs placebo) and 6 (p = 0.001 vs TZD; p = 0.08 vs placebo), and greater improvement in the cosmesis domain of the DAS at week 6 (p<0.01). TZD was not superior to placebo in tone reduction at either time point (p>or=0.09). The incidence of AE related to study treatment was higher with TZD than in the BoNT (p<0.01) or placebo groups (p = 0.001).

Conclusions: BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.

Trial registration: ClinicalTrials.gov NCT00430196.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Botulinum Toxins / adverse effects
  • Botulinum Toxins / therapeutic use*
  • Clonidine / adverse effects
  • Clonidine / analogs & derivatives*
  • Clonidine / therapeutic use
  • Double-Blind Method
  • Female
  • Fingers / physiology
  • Humans
  • Male
  • Middle Aged
  • Muscle Relaxants, Central / adverse effects
  • Muscle Relaxants, Central / therapeutic use*
  • Muscle Spasticity / drug therapy*
  • Neuromuscular Agents / adverse effects
  • Neuromuscular Agents / therapeutic use*
  • Treatment Outcome
  • Upper Extremity
  • Wrist / physiology
  • Young Adult

Substances

  • Muscle Relaxants, Central
  • Neuromuscular Agents
  • tizanidine
  • Botulinum Toxins
  • Clonidine

Associated data

  • ClinicalTrials.gov/NCT00430196