AA

Tizanidine

Download as a PDF

Tizanidine is an orally-administered imadazoline-based compound that is widely used to reduce spasticity in a variety of conditions with most evidence for its effectiveness coming from trials with MS patients (Kaman et al. 2008). As an a2-adrenergic agonist it acts at both a spinal and supraspinal level.

Table 19: Summary of Tizanidine Studies for Reducing Spasticity

Discussion

A randomized, placebo-controlled trial specifically conducted to elucidate the anti-spasmodic effect of tizanidine revealed significant spasticity improvements in favour of tizanidine over placebo where Ashworth and Pendulum were the primary measures used (p<0.0001 and 0.002, respectively; Nance et al. 1994). Although this study represents level 1b evidence, it is noteworthy to mention that 34% of subjects who received study treatment and discontinued prematurely due to adverse events, lack of efficacy and other reasons not specified, were not included in the study analysis. Another single dose, pre-post test study (Mathias et al. 1989) presented evidence to corroborate the reduction in spasticity as measured by Ashworth and furthermore revealed that muscle power was not affected at any stage in the study. That tizanidine did not have a negative impact on muscle strength was also reported by Chu et al. (2014). Tizanidine was found to have a stronger inhibitory effect on knee extensors and plantar flexors when compared to baclofen (Chu et al. 2014). The reverse was true for antispastic effects on knee flexors (Chu et al. 2014). More specifically, the impact of tizanidine on the spastic muscle was examined in a non-RCT (Mirbagheri et al. 2010) where there was an average of 25% reduction in peak-torque in the SCI subjects. Significant decreases in reflex stiffness post-tizanidine were found but not in intrinsic muscle stiffness. The latter was clarified in subsequent work of Mirbagheri et al. (2013) where several spasticity reduction patterns were observed: continuous reduction over the four-week treatment period; more pronounced reduction during the first week of treatment, significant reduction only over time; or no improvement in intrinsic stiffness. This suggests that tizanidine reduces reflex stiffness and intrinsic stiffness for a subset of patients.

Conclusions

There is level 1a evidence (from two RCTs and one prospective controlled trial; Chu et al. 2014; Nance et al. 1994; Mirbagheri et al. 2013b) to support the use of tizanidine in reducing spasticity.

  • Tizanidine is likely useful in treating SCI spasticity.