Clonidine, also an a2-adrenergic agonist (selective, central acting), has historically been used as an anti-hypertensive agent although studies demonstrating suppression of muscle activity in rats has led to its investigation as a possible antispastic agent in human SCI (Clark 2002).
There are 2 placebo controlled trials (Stewart et al. 1991; N=12 and Remy-Neris et al. 1999; N=11) providing evidence for clonidine’s effectiveness in reducing SCI spasticity. Stewart et al used oral clonidine in a randomized trial but the spasticity outcome measures are not validated or well-known clinically compared to the Ashworth measure used by Remy-Neris et al’s, intrathecal clonidine study. However the latter study was not randomized and therefore was less rigorous in design. Both studies had small sample sizes. Another non-randomized, placebo controlled study with a small sample size (Nance et al. 1989; N=6) concurred with clonidine’s antispasmodic properties through the use of a non-validated Vibratory Inhibition Index (VII) which is not commonly known clinically. A subsequent pre-post study by the same author (Nance 1994; N=25) using the Ashworth and Pendulum measures as well as the VII compared clonidine with cyproheptadine and baclofen for their anti-spastic properties. Although all three treatments were significantly beneficial in reducing spasticity as measured by the Ashworth and Pendulum tests, clonidine was significantly inferior to baclofen and cyproheptadine as measured by the VII. The remaining reports of antispastic effects of clonidine in various formulations (oral, transdermal and additional intrathecal studies) are derived from case series studies (Donovan et al. 1988, N=55; Weingarden & Belen 1992, N=17; Yablon & Sipski 1993, N=3; Remy-Neris et al. 2001, N=15). All presented results in favour of using Clonidine as an anti-spasmodic but all outcome measures chosen for each study were not specified and there were reports of several adverse events (Donovan et al. 1988). A 2003 study by Malinovsky presented evidence of the systemic and sedating effect of clonidine (150 ug i.m. or i.t.) in patients with traumatic spinal cord injury, regardless of the mode of administration. He concluded that patients receiving treatment for spasticity may be susceptible to this sedating effect because of an altered susceptibility rather than a delayed cephalad spread of medication. Although the majority of studies presented results in favour of clonidine for the treatment of spasticity, the evidence is not entirely convincing given the use of small sample size, predominantly non-validated outcome measures, reports of adverse events and less robust study designs. Furthermore, when directly compared to baclofen, clonidine was significantly inferior to baclofen in its anti-spastic properties.
There is limited level 1b evidence based on a single RCT and supported by two prospective controlled trials and several non-controlled studies in favour of using clonidine as a SCI anti-spasmodic although this must be interpreted cautiously given small study sample sizes, inadequate outcome measure selection, occurrence of adverse events (level 2 evidence for sedation) and less than robust study designs.
- Clonidine may be effective in treating SCI spasticity but more evidence is required to support its routine use.