Clonidine, 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 have been two placebo-controlled trials (Stewart et al. 1991; Remy-Neris et al. 1999) providing evidence for clonidine’s effectiveness in reducing SCI spasticity. Stewart et al. (1991) 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. 1999). However, the latter study was not randomized; therefore, it was less rigorous in design. Both studies had small sample sizes. In another non-randomized, placebo controlled study by Nance et al. (1989) with a small sample size (N=6), the results 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) 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) were derived from case series studies (Donovan et al. 1988; Weingarden & Belen 1992; Yablon & Sipski 1993; Remy-Neris et al. 2001). All presented results in favour of using clonidine as an anti-spasmodic but the 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 intramuscularly or intrathecally) in patients with traumatic SCI, 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 most 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 level 1b evidence (from one RCT, two prospective controlled trials: Stewart et al. 1991; Malinovsky et al. 2003; Remy-Neris et al. 1999) supported by 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 and less than robust study designs.