Effects of drugs on walking after spinal cord injury

Abstract

Clonidine, a noradrenergic agonist, and cyproheptadine, a serotonergic antagonist, have each been associated with improved walking in SCI subjects. Baclofen, a GABA agonist, is frequently prescribed for spasticity but its e ects on walking have not been well quanti®ed. The objective of this study was to compare the e ects of clonidine, cyproheptadine and baclofen on walking in SCI subjects with incomplete injuries. A motorized treadmill was used and harness support provided when necessary. A repeated single-subject design was employed for the twelve subjects. The greatest e ects were found in more severely disabled subjects. Cyproheptadine was associated with greatly reduced need for assistance, increases in maximum treadmill speed (MTS) and reduced clonus. Clonidine was associated with increases in MTS and a generally more upright posture. Baclofen was associated with minor changes in walking. In many cases of drug e ects, MTS increases and other changes were retained following washout of drugs. The signi®cance and implications of the drug e ects and the retention of e ects during washout periods are discussed. It is concluded that clonidine and cyproheptadine have di erent e ects but both appear useful for severely disabled SCI subjects. The e ects of baclofen on walking after spinal cord injury remains unclear.

Spasticity after spinal cord injury

“…9,10,34 Baclofen is a commonly used drug for spasticity in the SCI population. 21 It has been reported to be particularly effective for reducing flexor spasms. 9,10,34 However, the literature also suggests that baclofen may have no positive effect on walking ability or the performance of ADL.…”

“…9,10,34 However, the literature also suggests that baclofen may have no positive effect on walking ability or the performance of ADL. 9,21,34,48 Similar to other muscle relaxants, baclofen may impair the ability of the patient to walk or stand. 13,15 Baclofen has been shown to be safe and effective for long-term use, with no evidence for tolerance.…”

“…9,15 Clonidine has been found to be associated with improved walking ability in individuals with incomplete SCI (eg, longer cycles, increased treadmill speed, and more upright posture). 21,50 Tizanidine Tizanidine is an imidazole derivative and, like clonidine, is a centrally acting (spinally and supraspinally) alpha-2-adrenergic agonist. 9,10,13,34,48 Therefore, it acts by inhibiting the release of excitatory amino acids from the presynaptic terminals of excitatory spinal neurons.…”

“…9,10,13 Cyproheptadine Although less commonly reported among the drugs used to treat spasticity, cyproheptadine has been associated with an improvement in the walking pattern of individuals with SCI (eg, reduced need for manual assistance, increased treadmill speed, and reduced ankle clonus). 21,51,52 Cyproheptadine is a histamine and a serotonin antagonist, which is proposed to reduce spasticity via inhibition of motor neurons by 'neutralizing the spinal and supraspinal seratoninergic excitatory inputs'. 34 Cannabis Tetrahydrocannabinol (THC), available in the drug dronabinol, is the main active ingredient in cannabis.…”

“…19 In a study by Sko¨ld et al, 6 20 and 4% of their total sample perceived their spasticity to restrict ADL and cause pain, respectively. Although Krawetz and Nance 20 have identified that severity of spasticity is among the factors that can reduce the degree to which walking is effective in functional ambulators after SCI, Norman et al 21 have emphasized that, despite the common association between spasticity and clinical signs of abnormal gait, the nature of this relationship remains unclear. Furthermore, it must be noted that, although spasticity can have a negative impact on QOL, it has been suggested that symptoms of spasticity may increase stability in sitting and standing, facilitate the performance of some ADL and transfers, increase muscle bulk and strength of spastic muscles (thereby helping prevent osteopenia), and increase venous return (possibly diminishing the incidence of deep vein thrombosis).…”