A Systematic Review of the Effects of Pharmacological Agents on Walking Function in People with Spinal Cord Injury

Studies of spinalized animals indicate that some pharmacological agents may act on receptors in the spinal cord, helping to produce coordinated locomotor movement. Other drugs may help to ameliorate the neuropathological changes resulting from spinal cord injury (SCI), such as spasticity or demyelination, to improve walking. The purpose of this study was to systematically review the effects of pharmacological agents on gait in people with SCI. A keyword literature search of articles that evaluated the effects of drugs on walking after SCI was performed using the databases MEDLINE/PubMed, CINAHL, EMBASE, PsycINFO, and hand searching. Two reviewers independently evaluated each study, using the Physiotherapy Evidence Database (PEDro) tool for randomized clinical trials (RCTs), and the modified Downs & Black scale for all other studies. Results were tabulated and levels of evidence were assigned. Eleven studies met the inclusion criteria. One RCT provided Level 1 evidence that GM-1 ganglioside in combination with physical therapy improved motor scores, walking velocity, and distance better than placebo and physical therapy in persons with incomplete SCI. Multiple studies (levels of evidence 1-5) showed that clonidine and cyproheptadine may improve locomotor function and walking speed in severely impaired individuals with incomplete SCI. Gains in walking speed associated with GM-1, cyproheptadine, and clonidine are low compared to those seen with locomotor training. There was also Level 1 evidence that 4-aminopyridine and L-dopa were no better than placebo in helping to improve gait. Two Level 5 studies showed that baclofen had little to no effect on improving walking in persons with incomplete SCI. There is limited evidence that pharmacological agents tested so far would facilitate the recovery of walking after SCI. More studies are needed to better understand the effects of drugs combined with gait training on walking outcomes in people with SCI.