Impact of commonly administered drugs on the progression of spinal cord injury: a systematic review

Abstract

Complications arising from acute traumatic spinal cord injury (SCI) are routinely managed by various pharmacological interventions. Despite decades of clinical application, the potential impact on neurological recovery has been largely overlooked. This study aims to highlight commonly administered drugs with potential disease-modifying effects. This systematic literature review included studies referenced in PubMed, Scopus and Web of Science from inception to March 31st, 2021, which assess disease-modifying properties on neurological and/or functional recovery of drugs routinely administered following spinal cord injury. Drug effects were classified as positive, negative, mixed, no effect, or not (statistically) reported. Risk of bias was assessed separately for animal, randomized clinical trials, and observational human studies. We analyzed 394 studies conducting 486 experiments that evaluated 144 unique or combinations of drugs. 195 of the 464 experiments conducted on animals (42%) and one study in humans demonstrate positive disease-modifying properties on neurological and/or functional outcomes. Methylprednisolone, melatonin, estradiol, and atorvastatin are the most common drugs associated with positive effects. Two studies on morphine and ethanol report negative effects on recovery. Despite a large heterogeneity observed in study protocols, research from bed to bench and back to bedside provides an alternative approach to identify new candidate drugs in the context of SCI. Future research in human populations is warranted to determine if introducing drugs like melatonin, estradiol, or atorvastatin would contribute to enhancing neurological outcomes after acute SCI. Patients with spinal cord injury (SCI) are exposed to a wide range of medications treating health conditions arising as a consequence of the initial injury. The effect of providing patients with a large number of medications in the early period after injury, that is in the first days to weeks, on recovery from SCI, however, is typically not considered. This extensive and structured review of evidence from pre-clinical (animal) and clinical (human) studies quantifies these effects for the first time. 144 unique drugs or combinations of drugs previously reported to be administered in animal models or to patients with SCI have been studied for their effect on recovery across 486 distinct experiments. A small subset of drugs are associated with positive effects, and provide potential targets for further study to determine if they can be used to treat SCI. Bourguignon, Lukas et al. systematically review the effect of drugs commonly administered after traumatic spinal cord injury on the neurological recovery in both animal studies and humans. Extensive heterogeneity in study characteristics and results highlight the need for harmonization across the field but also the potential for drug repurposing.