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Objective To establish the efficacy of medications, incidence of adverse events (AEs), and withdrawal rates associated with the pharmacological management of chronic spinal cord injury pain. Methodology PubMed, MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and PsycINFO were searched (November 2017) and updated (January 2020). Two independent review authors screened and identified papers for inclusion. Results Twenty-one studies met inclusion requirements for efficacy analysis and 17 for AE and withdrawal rate analysis; no additional papers were included from the updated 2020 search. Treatments were divided into six categories: anticonvulsants (n = 6), antidepressants (n = 3), analgesics (n = 8), anti-spasticity medications (n = 2), cannabinoids (n = 1), and other (n = 2). Trials of anticonvulsants, antidepressants, and cannabinoids included long-term follow-up trials (2 weeks to 4 months), and trials of analgesics and anti-spasticity medications, among others, were short-term trials (0–2 days). Effectiveness for neuropathic pain was found for pregabalin (3/3 studies) and lidocaine (2/3 studies). Studies using ketamine also reported effectiveness (2/2), but the quality of these papers was rated as poor. The most frequently reported AEs included dizziness, dry mouth, nausea, and constipation. Pregabalin was associated with a higher risk of somnolence (risk ratio [RR] 3.15, 95% confidence interval [CI]: 2.00–4.98) and dizziness (RR 2.9, 95% CI: 1.58–5.30). Ketamine was associated with a higher risk of reduced vision (RR 9.00, 95% CI: 0.05–146.11), dizziness (RR 8.33, 95% CI: 1.73–40.10), and somnolence (RR 7.00, 95% CI: 1.73–40.1). Withdrawal rates ranged from 18.4% for antidepressants to 0–30% for anticonvulsants, 0–10% for anti-spasticity medications, 0–48% for analgesics, 28.6% for cannabinoids, and 0–22.2% for other medications. Conclusion Pregabalin was found to be effective for neuropathic pain vs placebo. Cannabinoids were ineffective for neuropathic pain. AEs are a common cause for withdrawal. The nature of AEs was poorly reported, and AE reporting should be improved in future randomized controlled trials. [ABSTRACT FROM AUTHOR]