The Efficacy, Adverse Events, and Withdrawal Rates of the Pharmacological Management of Chronic Spinal Cord Injury Pain: A Systematic Review and Meta-Analysis
Clare Canavan, Takayoshi Inoue, Sinéad McMahon, Catherine Doody, Catherine Blake, Bróna M. Fullen
Abstract
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.