Efficacy and Safety of Ketamine in the Treatment of Neuropathic Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Purpose Ketamine is a N-methyl-D-aspartate (NMDA) antagonist with strong analgesic properties. Its addition to the treatment of neuropathic pain may reduce pain intensity and improve overall quality of life. A systematic review and meta-analysis of randomized controlled trials was performed to investigate the addition of ketamine to the treatment of patients with neuropathic pain. Patients and Methods GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to rate the overall certainty of the evidence for each outcome. Eighteen (18) randomized controlled trials including 706 participants were included for further analysis. Results Ketamine addition to standard treatment of neuropathic pain (NP) resulted in a statistically significant reduction of pain intensity at one week after the end of treatment with ketamine (MD −2.14, 95% CI −2.65 to −1.63; p<0.00001) and after 30 days after the end of treatment with ketamine (MD −1.68, 95% CI −2.25 to −1.12; p<0.00001) and a statistically significant increase in discomfort (RR 4.06; 95% CI 1.18 to 13.95; p=0.03), and psychedelic effects (RR 4.94; 95% CI 2.76 to 8.84; p<0.00001). Conclusion There is a statistically significant pain reduction by adding ketamine to the treatment of chronic NP when compared to the standard treatment. However, such pain reduction comes at the expense of adverse outcomes, especially psychedelic effects related to the administration of ketamine. However, the overall quality of certainty of evidence is low due to the clinical heterogeneity among the intervention characteristics of the trials analyzed (different administration routes, dosing regimen, therapy durations, different clinical characteristics of the population investigated). Future large multi-centered trials are necessary to confirm or not the results of the present review.

A Systematic review and Network Meta-analysis of pharmaceutical interventions used to manage chronic pain

“…There are several guidelines recommending the use of Pregabalin, Gabapentin, Duloxetine, and Amitriptyline as first line drugs in the management of neuropathic pain [37] . However, the use of gabapentinoids is being challenged as it lacks favourable robust evidence for efficacy against pain syndromes other than fibromyalgia, post herpetic neuralgia and diabetic neuropathy, and many clinicians have also highlighted the potential for misuse and developing dependence [38,39,40] . The use of BTX-A, Ketamine, Ningmitai and THC for the management of various chronic pain conditions is popular and well established [12,13,14,15] and our study shows the effective use of these as analgesics when compared to placebo.…”

Ketamine for Chronic Non-Cancer Pain: A 2023 Update

“…The SR with meta-analysis (MA) by Guimaraes Pereira et al (2022) 13 included 18 RCTs (published between 1994 and 2019) with a total of 706 patients, ranging from 8 to 214 patients with NP in each RCT. All included studies were relevant to our report.…”

“…All included studies were relevant to our report. The authors of the SR 13 searched multiple databases since inception to November 18th, 2021, without restrictions for language, publication status, date of publication, or country. The authors calculated pooled risk ratio (RR) for dichotomous outcomes, mean difference (MD) for continuous outcomes and standardized mean difference (SMD) for continuous outcomes measured by different scales, with a corresponding 95% confidence interval (CI).…”

“…13,14 There were 2 primary studies that were included in both SRs. 13,14 The third SR 15 did not have any included studies that overlapped with those in the other 2 SRs. 13,14…”

“…13,14 The third SR 15 did not have any included studies that overlapped with those in the other 2 SRs. 13,14…”