Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 9:15:1011-1037.
doi: 10.2147/JPR.S358070. eCollection 2022.

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

José Eduardo Guimarães Pereira  1   2 , Lucas Ferreira Gomes Pereira  3 , Rafael Mercante Linhares  4 , Carlos Darcy Alves Bersot  5 , Theodoros Aslanidis  6 , Hazem Adel Ashmawi  1
Affiliations
Review

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

José Eduardo Guimarães Pereira et al. J Pain Res. .

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.

Keywords: chronic pain; ketamine; neuralgia; neuropathy; treatment.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study selection PRISMA flow diagram.
Figure 2
Figure 2
Risk of bias according to different domains.
Figure 3
Figure 3
Meta-analysis on the overall mean pain reduction. Forest plot is representing the comparison of the overall mean pain between group ketamine and ST.
Figure 4
Figure 4
Meta-analysis on the average mean pain reduction. Forest plot is representing the comparison of the mean pain between group ketamine and ST according to time after the end of treatment.
Figure 5
Figure 5
Meta-analysis on the average mean pain reduction over time. Forest plot is representing the comparison of the mean pain in the ketamine at different time points compared to baseline pain.
Figure 6
Figure 6
Meta-analysis on the average standardized mean pain reduction. Forest plot is representing the comparison of the mean pain between group ketamine and ST according to different multidimensional pain scales.
Figure 7
Figure 7
Meta-analyses on the incidence of adverse outcomes. Forest plot is representing the comparison between group ketamine and ST according to different adverse outcomes.
Figure 8
Figure 8
Publication bias. Funnel Plot representing the distribution of studies according to their results.
See this image and copyright information in PMC

References

    1. Van Hecke O, Austin SK, Khan RA, et al. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014;155(4):654–662. doi:10.1016/j.pain.2013.11.013 - DOI - PubMed
    1. Lépine JP, Briley M. The epidemiology of pain in depression. Hum Psychopharmacol. 2004;19(S1):1. doi:10.1002/hup.618 - DOI - PubMed
    1. Portenoy RK, Ugarte C, Fuller I, Haas G. Population-based survey of pain in the United States: differences among white, African American, and Hispanic subjects. J Pain. 2004;5(6):317–328. doi:10.1016/j.jpain.2004.05.005 - DOI - PubMed
    1. Yawn BP, Wollan PC, Weingarten TN, et al. The prevalence of neuropathic pain: clinical evaluation compared with screening tools in a community population. Pain Med. 2009;10(3):586–593. doi:10.1111/j.1526-4637.2009.00588.x - DOI - PMC - PubMed
    1. Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014;348:f7656. doi:10.1136/bmj.f7656 - DOI - PubMed