The effectiveness of oral and sublingual ketamine in pain management: a systematic review and meta-analysis

Aim: The aim of this study was to undertake a systematic review and meta-analysis to determine the effectiveness of oral and sublingual ketamine in pain management. 

Data Sources: A systematic search was conducted utilising four databases: MEDLINE, CINAHL, Embase, and Web of Science. 

Study Selection: The study included randomised controlled trials investigating the use of oral or sublingual ketamine in the management of pain in inpatient or outpatient settings compared to any alternative oral or sublingual comparator, including placebo. 

Results: Twenty-one studies were included for systematic review, all assessing oral ketamine, including one comparing oral to sublingual ketamine. Of these, 12 studies evaluated oral ketamine in procedural pain, with 10 studies finding oral ketamine significantly better than the comparator at reducing procedural pain. Two studies focused on oral ketamine in postoperative pain, both finding oral ketamine reduced the requirement for additional analgesia compared to placebo. Five studies investigated oral ketamine in chronic pain with heterogenous results. Of the remaining two studies, one compared various doses of oral ketamine and the other compared oral to sublingual ketamine. 

Fifteen studies were included for meta-analysis. Among them, seven studies compared oral ketamine to placebo and found oral ketamine was superior to placebo in reducing pain (p < 0.01). Eight studies compared oral ketamine to other oral medications such as methadone, codeine, midazolam, and dexmedetomidine and showed no significant benefit of oral ketamine in reducing pain (p = 0.18). 

Conclusion: The results suggest oral ketamine is an effective analgesic in the procedural setting.