Researchers conducted a systematic review of randomized trials to determine the efficacy of ketamine for patients with cancer.
For up to 72 hours following oncologic surgery, a dose of intravenous ketamine from 0.1 to 0.5 milligrams was deemed effective in improving pain amongst patients with cancer. However, in terms of treating the same population’s refractory pain, ketamine was considered less useful, leading researchers to recommend that its potential use depend on factors like dosage, route of administration, and patient population.
“Despite advancements in pharmacological therapies and understanding of the molecular mechanisms underlying cancer pain, the prevalence of cancer pain remains high. Systematic reviews and meta-analyses reveal that over one-third of patients experience pain related to cancer after curative treatment, and two-thirds of patients with advanced or metastatic cancer report symptoms of pain. Studies showed up to 20% of patients with cancer undergoing opioid titration develop refractory pain or experience a poor analgesic response and intolerable side effects,” wrote authors of a study published in Healthcare (Basel).1
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Issues surrounding the safe treatment of chronic and acute pain have long persisted within health care, and cancer diagnoses almost always come with a long list of chronic pain complications. In a previous narrative review, researchers stated that somewhere between 40% and 70% of all patients with cancer also experienced chronic pain.2 However, when it comes to ketamine’s role in treating chronic pain, providers have been slow to adopt this therapeutic option because of its chemical make-up and impact on digestive health, among other reasons.
“Ketamine use, however, is not without issues. Ketamine toxicity is a well-documented phenomenon, and hepatobiliary dysfunction has been reported with recurrent ketamine use,” according to authors of a study published in StatPearls.3 Furthermore, outside of treating patients with chronic pain, some individuals have used ketamine in an unauthorized capacity to treat psychiatric disorders, leading the FDA to promptly issue a warning in October 2023.4
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Starting with ketamine’s efficacy in treating chronic pain, researchers performed a systematic literature review focusing on “articles assessing the relationship between administering ketamine to adult patients with cancer and pain.”1 Two reviewers were tasked with selecting studies to include in the review. Researchers then identified various themes common among studies, including study outcomes and objectives, each participant’s type of cancer, dosage, physical setting, and more.
After analyzing nearly 1500 citations, a total number of 21 randomized clinical trials from 2001 to 2019 were included in the review. The quality for all 21 studies included in the review was deemed either “good” or “fair.” Covering routes of administration for the treatment of ketamine in patients with cancer and chronic pain, researchers analyzed intravenous, intrathecal, intramuscular, subcutaneous, topical, and oral administration routes.
“Significant improvements in pain scores and reduced morphine consumption were consistently observed with intravenous ketamine administration for postoperative pain control, particularly when combined with other analgesics such as morphine,” wrote the authors.1
Along with an intravenous approach, intrathecal administration of ketamine also significantly decreased pain scores amongst the included studies but only in conjunction with morphine. Aside from the intravenous and intrathecal pathways, other routes of administration were not deemed effective amongst the patient population.
The most common use of ketamine, in the context of this review, is through preoperative or intraoperative intravenous administration for postoperative pain control. Fewer studies have explored ketamine’s use for treating refractory pain outside of the hospital setting as well as the efficacy of stand-alone ketamine use without concomitant therapies.
“Intravenous ketamine, in dosages ranging from 0.1 mg/kg to 0.5 mg/kg, was most efficacious in improving pain scores in patients with cancer for up to 72 hours following surgery, particularly in conjunction with other analgesics such as morphine. Fewer studies examined the use of ketamine for pain therapy, and those that did found less benefit in terms of pain scores following treatment for refractory chronic cancer pain. Ketamine was well tolerated across all studies that examined the side effects associated with ketamine administration,” they concluded.1
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