Ketamine for cancer pain: what is the evidence?

Abstract

Ketamine is an N-methyl-D-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.

Ketamine for pain

“…Still, despite a lack of evidence for other indications, ketamine remains abundantly used clinically for treatment of acute and chronic cancer and non-cancer pain. In fact, numerous case reports, case series, and open-label studies show ketamine efficacy in the amelioration of acute and chronic pain 5 , 48 , 49 . Reasons for the apparent discrepancy in efficacy in RCTs versus open-label treatments are difficult to give.…”

“…Reasons for the apparent discrepancy in efficacy in RCTs versus open-label treatments are difficult to give. Various, often interacting, factors may play a role herein 5 , 48 : (i) One important issue is the duration of treatment. We previously showed that prolonging the duration of intravenous ketamine treatment to 10–100 hours increases the probability of therapeutic success 46 .…”

“…The efficacy of ketamine as an analgesic is still under debate, especially for indications such as neuropathic and cancer pain 2 , 5 . The use of ketamine for pain management is widespread among clinicians caring for patients in pain, despite a paucity of randomized clinical trials showing its efficacy as well as a lack of support from medical societies and practice guidelines 6 .…”

“…We retrieved three unique systematic reviews on the use of ketamine for pain relief in patients with cancer 5 , 46 , 47 . In all RCTs included in these reviews, ketamine was used as an adjuvant to opioid therapy.…”

“…In all RCTs included in these reviews, ketamine was used as an adjuvant to opioid therapy. The latest and most complete review dates from 2017 5 . This review includes four RCTs in 245 patients who received oral, intravenous, or subcutaneous ketamine.…”