Ketamine for chronic pain: risks and benefits

Abstract

The anaesthetic ketamine is used to treat various chronic pain syndromes, especially those that have a neuropathic component. Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor although other mechanisms are possibly involved, including enhancement of descending inhibition and anti-inflammatory effects at central sites. Current data on short term infusions indicate that ketamine produces potent analgesia during administration only, while three studies on the effect of prolonged infusion (4-14 days) show long-term analgesic effects up to 3 months following infusion. The side effects of ketamine noted in clinical studies include psychedelic symptoms (hallucinations, memory defects, panic attacks), nausea/vomiting, somnolence, cardiovascular stimulation and, in a minority of patients, hepatoxicity. The recreational use of ketamine is increasing and comes with a variety of additional risks ranging from bladder and renal complications to persistent psychotypical behaviour and memory defects. Blind extrapolation of these risks to clinical patients is difficult because of the variable, high and recurrent exposure to the drug in ketamine abusers and the high frequency of abuse of other illicit substances in this population. In clinical settings, ketamine is well tolerated, especially when benzodiazepines are used to tame the psychotropic side effects. Irrespective, close monitoring of patients receiving ketamine is mandatory, particularly aimed at CNS, haemodynamic, renal and hepatic symptoms as well as abuse. Further research is required to assess whether the benefits outweigh the risks and costs. Until definite proof is obtained ketamine administration should be restricted to patients with therapy-resistant severe neuropathic pain.

Keywords: NMDA receptor antagonist; chronic pain; ketamine; ketamine abuse; neuropathic pain; pain.

© 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

Figures

Figure 1

A-C. Resting state MRI areas of connectivity in the brain during low dose ketamine exposure in healthy volunteers relative to network of interest 1 (NOI1). The data are linked to the antinociceptive properties of the drug by assessment of pain relief to a heat pain stimulus and incorporation of pain relief as regressor in the statistical model. The statistical map gives the variations in connectivity explained by ketamine (yellow) and by pain relief (green). These green areas indicate that pain relief is associated with increased connectivity in the anterior cingulate cortex (ACC), orbitofrontal cortex, brain stem and amygdala in relation to the network of interest (in blue). These regions are involved in pain sensing, pain processing and activation of descending inhibition of pain. (Adapted from , with permission)

Figure 2

Psychotropic effects observed during intravenous low-dose ketamine (•) and placebo (○) treatment. A) Drug high, B) changes in internal perception (inner feelings that do not correspond with reality) and C) changes in external perception (misperceptions of an external stimulus or change in the awareness of the surroundings). NRS, numerical rating scale. (Adapted from , with permission)