Use of oral ketamine in chronic pain management: A review

Abstract

The analgesic effect of ketamine is primarily based on the antagonism of the N-methyl-d-aspartate (NMDA) receptor. Activation of NMDA receptors may play a crucial role in the pathogenesis of chronic pain. Little formal research has been performed on the efficacy and safety of ketamine in chronic pain, especially concerning long-term oral administration. This review provides an overview of the available clinical data on the use of oral ketamine in chronic pain management. A literature search was performed in MEDLINE, EMBASE and the Cochrane Library, resulting in 22 relevant articles. Because most retrieved articles were of a descriptive nature (e.g. case reports and case series) a quantitative analysis was not possible. There was no consistent dose-response relation. A recommended starting dosage in ketamine-naive patients is 0.5 mg/kg racemic ketamine or 0.25 mg/kg S-ketamine as a single oral dose. The dosage is increased by the same amount if required. For a continuous analgesic effect it is usually given 3-4 times daily. The injection fluid can be taken orally. When parenteral ketamine is switched to oral administration the daily dosage can be kept equal and, depending on clinical effect and/or adverse effects, is slowly increased. The pharmacologically active metabolite norketamine is believed to contribute to the analgesic effect of oral ketamine. Lack of evidence regarding efficacy, and the poor safety profile, do not support routine use of oral ketamine in chronic pain management. Oral ketamine may have a limited place as add-on therapy in complex chronic pain patients if other therapeutic options have failed.

Regulator of G protein signaling 4 is a crucial modulator of antidepressant drug action in depression and neuropathic pain models

“…5C). Ketamine is also known to exert antinociceptive effects in humans (28). We thus examined the actions of a low ketamine dose (3 mg/kg) in the SNI neuropathic pain model and found antiallodynic responses only in Rgs4KO mice (Fig.…”

“…One of the most promising is ketamine, which has been shown to exert rapid and robust antidepressant and antisuicidal effects in treatment-resistant patients in several clinical trials (23)(24)(25)(26)(27). Ketamine is also used for the treatment of certain chronic pain conditions (28). It was therefore of interest to study whether Rgs4 exerts a similar action on the behavioral effects of ketamine compared with traditional monoamine-based drugs.…”

Cerebral and Cardiovascular Effects of Analgesic Doses of Ketamine During a Target Controlled General Anesthesia-a Prospective Randomized Study

“…Ketamine was first used simply as an anaesthetic, although it is increasingly used at sub-anaesthetic doses as an analgesic in a wide range of pain settings, including the treatment of acute post-operative pain [1][2][3]. The anti-nociceptive effect of ketamine is primarily associated with the antagonism of the N-methyl-D-aspartate (NMDA) receptor [2,[4][5][6].…”

“…The anti-nociceptive effect of ketamine is primarily associated with the antagonism of the N-methyl-D-aspartate (NMDA) receptor [2,[4][5][6].…”

Semimechanistic Population Pharmacokinetic Model to Predict the Drug–Drug Interaction Between S‐ketamine and Ticlopidine in Healthy Human Volunteers

“…The so‐called “opioid crisis”2 emphasizes the need to reduce opioid use and to search for ways to improve multimodal analgesia in pain therapy. Activation of N‐methyl‐D‐aspartate (NMDA) receptors may play a crucial role in the pathogenesis of chronic pain,3 and, therefore, orally administered ketamine, a potent NMDA receptor antagonist, has been used to treat complex chronic pain 4. Orally administered ketamine undergoes extensive first‐pass metabolism, resulting in a bioavailability of ~17% 5.…”