Use of oral ketamine in chronic pain management: A review

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.