Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature.

Introduction: Chronic neuropathic pain (NP) is an incapacitating illness caused by a lesion of the somatosensory nervous system and is associated with several diseases or syndromes. Since current treatment options lack adequate efficacy in the majority of patients, ketamine is often administered to treat refractory NP.Areas covered: This review gives an overview of new ketamine pharmacokinetic data including data on intranasal and inhaled ketamine. The outcome of seven systematic reviews and meta-analyses, published since 2012, on ketamine efficacy in NP is discussed. The reader will additionally get an understanding of ketamine's complex metabolism with emphasis on the metabolite hydroxynorketamine.Expert opinion: Proof of sustained, large effects of ketamine in the treatment of NP from randomized controlled clinical trials is lacking, although we cannot exclude selective ketamine efficacy in patients with central sensitization, opioid-induced hyperalgesia or opioid tolerance. Interestingly, data from observational trials and case series do suggest the efficacy of ketamine in producing effective pain relief in NP with positive patient-related outcome measures. Additional randomized trials in often ill-defined groups of chronic pain patients are not useful and we suggest to conduct future studies in NP patients with central sensitization and/or with opioid refractory severe NP.