A Review of Non Anesthetic Uses of Ketamine in 2020

Abstract

Ketamine, a nonselective NMDA receptor antagonist, is used widely in medicine as an anesthetic agent. However, ketamine’s mechanisms of action lead to widespread physiological effects, some of which are now coming to the forefront of research for the treatment of diverse medical disorders. This paper aims at reviewing recent data on key nonanesthetic uses of ketamine in the current literature. MEDLINE, CINAHL, and Google Scholar databases were queried to find articles related to ketamine in the treatment of depression, pain syndromes including acute pain, chronic pain, and headache, neurologic applications including neuroprotection and seizures, and alcohol and substance use disorders. It can be concluded that ketamine has a potential role in the treatment of all of these conditions. However, research in this area is still in its early stages, and larger studies are required to evaluate ketamine’s efficacy for nonanesthetic purposes in the general population.

1. Introduction

Ketamine has been used as an anesthetic drug for over 65 years

[1]. An enantiomeric, lipid-soluble phencyclidine derivative, ketamine is one of the most commonly used drugs in anesthesia. As a nonselective NMDA receptor antagonist, it has equal affinity for different NMDA receptor types. NMDA is a subgroup of ionotropic glutamate receptors, along with AMPA and kainate. Ketamine is inexpensive and therefore widely used in developing countries. It additionally has particular utility for anesthesia induction in hemodynamically unstable patients

[2].The nonanesthetic clinical uses of ketamine have been the focus of extensive recent research, some of the most applicable and prevalent of which are explored here. For this scoping study, we sought to utilize the Arksey and O’Malley methodological framework to provide a broad overview of the field, with attention to ongoing research and current knowledge gaps [10]. Relevant literature from 2010 through the present was queried through the MEDLINE, CINAHL, and Google Scholar databases. Keywords included “ketamine” combined with terms including “non-anesthetic uses,” “depression,” “headache,” “neuroprotection,” “pain,” “pain syndromes,” “chronic pain,” “alcohol use disorder,” “substance use disorder,” and “seizure.” Sentinel research from prior to 2010 was also incorporated. Relevant original articles including randomized trials, retrospective studies, review articles, case reports, and preclinical animal studies were included. This paper will discuss some of the most common and promising nonanesthetic uses of ketamine, including its utility in the treatment of depression, pain syndromes including headaches, neurologic disorders including seizures, and alcohol/substance use disorders.

Ketamine administration has long been known to mediate a wide variety of pharmacological effects, including dissociation, analgesia, sedation, catalepsy, and bronchodilation. Though Ketamine crystal for sale is known most widely for its anesthetic properties, recent research has uncovered multiple novel uses for this drug, including neuroprotection, combating inflammation and tumors, and treatment of depression, seizures, chronic pain, and headache [3–5]. Racemic ketamine, a mixture of (S)- and (R)-ketamine (Figure 1), is commonly used in this research, though both (S)-ketamine and (R)-ketamine alone are also subjects of study. While (S)-ketamine carries roughly 3- to 4-fold greater potency as an anesthetic, it also carries a greater risk of psychotogenic side effects [6]. However, ketamine has an extensive side-effect profile and a potential for abuse that cannot be ignored, which has historically led to its avoidance in favor of other agents, and its safety is an area of ongoing research [3]. Additionally, there are a variety of adverse reactions that have been associated with ketamine use which must be considered, including self-resolving sinus tachycardia, neuropsychiatric effects, abdominal pain, liver injury, and dose-dependent urogenital pathology including ulcerative cystitis [7–9]. Currently, there are roughly 800 or more clinical trials exploring aspects of nonanesthetic uses of ketamine registered on ClinicalTrials.gov, illustrating the extensive ongoing interest in this area.