Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant

Abstract

Major depression is a serious psychiatric disorder and remains a leading cause of disability worldwide. Conventional antidepressants take at least several weeks to achieve a therapeutic response and this lag period has hindered their ability to attain beneficial effects in depressed individuals at high risk of suicide. The non-competitive Nmethyl-D-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in both rodents and humans. The emergence of ketamine as a fastacting antidepressant provides promising new insights into the development of a rapid treatment response in patients with clinical depression. However, its safety and toxicity remain a concern. In this review, we focus on the limitations of ketamine, including neurotoxicity, cognitive dysfunction, adverse events associated with mental status, psychotomimetic effects, cardiovascular events, and uropathic effects. Studies have shown that its safety and tolerability profiles are generally good at low doses and with short-term treatment in depressed patients. The adverse events associated with ketamine usually occur with very high doses that are administered for prolonged periods of time and can be relieved by cessation. The antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R-ketamine, are also discussed. R-ketamine has greater antidepressant actions than S-ketamine, without ketamine-related sideeffects. Future treatment strategies should consider using Rketamine for the treatment of depressed patients to decrease the risk of adverse events associated with long-term ketamine use.

What Is New about New Antidepressants?

“…Common adverse effects of ketamine include dizziness, neurotoxicity, cognitive dysfunction, blurred vision, psychosis, dissociation, restlessness, headache, nausea, vomiting, and cardiovascular and urological dysfunction [47, 53, 54]. Adverse effects tend to be brief in acute treatment with low doses, but they are more problematic at higher doses or over longer periods of administration [53].…”

“…Adverse effects tend to be brief in acute treatment with low doses, but they are more problematic at higher doses or over longer periods of administration [53]. Although acute treatment with ketamine may be neuroprotective, a more prolonged exposure may predispose to neurotoxicity and drug dependence [30]; other long-term adverse effects are not known [45, 47].…”

Analysis of print news media framing of ketamine treatment in the United States and Canada from 2000 to 2015

“…Prolonged usage of ketamine may lead to neurotoxicity, cognitive dysfunction [46], psychotomimetic effects, cardiovascular events, and uropathic effects [47]. The doses that cause toxicity vary among therapeutic doses (0.23–0.5 mg/kg) causing impairment of executive function [48], 2 mg/kg causing worsening cerebral atrophy [49], and very high doses (18.5 g/week) causing uropathy [50].…”

Drug addiction: a curable mental disorder?

“…Although ketamine has abuse potential per se, these data strongly support that subanestheic ketamine could be used as a novel pharmacotherapy to treat drug addiction. It is especially intriguing that subanesthetic ketamine has been shown to possess rapid antidepressant effects in both preclinical and clinical studies [35][36][37]. Abundant epidemiological data have revealed high comorbidity of drug addiction and major depression [38]; therefore, the above results suggest that subanesthetic ketamine could be especially effective to treat the comorbidity of drug addiction and depression [39].…”