Ketamine: Club drug turned antidepressant?

Major depressive disorder, colloquially known as depression, is defined as a depression state lasting for two weeks or more. Depression affects about 3.2 million Canadians; however, one third of these individuals fail current treatments, highlighting a need for novel therapies to treat patients with treatment-refractory depression (TRD). A recent article published in JAMA by Sanacora et al. highlighted the potential of intravenous ketamine hydrochloride, otherwise known as ketamine, for treatment of TRD.

Ketamine is used clinically as an anaesthetic, and has gained popularity as a “club drug” due to its ability to induce hallucinations. Remarkably, data from double-blind randomized clinical trials comparing ketamine to placebo have demonstrated it to have rapid and robust antidepressant effects. Ketamine, an uncompetitive antagonist of N-methyl D-aspartate glutamate receptors, was found to produce antidepressant effects in murine models by enhancing transmission through a differential class of glutamate receptors. However, a recent study published in Nature suggests that ketamine’s antidepressant properties may be due to alternative mechanisms. Overall, divergent literature demonstrates how poorly researchers understand how ketamine elicits its effects.

Ketamine as a novel treatment for TRD has generated a great interest in the field of psychiatry. However, Sanacora et al. caution against administration of ketamine without medical supervision, since to date,  few studies have investigated ketamine’s long-term efficacy and safety. Furthermore, long-term ketamine abuse has been associated with cognitive impairment, which raises concerns about its safety as a treatment. Despite ketamine’s promise as a therapeutic agent for TRD, further investigation is required to evaluate its short and long term effects and to elucidate its mechanism of action.

Written by Sama Anvari

References may be found in the journal. 

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