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Is ketamine ready to be used clinically for the treatment of depression?

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A single dose of ketamine produces rapid antidepressant effects, but attaining lasting remission remains a challenge

Some clinics in Australia and overseas have begun offering a course of ketamine treatments to patients with depression. However, this practice is premature, given that the efficacy and safety of this treatment approach has yet to be tested in controlled trials. Further, whether such a treatment approach leads to lasting response — that is, clinically meaningful effects — is as yet unknown. Ketamine differs from current antidepressant medications in that it acts primarily on the glutamate signalling system, rather than on the monoaminergic (eg, serotonin, noradrenalin) system. To date, eight randomised, placebo-controlled trials involving almost 200 participants with depression have shown robust antidepressant effects after a single, subanaesthetic dose of ketamine.1,2 These impressive clinical results have generated intense interest among researchers, clinicians and patients.

First, the onset of effects is much more rapid for ketamine than for other antidepressant treatments, with peak effects seen 24 hours after receiving a single treatment, in contrast with the several weeks required for most other treatments. Second, ketamine has a very high efficacy, as demonstrated by high overall remission rates,