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Ketamine as a Rapid-Acting Antidepressant: Promising Clinical and Basic Research

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Suicidal ideation and attempts are a common medical emergency, accounting for about 650,000 adult evaluations per year in emergency settings (1). Depressive disorders are a major driving force behind this, but first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), can take months to work, making them of limited use in acutely suicidal patients. Potentially safe and fast-acting interventions would be invaluable in acute situations until standard antidepressants have time to take effect.
Ketamine, best known as an N-methyl-d-aspartate receptor (NMDAR) antagonist commonly used as an anesthetic, has recently drawn attention for possibly filling the role. At lower doses it exhibits strong antidepressant effects in many patients, and it acts on the order of minutes. Despite these promising effects, its use as an antidepressant has been controversial, as ketamine is also a Schedule III controlled substance that is used recreationally for its dissociative and hallucinogenic effects. Furthermore, the full mechanism of action regarding its antidepressant effects has long remained unclear.
In the present article, we review research surrounding ketamine’s potential as a fast-acting antidepressant from a “two-pronged” approach: first, summarizing established and new knowledge on its mechanism of action and second, reviewing clinical research addressing its potential to quickly reduce depression and suicidality.
Tuck, A. N., & Ghazali, D. H. (2017). Ketamine as a Rapid-Acting Antidepressant: Promising Clinical and Basic Research. American Journal of Psychiatry Residents’ Journal12(3), 3-5. 10.1176/appi.ajp-rj.2017.120302
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