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Ketamine for depression: evidence, challenges and promise

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Major depressive disorder and bipolar depression are among the most prevalent and disabling mental disorders worldwide. Real-world effectiveness trials in major depressive disorder have underscored that most pharmacological options target monoamines, which are involved in a minority (15-20%) of synaptic contacts in the mammalian brain.

Most synapses (∼50%) use the amino acid glutamate as their primary neurotransmitter, and preclinical models of depression have implicated aberrant glutamatergic neurotransmission for 25 years. More recently, the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine was shown to produce rapid and robust antidepressant effects in patients with treatment-resistant major depressive disorder and bipolar depression.

Zarate, C. A., & Niciu, M. J. (2015). Ketamine for depression: evidence, challenges and promise. World Psychiatry, 14(3), 348-350.
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