Introduction
For over half a century, the pharmacological treatment of depression was dominated by a single idea: that depression results from a deficit of monoamine neurotransmitters -- serotonin, norepinephrine, and dopamine -- and that the solution is to increase their availability. SSRIs, SNRIs, and their predecessors all work on this principle. They also share a critical limitation: they take weeks to work, and roughly one-third of patients do not respond adequately even after multiple medication trials. Ketamine shattered this paradigm. A single intravenous infusion can produce antidepressant effects within hours -- even in patients who have failed every other treatment.
