psychiatric disorders
Medications for Treatment of Depression
Ketamine and Esketamine
 often produce a uniquely rapid, though typically short-lived, resolution of depressive symptoms in patients with treatment-resistant major depressive disorder ( Ketamine and esketamine references ). The s-enantiomer of The presumed mechanism of action of subanestheticketamineis of particular interest because it does not primarily involve action at monoamine receptors, as is the case with nearly all other currently approved antidepressants. Instead, effects are thought to begin with the blockade of theN-methyl-D-aspartic acid (NMDA) receptor that disinhibits glutamate release. This, in turn, increases brain-derived neurotrophic factor (BDNF) synthesis, and through the activation of both mammalian target of rapamycine (mTOR) and alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors, leads to rapid increases in dendritic spine density in the cortical pyramidal cells specifically affected by chronic stress and hypercortisolemia. The majority of patients given an antidepressant dose ofketamineexperience a global improvement in depressive symptoms that peaks in 3 to 4 hours and then, in most cases, wanes over the next 1 to 2 weeks. Multiple administrations over several weeks lengthen the duration of improvement, but relapse rates are high over the ensuing months. Manyketamineclinics titrate the interval between treatments, and some patients can maintain improvement with only monthly treatments Adverse effects are generally limited to a period of one to 2 hours following administration and include Depersonalization/Derealization Disorder , increases in blood pressure, nausea, and vomiting. Because Ketamineis typically given intravenously in this setting but is also available orally or intranasally.Esketamineis given intranasally. The patient should be monitored in the clinic for 2 hours after administration and be advised not to drive until the following day. Acutely increased blood pressure may require intervention. 1.Caddy C, Amit BH, McCloud TL, et al:Ketamineand other glutamate receptor modulators for depression in adults.Cochrane Database Syst Rev9:CD011612, 2015. doi: 10.1002/14651858.CD011612.pub2. Update in:Cochrane Database Syst Rev.9:CD011612, 2021. PMID: 26395901 2.Singh JB, Fedgchin M, Daly E, et al: Intravenousesketaminein adult treatment-resistant depression: A double-blind, double-randomization, placebo-controlled study.Biol Psychiatry. 80(6):424-431, 2016. doi: 10.1016/j.biopsych.2015.10.018 