Ketamine as a therapeutic agent for depression and pain: mechanisms and evidence

Ketamine is an anesthetic drug which is now used to treat chronic pain conditions and psychiatric disorders, especially depression. It is an N-methyl-D-aspartate (NMDA) receptor antagonist with additional effects on α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, opioid receptors, and monoaminergic receptors. This article focuses on ketamine's role in treating depression and pain, two commonly comorbid challenging conditions with potentially shared neurobiologic circuitry. Many clinical trials have utilized intravenous or intranasal ketamine for treating depression and pain. Intravenous ketamine is more bioavailable than intranasal ketamine and both are effective for acute depressive episodes. Intravenous ketamine is advantageous for post-operative analgesia and is associated with a reduction in total opioid requirements. Few studies have treated chronic pain or concurrent depression and pain with ketamine. Larger, randomized control trials are needed to examine the safety and efficacy of intravenous vs. intranasal ketamine, ideal target populations, and optimal dosing to treat both depression and pain.