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.