Ketamine Hydrochloride was originally synthesized in the 1960s by Dr. Calvin Stevens, the first physician to test its anesthetic properties on humans. However, over the past two decades, ketamine’s therapeutic use has expanded to treat symptoms of major depressive disorder (MDD) and chronic pain. 

Ketamine functions by binding to the NMDA receptor, which is located on many cells throughout our bodies. In larger doses, ketamine binds to these receptors and produces anesthetic effects. When given in smaller doses, ketamine can relieve symptoms of treatment resistant depression by producing excitation in the areas of the brain that are linked to mood regulation, such as the prefrontal cortex and limbic system. The conventional treatment for MDD consists of taking a selective serotonin reuptake inhibitor (SSRI), which can take 4-6 weeks to have an effect and is reported to improve symptoms in 60-70% of people. For those who are not responsive to SSRIs, ketamine infusions have gained popularity as the therapeutic effects can manifest within hours after an administration and can remain effective for multiple days afterward. Research suggests that ketamine does this by stimulating the release of glutamate, an excitatory neurotransmitter that is more abundant in the brain than serotonin. Furthermore, research shows that ketamine promotes new connections between neurons in areas of the brain that are involved with mood and cognition by acting on another type of receptor, the AMPA receptor. 

Response rates for ketamine infusions range from 50%-79% (a response rate would be considered ≥50% reduction in depressive symptoms from baseline). A nasal spray has also been approved by the FDA for treatment resistant depression, though it is 50-75% less potent than the IV infusion. Ketamine administration has shown a decrease in suicide ideation in those with MDD with the earliest decline after only 40 minutes of ketamine infusion. Additionally, studies have shown that ketamine produces similar response rates in those with bipolar depression.

Similarly to alleviating depressive symptoms, ketamine acts on NMDA receptors to relieve pain. Multiple studies have shown that low dose ketamine infusions provide pain relief in complex regional pain syndrome (CRPS) and refractory chronic pain syndromes. Study participants with CRPS reported that their pain had decreased from baseline for as long as ten weeks after ketamine infusion. 

Note: Patients with cardiovascular disease (eg, hypertension, angina) and history or risk of stroke should not use ketamine. Ketamine also has the ability to increase intraocular pressure should be avoided in patients at risk for or history of glaucoma.