Long-term effects of using ketamine for depression are uncertain

Low doses of ketamine, an N- methyl- D- aspirate glutamate receptor antagonist, can produce benefits that are unprecedented in the history of treating major depression.

“When have we ever had the ability to be sitting in front of a patient who is extremely suicidal and have an intervention that will work within [an] hour that will remediate?”

“Ketamine is that tool. If nothing else, that’s what ketamine already presents to us in this field.” However, much remains to be learned about its ideal role in the care of patients with treatment resistant major depression.

For example, ketamine’s benefits are transient, and it’s unclear how to best maintain those effects. Another limitation is that it cannot be self-administered because of the dissociative patient’s experience.

“They need to be monitored in a medical setting.”?“In addition, chronic repeated administration has not been well studied, [and] the long term side effects are uncertain.”

Then there’s the potential for abuse. “Will repeated use induce addiction in treatment-resistant depression patients?”

“What about other long term side effect?” A recent consensus statement acknowledged that data on the long-term effects of using ketamine in psychiatry practice are limited or nonexistent, even though an increasing number of clinicians are providing off-label ketamine for depression and other psychiatric disorders.

First synthesized in the 1960s, ketamine’s primary site on action in the central nervous system seems to be the thalamocortical projection system, said by a doctor, who has been providing the drug to patients since 2008. In a handout that accompanied his talk, he wrote that ketamine “Selectively depressed neuronal function in parts of the cortex and thalamus while stimulating parts of the limbic system, including the hippocampus.”

Ketamine creates acute subjective experiences that vary with dose, including a sense of “melting into people or things” at lower doses, and visions and hallucination at higher doses.

“At higher doses, they often experience a profound sense of connection to all things, an ineffable universal unity that can change their perspective on themselves and their depression.”

Antidepressant benefits with ketamine are annually dramatic. The drug is most commonly administered as an IV infusion over a 20-minute period at a dosage of 0.5 mg/kg. It also can be administered orally, intranasal, and intramuscularly.

“Patients may achieve response and even remission of depression within a day, even when the depression was previously medication refractory.”

“The benefits are usually lost in 3-21 days. Maintenance treatment with ketamine, scheduled once every 2-4 weeks, can maintain the treatment gains. Dissociative but very seldom problematic.”

It was noted that ketamine’s remarkable results have piqued the interest of pharmaceutical companies. “But it is off patent.” Several novel agents by different pharmaceutical companies quickly have been developed and are in development.