What about ketamine for depression or suicidal ideation?

Clinical depression is a common disorder with serious consequences. While it is treatable, a substantial proportion of patients do not respond to commonly used treatments. Ketamine was approved for use in the U.S. in 1970. It has traditionally been used for anesthesia, during which it produces a trance-like state, pain relief, sedation and memory loss. More recently, studies have found that ketamine can be a rapid-acting antidepressant. It is also possible that it can rapidly alleviate suicidal ideation.
A single intravenous ketamine infusion can produce antidepressant effects within 4 hours. While traditional antidepressant medications have substantial efficacy, they require weeks for full effect and a substantial proportion of people do not fully respond. Ketamine is an NMDA receptor antagonist, with a different mechanism of action than traditional medications. While Ketamine has not been approved for use as an antidepressant, the FDA approved its active enantiomer, esketamine, in a nasal spray formulation, for use in treatment-resistant depression. Patients are considered treatment-resistant if they have major depressive disorder and, despite trying at least two antidepressant treatments at adequate doses for an adequate duration in the current episode, have not responded to treatment.

Esketamine was approved based on one study that found a small but significant improvement compared with placebo, and a second discontinuation study that found a lower relapse rate with esketamine. Other studies did not show efficacy. Esketamine appears less effective in people 65 years and older. Recommended treatment is twice per week for four weeks, with boosters as needed, plus traditional antidepressants.

An FDA REMS specifies requirements for use of esketamine. It must be administered in a certified medical office where the health care provider can monitor the patient for at least two hours after receiving their dose, the prescriber and the patient must sign a Patient Enrollment Form stating that the patient understands they should make arrangements to safely get home and that the patient should not drive or use heavy machinery for the rest of the day on which they received the drug. The medication must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks.

Ketamine can produce euphoria and dissociation and has abuse potential. It has known side effects, including inducing psychotic episodes in at-risk individuals. The optimal dosing is unknown. The long-term side-effects, safety and effectiveness of esketamine are unknown.

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