These investigations demonstrated ketamines short duration of action and reduced behavioral toxicity made it a favorable choice over phencyclidine (PCP) as an anesthetic. The researchers wanted to call the state of ketamine anesthesia "dreaming", but Parke-Davis did not approve of the name. Hearing about this problem and about the "disconnected" appearance of treated people, Mrs. Edward F. Domino, the wife of one of the pharmacologists working on ketamine, suggested "dissociative anesthesia". Following FDA approval in 1970, ketamine anesthesia was first given to American soldiers during the Vietnam War.The discovery of antidepressive action of ketamine in 2000  has been described as the single most important advance in the treatment of depression in more than 50 years. It has sparked interest in NMDA receptor antagonists for depression, and has shifted the direction of antidepressant research and development. Society and culture
Legal status
While ketamine is marketed legally in many countries worldwide, it is also a controlled substance in many countries. In Australia, ketamine is listed as a schedule 8 controlled drug under the Poisons Standard (October 2015). In Canada, ketamine is classified as a Schedule I narcotic, since 2005. In December 2013, the government of India, in response to rising recreational use and the use of ketamine as a date rape drug, has added it to Schedule X of the Drug and Cosmetics Act requiring a special license for sale and maintenance of records of all sales for two years. In the United Kingdom, it became labeled a Class B drug on 12 February 2014.
One of the main challenges with ketamine treatment can be the length of time that the antidepressant effects lasts after finishing a course of treatment. A possible option may be maintenance therapy with ketamine which usually runs twice a week to once in two weeks. Ketamine may decrease suicidal thoughts for up to three days after the injection.An enantiomer of ketamine – esketamine commercially sold as Spravato – was approved as an antidepressant by the European Medicines Agency in 2019. Esketamine was approved as a nasal spray for treatment-resistant depression in the United States and elsewhere in 2019 (see Esketamine and Depression). The Canadian Network for Mood and Anxiety Treatments (CANMAT) recommends esketamine as a third-line treatment for depression.A Cochrane review of randomized controlled trials in adults with unipolar major depressive disorder, found that when compared with placebo, people treated with either ketamine or esketamine experienced reduction or remission of symptoms lasting 1 to 7 days. There were 18.7% (4.1 to 40.4%) more people reporting some benefit and 9.6% (0.2 to 39.4%) more who achieved remission within 24-hours of ketamine treatment. Among people receiving esketamine, 2.1% (2.5 to 24.4%) more encountered some relief at 24-hours and 10.3% (4.5 to 18.2%) more had few or no symptoms. These effects did not persist beyond one week, although higher dropout rate in some studies mean that the duration of benefit remains unclear.Ketamine may partially improve depressive symptoms among people with bipolar depression, at 24 hours after treatment, but not 3 or more days.