Ketamine was discovered in 1962 by Parke-Davis in an attempt to develop a safe anesthetic that could be given by an untrained person in certain situations such as the battlefield; it was used first during the Vietnam War. It was FDA approved in 1970. It then moved into the operating room and is often used on children because of its safety. It has also been adopted by veterinarians for animal anesthesia. It is currently a Schedule III controlled substance.

Ketamine also has anti-depressant effects. This was realized in the 1970s but formal studies weren’t initiated until the 1990s. The first paper was published in 2000 and the results have been replicated many times over for people particularly with treatment resistant depression (TRD). There are also indications for people with anxiety, post-traumatic stress disorder (PTSD), bipolar depression, and other conditions in the absence of other contraindications (identified below). When ketamine is used for these psychiatric purposes, it is used at sub-anesthetic doses which are significantly lower than doses used for anesthesia purposes.

About ⅓ of patients treated with traditional anti-depressants such as SSRIs and SNRIs do not respond, despite multiple different agents. Ketamine has become well regarded for safe and rapid relief of depressive symptoms. “Ketamine is the only legal potentially psychedelic medicine in use” and while its use for TRD is considered off-label, there is extensive research that supports it. Ketamine’s tolerability and safety have been demonstrated over almost five decades.

There are several routes of administration that ketamine can be given therapeutically. Only ketamine that is administered intravenously has 100% bioavailability because it enters the circulation and does not have to be absorbed through muscle or other mucosa. This makes the process of ketamine infusions incredibly consistent and predictable. In addition, ketamine is short-acting with a half-life of 2.5 hours; if there is any reason to stop the infusion, the effects of the ketamine wear off in a matter of minutes. 

Ketamine has a rapid onset within minutes and short duration of action. It can ease your symptoms during a ketamine session. You may experience optimal effects at 24 hours to seven days with a single dose. For an acute depressive episode, studies recommend 6 sessions (40 minutes each) in a 2-3 week period. Booster doses for maintenance therapy can be administered every 4-12 weeks.