Ketamine was first synthesized in 1962 at the Parke-Davis Laboratories in Michigan by Calvin Stevens, an organic chemistry professor at Wayne State University, Detroit. Compared to other anesthetics, it was mild in its side effects, immediately giving it a leg up over the others. It was approved by the FDA for use as an anesthetic in 1970 in children, adults, and the elderly, and has also been widely used by veterinarians for everything from house cats to giraffes.
A great advantage ketamine had over other drugs is its minimal effect on breathing and blood pressure. This made it more effective and safer than general anesthesia and intubation (i.e. inserting a breathing tube down a patient’s throat). Because of this, it was implemented as a “buddy drug” in the Vietnam War. Each soldier was able to safely carry a vial of ketamine for use in emergencies, effectively allowing for time to get the wounded to a field hospital with minimal discomfort. Ketamine is widely used by the military to this day.
Known as a dissociative anesthetic, ketamine has been known to cause hallucinations, feelings of being “spaced out” or floating, and temporarily losing feeling in arms or legs. These symptoms occur in about a third of patients at anesthetic dosages, and usually only last up to an hour after waking from surgeries. Because of its psychoactive qualities, it became popular alongside LSD in the 1970s. It was also used in psychedelic psychotherapy at that time, as were psilocybin (magic mushrooms) and LSD. When the dangers of mushrooms and LSD were discovered, however, they were all three banned from use for this purpose; ketamine is now the only drug of the group that is still legal for other purposes.
Although ketamine can produce dissociative thoughts and feelings in patients, it has been known to do so in a generally positive way. Soldiers treated with it have reported suffering less from post-traumatic stress than others, and some depression patients as early as the 1960s began using it illegally in lieu of other antidepressants that weren’t working for them. In 1997, E.M. Krupitsky et al. reported that they were able to rehabilitate alcoholics at a 65% success rate when combining ketamine treatments with standard treatments, a huge improvement over the 25% success rate achieved with the standard treatment alone. Similar results were found in a 1998 study on the treatment of eating disorders. Krupitsky noted that ketamine helps produce positive introspective and spiritual thoughts, which helped many study participants overcome addictive behaviors.
Over time, ketamine became a popular party drug, leading to stricter rules regarding its distribution and use. This has made it difficult for researchers to conduct further therapeutic-based trials of the drug, so significant progress in its use to combat depression was not made until the 2000s.
Because it targets a different part of the brain than most antidepressants, ketamine has been shown to be effective even in patients with treatment-resistant depression. In 2000, Robert Berman and John H. Krystal published results of a ketamine infusion trial (at 1/4 the standard anesthetic dosage) involving such patients. All subjects reported feeling better during the infusion, and half experienced a significant reduction in depressive symptoms for up to two weeks following treatment. Subjects did not feel that their improved emotional state was due to a “high”. Any side effects were very short-lived, and positive results for many were instantaneous. By comparison, most antidepressants can take several weeks to kick in. This trial was repeated with similar results at the Bethesda National Institute of Mental Health (NIMH) in 2006.
A. Kudoh et al. at the Department of Anesthesiology, Hakodate Watanbe Hospital, Amori, Japan found in 2002 that using ketamine as an anesthetic for surgical procedures led to patients reporting less post-operative pain and depression, particularly in depressed patients who tended to report more pain than non-depressed patients.
In 2006, Graeme Correll and Graham Futter found that long-time sufferers of depression found reprieve through low-dose, long-term (5 day) intravenous infusions of ketamine. Results were immediate, with depressive symptoms disappearing for anywhere from a couple of weeks to several months. Depressive relapses were later successfully treated by the same method. Later trials with 40-60 minute infusions at sub-anesthetic dosage levels also proved effective, though the shorter treatment method often needed repeating a few times over the course of a week or two in order to achieve the long-term effect found in the longer trial. As the 40-60 minute infusions are significantly more practical than 5 day infusions, they have become the norm in depression treatments today.
As noted above, there is a tendency for relapse of symptoms with ketamine treatment. This suggests that it does not present a cure for most patients. However, repeat infusions coupled with psychotherapy and other long-term medications can produce both rapid and long-lasting results. Many people with depression and suicidal tendencies can experience an increase in suicidal thoughts before a new antidepressant medication kicks in, so the fast-acting nature of ketamine can be life-saving for them. This quality has made it useful in emergency rooms as well, where people at risk for suicide have been able to come and receive immediate relief via ketamine treatments.
Whereas abusers of the drug have been known to present with liver problems later on, the much-lower dosages administered to those suffering from depression, bipolar disorder, and other mental health problems will at worst experience dizziness or brief hallucinations. In the controlled environment of a clinic, repeated infusions of ketamine have shown to be safe even for pediatric patients. A 2010 study of 40 pediatric bipolar patients aged 6-19 years old treated with intranasal ketamine found that the short-lived side effects of ketamine were easy for this age group to adjust to and did not alter their state of being in a dangerous way. Therefore, even in youth and children suffering from mental health issues, ketamine may be a safe and effective treatment option.
Ketamine has now been used in the treatment of thousands of people suffering from depression in clinics throughout the United States and the world. Although it is not yet listed by the FDA as an officially-approved antidepressant, it has proven to be both safe and effective for mental health-related issues. The doctors and clinicians at Noetic Psychiatry have been among the administrators of ketamine for this purpose for well over a year, and have seen it to be an excellent help to many individuals in overcoming their depression.
Daniel Moster is an office/IT intern at Noetic Psychiatry, who also occasionally moonlights as a writer, mandolin player, and student of Family Life at Brigham Young University. In his free time, he enjoys collecting hobbies, eating sugary foods, and spending time with his beautiful wife.