A History of Ketamine and How Ketamine is Used to Treat Mental Health Diagnoses

Ketamine is an unusual type of psychedelic drug - called a dissociative - that is undergoing a resurgence in popularity. Originally derived from PCP, or "angel dust," ketamine has been used in hospitals and veterinary clinics as an anesthetic for decades, and has been cited as a drug of misuse under the moniker "special K."
It is the effects that ketamine reliably produces that underlie both its medical and recreational uses: pain control, forgetfulness, intoxication, disassociation, and euphoria. Recently, it has been used more widely due to its approval for treatment-resistant depression (TRD) - that is, severe depression that has not improved via other therapies, including people who are experiencing suicidal thoughts.
Evidence of the benefit of ketamine
A prescription version of ketamine called esketamine (Spravato), given through a nasal spray, was approved in 2019 by the FDA for TRD; however, according to the guidelines, it is only to be used "under the supervision of a health care provider in a certified doctor's office or clinic." That means medical professionals need to watch you use it, and then follow you after you've taken your dose, checking your vital signs and how you are doing clinically.
The effectiveness of ketamine for TRD was first demonstrated for short-term treatment in research that resulted in clinically and statistically significant decreases in depression scores for ketamine versus placebo (In both groups in this study, the patients continued with their regular antidepressants because of concern of not treating TRD in the placebo arm.) Nasal ketamine was shown to have longer-term efficacy, in a study where ketamine (plus the regular antidepressant) helped people stay in stable remission 16 weeks into treatment.
Relief from TRD with ketamine happens rapidly. Instead of waiting for an SSRI to hopefully provide some relief over the course of weeks, people who are suffering under the crushing weight of depression can start to feel the benefits of ketamine within about 40 minutes.
What are the side effects?
Ketamine is generally considered safe, including for those who are experiencing suicidal ideation (thoughts or plans for suicide). The main side effects are dissociation, intoxication, sedation, high blood pressure, dizziness, headache, blurred vision, anxiety, nausea, and vomiting. Ketamine is avoided or used with extreme caution in the following groups:
-people with a history of psychosis or schizophrenia, as there is concern that the dissociation ketamine produces can make psychotic disorders worse
-people with a history of substance use disorder, because ketamine can cause euphoria (likely by triggering the opioid receptors) and some people can become addicted to it (which is called ketamine use disorder)
-teenagers, as there are some concerns about the long-term effects of ketamine on the still-developing adolescent brain
-people who are pregnant or breastfeeding
-older adults who have symptoms of dementia.
More detailed research needs to be done on the longer-term benefits and side effects of ketamine treatment, and on its safety and effectiveness for teens and older adults, as well as for the emerging indications of ketamine therapy for PTSD, OCD, alcohol use disorder, and other mental health conditions.
Finally, there is some concern that, with repeated dosing, ketamine can start to lose its effectiveness and require larger doses to produce the same effect, which is not sustainable.
Ketamine could provide hope for people with serious depression
Serious, treatment-resistant depression can rob people of hope for the future and hope that they will ever feel better. Ketamine can provide help and hope to patients who have not found relief with any other treatments. Given its efficacy in people considering suicide, it is plausible that ketamine may be lifesaving.
As we learn more from research on ketamine and from people's experiences in newer clinics, we will be better able to answer the questions of ketamine's longer-term effectiveness and what safeguards are needed for treatment. We may also learn who is most likely to safely benefit from ketamine therapies, and the best method of administration: intravenous infusion, a nasal spray, or a pill.
www.health.harvard.edu/blog/k...