Ketamine is a well-known dissociative anesthetic that has also been misused as a hallucinogenic club drug (“special K”). Recently, this NMDA receptor antagonist has shown promise in rapidly reversing the symptoms of depression and acute suicidality. I got really excited about ketamine back in residency, and read all the papers by Carlos Zarate, one of the pioneers of ketamine research. I presented my findings at our monthly VA conference, but there wasn't much information back then. All I knew was that I was excited to have an alternative, something that could work fast for patients who were in great distress and really couldn't stand another minute of being in pain.
Since research began around 10 years ago, ketamine infusion clinics have sprung up throughout the US, despite the limited number of clinical trials that have been performed. Additionally, a number of the doctors providing the infusions are not even psychiatrists or anesthesiologists. This is troubling to some, as ketamine is primarily administered intravenously, which is somewhat more invasive than just taking a pill. For depression, ketamine is given at a dose much lower than that given in anesthesia, at 0.5 mg/kg (some clinics will dose higher in patients with more lean body mass, lower in those with less) over about 40 minutes. 
In response to the proliferation of ketamine clinics, a group of psychiatrists at the American Psychiatric Association created A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders and published it recently in JAMA Psychiatry. Interestingly, Carlos Zarate was absent from the list of authors, who included Gerard Sanacora, Mark Frye, and Charles Nemeroff.
The statement is brief and covers issues of efficacy and safety. Here's what I took away from reading the statement, with my commentary (which is not intended to be medical advice):
Ketamine treatment is, as far as we know, a medication whose antidepressant effects are only short-lived, and the authors suggest that perhaps giving the treatment twice per week could extend its efficacy, but the goal is to taper it down to once-a-week dosing by the second month, and eventually discontinue it entirely, since we don't know the long-term effects of taking ketamine regularly. However, there hasn't been much research done to figure out the optimal frequency of ketamine dosing. I have heard some patients say they needed several doses weekly, and others claim they only get it every six months. It may be patient-dependent. Twice-weekly dosing of ketamine would likely be cost prohibitive for most people, with treatment prices ranging anywhere from $400 to $1000 or more per IV infusion. Furthermore, ketamine as a depression treatment is experimental, so it's not covered by insurance.
Ketamine should be administered by trained medical personnel in a facility with at least basic medical equipment. The person administering the ketamine should be trained in ACLS (Advanced Cardiac Life Support), in the event it is needed. This is basic common sense, and I agree. There have been a few cases of tachycardia and high blood pressure in patients receiving ketamine, and at least one person fainted. Ketamine can also make people psychotic, though symptoms are usually quite transient.
The authors note that it would also be a good idea to have a psychiatrist actually diagnose these patients with treatment-resistant depression (i.e., they have tried and failed to get better on multiple antidepressants) and do a thorough evaluation to rule out possibility of other psychiatric disorders (substance abuse, psychosis) that could be exacerbated by treatment before flooding their brains with a highly psychoactive drug. The authors also strongly encourage ketamine prescribers to obtain collateral information, past psychiatric records, and a urine drug screen to help rule-out opiate and benzodiazepine use. There should also be a clinician who is familiar with managing behavioral emergencies (interestingly the don't use the word "psychiatrist" here – it could be any clinician with such experience) available in-house or on-call to manage any behavioral emergencies and provide rapid followup after the infusion.
Also, these patients will need to have their baseline symptoms recorded so we can actually see if they are getting better. They will need periodic psychiatric followup. (In my opinion, it would be even more beneficial to ensure that patients are actively participating in psychotherapy, especially right after an infusion, as they will probably get even more out of therapy once their depressive symptoms have subsided. Then, if and when the symptoms return, they will at least be equipped with coping skills and have a therapist for support.)
Just as with any anesthesia procedure, the physician should do a review of systems, ask about allergies, obtain labs, and basically rule out any potential risk factors associated with ketamine treatment (the authors suggest "Functional Exercise Capacity" as this is used to screen patients prior to anesthesia procedures).
Finally, we should remember to provide informed consent. Patients need to know the potential risks and benefits, the fact that this is an off-label use of ketamine, and that there are (theoretically) alternative treatment options. The authors go on to suggest that the informed consent include written materials, not just verbal dissemination of the information. This makes sense, and doctors usually get similar types of informed consent for anesthesia procedures, so these materials could be adapted for ketamine.
Although the evidence is limited at the moment, ketamine appears promising as a treatment for severe, otherwise treatment-resistant depression. Some of my former colleagues are researching whether it can be used in emergency rooms to rapidly reverse suicidality and reduce the need for costly inpatient hospitalizations. However, we really don't know the long-term risks and benefits associated with ketamine as a depression treatment, and, since it is experimental and quite costly to infuse, it remains out of reach for many patients. We have to be good stewards of our patients and remember our pledge to “first do no harm," while remaining cautiously optimistic about the future of depression treatment.
Disclaimer: The opinions expressed in this article are solely those of the author and do not reflect the views and opinions of Virtual Medical Staff, Methodist Hospital San Antonio, or Midland Memorial Hospital. None of the opinions expressed in this article are intended to be medical advice. If you suffer from severe depression, check out the resources at The Depression and Bipolar Support Alliance. If you are suicidal, go to the nearest ER, call 911, or call the National Suicide Prevention Lifeline at 1-800-273-8255. If you are interested in participating in clinical trials for ketamine, visit ClinicalTrials.gov.
Written by

Jacquelyn "Michele" LaGrone MD, MBA
Child, Adolescent, and Adult Psychiatrist