Depression: What About Ketamine?
For those considering using it, here's what you need to know.
Posted Aug 20, 2017
You’ve likely seen ketamine in the news lately. It’s rapid action in reducing/eliminating depression is sparking enthusiasm in both psychiatrists and patients. But recently, because of the limitations in knowledge about the effects of long-term treatment with it, researchers publishing in the scientific literature are sounding a note of caution.
Here’s an example of how ketamine can seem like magic to those with treatment-resistant depression. Over a decade ago, a man with treatment–resistant depression was searching the Internet for any potential new treatments to try, since all available treatments did not work. He came across a few case reports of a drug that might help: an anesthetic called ketamine. Soon thereafter, he needed to have surgery requiring a general anesthetic. He asked a psychiatrist about ketamine for depression, but the psychiatrist had never heard of it (as was true for most psychiatrists at that time). The man asked his anesthesiologist to use it during surgery, and the doctor agreed (ketamine has long been an approved standard drug for anesthesia).
What happened? After he awoke and his mind cleared from the lingering effects of the anesthesia, he noticed that his depressed mood was gone. Completely. And it was gone the next day, and the next. For almost 2 weeks, his mood was normal – and what a wonderful feeling that was. After that, the depression returned.
Now, many years later, psychiatrists and patients have definitely heard about ketamine. It is being used for treatment-resistant depression at doses much lower than those that produce anesthesia. Many academic centers are studying and treating patients with it. Private practice centers in the community, usually run by anesthesiologists or psychiatrists, administer ketamine.
Should I consider treatment with ketamine?
There is some evidence that one dose of intravenous ketamine may greatly decrease suicidal thoughts for up to a week. If so, that would decrease the risk of suicide and also provide time for a treatment plan to be made, and treatment started.
As an antidepressant, as a general principle, consider treatment with ketamine if you have treatment-resistant depression. And not before you know all the facts.
Ketamine is a most promising treatment for people with treatment resistant depression, after a number of antidepressant medications have been utilized without benefit. However, its use as an antidepressant is still so new that there are only very limited longer–term safety and effectiveness data available.
Ketamine is not approved at this time by the FDA as a specific treatment for depression (for lack of necessary scientific trials). However, an American Psychiatric Association Task Force did publish a statement about best practices when ketamine is used for patients with treatment-resistant depression due to primary depressive disorder or bipolar disorder.
How is it given?
In a medical setting, it is given intravenously over 40 minutes, or it may be given in an intranasal form (esketamine). An oral form of ketamine is also available. All these routes of administration have been approved by the FDA.
What are potential immediate side effects?
Temporary side effects may occur, and some may be serious. Headaches and dry mouth may appear. There may be elevations in both heart rate and blood pressure. Psychological effects during or after the infusion include a sense of unreality, feeling out of one's body, or hallucinations. These are usually resolved by two hours after the treatment is completed.
Who's the doctor and the setting?
A licensed physician in a variety of specialties can administer it. However, because of the potential side effects, the doctor should monitor cardiovascular function, and be prepared and able to manage both cardiovascular and behavioral side effects, should they occur.
Will I have a positive response?
At this time, doctors are not yet able to predict beforehand who will respond. If there is a good response and depression is lifted, it can last from 3 to 14 days. In studies using three infusions in a week for 1 to 2 weeks, between 40 to 80 percent of people had their depression lift, often after the very first infusion. With oral ketamine, less people may show a response, and it is is usually just a mild to moderate one.
Will I need repeated doses?
If there is a response, it can last for 3 to 14 days. Therefore, for a continued effect, repeat dosing is needed, usually at least once a week and then possibly at longer intervals.
It's expensive. Insurance almost certainly will not cover it. A single infusion costs many hundreds of dollars.
What are possible side effects of repeated doses?
This is the big unknown. In people who used ketamine for either chronic pain or as a drug of abuse, changes in brain structure and function and bladder cystitis have been reported. The amount of ketamine used in treatment of depression is much lower, which is an important difference. But there is, as yet, little information from studies of longer-term administration. So far, no alterations in cognition have been reported after two-week scientific trials.There is no information available yet about the potential for developing addiction/abuse of ketamine after short or long-term administration.
Continuing assessment is needed during longer-term treatment
Just as the doctor should monitor vital signs during all treatments, the doctor should also be asking and checking regularly for the known possible effects of longer-term treatment – as well as any other physical or mental changes. While there are not yet sufficient clinical trials, the few that exist suggest that people with treatment-resistant depression continue to benefit from longer-term maintenance (for many months) with ketamine without serious unwanted side effects.
For those thinking about a trial of ketamine: Consider participating in a research study.
There are currently a great many approved studies of ketamine for depression in the United States and around the world. Becoming a participant in one of these studies has several advantages. You can get some treatment free of charge and be assured of having knowledgeable doctors and excellent care. You will also be helping to generate much-needed new knowledge Here is a website that lists available trials: clinical trials.gov. Where asked to enter Condition, enter depression. Following that, where asked for Other Terms, enter ketamine. Search regularly, as more sites and more studies are continuously being approved.
Samuel T. Wilkinson, MD. and Gerard Sanacora, MD, PhD (2017): Considerations on the Off-Label Use of Ketamine as a Treatment for Mood Disorders. JAMA Published online August 14.
Brooke Short, MD et al (2017) Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry, July 2017 (17)30272-9
William V. Bono et al (Spring 2020) Next-Step Treatment Considerations for Patients With Treatment-Resistant Depression That Responds to Low-Dose Intravenous Ketamin . Focus 18:2, 181-192