When patients with depression who have not done well with traditional oral antidepressants come to my clinic for other options, I often offer ketamine as one potential treatment. I tell them the standard ketamine therapy for someone in a current depressive episode is six to eight ketamine administrations over two to three weeks. Some of the typical questions I get in response are “So if I do all the treatments, will I be cured?” “Can I come off my antidepressants?” “ Will I need any more treatments?”
In addition to letting patients know ketamine is a medicine used for anesthesia and pain relief and not FDA approved for depression, I also make sure they know there is very little research regarding the long term effectiveness of ketamine, whether it can prevent future episodes of depression, or if patients who have responded to ketamine need maintenance treatments. We don’t know if tolerance to ketamine develops and whether higher doses will be required over time for the drug to work. We have to make up for the lack of research in this area with our many years of clinical experience with ketamine therapy to guide us. This is similar to standard oral antidepressant treatment. There are surprisingly few studies that answer questions like “How long you need to take antidepressants to stay well?”” Does antidepressant dosing change over time?”“ Will antidepressants stop working over time?”
Whether it's an antidepressant pill or ketamine, a good psychopharmacologist should adjust a patient's treatment over time based on that patient’s individual needs. In other words, one size doesn't fit all.
We know that when ketamine works, it works quickly. Studies show the benefits of a single dose of ketamine often wears off within seven days. A few small, published studies show that a course of six treatments over two to three weeks will help sustain the benefit for longer. What about after that? Three or six months down the road?
Our clinic and similar clinics across the world are capturing long term data to help answer these questions. Some of the observations we and our colleagues have made about the need and effectiveness of ketamine as a maintenance therapy is the following:
- Most patients receiving ketamine treatment have been on an exhaustive list of antidepressants or have suffered for many years without relief. There are some who may be experiencing a single episode of depression over a short period of time (less than 1 year) and are being treated with ketamine. They be acutely suicidal or they need more immedate relief and cannot wait the four to six weeks required for each trial of an antidepressant. These patients may only need a few ketamine treatments to get better and may not require any maintenance therapy.
- Patients with chronic depression or multiple depressive episodes over their lifetime, who have responded to an initial course of six treatments, often experience a relapse within a few months after stopping ketamine. However, by incorporating other interventions, such as starting a more effective antidepressant than they have had in the past, making healthy lifestyle changes, and/or engaging in an effective psychotherapy regiment on a regular basis, they have more success staying well without the need for maintenance ketamine. There are others though that even with making those changes still require periodic ketamine “boosters.” These “boosters” could occur as frequently as once every one to two months or as infrequently as once or twice a year.
- We have found an effective relapse prevention strategy is having patients come weekly for four weeks after their initial six treatments. Then have the next treatment in a month, then two months, then three months and so on. The optimal length of time between treatments varies from patient to patient. Some cannot go longer than one month before their next treatment. Some patients can go two or three months. Others come once or twice a year when they feel themselves backsliding. The length of time between treatments can also vary for any one person. Some find they need more frequent treatments during certain seasons, times of year such as anniversaries of difficult past life events, or during stressful current life events such as the start of school or changes in work environment. Again, one size doesn’t fit all.
- We do find tolerance to dosing can develop and some patients, though not all, may need a dose increase at some point. The intensity of the dissociative experience can lessen over time and we need to educate patients that the intensity of dissociation does not always directly correlate with the antidepressant effect.
- Many patients have been able to lower the doses of their antidepressant when being treated with ketamine. Some have been able to discontinue certain medications if they are taking multiple antidepressants at the same time. We have patients that opt to take no medication once they start with ketamine but we find these individuals often require more frequent ketamine ”boosters” than those still on antidepressants.
- Lastly, and most importantly, ketamine therapy is not a passive therapy where “the magic medicine” does all the work for you. You need to work with the ketamine to optimize the benefits and prevent another episode. What does that mean? Eating healthy, getting enough sleep, staying physically and mentally active, not using illicit drugs and alcohol, avoiding stressful life events, taking time to recharging yourself, and engaging in some type of counseling or therapy that meets your needs.
- Alone, ketamine will likely not “cure” depression but can be a powerful tool among many to reduce the likelihood of another episode.
There is much we know and much we still need to learn about ketamine as a maintenance treatment for depression. Ketamine is a potential life changing treatment option for those with depression who need to get better quickly, for those with intolerance or non-response to standard antidepressant medications, or someone with acute suicidal ideation. Hopefully this answers some of your questions about if it works, how can we make sure it keeps on working?