Why Use Ketamine for Depression?


Despite significant progress, depression remains a disabling condition that affects millions of people. Both psychotherapy and antidepressant medications are the current standards of care. For those with more severe depression, medications are often required for recovery. However, the current available treatments are based on modulating the neurotransmitters in the brain like serotonin, dopamine, and norepinephrine.  About 35% of patients remain symptomatic after several treatments. When these antidepressant medications do work, there is a typical delay of weeks before response is achieved. In those first few weeks, antidepressant treatment may increase risk of suicidal behavior. With the lack of rapid response from existing medications, and the apparent risk until such a response occurs, there is urgent need for development of rapid acting treatment alternatives for depression. For severe depression, electroconvulsive therapy (ECT) is the only intervention with the potential of a rapid effect, though side effects often limit its use.

Ketamine was developed in 1963, first tested on humans in 1964, and FDA approved for roles in anesthesia in 1970.  It was not until 2000 that ketamine was concretely demonstrated to have antidepressant properties. Ketamine has demonstrated the potential for significant improvement - including reduction in suicidal thoughts - within hours of administration. Ketamine has emerged as a novel therapy for treatment-resistant depression, demonstrating rapid benefits in both unipolar and bipolar depression. The duration of benefit from a single dose varies between these subtypes, but appears to last longer in unipolar depression. Strategies to extend the duration, with repeat doses, maintenance treatment, or subsequent augmenting medications have yielded promising results, and offer a potential solution to the typically short duration of benefit observed in treatment plans that involve just one ketamine administration. Another unique property of ketamine is a rapid reduction in suicidality demonstrated in the research. Side effects are typically short-term, mild, and well-tolerated. More detailed discussion of the risks and benefits of our treatment protocol are discussed at length during the evaluation, and we encourage questions and concerns be addressed before starting this or any treatment.  

While most research on ketamine thus far have looked at longer IV infusions, other routes - such as intramuscular injection - have similar strong, rapid, and robust antidepressant benefits. By administering ketamine intramuscularly, we are able to reduce costs without scientific evidence of compromise in effectiveness or safety. Our protocol also allows the extension of benefit for the longer term, using an evidence-based repeated-treatment plan for a short period of time. Scientific data suggests there may be a cumulative dose effect similar to ECT, where a series of treatments is needed to provide lasting relief. Indeed, several studies concluded that some patients require more than one treatment, and that the percent of people to see benefit, and duration of these benefits is increased with increased treatments. Another benefit of intramuscular administration is that it is greater than 95% bioavailable (the closest to IV of any other route of administration) and its rapid absorption provides a peak concentration that leads to increased dissociative and subjective effects. This effect has been described as psychedelic, and growing evidence from the clinical study of other psychedelics such as psilocybin, suggests that this effect has healing potential itself. With our team consisting of leading researchers and clinicians in the field of psychedelic research and harm reduction, we are uniquely positioned to make the most of this subjective experience that other ways of administering ketamine may take for granted or overlook entirely. By administering ketamine in this way, we offer a combined opportunity for healing through the well-demonstrated biological effects of ketamine on depression while capitalizing on the opportunity to integrate a profound experiential component that ketamine provides, though it is frequently dismissed as an unintended side effect. All of our patients will integrate this often profound experience with licensed professional mental health providers with specialized training and experience in working with psychedelic states for the purpose of healing.

It is not entirely clear from any one study, or one clinicians experience what the optimum dose, frequency, duration, and number of treatments is, and how this might best be individualized. However,  Dr. Marta has done extensive research and analysis on all of these important and concerning factors. The result of years of inquiry has been the publication of several peer-reviewed articles, scientific presentations,  and a book chapter on the compiled data. That expertise on the scientific evidence, combined with clinical experience in treating patients with ketamine since 2014, are the basis for our decision-making in creating an evidence-based treatment plan specific to the individual client here at the California Center for Psychedelic Therapy.  

Reference: Ryan WC, Marta CJ, Koek RJ (2016). Ketamine and depression: a review in The Ketamine Papers--Science, Therapy and Transformation. Santa Cruz, CA: Multidisciplinary Association for Psychedelic Studies. [ order the book via the publisher, or via amazon ]