According to the American Psychiatric Association (APA), depression is a common and serious medical illness that negatively affects how one feels, thinks, and acts. We all experience moments of sadness we quickly cure with various methods, like self-care. Clinical depression is different. It doesn't just go away. Instead, it lingers for at least two consecutive weeks and significantly interferes with one's ability to work, play, or love.  According to the APA, one in six people will experience depression at some point. Depression can occur at any period in one's life, however, it commonly appears during the late teens to mid-20s, with higher incidences in women.  Fortunately, depression is treatable.
When we think of treatment options for depression, our mind’s might automatically go to antidepressants and psychotherapy. These traditional treatment methods have proven successful for many of those battling depression, but not everyone is so fortunate. Too few patients respond to antidepressants. Up to 60% of patients diagnosed with depression do not achieve an adequate response.  Depressive symptoms may reduce within weeks after starting conventional antidepressants, but resistance concerns one-third of patients. Treatment-resistant depression, or TRD, refers to inadequate response to at least one antidepressant trial.  While there is still much to learn, recent advances shed new light on understanding and managing TRD.
Ketamine is said to have antidepressant properties and could be seen as a treatment option for TRD. In multiple studies, ketamine provided a rapid-onset antidepressant effect with a maximum efficacy of 24 hours.  Researchers believe that ketamine targets a different system in the brain than typical antidepressants. In depression, the number and strength of synapse connections decrease. Ketamine triggers the brain's resilience mechanisms to promote the maintenance of healthy circuits in the brain, thus, regrowing the synapse connections.  There are two main types of ketamine used to treat TRD, racemic ketamine, administered as an infusion into the bloodstream, and Esketamine (Spravato), given as a nasal spray. The two types of ketamine interact differently within the brain.  How you take ketamine affects the overall effectiveness and side effects. There is still a lot to discover about ketamine and depression, so side effects and long-term results are still yet to be determined. However, here are some ketamine facts to consider:
Similar to opioids, ketamine has addictive properties.
A lower dose of ketamine is administered for depression treatment than the necessary dose for anesthesia.
Racemic ketamine typically works within one to three infusions.
1. Corriger, A., & Pickering, G. (2019). Ketamine and depression: a narrative review. Drug design, development, and therapy, 13, 3051–3067.
2. Rong C, Park C, Rosenblat JD, Subramaniapillai M, Zuckerman H, Fus D, Lee YL, Pan Z, Brietzke E, Mansur RB, Cha DS, Lui LMW, McIntyre RS. Predictors of Response to Ketamine in Treatment-Resistant Major Depressive Disorder and Bipolar Disorder. International Journal of Environmental Research and Public Health. 2018; 15(4):771.
3. Lee, E. E., Della Selva, M. P., Liu, A., & Himelhoch, S. (2015). Ketamine as a novel treatment for major depressive disorder and bipolar depression: a systematic review and quantitative meta-analysis. General hospital psychiatry, 37(2), 178-184.
4. Fava M. (2003). Diagnosis and definition of treatment-resistant depression. Biological psychiatry, 53(8), 649–659.
5. Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., ... & Mathew, S. J. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. American Journal of Psychiatry, 170(10), 1134-1142.
Author: Ariqa Everett
Editor: Lauryn Agron
Health scientist: Ariqa Everett