Party Drug as Antidepressant

While shadowing in the emergency department, I remember a physician recommending a ketamine clinic to a patient struggling with depression. I had only ever heard ketamine used as either an anesthetic during conscious sedations or an illegal club drug. How could this drug be acting as an antidepressant? 

  

Depression is the leading cause of disability worldwide and up to 7.4 million American adults suffer from treatment resistant depression (Muneer,2017). In March of 2019, the Food and Drug Administration approved a ketamine nasal spray, Esketamine, for major depression. This approval is the first new antidepressant medication that has been brought to the market in decades. 

Although, used as an anesthetic in hospitals and a party drug in nightclubs, ketamine has recently been used to treat depression after researchers discovered it alleviates depressive symptoms in a matter of hours (Murrough, 2013). This contrasts sharply with existing antidepressants, which can take weeks or months to take effect. 

Unlike most commonly used antidepressants that act on monoamine neurotransmitters (serotonin, norepinephrine, and dopamine), ketamine acts on the excitatory neurotransmitter glutamate. Although the exact mechanism of action of ketamine is not fully understood, studies from Yale research labs have shown that ketamine triggers glutamate production and ultimately prompts the brain to form new neural connections (Daly, 2018). The idea is that the brain will be more adaptable and will be able to create new pathways, allowing patients to develop more positive thoughts and behaviors. 

Dozens of “ketamine clinics” have opened up across the United States in recent years, administering intravenous ketamine to people with resistant depression. The price of ketamine infusions range from $400 to $800 per treatment and approximately 6 treatments are required over a 2-3 week time period (Daly, 2018). The newly FDA approved Esketamine is a slightly different form of ketamine but the effects are essentially the same. A patient will go to their doctor once or twice a week to get the nasal puffs, which is more accessible for patients than the IV treatments.

There are possible side effects including dizziness, a rise in blood pressure, and addiction. Many also worry that since ketamine is sometimes abused (as club drug Special K), making this drug more readily available increases the likelihood of it getting into the wrong hands. Despite this concern, the FDA approval does give doctors another valuable tool and approach for depression treatment. 

Daly, E. J., Singh, J. B., Fedgchin, M., Cooper, K., Lim, P., Shelton, R. C., … Drevets, W. C. (2018). Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression. JAMA Psychiatry, 75(2), 139. doi: 10.1001/jamapsychiatry.2017.3739

Muneer, A. (2017). Major Depressive Disorder and Bipolar Disorder: Differentiating Features and Contemporary Treatment Approaches. Understanding Depression, 15–34. doi: 10.1007/978-981-10-6577-4_2

Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., … Mathew, S. J. (2013, October). Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992936/.