While working in an emergency department (ED), I was surprised by the variety of uses for ketamine, including pain management, procedural sedation, analgesia, and calming the all-too-frequent agitated patient. When given a higher dose, typically for procedural sedation, patients are said to fall into a "k-hole". Ketamine has many advantages in emergency medicine as it is fast and short acting, is an alternative to opioids, can be given in multiple routes (intravenous, intramuscular, intranasal, and oral), and preserves airway patency (Sheikh, S., Hendry, P., 2017). More recently, researchers have been exploring other uses for ketamine including treatment for depression and suicidality.
I was exposed to a diverse patient population and wide variety of complaints working in an ED in the Denver Metro Area. There was no shortage of individuals who presented for mental health issues, whether it be for an anxiety attack, suicidal thoughts, or a suicide attempt. Patients who are placed on an “M1”, a psychiatric hold for 72 hours, receive a psychiatric evaluation and are sometimes admitted to the hospital. There has been no scientific evidence showing that inpatient psychiatric hospitalization decreases the chances of these individuals completing a suicide attempt in the future (Scott, J., 2020).
In a randomized, double-blind, placebo-controlled, proof-of-concept trial completed at the University of Alabama, researchers studied 18 depressed patients with acute suicidal ideation who required hospitalization. Nine individuals received a single dose of of IV ketamine, and nine in the placebo group received a bolus of saline. Ninety minutes after infusion, 33% of the placebo group achieved remission of suicidal ideation, compared to 88% of the ketamine group. These effects seemed to linger for roughly three days (Domany Y., Shelton RC., McCullumsmith CB., 2020). These results support further study of ketamine for depression and suicidality, and potentially other disorders such as PTSD or anxiety.
References:
Domany Y, Shelton RC, McCullumsmith CB. Ketamine for acute suicidal ideation. An emergency department intervention: A randomized, double-blind, placebo-controlled, proof-of-concept trial. Depression & Anxiety (1091-4269). 2020;37(3):224-233. doi:10.1002/da.22975.
Scott, J., 2020. Ketamine For Depression And Suicidality. [podcast] Emergency Medical Minute. Available at: <https://emergencymedicalminute.com/podcast-584-ketamine-for-depression-and-suicidality/> [Accessed 27 September 2020].
Sheikh,
S., Hendry, P. (2017). Why Emergency Departments Love
Ketamine [PowerPoint presentation]. Pain Week, Las Vegas. https://rsds.org/wp-content/uploads/2017/10/EMD-04-Why-EDs-Love-Ketamine-Hendry-and-Sheikh-9.4.16-HW.pdf
Preliminary ketamine research has proven effective against depression and suicide (Ryan et al. 2014). However, it has been undetermined on the severity of long term effects of continual ketamine use (Ryan et al. 2014). Likewise, the short term effects of ketamine use can be dangerous. From hallucination to respiratory distress, the delicate dance between finding a cure or forcing comatose on patients is yet to be had in regard to mass ketamine use. More research is a necessity before we hold onto the potential benefits of ketamine.
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Ryan, W. C., Marta, C. J., & Koek, R. J. (2014). Ketamine and depression: a review. The International Journal of Transpersonal Studies, 33(2), 40–74.
I agree with Austin in that ketamine research has been shown to combat depression when comparing a group given esketamine 2 times a week randomly for 4 weeks that is also receiving standard treatment to a group given a placebo for the same duration and frequency as well as standard treatment (Canuso et al., 2018). The experimental group showed significantly lower scores on the depression scale than the control group. While the results indicate that intranasal esketamine may be effective in decreasing the severity of depressive symptoms, and to some extent suicidal ideation, especially in those who are depressed and are at imminent risk for suicide. However, the largest issue with ketamine are the adverse/dangerous side effects that are associated with usage such as nausea, dissociation, and headaches.
ReplyDeleteCanuso, C. M., Singh, J. B., Fedgchin, M., Alphs, L., Lane, R., Lim, P., Pinter, C., Hough, D., Sanacora, G., Manji, H., & Drevets, W. C. (2018). Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. The American journal of psychiatry, 175(7), 620–630. https://doi.org/10.1176/appi.ajp.2018.17060720
After reading the results of ketamine’s ability to suppress suicidal ideations I began to wonder what this treatment plan would look like when administering ketamine as a medication. I assumed the treatment plan would consist of prolonged doses similar to most antidepressant medications and immediately associated negative effects such as abuse and dissociative properties, that would result from prolonged use of ketamine. However, to my surprise I found that ketamine influences brain plasticity. Ketamine may act in a complementary manner to exert acute changes in synaptic plasticity, leading to sustained strengthening of excitatory synapses, which are necessary for antidepressant behavioral actions (Zanos et al., 2018). To my current knowledge most antidepressants are long-term administered medications that have a high rate of negative side effects and do not show positive alterations in the brain. The fact that ketamine can sustain excitatory synapses with a single use has actually led me to believe that ketamine may be an extremely promising alternative to current antidepressant drugs.
ReplyDeleteZanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018 Apr;23(4):801-811. doi: 10.1038/mp.2017.255. Epub 2018 Mar 13. PMID: 29532791; PMCID: PMC5999402.