Depression has impacted many individuals and has even been described as an epidemic; the World Health Organization believes that in the next two decades, depression will be #2 on the list of the global disease burden, just behind cardiovascular disease (Üstün et al., 2004). While depression is certainly not a new disorder, descriptions of depression have been found in The Old Testament as well as Homer’s Iliad, research has established that cases of depression have only increased with time (Ban, 2014). On top of an increase of depression, suicide rates increased about 30% from 2000 to 2018; this demonstrates the magnitude of depression and the exigency of finding a productive treatment plan (CDC, 2020).
Even though depression is becoming more prevalent with time, one could argue that the headway in developing new treatment options for depression has reached a stalemate. Since Prozac’s introduction to the market in 1987, often referred to as a “breakthrough drug” since Prozac and other SSRIs have less side effects compared to older antidepressants, there hasn’t been another major development in treatment options. However, studies have shown that roughly 30 – 40% of patients being treated for depression do not experience an alleviation of symptoms (Souery et al., 2006). This phenomenon is referred to as Treatment Resistant Depression and has incentivized scientists to find a more effective treatment option for depression.
It was groundbreaking with the FDA approved esketamine, sold under the brand name of Spravato as a nasal spray, for treatment of Major Depressive Disorder. Esketamine, derived from ketamine, has been proven to produce rapid antidepressant effects in patients that have previously been unresponsive to other antidepressants. Ketamine works in a completely different way compared to other antidepressants. SSRIs are the most commonly prescribed antidepressants and they are thought to increase serotonin levels in the brain. On the other hand, ketamine primarily increases glutamate levels in the brain (this effect is thought to be responsible for Ketamine’s antidepressant effect).
However, one study found that psychedelics, specifically psilocybin and LSD, may provide longer lasting antidepressant effects compared to ketamine. This research is significant due to the stigma surrounding psychedelics; research on the healing properties of psychedelics has only recently been explored again due to the lingering effects of President Nixon’s “war on drugs” from the 1960s. This study aimed to investigate the antidepressant effects of psilocybin, LSD, and ketamine in a rat model of depression. The findings demonstrate that all three drugs reduced depression-like behaviors in rodents (measured by the established forced swim test). However, although ketamine decreased depression-like behaviors, the ketamine-related behavioral changes were transient in comparison to LSD and psilocybin. Additionally, both psilocybin and LSD reduced depression-like behaviors in rats 5 weeks after administration. On the other hand, 5 weeks after the ketamine treatment, the performance of the ketamine rats were not statistically distinguishable from the rats in the control condition (who received an injection of a saline solution instead). Moreover, there was no indication that the effects of psilocybin became weaker over time. This suggests that the therapeutic effects from a single administration of psilocybin lasts longer than 5 weeks. Since developments in treatment options for depression have been long-awaited, it’s exciting to see that other options, besides ketamine, also produce antidepressant effects and can be explored further.
The recent progress in treatments for depression are very promising. Since ketamine and psychedelics act on different brain systems than traditional antidepressants – while still producing antidepressant effects – advancements in depression treatments can potentially reveal the biological basis of depression.
Ban, T. A. (2014). From melancholia to depression: a history of diagnosis and treatment. International Network for the History of Neuropsychopharmacology, 19, 2015.
CDC. CDC WONDER: Underlying cause of death, 1999–2019. Atlanta, GA: US Department of Health and Human Services, CDC; 2020. https://wonder.cdc.gov/Deaths-by-Underlying-Cause.html
Hibicke, M., Landry, A. N., Kramer, H. M., Talman, Z. K., & Nichols, C. D. (2020). Psychedelics, but not ketamine, produce persistent antidepressant-like effects in a rodent experimental system for the study of depression. ACS chemical neuroscience, 11(6), 864-871.
Souery, D., Papakostas, G. I., & Trivedi, M. H. (2006). Treatment-resistant depression. Journal of Clinical Psychiatry, 67, 16.
Üstün, T., Ayuso-Mateos, J., Chatterji, S., Mathers, C., & Murray, C. (2004). Global burden of depressive disorders in the year 2000. British Journal of Psychiatry, 184(5), 386-392. doi:10.1192/bjp.184.5.386