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.
References
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
On Psychology and Neuroscience 
Hi Julia, Your post gets at the key issue in the clinical psychology field of treatment resistant mental health disorders such as depression. Why do you think there have been few “breakthroughs” in this realm since Prozac was introduced in 1987 if there is still such a large number of individuals who don’t respond to the current available treatments? Moreover, this is even more striking in the midst of the few studies that have recently demonstrated the effectiveness of ketamine and psychedelics in rodent models of depression. You discussed the influence that the “war on drugs” and counterculture have had on the acceptance of these substances as treatments for depression; how have similar or additional factors (such as economic influences, the pharmaceutical industry, the Harvard Psilocybin Project, etc.) influenced the lack of research trials involving these drugs in the context of depression? -Katia
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Hi Julia, this article was really insightful into why our country has handled the treatment of depression in the way that it does. This reminded me of some articles I’ve read about the positive effects of shrooms when used to treat depression. Certainly, those findings, as well as the ones you highlighted can help lead us to a much more effective treatment for depression. My hope is that our generation as well as those who follow us, are much more receptive to these solutions. Given your insight on how the war on drugs has affected the stigma around psychedelics, I think we would have a great opportunity to make these changes once the current generation of office holders ages out.
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I thought this post was really interesting because it not only highlights various treatment methods for depression but also is digging into how we can understand the biological basis of depression. I am very curious as to why depression levels rose so drastically between 2000 and 2018. Is it simply because depression is being more easily recognized today than it was a few decades ago? If not, did your research show anything that signified why people, on average, are becoming more depressed over time? Overall, I thought this was an excellent blog post and was really informative, especially when discussing the role of psychedelics in treating depression – something I didn’t realize was being used as a potential cure.
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I loved reading this article! It was very interesting. I was surprised to learn that ketamine is used to treat depression! Prior to reading this article, I had only heard of ketamine being used in an abusive way. I learned that LSD and psilocybin produce longer-lasting effects on treating depression symptoms than ketamine. This was also surprising to learn. I think it is really interesting to start to think about and discover the biological basis of not only depression but other psychological disorders. I am curious to see information on the biological basis of depression grow as new treatment options are explored and implemented in the future.
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Hi!
My mom works for Gilead, a pharmaceutical company, so I’ve heard a good amount about the awkward supply and demand balance of medicine and the need for it. Whenever a breakthrough occurs in medicine, it will either lead to more or less investment into the area. If the breakthrough demonstrates a market for research in the area, suppliers will flood in. If the breakthrough ends a race for a certain drug, the race will stop, funding, will dry up, and focuses will shift to the new “first of its kind” drug. The biggest problem with this dynamic is when the solution isn’t actually the end of the road; depression wasn’t eradicated, but a lot of companies pursuing treatments for depression saw the options in the market as good enough and shifted their focus. This isn’t to say everyone stopped looking for treatment options, just Prozac (if I’m remembering correctly) was enough to stop a lot of companies from tackling mental health with the same determination as they had in the past.
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Hey Julia! This is a really fascinating topic and I’m so glad you studied it, especially in tandem with the hot debate over the decriminalization of drugs such as marijuana. The idea of taking ketamine and psychedelic drugs is highly stigmatized and stereotyped in popular culture and media, but through research like this, we can see that these drugs hold serious potential in the pharmaceutical field, acting on novel brain systems while still producing antidepressant effects. If these drugs were destigmatized and utilized alongside or in replacement for antidepressant drugs, we could break real ground in our understanding of mental illnesses. Thanks for making an important and informed addition to this pertinent psychological discussion!
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It was very impactful to learn that the World Health Organization believes that depression will be the second on the global disease list. I did not realize before this piece that depression was this rapidly spreading, and caused so much harm to so many individuals. It also makes you wonder, how many people are going about the world undiagnosed that would benefit from help. It was also very interesting to learn that since the debut of Prozac, there hasn’t been another drug that has stepped up to the plate in terms of impactfulness. Additionally, it was intriguing to see that 30%-40% of patients being treated do not get any relief from their depression symptoms. Overall, I learned that psychedelics could become to play a key role in helping treat depression.
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This was an interesting perspective on depression treatment that I was unfamiliar with before this post. I did not know that psychedelics were ever considered in treating mental health disorders, and this could be due to the stigma around them that was created in the 1960’s (as mentioned in the post). A lot of solid references were provided which I appreciate. I look forward to hearing future news about this development of LSD and psilocybin as depression treatment.
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I really appreciate your perspective on the “war on drugs”. One thing I learned from your post is that LSD can have anti-depressant effects. I was really surprised to hear the effects of psilocybin can last for five weeks in alleviating depression symptoms. I would love to hear more about your thoughts on what the best course of treatment for depression would be, and why.
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Hi Julia,
I appreciated that you mentioned how 30-40 percent of patients with depression do not respond to treatment. I took a seminar on clinical interventions this semester where we talked about how most people diagnosed with a psychological disorder, including Major Depressive Disorder, will only receive pharmacological treatment, even though psychotherapy and combination treatments are often more effective and preferred by clients. Do you think using ketamine and psychedelics in combination with psychotherapy would be even more beneficial?
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It is so interesting how stigma can prevent and/or slow down major breakthroughs in the field of clinical psychology. I wonder… how exactly, on a biological level, do psychedelics relieve depression? I had heard this was true before, but I always just assumed it was because they temporarily distracted people from depressing thoughts. Yet, if the effects can last for up to 5 days, then psychedelics must be relieving depression through some mechanism other than distraction. Also, do you think social destigmatization of psychedelics is necessary for practical implementation in the medical world, or do psychedelics need to first be destigmatized in the hospital before they are destigmatized in the social world?
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