July 8, 2024

Why Traditional Antidepressants Aren’t Cutting It

Text saying "why traditional antidepressants aren't cutting it" with a pill bottle spilling pills in the shape of a question mark

As Americans increasingly recognize the importance of mental wellness, many patients seeking help find that their depression lingers even after undergoing treatment. While some find relief with conventional antidepressants like Zoloft and Prozac, new research suggests that treatment success rates with these medications may be significantly lower than previously thought.

The Antidepressant Problem

SSRI and SNRI antidepressants are often the first line of treatment for individuals suffering from depression, but the prevalence of these medications may not accurately reflect their success rates. Recently, researchers have suggested that traditional antidepressants are only effective for a small portion of the population—meaning that for many, symptoms of depression may not improve even after taking medication.

How have antidepressants become so popular if they only work for a small number of patients? One explanation is that clinical trials for antidepressants tend to focus on individuals with severe depression, leaving out other forms of depression and patients with coinciding disorders like anxiety. Since most people suffering from depression have mild or moderate cases, antidepressants can have promising results in studies but still not work for the majority of people.

In addition to not representing the average person seeking treatment, research on antidepressants also has a history of being biased towards positive findings. While the vast majority of published studies show positive results, recent research has revealed that less optimistic studies often are simply not published. While analyzing 74 FDA studies on antidepressants, researchers with the New England Journal of Medicine discovered that almost half of the trials had negative results. This is surprising news to both the scientific world and the public: this information was only discovered when researchers like Dr. Erick Turner began investigating the reporting methods behind clinical trials.

If success reported in clinical trials does not accurately reflect the real-life success of antidepressants, “treatment-resistant” depression could be even more common than previously thought. This may sound discouraging, but understanding this is actually an important part of developing effective treatments. As researchers become aware of problems in how data is collected and reported, we gain important knowledge for advancing mental health treatment and improving future studies. And as better ways of conducting research are implemented, new, more sophisticated treatments can be developed.

Moving Forward

As medical science advances, so too do treatment options. While finding the right medication is a unique process for every patient, modern understandings of depression suggest that new treatments may provide a more reliable road to promising breakthroughs.

Studies show that ketamine works differently in the body compared to conventional antidepressants, which is part of what makes it so effective.  Yale’s Dr. John Krystal explains: “With most medications like valium, the anti-anxiety effect you get only lasts when it is in your system … When you take ketamine, it triggers reactions in your cortex that enable brain connections to regrow. It’s the reaction to ketamine, not the presence of ketamine in the body that constitutes its effects.” With typical antidepressants, the medication must be taken daily to keep it working in the body. On the other hand, ketamine treatment works by physically reshaping the depressed brain. As a result, research so far indicates that ketamine is more effective and requires much less frequent treatment compared to SSRIs and SNRIs.

If you’ve dealt with mental health struggles even after attempting treatment, you aren’t alone. Psychiatry has come a long way since antidepressants first became available to the public nearly 70 years ago, but new advances are still constantly being made. As twenty-first century technology makes scientific progress more reliable than ever, the way we think about mental health is fundamentally changing—and treatments like ketamine may offer a new path forward.

Learn more about how ketamine infusions could be the key to treating depression here


Carroll, A. E. (2018). Do antidepressants work? The New York Times. Retrieved from https://www.nytimes.com/2018/03/12/upshot/do-antidepressants-work.html

Chen, J. (2022). How ketamine drug helps with depression. Yale Medicine. Retrieved from https://www.yalemedicine.org/news/ketamine-depression

Kirsch, I., Huedo-Medina, T. B., Pigott, H. E., & Johnson, B. T. (2018). Do outcomes of clinical trials resemble those “real world” patients? A reanalysis of the STAR*D antidepressant data set. Psychology of Consciousness: Theory, Research, and Practice. Advance online publication. https://dx.doi.org/10.1037/cns0000164

López-Muñoz, F., & Alamo, C. (2009). Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Current pharmaceutical design, 15(14), 1563–1586. https://doi.org/10.2174/138161209788168001

Turner, E. H., Matthews, A. M., Linardatos, E., Tell, R. A., & Rosenthal, R. (2008). Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine, 358(3), 252–260. https://doi.org/10.1056/nejmsa065779

Turner, E. H., Cipriani, A., Furukawa, T. A., Salanti, G., & de Vries, Y. A. (2022). Selective publication of antidepressant trials and its influence on apparent efficacy: Updated comparisons and meta-analyses of newer versus older trials. PLOS Medicine, 19(1). https://doi.org/10.1371/journal.pmed.1003886

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