Current Theory of Common Depression Medications Appears to Be Wrong

Selective serotonin reuptake inhibitor (SSRI) medications have been the mainstay of depression treatment for decades, despite a glaring lack of evidence about how they impact symptoms.

The prevailing theory has been that people with symptoms of depression have a lack of serotonin in their system, and that giving SSRI medications increases the amount of available serotonin in order to improve symptoms. A new research-based model of depression and medication treatment (Andrews et al., 2015) is turning this theory on its head, shedding more light on how inaccurate our current understanding may be.

This new analysis of the research demonstrates that lack of serotonin is actually not the problem in depression. It also shows why giving SSRI medications initially makes symptoms worse, a phenomenon experienced by many people when they start these drugs. The authors state that the reason people don’t experience improvements right away with SSRI medications is because the improvement is actually due to the brain’s attempts to correct the problems the medication causes. The medication creates an imbalance in the brain that actually causes more difficulties, and the brain has to work to correct them. When the brain has to overcompensate for these problems, it balances itself in a way that improves the original symptoms. This also explains why symptom improvement is typically not permanent with SSRI medications, as many people go back to their original symptom baseline somewhere between 6 and 12 months after starting treatment. The authors explain that this is likely due to the brain’s inability to continue compensating for the problems the medications cause, and then symptoms return.

This research is very important because it spotlights major flaws in the current story of how SSRI medications work to resolve depression. Keep in mind that the current theory of SSRIs has never been proven, and there have actually been numerous studies that have brought into question whether the current theory is accurate at all. However, this has not stopped pharmaceutical companies from continuing to promote this theory in an effort to sell SSRI drugs such as Prozac, Paxil, Zoloft, and others. We desperately need more research and analysis, such as this current study, to understand the true mechanisms of action in SSRI medications. Only then can we determine when and how these medications may be beneficial. What this research continues to make clear is that the old story of low serotonin as the cause and target for antidepressant medication is likely inaccurate, and may actually be making people’s conditions worse.


Andrews, P.W., Bharwani, A., Lee, K.R., Fox, M., Thompson Jr., J.A. (2015). Is serotonin and upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neuroscience and Biobehavioral Reviews, 51, 164-188.

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