Why Antidepressants Make You Feel Worse - At First

Fri, 15 Aug 2025 21:49:50 +0000

This problem of antidepressants making you feel worse can happen when we use it for anxiety or depression. With depression, you can feel even more depressed after you take it, but if you keep taking it, that effect wears off. The problem is more pronounced with anxiety. Taking it can make your anxiety spike and feel even worse than before you took the medication.

So why would we even use this medication to treat anxiety? Because the effect is usually transient, meaning it goes away after several days. For some people it may persist and then they have to stop the medicine, but it usually goes away.

Why does it happen?
Researchers from the University of North Carolina identified another pathway in the brain that gets activated with serotonin. Serotonin activates one pathway that helps mood and anxiety, but it also activates another pathway that increases a brain chemical called corticotropin releasing factor also called corticotrophin releasing hormone. This hormone is normally secreted in response to stress or a perceived environmental threat. This activates the body's fight or flight response that is intended to protect you from a threat. But when there is not real threat to respond to, you experience that adrenal response as anxiety.

The researchers found that serotonin can trigger this stress response through the corticotrophin hormone release. This finding has led to new research on a drug that can block this hormone during the initial phase of your treatment until you get fully onboarded with the antidepressant.

To address this problem, we start with a low dose of antidepressant and slowly increase the dose to reach a therapeutic dose (titration). Sometimes we will use When you are fully onboarded with your medication, your doctor would taper you off the benzodiazepine and you would remain only on the antidepressant to treat your anxiety.

References
Catherine A. Marcinkiewcz, Christopher M. Mazzone, Giuseppe D'Agostino, Lindsay R. Halladay, J. Andrew Hardaway, Jeffrey F. DiBerto, Montserrat Navarro, Nathan Burnham, Claudia Cristiano, Cayce E. Dorrier, Gregory J. Tipton, Charu Ramakrishnan, Tamas Kozicz, Karl Deisseroth, Todd E. Thiele, Zoe A. McElligott, Andrew Holmes, Lora K. Heisler, Thomas L. Kash. Serotonin engages an anxiety and fear-promoting circuit in the extended amygdala. Nature, 2016; DOI: 10.1038/nature19318

Li Z, Pfeiffer PN, Hoggatt KJ, et al. Emergent anxiety after antidepressant initiation: a retrospective cohort study of Veterans Affairs Health System patients with depression. Clin Ther. 2011;33(12):1985-1992.e1.

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