Antidepressants, particularly those of the SSRI class, are the first-line treatment for Major Depressive Disorder and used in a range of other conditions. The first synthesized antidepressant was discovered by chance based on a medication prescribed for tuberculosis noted to cause “a subtle general stimulation” in the United States. French doctors were noting the same thing, so they started investigating and the first FDA approved “psych energizer”, Imipramine, was patented in 1951.

The scientific community and pharmaceutical industry were curious about how these medications helped depressed patients and started researching, leading to the conclusion that depression was caused by a “chemical imbalance”, or, basically, that depressed patients had “low serotonin”. Fluoxetine was designed as the first medication to affect almost exclusively the neurotransmitter believed to be the culprit of depression: serotonin. Prozac (Fluoxetine) was literally labeled a “Miracle Drug” when it was discovered, the solution to one of the world’s most terrible problems. The bestselling “Listening to Prozac”, written in 1993, discussed if Prozac could even improve healthy people’s lives.

Currently, antidepressants are prescribed to one in nine Americans. Some very relevant groups in the medical and scientific community are worried that, not only they may be inefficient, but that their risks may outweigh their benefits in most of the cases. Although many (or most) psychiatrists still believe in the serotonin theory, the scientific community is almost sure that it was a mistake, as showed by numerous more recent studies [1]. Turns out that the cause of depression is “not that simple”.

The controversy around the efficacy of antidepressants probably arose from Dr. Irving Kirsch of Harvard Medical School findings in 2008. He used the Freedom of Information Act to access trials submitted by pharmaceutical companies on several antidepressants. Not only the ones that showed that they work, but the ones that showed that they didn’t work too, which were, unfortunately, most of them. More and more recent studies are finding the same thing [2] [3], while others even address that their potential harm is higher than we previously thought too [4]. Apparently, everything points to the conclusion that antidepressants are no different from placebo for most people, although they did find an unexceptional but significant improvement in those with more severe depression.

Depression is often a debilitating condition, and, besides the controversy, antidepressants are still one of the tools we possess to fight it. While the role they are currently playing may not be the ideal, and there are valid, scientifically approved alternatives, their importance is not to be discarded. We hope that, in the nearest future, we understand more about our brains and find more proper ways to take care of it.




[1] Andrews, P. W., Bharwani, A., Lee, L. R., Fox, M., & Thomson Jr, J. A. (2015). Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neuroscience & Biobehavioral Reviews, 51: 164 DOI: 10.1016/j.neubiorev.2015.01.018

[2] Fournier, J.C., DeRubeis, R.J., Hollon, S.D., Dimidjian, S., Amsterdam, J.D., Shelton, R.C., et al.  (2010).  Antidepressant drug effects and depression severity: a patient-level meta-analysis.  JAMA, 303, 47-53.

[3] Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R (January 2008). “Selective publication of antidepressant trials and its influence on apparent efficacy”. The New England Journal of Medicine. 358 (3): 252–60. doi:10.1056/NEJMsa065779. PMID 18199864

[4] Jakobsen, Janus Christian; Katakam, Kiran Kumar; Schou, Anne; Hellmuth, Signe Gade; Stallknecht, Sandra Elkjær; Leth-Møller, Katja; Iversen, Maria; Banke, Marianne Bjørnø; Petersen, Iggiannguaq Juhl (2017-02-08). “Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis”. BMC Psychiatry. 17. doi:10.1186/s12888-016-1173-2. ISSN 1471-244X. PMC 5299662 Freely accessible. PMID 28178949.