Critically Reviewing the Evidence for SSRIs: A Book Review of Antidepressed

By Kyla Trkulja

Ihave a soft spot for science books. I love reading about scientific history and research in ways other than complicated, jargon-heavy journal articles, so when my Health & Pharmaceuticals class announced that one of our assignments was going to be a book review, I was thrilled that I would be able to dive into a new topic. We got a list of 25 books to choose from, but right away Antidepressed 1 stood out to me. The book was described as one that shares the real evidence surrounding antidepressant medications, mostly selective serotonin reuptake inhibitors (SSRIs) that are taken by millions of people every day around the world. As someone who knows dozens of people currently on SSRIs, I wanted to learn how they really work.

I was not prepared for what I was about to uncover, for one, the “serotonin hypothesis” of depression having no real scientific merit. For years we’ve been hearing that deficits in serotonin are what cause depression symptoms, which is why prescribing medications to increase serotonin in the brain seemed like a valid treatment for depression. This hypothesis originated in the 1960s due to the knowledge of serotonin’s important role in regulating mood, as well as the observation that many individuals with depression have deficits of this neurotransmitter. 2 However, this data is incredibly inconsistent, and there is no credible scientific evidence to support this theory 1 – no scientific experiments or analyses, just observational speculations. In fact, some individuals with depression have too much serotonin in their brains, 3 indicating that if serotonin is playing a role, it’s not one that can be generalized as a treatment for millions of people.

The book described the formulation and acceptance of this hypothetical explanation as being orchestrated by the pharmaceutical industry to gain lifelong customers for their SSRI drugs. While I don’t doubt that Big Pharma played a role in this, I appreciated the other explanations for why this hypothesis spread like wildfire: we want a simple explanation with an easy fix. We as a society want to believe that there’s a generalizable biological process for depression that can be fixed by taking a pill once a day instead of reforming social and societal systems in place to better support people’s well-being. While the latter requires time, money, and structural changes to education, medicine, and social programmes, prescriptions can be written in the span of seconds and don’t require any additional effort on anyone else’s part.

This is a very dangerous way of approaching depression. Instead of meaningful change, millions of people are being prescribed medications that work no better than placebo pills in 85% of people. 1 They create a chemical imbalance in the brain instead of fixing one, as increasing serotonin available for the brain to use shuts down the production of this key neurotransmitter, often making depression worse in the longterm. Even Dr. Candace Pert, the neuroscientist and pharmacologist whose work was key to the development of SSRIs wrote to the New York Times in 1997 saying she was “alarmed by the monster that Johns Hopkins neuroscientist Solomon Synder and I created when we discovered the simple binding assay for the drug receptors 25 years ago. The public is being misinformed about the precision of these SSRIs when the medical profession oversimplifies their action on the brain.” 4

The Hidden Side of SSRIs

“Oversimplified” is a great way to describe the knowledge shared with us about SSRIs. The association between serotonin and depression, the way these drugs act in the brain, and the effects they have biologically and clinically, are all oversimplified and vary so dramatically from person to person that it’s hard to know how someone will react to these medications. For many people, they often cause depression to become worse before it gets better, and the increased risk of suicidality – especially in adolescents – has resulted in the FDA issuing a Black Box warning for SSRIs due to a potentially fatal side effect. 5

Graphic design by Joshua Koentjoro

Antidepressed discusses a wide range of other issues regarding the widespread prescription of SSRIs, including personality changes, a lack of informed consent, dependence and withdrawal symptoms that prevent users from getting off the medication, and severe side effects. 1 “They should be called anti-sex drugs rather than antidepressants,” child psychiatrist Dr. Jon Jureidini explains, as “it’s more reliably predictable that they’re going to get rid of sexual function than it is that they’re going to get rid of depression.” 1

Alternative Treatments

The risks of SSRIs are important to consider, especially since there are other treatment options that have more scientific evidence to support their efficacy without as many side effects, such as therapy, support systems, and even just time. 1 In fact, just family and friend support without help from antidepressants allows full recovery for 22% of people within one month, 67% of people within six months, and 85% of people within one year, making it “extremely difficult for any intervention to demonstrate a superior result to this.” 1 Antidepressed therefore allowed me to unlearn some of the myths and misconceptions surrounding SSRI use and made me question whether they are even needed for most people.

The book did miss the mark on one thing though – Thomson made it seem like antidepressants benefit no one, no one should use them unless they want their lives changed for the worse, and their entire market is a ploy by Big Pharma to bring in money. While I don’t doubt Pharma’s intentions, Thomson’s extreme stance was one-sided and didn’t consider the people SSRIs actually help. These mediations do work in people with severe depression, or those with a family history of it. 6 Some people also need them temporarily to go through a hard time and are able to get off them with no problems, although I recognize that these cases may not be as common as I thought. If anything, these risks and unlikely benefits just emphasize the importance of informed consent so individuals with depression know all of the information about all of their available options, thus allowing them to make the right choice for themselves.

References

1. Thomson B. Antidepressed: A breakthrough examination of epidemic antidepressant harm and dependence. Long Island City, NY: Hatherleigh; 2021.

2. Albert PR, Benkelfat C, Descarries L. The neurobiology of depression—revisiting the serotonin hypothesis. I. Cellular and Molecular Mechanisms. Philosophical Transactions of the Royal Society B: Biological Sciences. 2012;367(1601):2378–81. https://doi. org/10.1098/rstb.2012.0190

3. American Medical Association. American Medical Association Essential Guide to Depression. Pocket; 1998.

4. Pert CB. Letter to the Editor. TIME Magazine. 1997:8

5. Friedman RA. Antidepressants’ black-box warning — 10 years later. New England Journal of Medicine. 2014;371(18):1666–8. doi: 10.1056/NEJMp1408480

6. Naber D, Bullinger M. Should antidepressants be used in minor depression? Dialogues in Clinical Neuroscience. 2018;20(3):223228. https://doi.org/10.31887/dcns.2018.20.3/dnaber