The Efficacy of SSRIs: Are We Truly Treating Depression?

Selective Serotonin Reuptake Inhibitors (SSRIs) are interesting. Despite their evident popularity, the prevalence of depressive disorders has not declined since their injection into modern society. The prevalence of major depression is estimated at 6-10% worldwide. In the United States, about 8.3% of adults experienced at least one major depressive episode in 2021.

Looking at the early 2000s, depression prevalence rates were estimated remarkably similarly to today; between 6-8%. Similarly, in the 1990s, the prevalence of depression was estimated at 5-7%. Much has changed in the diagnostic landscape since the early 1990s but the estimated prevalence of depression appears to have remained constant.

When this is juxtaposed with the fact that SSRIs are being prescribed in larger quantities and to more people than ever before, a conundrum becomes evident: If SSRIs effectively treat depression, why do the prevalence rates not drop?

Surely we as a society would mandate that the drugs we prescribe actually have their advertised effect? In the case of SSRIs, we’d expect depression prevalence to decline. But it just doesn’t. Why?

I want to preface this by noting that I don’t have a horse in this race. If SSRIs work for you, then more power to you! Pharmaceutical drugs are complex and I realize that there is not a one-size-fits-all solution here. With that out of the way let’s look at some interesting characteristics of SSRIs.

Side Effects of SSRIs

Common side effects of SSRIs include:

• • Changes in one’s appetite

• • Trouble sleeping

• • Restlessness/irritability

• • Tiredness

There are of course many more side effects than these four, but precisely these four caught my attention. Why? Because they are four of the nine symptoms needed to qualify for a diagnosis of major depression.

If a person experiences the abovementioned four side effects (i.e., symptoms of depression) and also either a depressed mood or anhedonia, then a depression diagnosis can justifiably be made.

But isn’t that strange? The drug advertised to combat depression can actually cause the very disorder it is supposed to alleviate (and commonly enough to be listed as common side effects). I find that interesting, to say the least.

I do realize that all pharmaceutical products have some side effects. These particular ones are just quite ironic.

But Who Cares: If They Work, They Work, Right?

I’d argue that these SSRIs don’t actually work. At least not in the way they are advertised to work. SSRIs can give the appearance of working. Still, it is not obvious that their effects cannot be better explained using two basic psychological constructs: The Placebo effect and the Hawthorne effect.

The placebo effect refers to the actual neurological impact of a non-active substance on the brain that arises due to expectancy. In other words, if you believe that the big red pill will help you, then it probably will. This effect has been replicated time and time again. The stronger the belief, the greater the effect.

The Hawthorne effect refers to a phenomenon wherein behavior changes as a result of behavior being observed. Put differently, observing a process changes the process. In the context of SSRIs, observing one’s mood changes one’s mood. This has been known to be true for decades and predicted by the behavioral models of depression. For example, this is predicted by Ferster’s behavioral model of depression as well as Lewinsohn’s behavioral activation therapy for depression. Both Ferster and Lewinsohn were pioneers of the behavioral treatment tradition in the 1970s.

Taken together, SSRIs work (maybe) but definitely not through their initial hypothesized mechanism of action. Recent findings that have called the “serotonin hypothesis” into question further corroborate this notion. In brief, the serotonin hypothesis suggested a chemical imbalance to explain depression, but recent research has more or less debunked that notion.

Summary

SSRIs are more popular than ever but depression rates do not reflect this. If anything, the prevalence of depression is higher today than 20 years ago. SSRIs have interesting side effects, some of which line up perfectly with the diagnostic criteria for depression. Finally, the mechanism of action for SSRIs is probably not correctly advertised. It seems more likely that our belief in these drugs and the behavior and mood self-monitoring they induce explain why they work for some people.

Obviously, SSRIs (and pharmaceuticals in general) are complex. I have selectively described some of the things I find interesting about them and I don’t intend this post to be comprehensive on the topic.

I do however firmly believe that SSRIs are prescribed too abundantly, for too long without medical supervision, and too often without proper rationale or psychological testing.

Leave a comment below or contact me if you want to open a discussion on this topic!