In the 1980s, people generally thought of depression as a meaningful response to a crisis. A job loss. A divorce. Struggling to fit in at school. The angst of realizing life didn’t turn out as you’d hoped. (Indeed, some evidence suggests that up to 80% of episodes of depression are responses to negative life events.)
During the 1990s, partly owing to psychiatrists, advocacy groups, and the pharmaceutical industry, our cultural beliefs about depression shifted. We began seeing depression as a chemical imbalance in the brain, a disease like any other. As President Biden recently put the point, “I don’t know the difference between breaking your arm and having a mental breakdown. It’s health.”
For a time, the most popular theory was that depression stemmed from an abnormality with the neurotransmitter serotonin. After all, the theory went, drugs like Prozac boost brain serotonin. Doesn’t that mean depression comes from a serotonin deficiency?
Unfortunately, the serotonin theory failed to stand the test of time. There’s little evidence that depression stems from serotonin abnormalities. Just as alcohol can shape our mood without “reversing an alcohol deficiency,” SSRIs can shape our mood without reversing a serotonin deficiency.
Do antidepressants “work”?
Still, doctors often say, the drugs work, even if we don’t know exactly how. Isn’t that a good enough reason to take them?
In her new book, Chemically Imbalanced: The Making and Unmaking of the Serotonin Myth, University College London psychiatrist Joanna Moncrieff critically examines this popular idea.
What about the testimony of patients? I can speak from my own experience here. In the early 1990s, as a teenager, I experienced severe depression. I was hospitalized and put on Prozac. After a few months, the depression lifted, and I stopped taking the Prozac. Isn’t that proof that Prozac worked for me?
The problem, of course, is that there were many reasons my depression may have lifted. When I finally sought help for my depression, I was given an outpouring of support from family, doctors, and other teens facing similar problems. I realized I wasn’t alone. I felt hopeful about the future. It’s possible that the Prozac was no more powerful than a placebo.
But aren’t there scientific studies that prove that SSRIs are superior to placebos? It’s true that there have been hundreds of double-blind trials in which depressed patients have either been given SSRIs or a placebo. Some of the studies show that SSRIs strictly outperform placebos. But Moncrieff argues that the studies don’t stand up to scrutiny for many reasons.
The “amplified placebo” effect
One problem is that the actual difference between SSRIs and placebo is quite small. A scale that’s often used to measure depression is the Hamilton Depression Rating Scale. It’s a 52-point scale. Recent meta-analyses (such as here and here) suggest that the difference between SSRIs and placebo amounts to a mere 2 points on that scale.
Still, a small difference is better than nothing, particularly for severe depression. But there’s another possible cause of that difference: the “amplified placebo effect.”
Here’s the problem. When a depressed patient enters a double-blind study of this nature, they usually want to know which group they are in. Am I getting a placebo or the real thing?
SSRIs have various psychoactive effects, like dizziness and sleep problems. Effects such as these can tip me off that I’m getting the SSRI. They “unblind” the study. That knowledge can give me the extra hope and optimism that boosts my mood.
The problem of amplified placebo effects has been known for decades, but it’s rarely considered in the literature. Yet Moncrieff points to evidence that it’s quite real. For example, in one study she discusses, most of the people in the Prozac group correctly guessed they were on Prozac; only about half of the people in the placebo group thought they were on Prozac.
Moncrieff discusses other problems too, such as the well-knwon problem of negative results. In her book, Moncrieff documents the frequent failure of drug companies to publish studies of SSRI trials yielding negative results, thus distorting public and professional opinion.
Moncrieff’s verdict? We have little reason to think that SSRIs work better than placebos.
What’s wrong with placebos?
Of course, a placebo effect can be a meaningful benefit for desperately suffering people. What’s so bad about them?
The problem is that drugs like Prozac can come with negative side effects, some of which are poorly understood. When we take those effects into account, it’s not clear that the benefits outweigh the harms.
For example more than half of SSRI users experience lowered sex drive or related sexual problems. A subset of these patients report that the lowered sex drive continues after stopping the pills. This phenomenon is known as “post-SSRI sexual dysfunction” (PSSD).
It is difficult to estimate the prevalence of PSSD, partly because patients often feel that doctors dismiss their experiences.
After SSRIs
If drugs like Prozac don’t work, what are the alternatives?
An emerging alternative, one I’ve written about here and here, comes from the school of thought known as evolutionary psychiatry. The idea is that depression, far from being a brain disorder, is actually your brain’s designed signal. It’s there to let you know that something in your life isn’t going well and needs more attention.
The problem could be a life goal, a career plan, or a relationship. But something in your life needs more attention, and depression is trying to tell you that—just as pain is your brain’s attempt to tell you that something in your body needs to be looked at.
If the evolutionary view is right, then, for many, the first step in treating depression would be to find a therapist who is willing to see it as a purposeful response to a life problem and to provide guidance for moving forward.
Intriguingly, there’s preliminary evidence that seeing depression as a functional signal is actually more likely to give patients hope and optimism about recovery than the traditional brain disorder model.
That alone makes it worth exploring as a first step toward healing.