Building on Twarog’s work, the influential biochemist Dilworth Wayne Woolley suggested that serotonin might play an important role in mental illness. In 1974, researchers developed the first serotonin reuptake inhibitor, or SSRI, intended to treat depression. It was called fluoxetine, better known by the brand name Prozac.
Today, millions of Americans are on antidepressants—not just SSRIs, but other serotonin, dopamine, and norepinephrine modulators. These prescriptions are informed by the biological theories of the last century. But the drugs themselves have been evaluated in clinical trials that document their effect on patients in the real world. The results have been mixed: In adults with moderate to severe depression, between 40 and 60 percent improved with antidepressants, compared to 20 to 40 percent who took a placebo. But the response varies widely between individuals; antidepressants don’t appear to improve health-related quality of life overall, and the side effects can be severe. To make the whole thing more dubious, numerous other studies on antidepressant efficacy, many with even worse outcomes, have been systematically suppressed by manufacturers.
The serotonin hypothesis was, at best, a metaphor for the way we understand the complex mental experiences we call “depression.”
It’s important to say that no one should discontinue any medication without consulting with their doctor. If someone feels they are being helped by their antidepressants, they probably are. In the future, alternative mechanisms for why antidepressants work may help researchers to understand why. Unfortunately, the public flame out of the serotonin hypothesis leaves the average depressed person to either muddle through life with an oversimplified, or even falsified, understanding of depression, or to fall into what philosophers call an epistemological gap—“the disparity between what is and what is believed,” writes César Augusto Fontanillo López. In a piece on the problems posed by “neuro-realism,” López argues that the “uncritical validation” of any data derived from brain research has only set us up for failure, as new evidence undermines old explanations. Fortunately, it doesn’t have to be this way.