Excavating the truth about who benefits from antidepressants

Do antidepressants ease depression and, if so, for whom? In my work as a psychiatrist, I have seen these medications work for people with all levels of depression. But because critics have cast doubt on the worth of antidepressants, I have spent five years combing through the research. One thing I have learned is that the media, consumers, and perhaps even editors of medical journals are more interested in the drugs’ shortcomings than their strengths.

Major depression is a common and debilitating disorder. It affects people’s ability to function at home and in the workplace. It is a progressive condition that can lead to harmful changes in organs ranging from hormone-producing glands to bone and the brain. It is linked to shortened life spans. There’s a spectrum of major depression, but even the least grave (and most common) form, “mild major depression,” is highly debilitating.

When antidepressants were first developed in the 1950s, it was thought they would help only people with the most severe depression. This supposed limitation lined up with the prevailing school of thought, that midrange mood disorders were the domain of psychotherapy. But early research showed marked benefits even in mild major depression. When Prozac and other new antidepressants became available, some doctors thought that their best use would be for chronic, low-level mood disorders, a broad category that overlaps with mild major depression. They work well there, but again, research found benefits across the spectrum.

The past 20 years have seen the “severity hypothesis” — the notion that antidepressants have a limited range — crop up in all sorts of forms. Conflicting studies have shown that medication works best for mild depression, severe depression, and midrange disorders. What made the results unconvincing was that most research focused on the gravest conditions. Few trials were designed to look directly at mild major depression.

One study that appeared in the prestigious Journal of the American Medical Association in 2010 has dominated the recent discussion. It included a broad range of patients (including 103 with mild to moderate major depression) and concluded that only those with severe depression were benefitting from the drugs. USA Today trumpeted the result under the headline “Study: Antidepressant Lift May Be All in Your head.” The New York Times weighed in more soberly with “Popular Drugs May Help Only Severe Depression.” If you’ve heard that antidepressants may be doing nothing for most major depression, that claim likely can be traced back to this one overview.

Shortly afterward, a study by equally eminent researchers arrived at the opposing conclusion: antidepressants work well in nonsevere depression. The research team, out of Columbia University, turned to their own research and found usable data on 825 patients with mild to moderate major depression. For them, antidepressants produced response rates matching those for the severely depressed patients tracked in the JAMA paper.

If the JAMA researchers’ conclusion that antidepressants don’t work in nonsevere major depression was news, then surely the Columbia rebuttal that these drugs are effective up and down the severity spectrum should have been news as well. But the press gave it no play.

I’ve examined the two studies in detail in my new book. In terms of quality, they are similar. Each has special strengths and special weaknesses. Arguably, the Columbia overview’s size should give it an edge. But the JAMA paper has defined the public discussion ever since.

The reason, I think, has to do with its conclusions. Just as psychiatrists did 60 years ago, we — medical journal editors, journalists, and the public — buy into the notion that antidepressants don’t work for less severe depression because we are comfortable with the idea that lower-level depression is the proper domain of psychotherapy, not pharmacotherapy. And in an era when Big Pharma can assume the role of box office villain, debunking drugs is a comfortable stance for journalists.

But the press should not be like a Freudian dream, expressing unacknowledged wishes. News reports should reflect science.

I’m not saying that an antidepressant should be the first-choice treatment for mild forms of major depression. Psychotherapy is effective, has few side effects, and instructs us about ourselves. But the ultimate test of a depression treatment is whether it works. Because persistent major depression — at any level of severity — is harmful, we should want to interrupt its course. We need to know that in a pinch we can turn to antidepressants and find relief.

The lesson I’ve learned from reviewing the medical literature in detail is that antidepressants are reliable in severe and mild depressions alike. To get at that truth, the public should not have to do what I did. That’s a job for science journalists. They must be even handed. If studies that undercut medication for depression are worth reporting, so are those that confirm its benefits.

Peter D. Kramer, MD, is clinical professor emeritus of psychiatry and human behavior at Brown University and author of “Ordinarily Well: The Case for Antidepressants” (2016).