Do Antidepressants Really Work? - The New York Times

While the drugs are widely used, a new study sheds light on how little is known about their long-term benefits.

The more popular antidepressants become, the more questions they raise. The drugs are one of the most widely prescribed types of medications in the United States, with more than one out of eight Americans over 18 having recently taken them, according to a survey from the Centers for Disease Control and Prevention. Yet we know very little about how well antidepressants work over the long term, and especially how they affect overall quality of life, experts say.

Most clinical drug trials have followed people taking antidepressants for only eight to 12 weeks, so it's unclear what happens when patients take them for longer than that, said Gemma Lewis, a research psychologist at University College London who studies the causes, treatment and prevention of depression and anxiety.

"We definitely need longer follow-ups of people who are using or are not using antidepressants, to see what the long-term outcomes are," Dr. Lewis said.

A study published yesterday in the journal PLoS One aimed to close this knowledge gap by comparing, over the course of two years, the changes in quality of life reported by Americans with depression who took antidepressants versus the changes reported by those with the same diagnosis who did not take the medications.

The study included people who took all types of antidepressants, including selective serotonin reuptake inhibitors like Prozac, serotonin-norepinephrine reuptake inhibitors like Effexor and older antidepressants such as clomipramine and phenelzine. Researchers assessed both mental and physical quality of life with a survey that asked questions about subjects' physical health, energy levels, mood, pain and ability to perform daily activities, among other things.

The paper found no significant differences in the changes in quality of life reported by the two groups, which suggests that antidepressant drugs may not improve long-term quality of life. Both groups reported slight increases in the mental aspects of quality of life over time, and slight drops in their physical quality of life. But the study is imperfect, researchers say, and it certainly doesn't settle the debate over the effectiveness of these drugs.

One problem is that the study, which was based on data from more than 17 million Americans who participated in the United States' Medical Expenditures Panel Survey, compared groups of people who may have been experiencing different levels of depression.

It's likely that individuals who are prescribed antidepressants are more depressed than individuals who aren't prescribed drugs, said Dr. F. Perry Wilson, a physician and clinical epidemiologist at the Yale School of Medicine, who was not involved in the study. So it's hard to make conclusions based on the findings, because "people with more severe depression might be less likely to improve their mental quality-of-life scores over time," he said, for reasons that have nothing to do with the antidepressants they take.

Another issue with the study is that the people who were taking antidepressants may have been taking them for a while — so some quality-of-life improvements may have occurred before the study began following them, Dr. Lewis said. This kind of study "works best when you can measure quality of life before they go on the antidepressant," she explained, and when researchers can watch how the subjects' lives change both immediately after starting the drug and later on.

Omar Almohammed, a pharmacologist at King Saud University in Saudi Arabia and a co-author of the study, countered that it's still reasonable, however, to expect continued increases in quality of life even long after an antidepressant is started.

"If we don't expect improvement from the continuous use of these medications, then the correct decision might be to stop the continuous use of these medications," he said, or to add another kind of treatment, like cognitive behavioral therapy, which aims to change people's thought patterns.

Yet pills are often easier and cheaper: It can be hard for people to access therapy because there aren't enough providers, and mental health treatments often aren't fully covered by insurance.

"There's just so much that's not known," said Robert DeRubeis, a psychologist at the University of Pennsylvania who studies the causes and treatments of mood disorders. "It's not at all clear that even in the short term, pharmacological approaches, on average, are more effective than psychological ones," he added.

Clinical trials suggest that although antidepressants do improve depression symptoms over the first few months, their benefits are modest and are much less pronounced among people with mild depression compared with those with severe depression. (This is worrying considering that, according to one study, 73 percent of Americans prescribed antidepressants don't even have a diagnosis of depression.) And experts are divided over whether these small benefits make a noticeable difference to people's moods or overall functioning.

Some doctors, for instance, have argued that the improvements people experience while taking antidepressants are not much larger than what they might experience taking sugar pills.

"They have marginal effects in the short term compared to placebo," said Mark Horowitz, a research psychiatrist at University College London. That's not to say that many people don't feel better taking the drugs — it's just that much of their improvement could stem from the placebo effect, rather than the medication itself.

Other researchers, including Dr. Lewis, argue that the benefits from antidepressants are significant enough to make a positive difference in people's lives, at least for a few months. "There's strong evidence that antidepressants can be effective for people experiencing a wide range of depressive symptoms," she said. But, she added, the drugs "do not work for everybody."

And again, it's unclear how helpful these drugs are when taken for more than a few months — which raises concerns for the many adults who have been taking the drugs for a long time. According to a Times analysis, 15.5 million Americans have been taking antidepressants for at least five years. Dr. Horowitz argued that the drugs will probably have increasingly smaller benefits the longer people take them, in part because patients can build up a tolerance to the medications, he said.

Research suggests that people can also experience unpleasant withdrawal symptoms, known as antidepressant discontinuation syndrome, when they stop taking antidepressants, sometimes for weeks or months, and that the drugs can pose other risks, perhaps increasing the likelihood of strokes, heart attacks, falls and even death. And of course, like any medication, antidepressants can cause side effects, including nausea, agitation, weight gain, lower sex drive and indigestion.

If you are on antidepressants, Dr. Horowitz suggested checking with your doctor to see if you should continue taking them and, if so, to ensure you are still taking an appropriate dosage. The American Psychiatric Association recommends that patients who have experienced just one episode of depression take antidepressants for between four and nine months. But "people should not stop cold turkey. They should do so slowly," Dr. Horowitz said, and ideally under the supervision of a doctor.

Many people can get real, life-changing benefits from these drugs and may benefit from taking them over the long term. But we all deserve to know more about how well they work, and the risks they may pose, when taken for years and even decades.

If one thing is clear, it's that we need more careful research on how best to help the more than 16 million Americans who currently suffer from depression — and whose symptoms may well have worsened during the pandemic.

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