This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.
Every year in the US, more than 40 million adults receive a prescription for an antidepressant. That's 15% of the adult population. In the pandemic era, that number is even higher.
Despite a small, and vocal, group of physicians who argue that antidepressants are not effective, the empirical data are fairly consistent: The drugs do have a significant, albeit modest, effect on a multitude of depression outcomes. Randomized trials show that drugs like selective serotonin reuptake inhibitors (SSRIs) reduce scores on depression inventories and increase the remission rate above placebo by about 30%.
Today, we'll examine whether that translates into improved quality of life.
Much-publicized concerns about the risk for suicide in those taking SSRIs have been supported in some populations of adolescents, but not in adults. Indeed, people tend to initiate antidepressants when they are in their worst mental state, which may explain increased suicide risk in the same time period as well as the general improvement in symptoms even among those exposed to placebo — a regression to the mean effect. A recent Swedish study of more than 500,000 individuals, for example, found the highest risk for suicidal behavior occurred in the 30 days before initiation of an SSRI and was reduced thereafter.
I appreciate that the data are a bit murky here. Overall, these seem like decent, if not game-changing, drugs, and they have a particular role in the acute treatment of major depression. But this week, a new study appearing in PLOS One asks an important question: Do antidepressants actually improve quality of life? That's not quite the same thing as asking whether they treat depression.
The study leverages the Medical Expenditure Panel Survey — this is a nationally representative longitudinal survey that tracks a variety of health conditions and, importantly, quality of life as measured by the standard Short Form (SF)-12 instrument. The output of the SF-12 gives a score for both physical and mental quality of life.
The authors looked at a 10-year period from 2005 to 2016. Each year, around 20 million individuals were diagnosed with depression and about 60% were treated with antidepressants. We don't know which antidepressants, which is a limitation of this study — but given prescribing trends, we can be pretty sure the majority were SSRIs.
There were some differences between people who got treated and those who did not. Treated individuals were more likely to be female, white, married, and of higher socioeconomic status. Importantly, those who were treated also had lower quality-of-life scores at baseline.
And, as multiple other studies have shown, mental health improved over time, regardless of treatment status. That is the way of regression to the mean. Depression is a waxing and waning disease; one tends to get the diagnosis when it is waxing, meaning that the natural history (for most, but certainly not all) is improvement.
The big question, of course, is whether quality-of-life scores improved more in the group who received antidepressants. And the answer is, not really. Even after adjustment for all those baseline differences, mental quality of life scores go up by about 1 point in both groups, and physical quality of life declines a bit.
So what's going on here?
There will be some who will use these data to argue that antidepressants are not effective in the long term — that any use should be time-limited, and ideally coupled with psychotherapy. Of course, a recent randomized trial appearing in The New England Journal of Medicine found a significantly increased risk for relapse when SSRIs were stopped compared with continued among individuals doing well on treatment. So we might need to be careful here.
There are other explanations for the observed data, though. Most important is residual confounding. We know there are a variety of differences between those being treated for depression and those not being treated; some of these were measured and adjusted for, and some were not. An important confounder not measured? Depression severity.
If the treated group had more severe depression, regardless of quality of life, we might not expect them to improve as dramatically as the untreated group. In fact, we might be happy if quality of life stood still if the counterfactual was further decline.
The other consideration is that we may be using antidepressants too broadly. It is likely that some individuals benefit significantly from the treatment and others don't. By prescribing broadly, we dilute the observed effect sizes at the population level. Not every drug needs to be a blockbuster.
And of course, the last thing to remember is that quality of life is a difficult thing to measure — and, as venerated as the SF-12 is, it is still a rather blunt tool to probe the well-being of an individual or a population. What is going on in our heads and in our hearts is quite a bit more profound than what can be captured with 12 questions and a Likert scale.
For Medscape, I'm Perry Wilson.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.
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Cite this: Antidepressants Don't Increase Quality of Life? - Medscape - Apr 20, 2022.
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