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When children are asked, antidepressants are no more effective than placebo, study finds

The Metro State and University of Wisconsin researchers’ study suggests that the overall benefits of antidepressants among youths have been overstated.

When children are asked, antidepressants are no more effective than placebo
Although the psychiatrists and other clinicians involved in the studies were reporting that the antidepressants were leading to improvements in symptoms, the children themselves were often saying something else.

For the past 15 years or so, Glen Spielmans, an associate professor of psychology at Metropolitan State University in St. Paul, has been closely following the clinical-trial literature on antidepressant drugs and their use as a treatment for depressed children and adolescents.

As he read each new study, he noticed that the results that got the attention were those reported by the children’s psychiatrists — not by the children and teens themselves. Some of the studies had self-reports from the young people about how their symptoms fared while they were being treated with an antidepressant (or a placebo), but those reports were almost always downplayed or ignored.

“It didn’t seem to get discussed very often,” said Spielmans in an interview with MinnPost Tuesday, “but I informally noted that there didn’t seem to be any benefit for the drugs over placebo in terms of [the children’s] self-reports of depression and things like quality of life.”

In other words, although the children’s psychiatrists and other clinicians involved in the studies were reporting that the antidepressants were leading to improvements in symptoms, the children themselves were often saying something else.

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“An informal observation doesn’t do the world much good,” added Spielmans, “so I decided to delve into it more systematically.”

‘No meaningful benefit’

This month he published that systematic analysis — what is known as a meta-analysis — in the journal Psychotherapy and Psychosomatics. Spielmans found what he had suspected from his earlier reading of the literature: there was a non-significant difference between so-called second-generation antidepressants (drugs such as Prozac, Paxil, Zoloft and Wellbutrin) and placebo in terms of the symptoms reported by the depressed children themselves and their overall well-being.

“We found no evidence that antidepressants offer any sort of clinically meaningful benefit for youth on self-report measures of depression, quality of life, global mental health, or parent reports of autonomy,” write Spielmans and his co-author, Katherine Gerwig, a graduate student at the University of Wisconsin in Madison, in their paper. “The debate around antidepressant efficacy among youth has nearly entirely involved differing opinions of how to interpret small but statistically significant effect sizes on clinician-rated measures of depression severity.”

This finding was true even for fluroxetine (Prozac), which has been cited by some researchers as the most effective antidepressant for children and teens.

“Even in the studies where fluroxetine had a pretty good effect on clinician-rated measures, that didn’t really carry over in terms of things like self-reports and mental health in general,” said Spielmans.

Based on tradition, not evidence

Spielmans acknowledges that his meta-analysis was limited by a small number of clinical trials (eight). But the number was small because few placebo-controlled studies involving antidepressants and children have either asked the children about their symptoms or measured outcomes that reflect the young people’s overall well-being.

Glen Spielmans
Glen Spielmans

“Psychiatry research has traditionally valued clinician-rated measures over self-reports,” he said. “But there really isn’t a lot of great evidence [to support that approach]. It’s based more on tradition than on great evidence that that’s the best way to do things.

“I think it’s valuable to get clinician input,” Spielmans added, “but in the end, it would seem like the opinion of the child or adolescent — or in adult studies, the adult patients — should be pretty valuable.”

Most depressed people — including children and teens — are able to provide accurate ratings of their own mental state, he stressed.

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“After all, we’re talking about depression here, not psychosis,” he said.

Not without risks

Although it’s not clear exactly how outcome measures should be weighed in placebo-controlled clinical trials involving antidepressants and children, the results of this new meta-analysis suggest, as Spielmans and Gerwig write, “that the overall benefits of antidepressants in youth have been overstated and that their overall benefit over placebo may be vanishingly small.”

And these drugs are not without their risks. Studies have reported that children, teens, and young adults who take antidepressants for depression are at greater risk of thinking about and attempting suicide than their peers who do not take these drugs to treat their depression. They are also more likely to become agitated and hostile.

The use of antidepressants in the United States has skyrocketed among all age groups during the past two decades. Currently, 3.2 percent of American adolescents, aged 12 to 19, are taking the drugs — the same percentage who take prescription drugs for attention deficit hyperactivity disorder (ADHD).

“As somebody who has looked at the evidence base pretty closely and who has compared that pretty unimpressive evidence base to what’s happening in terms of the rates of prescribing, it’s pretty hard to square those two things,” said Spielmans.

You’ll find an abstract of Spielmans’ study on the Psychotherapy and Psychosomatics website. Unfortunately, the study itself is behind a paywall.

(Full disclosure: I teach writing and editing courses at Metro State.)