Do antidepressants make aggressive behavior more likely in kids? A new analysis of old clinical trial data says maybe — but it also highlights serious problems in how drug companies collect and report side effects.
The paper, a retrospective look at more than 18,000 participants in clinical trials for several different antidepressants, was published in the journal BMJ on Wednesday. It concluded that children who took antidepressants in clinical trials were twice as likely to show aggressive behavior as those who took placebos — a rate much higher than previously reported.
“I knew going into the project that publication bias is a problem, but I was quite surprised by how much," Tarang Sharma, a graduate student at the Nordic Cochrane Center in Denmark and first author of the study, told BuzzFeed News.
Antidepressant side effects have been under debate for a long time. Several drugs have been linked to higher rates of suicide and suicidal thoughts in young people, leading to a black box warning on pill bottles about the risk. But depressed young people are highly suggestible, especially when it comes to suicide, and some researchers believe the label itself may have increased rates of suicide attempts.
To look more closely at the range of side effects, Sharma’s team asked European and U.K. drug regulators for the raw clinical trial data on five common antidepressants — Cymbalta, Prozac, Paxil, Zoloft, and Effexor — as well as reports of trial results on Cymbalta and Prozac from pharmaceutical giant Eli Lilly’s website.
In total, the researchers received data from 70 trials involving more than 18,000 people, including detailed patient information from about half of the trials.
They then tried to compare the side effects in each trial by searching the nearly 65,000 pages of documents for terms that could indicate suicidality, aggressive behavior, or akathisia, a deeply unpleasant feeling of restlessness.
The researchers found more cases of aggressive behavior in children than had previously been made public, as well as four deaths that were reported incorrectly.
Other researchers agree that pinning down side effects is important, so patients can make informed decisions. But the trouble with the new study is that it didn’t compare apples to apples, noted Bryan King, director of child and adolescent psychiatry at the University of Washington in Seattle. Almost nothing is standardized about how clinical trials look for side effects — including how researchers ask volunteers about them or code them in the data.
“There clearly is a need for more standardization,” King told BuzzFeed News. “[I’ve] participated in many clinical trials, and I don’t think any two have been alike in terms of how potential side effects are being collected and evaluated.”
For instance, according to King, if a researcher just asks trial participants to report any changes, parents might not report their kid getting a cold, or falling down on the playground. But if colds or falls are a lot more common in kids taking the drugs than in those taking a placebo, it could mean the drug is affecting the immune system or a child’s balance.
Members of both European and American pharma industry groups have pledged to make more clinical trial data available to researchers and the public, though Sharma says her team struggled to get access to the data they wanted.
The new study is part of a recent push by the editors of BMJ and others to pay more attention to scientific integrity. Journal editors have been encouraging scientists to take hard looks at old medical data, especially around clinical trials. And many researchers are pushing for pharmaceutical companies to make their clinical trial data public.
A similar analysis of old antidepressant clinical trial data published in the BMJ last year found that researchers had underplayed side effects, especially the risk of suicide in children using the drugs.
But untangling the effects of medication on behavior can be incredibly difficult, especially when the side effects — such as aggression and suicidality — are also symptoms of the disorder.
“I think it’s really difficult to pin something on the drug,” Helen Farrell, an instructor in psychiatry at Harvard Medical School, told BuzzFeed News. “People often think of depression as a person who’s very unmotivated, apathetic, and sad, but irritability and anger are key features.”
Sharma told BuzzFeed News that she thinks doctors and patients should be aware of the true harms of the drugs they take, and also know about effective, pill-free interventions like talk therapy and exercise.
Farrell agrees that therapy and exercise can be valuable treatments, but worries that fears about dangerous pills will keep depressed people from seeking the help they need.
“The World Health Organization has declared depression the number one disability in terms of risk without treatment,” Farrell said. “It’s very important to be aware and comprehensive in the approach, which may include exercise, diet, psychotherapy, and medication.”