More than one in 10 Americans older than 12 takes antidepressants, according to a 2011 report by the National Center for Health Statistics. A significant but unknown number of children younger than 12 take them, too. Although most such drugs are not approved for young children, doctors have prescribed them off-label for years because they have been thought to have relatively mild side effects. Yet recent reports have revealed that important data about the safety of these drugs—especially their risks for children and adolescents—have been withheld from the medical community and the public.
In the latest and most comprehensive analysis, published in January in the BMJ, researchers at the Nordic Cochrane Center in Copenhagen showed that pharmaceutical companies have not been revealing the full extent of serious harm in clinical study reports, which are detailed documents sent to regulatory authorities such as the U.S. Food and Drug Administration and the European Medicines Agency (EMA) when applying for approval of a new drug. The researchers examined reports from 70 double-blind, placebo-controlled trials of two common categories of antidepressants—selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs)—and found that the occurrence of suicidal thoughts and aggressive behavior doubled in children and adolescents who used these drugs.
The investigators discovered that some of the most revealing information was buried in appendices where individual patient outcomes are listed. For example, they found clear instances of suicidal thinking that had been passed off as “emotional lability” or “worsening depression” in the report itself. This information, however, was available for only 32 out of the 70 trials. “We found that a lot of the appendices were often only available on request to the authorities, and the authorities had never requested them,” says Tarang Sharma, a Ph.D. student at Cochrane and lead author of the study. “I'm actually kind of scared about how bad the actual situation would be if we had the complete data.”
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This study “confirms that the full degree of harm of antidepressants is not reported,” says Joanna Moncrieff, a psychiatrist and researcher at University College London who was not involved in the study. “[These harms] are not reported in the published literature—we know that—and it appears that they are not properly reported in clinical study reports that go to the regulators and form the basis of decisions about licensing.”
The researchers struggled for many years to get access to the clinical trial reports, which are often withheld under the guise of commercial confidentiality. “All this secrecy actually costs human lives,” says Peter Gøtzsche, a clinician researcher at Cochrane and a co-author of the recent study. Eventually the EMA provided access after being publicly accused of mismanagement, but in the U.S. these documents remain inaccessible. “It's deeply unethical when patients volunteer to benefit science, and then we let drug companies decide that we cannot get access to the raw data,” Gøtzsche says. “The testing of drugs should be a public enterprise.”
The fact that antidepressants may cause suicidal ideation has been shown before, and in 2004 the FDA gave these drugs a black box warning—a label reserved for the most serious hazards. The EMA has issued similar alerts. There are no labels about risks for aggression, however. Although hints about hostile behavior existed in case studies, the BMJ study was the first large-scale work to demonstrate an increase in aggressive behavior in children and adolescents. “This is obviously important in the debate about school shootings in the [U.S.] and in other places where the perpetrators are frequently taking antidepressants,” Moncrieff says.
Taken together with other research—including studies that suggest antidepressants are only marginally better than placebos—some experts say it is time to reevaluate the widespread use of these drugs. “My view is that we really don't have good enough evidence that antidepressants are effective, and we have increasing evidence that they can be harmful,” Moncrieff says. “So we need to stop this increasing trend of prescribing them.”
