Studies Lacking Youth Antidepressant Effects Data?
By Dennis Thompson
WEDNESDAY, Jan. 27, 2016 (HealthDay News) — Antidepressants appear to be much more dangerous for children and teens than reported in medical journals, because initial published results from clinical trials did not accurately note instances of suicide and aggression, a new study suggests.
Young people actually have a doubled risk of aggression and suicide when taking one of the five most commonly prescribed antidepressants, according to the new analysis published in the Jan. 27 issue of BMJ.
Earlier published drug trial results masked those risks by not accurately reporting suicide attempts or suicidal thoughts, and by not emphasizing instances of increased aggression, said study author Tarang Sharma, a researcher with the Nordic Cochrane Centre at the University of Copenhagen in Denmark.
The new analysis revealed these risks by skipping the published studies, and instead gathering information from detailed clinical study reports filed with government regulators as part of the drug approval process, Sharma explained.
Sharma said the differences between the published results and the data provided to regulators has shaken her faith in the summary findings of clinical trials that appear in medical journals.
“For me, the biggest lesson was never to trust a journal publication of a trial again,” she said, arguing that all drug trial data should be made public. “We all need to move towards developing guidance and doing systematic reviews using the original complete data, at the individual patient level.”
The Pharmaceutical Research and Manufacturers of America responded to the new analysis by pointing out a set of principles for responsible clinical drug trial data sharing that went into effect for its members in 2014.
“While we cannot comment on the specific clinical trials of various companies, our members are committed to sharing data,” the industry trade group said in a statement.
Anecdotal reports have been piling up of suicidal behavior and aggression in children taking two types of antidepressants — selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), the study authors said in background information.
The U.S. Food and Drug Administration issued a public warning in 2004 about the risk of suicide in children and teens treated with SSRIs.
That warning came after a government review found youngsters who took the drugs were twice as likely to try to harm themselves as those who took inactive “placebo” pills. The agency expanded its black box warning on the drugs in 2007 to include adults younger than age 25.
But more recent research has challenged the idea that antidepressants are dangerous for kids and young adults.
To try to assess the true extent of the dangers, Sharma and her colleagues requested clinical study reports for approved SSRIs and SNRIs from two European regulatory agencies.
The research team wound up focusing on 68 clinical study reports from 70 drug trials that involved more than 18,500 patients. The trials involved five specific antidepressants: duloxetine (Cymbalta), fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft) and venlafaxine (Effexor).
Researchers analyzed the data in those reports, and compared their findings to results published in medical journals.
Their analysis concluded that the risk of aggression and suicide doubled in kids taking one of these antidepressants, a result that had not been reported in earlier published reports. They found no similar association in adults.
Risks to children from antidepressants included deaths, suicidal thoughts and attempts, as well as aggression and akathisia, a form of restlessness that may increase suicide and violence.
Published reports from clinical trials appeared to misclassify deaths and suicidal events in people taking antidepressants, the researchers found.
For example, four deaths were misreported by a pharmaceutical company, in all cases downplaying the role of the antidepressant, the authors of the new analysis said.
Researchers also found more than half of the suicide attempts and instances of suicidal thoughts in the clinical trials were coded as “emotional lability” or “worsening of depression,” again downplaying the seriousness of side effects, the study authors said.
In summary trial reports from drug maker Eli Lilly and Co., almost all deaths were noted but suicidal attempts were missing in 90 percent of instances, and information on other outcomes was incomplete, according to the new analysis.
“I would not like to speculate whether the drug companies left out certain information from their results on purpose or why,” Sharma said. “That said, most of the errors favored the drug of interest, which is disturbing, and the obvious financial conflict of interest is overwhelming.”
In response to the findings, Eli Lilly issued a statement “to set the record straight.”
“There is nothing more important to Lilly than the safety of our medicines. The medical issues about these antidepressants have been addressed in our data submissions to the FDA [U.S. Food and Drug Administration] or regulators in other countries and in scientific journals and conferences for more than 20 years,” the statement said. “No regulatory authority has ever determined that Lilly withheld or improperly disclosed any data related to these medications.”
Joanna Moncrieff, a senior lecturer of psychiatry at University College London in England, said this is the first analysis that links antidepressants to increased aggression in children.
“Doctors should be more cautious about prescribing to everyone and to young people especially, and regulators should put a warning on drug labels about aggressive behavior as well as suicide,” said Moncrieff, who wrote an accompanying editorial in the journal.
Sharma suggested that parents whose children take antidepressants should talk with their doctor.
“No one should stop taking their antidepressants suddenly, that would be very dangerous,” she said. “In my view, patients and their families should work with their clinical professionals to plan a stopping strategy, which could be a very long process as many people have long-lasting withdrawal effects from the drugs. This should also be done in combination with starting other effective alternative therapies.”
Sharma and her colleagues also expressed concern that the risks to kids may be even greater than what they reported in their new analysis. Clinical study reports could not be obtained for all drug trials and all antidepressants, and individual listings of adverse outcomes for all patients were available for only 32 trials.
Moncrieff and Sharma agreed that the data from these drug trials need to be made publicly available, so independent researchers can assess the true risks of antidepressants.
However, Moncrieff said even that may not be enough to gain a complete understanding.
“Drug company information, even that supplied to regulators, is not reliable,” she said. “We need studies of risks and benefits of antidepressants and other drugs that are funded and conducted by organizations that do not have profits at stake.”