Antidepressants commonly prescribed for children and adolescents are no more effective than a placebo for treating major depression — and in some cases, can be downright harmful, according to a landmark new study.
Published in the Lancet, the research denotes the “first comprehensive comparison of commonly prescribed antidepressant drugs so far.” Medical researchers analyzed 34 pharmaceutical trials involving 5,260 participants ranging in average age from 9 to 18 years.
Of 14 common antidepressants studied, only fluoxetine — best known under the brand name, Prozac — proved marginally more effective in treating major depression than a placebo. Alarmingly, venlafaxine, brand name Effexor, “was linked with an increased risk of engaging in suicidal thoughts or attempts” when compared to both placebo and five other medications.
“The balance of risks and benefits of antidepressants for the treatment of major depression does not seem to offer a clear advantage in children and teenagers, with probably only the exception of fluoxetine,” summarized Prof. Peng Xie, study co-author from The First Affiliated Hospital of Chongqing Medical University, China. “We recommend that children and adolescents taking antidepressants should be monitored closely, regardless of the antidepressant chosen, particularly at the beginning of treatment.”
However, despite such damning revelations, study authors also rebuked the pharmaceutical industry for making unbiased and thorough data available for research using the shield of patient privacy to invoke intellectual property rights.
“Without access to individual-level data it is difficult to get accurate effect estimates and we can’t be completely confident about the accuracy of the information contained in published and unpublished trials,” warned study lead author, Dr. Andrea Cipriani of the University of Oxford, U.K. “It has been widely argued that there needs to be a transformation of existing scientific culture to one where responsible data sharing should be the norm.”
Diagnosed major depressive disorder affects a statistically striking number of young people — 3 percent of children between 6 and 12 years of age and 6 percent of teens between 13- and 18-years-old. Accuracy of diagnostic methods or possible over-diagnosis were not covered by this study.
For this massive project, the authors analyzed data from all randomized trials — both published and unpublished — of the 14 most common antidepressants. Efficacy of medication, how well subjects tolerated any side effects, whether subjects discontinued treatment for any reason, and risk of actual harm, such as suicidal thoughts, were all taken into account.
In addition to venlafaxine, imipramine (brand name, Tofranil) and duloxetine (Cymbalta) were least tolerated by patients and resulted in the highest discontinuation rates.
Study authors admonished Big Pharma for seemingly skewed information and gaps in data from the lack of individual patient information. As noted in a ‘linked’ comment on the study, Dr. Jon Jureidini from the University of Adelaide noted the potential ‘suicidal events’ to be unaccounted for:
“The effects of misreporting is that antidepressants, possibly including fluoxetine, are likely to be more dangerous and less effective treatments than has been previously recognised, so there is little reason to think that any antidepressant is better than nothing for young people … Patients who take part in randomised controlled trials have a right to expect that maximum benefit will come from the data they generate.”
He added that doctors and researchers “are failing” patients because such data from individuals remains unavailable, and successful understanding of antidepressants will only come when patient-level data can be obtained for analysis.
“Patients’ privacy must be guaranteed by adequate policies and technological measures, but delay in implementing responsible data sharing policies has negative consequences for medical research and patient outcomes, as demonstrated by this study,” said Dr. Cipriani. “Access to raw clinical trial data provides the unique opportunity not only for validation and replication of results but also the in-depth study of specific factors that may affect treatment outcome at the individual patient level.”
Removing barriers from patient information is imperative to the accurate study of antidepressants, but more so to increase patient safety. As noted by study authors, despite the issuance by the FDA in 2004 of a black box warning to not prescribe antidepressants in youth up to age 24, since 2005, the number of prescriptions written to those aged 0 to 19 years actually increased from 1.3 percent to 1.6 percent in the U.S.
Authors remain concerned about their findings — particularly the potentially harmful effects hidden by the glaring dearth of information. As Dr. Jureidini advised,
“Claims that appropriate access to such data is incompatible with intellectual property constraints and patient privacy must be strongly resisted.”