Most antidepressants prescribed for children and teenagers with major depression are ineffective, and could even be unsafe, a major review shows.
The comprehensive review found that of 14 antidepressant drugs, only fluoxetine (Prozac) was more effective at relieving the symptoms of depression than a placebo. Taking venlafaxine (Effexor) was linked with an increased risk of suicidal thoughts and even attempts, compared to a placebo and five other antidepressants.
This was a large network meta-analysis looking at evidence from trials in PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials, according to the paper’s abstract.
Co-author Professor Peng Xie from The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, said:
“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. We recommend that children and adolescents taking antidepressants should be monitored closely, regardless of the antidepressant chosen, particularly at the beginning of treatment."
The FDA has been including a black-box warning on antidepressants since 2004, stating that in some cases, children, teenagers, and young adults under 25 may experience an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed.
This warning from the U.S. Food and Drug Administration (FDA) also says that patients of all ages taking antidepressants should be watched closely, especially during the first few weeks of treatment.
The study authors say that the true effectiveness and risk of serious harms such as suicidal thoughts and attempts remains unclear because of the small number and poor design of clinical trials assessing these antidepressants, as well as the selective reporting of findings in published trials and clinical study reports.
The study was funded by the National Basic Research Program of China. Of the research reviewed, 22 (65%) trials were funded by pharmaceutical companies. Ten (29%) trials were rated as high risk of bias, 20 (59%) as moderate, and four (12%) as low, according to the paper.
Depression Common In Children And Adolescents
Major depressive disorder is common in children and adolescents. Around 3% of children aged 6 to 12 years and about 6% of teenagers aged 13 to 18 years are affected. Psychological treatments are recommended as the first-line treatment for depression in many clinical guidelines.
“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. 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,"
says lead author Dr Andrea Cipriani at the University of Oxford in the UK.
“Hundreds of thousands of people worldwide have agreed to participate in trials aiming to find better treatments for their disorders and, ultimately, help the progress of medical science. 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.
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."
The use of antidepressants has slowly increased between 2005 and 2012 for young people. For example, the proportion of US children and teenagers (aged 0-19 years) taking antidepressants increased from 1.3% to 1.6%, and in the UK from 0.7% to 1.1%. Sertraline is the most widely prescribed antidepressant in the USA and fluoxetine is the most common in the UK.
Dr Jon Jureidini at the University of Adelaide in Australia points out in a commentary that many more suicidal events might have been revealed had individual patient-data been available.
“[For example], in four trials of paroxetine versus placebo, only 13 (3%) of 413 events were reported in the paroxetine group; this seems implausible when individual patient-level data reanalysis of just one of those studies found ten events in only 93 patients given paroxetine (10.8%).
The effect 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.
We doctors and researchers are failing to meet our obligation to research participants and to our patients, and we will only succeed if independent researchers such as Cipriani and colleagues are able to analyse individual patient-level data. Claims that appropriate access to such data is incompatible with intellectual property constraints and patient privacy must be strongly resisted."
Indeed, such was the case in 2015 when GlaxoSmithKline revealed full data about one of its previous studies. In teenagers, the rate of side effects such as suicidal thoughts was much greater than it at first had seemed.
Another study published around the same time in PLoS Medicine found that those under-25 taking SSRIs are more likely to commit violent crime (PLoS Medicine, DOI: 10.1371/journal.pmed.1001875).
Cipriani, Andrea et al. Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis The Lancet, DOI: http://dx.doi.org/10.1016/S0140-6736(16)30385-3