Published data on antidepressant risks are inadequate
The true extent of the adverse effects of antidepressants is likely hidden by inadequate, inaccessible, and even misleading publication of clinical trials in the scientific literature, concludes new research.
An analysis of 70 clinical trials of commonly prescribed antidepressants has found discrepancies between patient accounts of their side effects and the conclusions presented in published trials.
The scientists behind the new research believe that the scientific literature is so poor that it does not show the true extent of the risk of serious harm when using antidepressants. In some cases, they say, the literature may even be misleading.
This study has shown limitations in trials, not only in design, but also in reporting of clinical study reports, which may have lead to "serious under-estimation of the harms," writes Joanna Moncrieff, a senior research fellow in psychiatry at University College London, in an editorial that accompanies the study.
"The true risk for serious harms is still unknown [because] the low incidence of these rare events, and the poor design and reporting of the trials, makes it difficult to get accurate effect estimates," she writes.
The new results are published in the British Medical Journal.
Doubled risk of suicide in children taking antidepressants
The scientists behind the new research focused on four types of harmful behaviour: suicide, suicidal behaviour (suicidal ideation, suicide, and self-harm), aggressive behaviour, and akathisia (an extreme form of unrest), and they examined five of the most widely used antidepressants in Denmark.
Out of these 70 trials, they could only draw one concrete conclusion: children and young people are twice as likely to experience suicidal behaviour and aggression if they take one of these antidepressants.
They found no link between the use of antidepressants and suicidal behaviour, suicide, aggression, and akathisia, in adults. But Peter Gøtszche, co-author of the new study and director of the Nordic Cochrane Centre at Rigs-hospital, Denmark is nevertheless convinced that this relationship exists.
"I think that antidepressants are risky for adults, but we don’t show it in our study. The knowledge we have about the risk of suicide in adults today is totally misleading," says Gøtszche.
Lead-author: shocked and worried
The damage associated with anti-depressants is often left out of published reports of drug trials, the authors explain.
So they focused their analyses on the so-called 'clinical study reports'--the reports prepared by pharmaceutical companies for marketing and comprehensive test reports, which usually include more information than the trials published in scientific journals.
"I’d expected some inconsistencies in both the published literature and the clinical study reports based on previous research in this area, but the extent of these [inconsistencies] surprised me,” writes lead-author Tarang Sharma, from the Nordic Cochrane Centre, Denmark, in an email to ScienceNordic.
“Maybe I was naive, but the extent of what had been buried in the annexes was quite shocking and worrying to me," writes Sharma.
Clinical Associate Professor Anne Katrine Pagsberg, from the Department of Clinical Medicine at the University of Copenhagen, Denmark, has read the study and describes Sharma’s evidence--based on the original clinical study reports--as some of the best form of evidence upon which to judge the side-effects of anti-depressants.
“This type of meta-analysis is in principle, when discussing evidence-based treatment, the highest [form of] evidence, one can get," says Pagsberg.
Translated by: Catherine Jex
- "Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports", BMJ (2016), DOI: DOI: 10.1136/bmj.i65
- "Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder: comparison of clinical study reports, trial registries, and publications", BMJ (2014), DOI: 10.1136/bmj.g3510