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See also BMJ article: Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports
FirstWordPharma
January 28th, 2016
By: Joe Barber
Research findings published in the BMJ suggest that selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may double the risk of suicidality and aggression among children and adolescents. Based on the results, the authors recommended “minimal use of antidepressants in children, adolescents and young adults,” but cautioned that there was not enough patient data available from clinical trials to assess the true risk of all associated serious harms.
Investigators conducted a systematic review and meta-analysis of clinical study reports involving 70 placebo-controlled trials that contained any patient narratives or individual patient listings of harms. All together, the trials encompassed a total of 18 526 patients. Data sources included study reports for duloxetine, fluoxetine, paroxetine, sertraline and venlafaxine obtained from European and UK drug regulators, as well as summary trial reports obtained from Eli Lilly’s website for duloxetine and fluoxetine, which the company markets as Cymbalta and Prozac, respectively. Primary outcome measures assessed in the BMJ study were mortality and suicidality, while secondary outcomes were aggressive behaviour and akathisia.
Results illustrated that for adults, odds ratios were 0.81 for suicidality, 1.09 for aggression and 2.00 for akathisia, whereas corresponding values among children and adolescents were 2.39, 2.79 and 2.15. The researchers also found that the trials “had limitations in study design and discrepancies in reporting, which may have led to serious under-reporting of harms,” citing as an example that some outcomes appeared only in individual patient listings in appendices, which were available for just 32 of the trials. Investigators also said that in the summary trial reports on Eli Lilly’s website, “almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.”
Co-author Tarang Sharma explained the new analysis was able to shed light on the risks by gathering information from detailed clinical study reports filed with government regulators as part of the drug approval process, rather than relying on published studies. “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. Sharma also indicated there is a “need to move towards developing guidance and doing systematic reviews using the original complete data, at the individual patient level.”
Commenting on the news, a spokesman for Eli Lilly stated “the medical issues about these antidepressants have been addressed in our data submissions…for more than 20 years.” The spokesman added that the company “is committed to sharing the results of our clinical trials and ensuring this information is available to the people who need it.”