A review of clinical trial literature suggests that harmful outcomes occurring during antidepressant drug trials may be downplayed, and may hide the risks of serious harm posed by the drugs.
Clinical trials are a form of experiment used to test treatment methods, including new drugs, and are done on human participants. Because they typically involve novel interventions whose effects and efficacy are not yet fully known, clinical trials must be approved by regulatory bodies – whose job is to evaluate the risks, benefits and ethics of the proposed research – before they can be undertaken. However, approval does not certify that the trial is without risk; in fact, harmful outcomes do occur in clinical trials, and typically are required to be reported, along with the overall results gleaned from the research.
Clinical trials of certain antidepressant drugs, called selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are one area of research that has generated considerable controversy. This is because the harmful outcomes that can result from these drugs are fairly severe, including violent behaviour and suicide. In addition, it has not been clear whether these outcomes are attributable to the mental disorders in themselves, or may, in fact, be a side-effect provoked by the medications.
Scientists affiliated with the Nordic Cochrane Centre, which is an independent research and information centre located in Copenhagen, Denmark, recently conducted a study that sought to quantify the risk of suicide and violence arising from clinical trials involving SSRIs/SNRIs. The study is published in the Journal of the Royal Society of Medicine. In particular, the study looked at trials where SSRIs/SNRIs were administered to healthy adults – individuals with no history of mental disorder – in order to evaluate the impact of the drugs alone.
Researchers reviewed results from published, double-blind, placebo-controlled trials found on PubMed and Embase, as well as clinical study reports obtained from European and UK drug regulators. In particular, they looked for trials involving healthy adult volunteers where incidents of suicide, violence, activation events, psychotic events, mood disturbances, or precursor events were reported.
Overall, 130 trials met the criteria for inclusion in the review; however, the vast majority of them failed to provide helpful data permitting assessment of adverse outcomes. Ultimately, only 11 published trials and two clinical study reports obtained from the regulatory agencies were used for the study. The drugs involved in those trials were citalopram, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine, all administered orally.
Results of the analysis of the 13 trials were somewhat concerning. They showed that treatment of adult healthy volunteers (no history of mental disorder) with antidepressants doubled their risk of adverse outcomes related to suicide and violence.
Authors of the study suggest that this result raises serious questions about the widespread belief that the increased incidence of suicide among depressed patients in the early period of treatment is a result of the increased energy and motivation that comes with recovery. Essentially, this view is premised on the assumption that the drug treatment is working and should be continued. However, authors of this latest study suggest that the truth may, in fact, be the opposite – that the increased risk of suicide may result from the drugs themselves.
In addition, the authors of the study consider that they have likely underestimated the risks of antidepressant drugs, since 11 of the 13 trials used in their analysis provided only the published article about the trial, not the clinical trial reports, and drug companies are well-known to underreport, dissimulate or simply omit harmful outcome events from publications about their trials.
Based on the results of their review, the authors of the study suggest that the belief that antidepressant drugs are not harmful for adults may be a dangerous misconception, and should be reconsidered.
Written By: Linda Jensen