Suicide Rates in Short-term Randomized Controlled Trials of Newer Antidepressants

Division of Neuropharmocological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993-0002, USA.
Journal of Clinical Psychopharmacology (Impact Factor: 3.24). 05/2006; 26(2):203-7. DOI: 10.1097/
Source: PubMed


Concerns have been raised about the appropriateness of placebo controls in clinical trials for major depressive disorder (MDD), given that there are approved treatments for this illness. Critics have argued that patients with untreated depression would be exposed to an unnecessary risk of suicide. There is also a competing concern that antidepressant drug treatment itself may induce suicidal behavior and thinking (suicidality). To examine this question, we have evaluated the rate of suicide in placebo- and active drug-treated groups of patients with MDD and various anxiety disorders participating in short-term randomized controlled trials (RCTs). We examined data from all manufacturer-sponsored short-term RCTs of 9 commonly used antidepressants in patients with MDD and various anxiety disorders. All short-term RCTs of antidepressants in patients with MDD and various anxiety disorders were included. Individual patients' data were available for all trials. Data were available for the 207 trials conducted in patients with MDD, including a total of 40,028 patients. There were 21 cases of suicide in these patients. Forty-four trials were conducted in patients with various anxiety disorders, including a total of 10,972 patients. There were 2 cases of suicide in these patients. Overall, at least 1 case of suicide occurred in 21 of the 251 trials. Sixteen of the suicides in MDD trials occurred in trials that had only an active control comparison group, and most of these (14 cases) were observed in the non-North American trials. In the placebo-controlled MDD trials, the rate ratios of suicide in the combined drug groups compared with placebo were 1.07 (0.1-63.4) and 0.5 (0.0-36.7) for the non-North American and North American trials, respectively. In the anxiety disorder studies, the overall rate ratio of suicide for the selective serotonin reuptake inhibitors compared with placebo was 0.9 (0.0-71.4). Neither use of placebo nor of antidepressants in short-term RCTs was associated with an increased risk of completed suicide among patients with MDD or various anxiety disorders. Nonetheless, because of the small numbers of suicides in these trials and the subsequent lack of statistical power, an increased risk of completed suicide in association with either drug or placebo treatment cannot be definitively excluded.

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    • "When examining the younger subgroups that might be especially at risk, the negative association between prescription of AD and SSRI ± Ve on the one hand and suicide rates on the other is confirmed. The increase in suicide risk in children and adolescents found in previous research is largely based on an increase in suicidal ideation and nonfatal suicidal behaviour in studies comparing efficacy of AD versus placebo (Hammad et al. 2006; Stone et al. 2009). The risk factors for nonfatal suicidal behaviour (e.g. "
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    ABSTRACT: There is an ongoing discussion on the relation between risk of violent behaviour and the use of antidepressants. The claim that the use of antidepressants can cause violent behaviour would gain credibility if a positive association between the two could be established. The objective of this study is to evaluate the relationship between homicide, suicide and homicide-suicide rates and the rates of antidepressant use by gender and age group. Nationwide data from the Netherlands on antidepressant prescriptions (ADs, SSRI and venlafaxine) and lethal violence were analysed over the 15-year period from 1994 to 2008. The findings indicated a significant negative association between lethal violence (homicide and suicide) and prescription of antidepressants in the Netherlands, indicating that in a period in which the exposure of the Dutch population to antidepressants increased, rates of lethal violence decreased. These data lend no support for an important role of antidepressant use in lethal violence.
    Psychopharmacology 03/2012; 222(3):499-506. DOI:10.1007/s00213-012-2668-2 · 3.88 Impact Factor
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    • "Les agences européenne (EMEA) et américaine ont procédé à des analyses des essais publiés et non publiés avec les antidépresseurs de nouvelle génération chez l'enfant et l'adolescent. Des difficultés dans l'analyse des effets indésirables ont conduit à passer en revue 23 essais conduits par l'industrie ainsi que l'étude TADS avec de nouveaux critères pour classifier les effets adverses sérieux [1]. Cette analyse a concerné neuf antidépresseurs ISRS et non ISRS chez plus de 4500 patients. "
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    ABSTRACT: The evidence of the past years has shown that specific studies in children and adolescents were mandatory, as important differences in the efficacy and safety profiles of psychopharmacological drugs have been documented between pediatric and adult populations. This applies in particular to antidepressants, in which age-dependent psychobehavioral effects have been shown in a small but significant proportion of young patients. Our review focuses on current efficacy and tolerability data on antidepressants in children and adolescents. Recent collaborative multicenter trials in pediatric psychopharmacology have provided evidence-based data on the use of antidepressants as part of the treatment strategies for internalized disorders in children and adolescents. Fluoxetine has been shown effective in pediatric major depression, with a label for children above eight years old. The efficacy of specific serotonin reuptake inhibitors (SSRIs) has been documented in obsessive-compulsive disorder (OCD), with some SSRIs labeled for children and adolescents in this indication in both the USA. and Europe. In non-OCD anxiety disorders, clinical trials support efficacy for a number of SSRIs and venlafaxine in children and adolescents, although none has a pediatric label in these indications. We also review available data on tolerability and safety (psychobehavioral effects, including treatment-induced suicidality, long-term tolerance, lethal risk). In conclusion, we suggest decision options including all treatment modalities available for depression, OCD and other anxiety disorders in children and adolescents.
    Neuropsychiatrie de l Enfance et de l Adolescence 01/2012; 60(1). DOI:10.1016/j.neurenf.2011.03.001
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    • "Importantly, while these rates are higher than those from antidepressant trials, they are lower than expected suicide rates for a severely depressed population (Bostwick & Pankratz, 2000; Guze et al., 1970; Hammad et al., 2006). "
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    ABSTRACT: Antidepressant treatments, including pharmacotherapy and psychotherapy, do not result in remission for the majority of patients with major depressive disorder. The high prevalence of treatment resistant depression (TRD) poses a significant issue for patients as well as both societal and economic costs. Due to the limited efficacy of existing therapies in this sub-population, alternative somatic treatments are being explored. Both vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are neurostimulation treatments for TRD. While VNS has Food Drug Administration approval as an adjunctive therapy for MDD, DBS is still in the experimental stages. This article will review the evidence supporting the clinical utility of these therapies.
    International Review of Psychiatry 10/2011; 23(5):424-36. DOI:10.3109/09540261.2011.630993 · 1.80 Impact Factor
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