Article

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: 3.76). 05/2006; 26(2):203-7. DOI: 10.1097/01.jcp.0000203198.11453.95
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
72 Views
  • Source
    [Show abstract] [Hide abstract]
    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; DOI:10.1016/j.neurenf.2011.03.001
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To examine suicidal behaviour risk in the short-term placebo-controlled studies of mirtazapine in Major Depressive Disorder (MDD). Longitudinal Generalized Estimating Equations analyses were performed on pooled data from 15 placebo-controlled, randomized, double-blind, short-term trials of mirtazapine, using the suicide item scores from the Hamilton Depression Rating Scale (HAMD) as a proxy outcome measure for suicidality risk. The overall analysis using the convention that a patient is at risk if the HAMD suicide item score is > or =3, and excluding patients at risk at baseline, demonstrated a statistically significantly lower risk for mirtazapine- compared to placebo-treated patients on the HAMD (odds ratio mirtazapine versus placebo 0.38; 95% confidence interval 0.21-0.66; P= 0.0008). Our results based on pooled data from 15 placebo-controlled, short-term studies of mirtazapine in MDD using the suicide item scores from the HAMD as a proxy outcome measure for suicidality risk, demonstrate that mirtazapine was associated with statistically significantly lower suicidality risk compared to placebo.
    The World Journal of Biological Psychiatry 02/2010; 11(1):36-44. DOI:10.3109/15622970701691503 · 4.23 Impact Factor