Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

Abstract

ObjeCtiveTo study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis. Main OutCOMe MeasuresMortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Data sOurCesClinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website.eligibility Criteria fOr stuDy seleCtiOn Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Data extraCtiOn anD analysisTwo researchers extracted data independently; the outcomes were meta-analysed by Peto's exact method (fixed effect model). resultsWe included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious underreporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). 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.

Precursors to suicidality and violence on antidepressants: systematic review of trials in adult healthy volunteers

“…It included events both during treatment and in the subsequent withdrawal phase and found a doubling in hostility events (odds ratio 2.10, 95% confidence interval 1.27 to 3.48). 23 While it is now generally accepted that antidepressants increase the risk of suicide and violence in children and adolescents 5,12 (although many psychiatrists still deny this 10 ), most people believe that these drugs are not dangerous for adults. This is a potentially lethal misconception.…”

“…[3][4][5] We checked whether the clinical study reports had been published by searching for investigator names and drugs on PubMed and Embase.…”

“…For 11 of our 13 trials, we only had access to the published article, and it well documented that the drug companies underreport seriously the harms of antidepressants related to suicide and violence, either by simply omitting them from the reports, by calling them something else or by committing scientific misconduct. [2][3][4][5]7,10,27 In trials of duloxetine and sertraline, for example, only 33 of 45 cases of suicidal ideation, attempt or injury listed in a trial register were also mentioned in the published reports. 2 Psychiatrists believe that the suicide risk with antidepressants is only increased till age 24, but this misconception builds on seriously flawed trial data that the FDA has published.…”

“…4 Based on the 70 clinical study reports we received, we found that antidepressants more than doubled the risk of suicidal and aggressive behaviour in children and adolescents. 5 A 2012 systematic review of 33 trials in healthy volunteers documented various effects of selective serotonin reuptake inhibitors but only mentioned the adverse events in a few words. 6 The review was based on published articles and none of these lived fully up to the CONSORT guideline for good reporting.…”

A rare case with suicide due to akathisia after use of single dose venlafaxine

“…Bununla birlikte antidepresan tedavi alan tüm yaþ gruplarýndaki hastalarýn klinik kötüleþme, davranýþlarda alýþýk olmadýk deðiþiklikler ve özkýyým davranýþý açýsýndan yakýndan gözlenmesini önermektedir (16). Bazý kaynaklar ise antidepresan kullanýmý ile akatizi ve özkýyým gibi ciddi zararlar için gerçek riskin hala belirsiz olduðunun ve bu alanda doðru veri için çalýþmalara ihtiyaç olduðu-nun altýný çizmektedirler (17).…”