Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

Abstract

Background: It is unclear whether antidepressants can prevent suicides or suicide attempts, particularly during long-term use. Methods: We carried out a comprehensive review of long-term studies of antidepressants (relapse prevention). Sources were obtained from 5 review articles and by searches of MEDLINE, PubMed Central and a hand search of bibliographies. We meta-analyzed placebo-controlled antidepressant RCTs of at least 3 months' duration and calculated suicide and suicide attempt incidence rates, incidence rate ratios and Peto odds ratios (ORs). Results: Out of 807 studies screened 29 were included, covering 6,934 patients (5,529 patient-years). In total, 1.45 suicides and 2.76 suicide attempts per 1,000 patient-years were reported. Seven out of 8 suicides and 13 out of 14 suicide attempts occurred in antidepressant arms, resulting in incidence rate ratios of 5.03 (0.78-114.1; p = 0.102) for suicides and of 9.02 (1.58-193.6; p = 0.007) for suicide attempts. Peto ORs were 2.6 (0.6-11.2; nonsignificant) and 3.4 (1.1-11.0; p = 0.04), respectively. Dropouts due to unknown reasons were similar in the antidepressant and placebo arms (9.6 vs. 9.9%). The majority of suicides and suicide attempts originated from 1 study, accounting for a fifth of all patient-years in this meta-analysis. Leaving out this study resulted in a nonsignificant incidence rate ratio for suicide attempts of 3.83 (0.53-91.01). Conclusions: Therapists should be aware of the lack of proof from RCTs that antidepressants prevent suicides and suicide attempts. We cannot conclude with certainty whether antidepressants increase the risk for suicide or suicide attempts. Researchers must report all suicides and suicide attempts in RCTs.

Population scale data reveals the antidepressant effects of ketamine and other therapeutics approved for non-psychiatric indications

“…The long lag period renders the standard of care antidepressants ineffective for suicidal patients who can’t afford to wait 2–6 weeks. Aside from the lag in antidepressant effects, there is insufficient evidence that antidepressants prevent suicide during long-term treatment 7 , and in many cases the antidepressant increases the risk of suicidal thoughts and actions 8 . Efficacy is another issue affecting depression treatment.…”

The Safety, Tolerability and Risks Associated with the Use of Newer Generation Antidepressant Drugs: A Critical Review of the Literature

“…Since 2014, the US Food and Drug Administration (FDA) issued a black box warning regarding the risk of suicidality related to the use of antidepressants in children and adolescents [179]. The incidence of suicide and attempted suicide has been a frequently underreported adverse outcome across antidepressant RCTs [180]. The first association between the use of SSRIs and suicidality was reported in 1990 [181].…”

“…Two recent meta-analyses have not identified a clear increased risk of treatment-emergent suicidality in adult individuals treated with antidepressants in RCTs [180,183]. Notwithstanding that the use of antidepressants is efficacious for the treatment of MDD in adults, there is no clear evidence for either specific protective effects or increased risk related to suicidality.…”

Suicidal Ideation and Suicidal Behavior as Rare Adverse Events of Antidepressant Medication: Current Report from the AMSP Multicenter Drug Safety Surveillance Project

“…The most recent meta-analysis on long-term RCTs of ADs found an increased rate of suicide attempts during long-term treatment with ADs. Nevertheless, the authors concluded that it is still unclear whether ADs increase the risk of suicide attempts (Braun et al, 2016). …”