Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials

Abstract

Objective To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts. Design Systematic review of randomised controlled trials. Data sources Medline and the Cochrane Collaboration's register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group. Selection of studies Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week. Results Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42). Discussion Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.

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

“…Accordingly, the present study is restricted to studies with information on suicides and suicide attempts. Similar to our experience, Fergusson et al [23], in their meta-analysis of suicide attempts under SSRIs, found that less than half of all trials reported on suicide attempts. They also concluded that ‘a substantial proportion of suicide attempts have gone unreported'.…”

“…Our result of a lack of proof regarding a protective effect of antidepressants on suicide or suicide attempts is in line with meta-analyses primarily focusing on acute treatment studies: none of the 8 meta-analyses of antidepressant RCTs known to the authors resulted in statistically significant superiority compared to placebo [18,19,20,21,22,23,65,66]. The suicide event rate is low, precluding definite conclusions, but if there is any signal from these meta-analyses, it is that there may be a marginal suicide risk increase with antidepressants.…”

“…However, completed suicides and suicide attempts matter most to patients. Interestingly, other authors did not find a beneficial effect of antidepressants on suicide in placebo-controlled acute treatment trials [18,19,20,21,22,23,24]. In addition, Storosum et al [24] presented raw numbers of suicide and suicide attempts from several randomized long-term studies and concluded that their frequency was not higher in placebo groups.…”

State Medicaid Expansions and Mortality, Revisited: A Cost-Benefit Analysis

“…11 Meanwhile, the OHIE showed that the acquisition of Medicaid significantly reduces depression rates (Baicker et al, 2013), raising the possibility that coverage might also reduce suicide rates. While some trials of specific cognitive interventions have been shown to reduce recurrent suicide attempts (Brown et al, 2005), the most common medical intervention for depression (antidepressant use) has not been shown to reduce suicides in randomized trials (Fergusson et al, 2005), and the overall evidence base is mixed as to whether medical care reduces the risk of self-harm (Hawton et al, 2000). Thus, it is reasonable to assume that any mortality effects mediated by insurance coverage should be larger for healthcareamenable causes than for these other causes of death.…”

Paroxetine-Induced Increase in Activity of Locus Coeruleus Neurons in Adolescent Rats: Implication of a Countertherapeutic Effect of an Antidepressant

“…Independent review of adverse events from data from 24 placebo-controlled trials of AD use in children and adolescents found that suicidality significantly increased with SSRI treatment compared to placebo, leading the FDA to issue a “black box” warning (see Brent, 2004; Goodman et al , 2007; Newman, 2004). Additional studies have likewise found evidence of increased suicidality with use of SSRIs in juveniles, suggesting that there may be an unfavorable risk to benefit ratio for SSRIs (with fluoxetine as a possible exception) (Bailly, 2008; Barbui et al , 2009; Bridge et al , 2007; Cipriani et al , 2005; Doggrell, 2005; Fergusson et al , 2005; Goodman et al , 2007; Hammad et al , 2006; Laughren, 2006; Mosholder and Willy, 2006; Olfson and Marcus, 2008; Olfson et al , 2006; Richmond and Rosen, 2005; Ryan, 2005; Scahill et al , 2005; Tiihonen et al , 2006; Vitiello and Swedo, 2004; Whittington et al , 2004; Wohlfarth et al , 2006). Many of these and other studies have pointed out difficulties in interpretation of the data and have stated that there is considerable risk for suicidality if pediatric patients are not adequately treated (e.g., Bridge et al , 2007; Mann et al , 2006).…”