Suicide-related events and the new generation of antidepressants: a comprehensive review

Antidepressants are widely used worldwide for the treatment of depression. The risk of suicide-related events during antidepressant use has been reported, leading to warnings in product labeling. However, this association has not been conclusively established, and meta-analyses to date have yielded inconsistent results. Therefore, an umbrella review and reanalysis were conducted to address this inconsistency. We performed a systematic search of meta-analyses and systematic reviews in PubMed and the Cochrane Library regarding the associations between new-generation antidepressants and suicide-related events. A comprehensive review and reanalysis of the data from the 25 ultimately selected studies were conducted to estimate the pooled odds ratio (OR) of suicide-related events between antidepressants and placebo. Additional analyses were also performed for different antidepressant categories and patient age subgroups. The pooled OR for suicide-related events associated with new-generation antidepressants, adjusted for publication bias via the trim-and-fill method, was 1.00 [0.90–1.12]. In the SSRI group, SNRI group, and non-SSRI/SNRI group, the adjusted ORs were 1.04 [0.91–1.19], 0.89 [0.71–1.12], and 0.98 [0.67–1.42], respectively, none of which were statistically significant. Similar nonsignificant results were observed in the pediatric and adolescent groups (1.11 [0.93–1.34]). Furthermore, the adjusted ORs for the SSRI and SNRI groups in children and adolescents were 1.06 [0.88–1.28] and 0.91 [0.39–2.15], respectively, which was not statistically significant. However, among the individual medications in these groups, venlafaxine alone had a high and statistically significant OR of 5.77 [2.18–15.31]. This study has several limitations, including the ambiguity of the definition of suicidal tendencies, inconsistencies in the definition and classification of depression, and the possibility of publication bias; thus, further research is needed to validate these findings. Nevertheless, this study highlights the warning that venlafaxine, a new-generation antidepressant, may increase the risk of suicide-related events in children and adolescents. Physicians and pharmacists should exercise caution when prescribing venlafaxine and be fully aware of the potential for suicide-related events associated with this new-generation antidepressant. (Grant: None. (Registration: None)).