Selective serotonin reuptake inhibitors and suicidal behaviour: a population-based cohort study

Tyra Lagerberg,Clara Hellner,Paul Lichtenstein,Arvid Sjölander,Zheng Chang,Seena Fazel

doi:10.1038/s41386-021-01179-z

Abstract

There is concern that selective serotonin reuptake inhibitor (SSRI) treatment may increase the risk of suicide attempts or deaths, particularly among children and adolescents. However, debate remains regarding the nature of the relationship. Using nationwide Swedish registers, we identified all individuals aged 6–59 years with an incident SSRI dispensation (N = 538,577) from 2006 to 2013. To account for selection into treatment, we used a within-individual design to compare the risk of suicide attempts or deaths (suicidal behaviour) in time periods before and after SSRI-treatment initiation. Within-individual incidence rate ratios (IRRs) of suicidal behaviour were estimated. The 30 days before SSRI-treatment initiation was associated with the highest risk of suicidal behaviour compared with the 30 days 1 year before SSRI initiation (IRR = 7.35, 95% CI 6.60–8.18). Compared with the 30 days before SSRI initiation, treatment periods after initiation had a reduced risk—the IRR in the 30 days after initiation was 0.62 (95% CI 0.58–0.65). The risk then declined over treatment time. These patterns were similar across age strata, and when stratifying on history of suicide attempts. Initiation with escitalopram was associated with the greatest risk reduction, though CIs for the IRRs of the different SSRI types were overlapping. The results do not suggest that SSRI-treatment increases the risk for suicidal behaviour in either youths or adults; rather, it may reduce the risk. Further research with different study designs and in different populations is warranted.

Highlights

Suicide is the tenth leading cause of death in North America, and the leading cause in those aged 15–24 years worldwide [1]
While we find that the risk of suicidal behaviour was highest immediately prior to initiation and that the risk declines over treatment time, we found that risk during on-treatment periods remained elevated compared to the month 1 year before
In this population-based cohort study of 538,577 individuals who treatment initiation. This suggests that, in the first year of initiated selective serotonin reuptake inhibitor (SSRI) treatment, we found that the risk for suicidal treatment, SSRI medication does not bring the risk of suicidal behaviour was highest in the month immediately preceding the behaviour to baseline, which may be related to findings from first recorded SSRI initiation

Summary

INTRODUCTION

Suicide is the tenth leading cause of death in North America, and the leading cause in those aged 15–24 years worldwide [1]. RCTs tend to have short follow-ups and limited generalisability to real-world settings, and individual RCTs are under-powered for rarer outcomes such as suicide attempt and completion. They routinely exclude high-risk groups, such as individuals with a history of suicidal ideation or attempts [14, 15], and people with common comorbidities, such as substance misuse. Observational studies can provide valuable evidence from representative populations with longer follow-up Previous studies using these designs have generally found an association between SSRI use and suicidal behaviour in children and adolescents [16, 17], with some conflicting evidence among adults [18,19,20].

MATERIALS AND METHODS

RESULTS

DISCUSSION

Strengths and limitations

CONCLUSION