Selective Serotonin Reuptake Inhibitors and Risk of Noncardioembolic Ischemic Stroke: A Nested Case-Control Study.

BACKGROUND: Multiple studies have reported that the use of selective serotonin reuptake inhibitors (SSRIs) is associated with an increased risk of ischemic stroke; however, this finding may be the result of a confounding by indication. We examined the association using different approaches to minimize such potential bias. METHODS: A nested case-control study was carried out in a Spanish primary health-care database over the study period 2001 to 2015. Cases were patients sustaining an ischemic stroke with no sign of cardioembolic or unusual cause. For each case, up to 5 matched controls (for exact age, sex, and index date) were randomly selected. Antidepressants were divided in 6 pharmacological subgroups according to their mechanism of action. The current use of SSRIs (use within a 30-day window before index date) was compared with nonuse, past use (beyond 365 days) and current use of other antidepressants through a conditional logistic regression model to obtain adjusted odds ratios and 95% CI. Only initiators of SSRIs and other antidepressants were considered. RESULTS: A total of 8296 cases and 37 272 matched controls were included. Of them, 255 (3.07%) were current users of SSRIs among cases and 834 (2.24%) among controls, yielding an adjusted odds ratio of 1.14 (95% CI, 0.97-1.34) as compared with nonusers, 0.94 (95% CI, 0.77-1.13) as compared with past-users and 0.74 (95% CI, 0.58-0.93) as compared with current users of other antidepressants. No relevant differences were found by duration (≤1, >1 year), sex, age (<70, ≥70 years old) and background vascular risk. CONCLUSIONS: The use of SSRIs was not associated with an increased risk of noncardioembolic ischemic stroke. On the contrary, as compared with other antidepressants, SSRIs appeared to be protective.

Differential effects of antidepressant subgroups on risk of acute myocardial infarction: A nested case-control study.

The primary objective of this study was to investigate the association between antidepressants use and the risk of acute myocardial infarction (AMI). METHODS: We conducted a nested case-control study using a primary care database over the period 2002-2015. From a cohort of patients aged 40-99 years, we identified incident AMI cases and randomly selected 5 controls per case, matched to cases for exact age, sex and index date. Exposure to antidepressants were categorised as current, recent, past and nonusers. Adjusted odds ratio (AOR) and 95% confidence interval (CI) were computed using conditional logistic regression to assess the association between the current use of different antidepressants subgroups and AMI as compared to nonuse. Dose and duration effects were explored. RESULTS: Totals of 24 155 incident AMI cases and 120 775 controls were included. The current use of antidepressants as a group was associated with a reduced risk (AOR = 0.86; 95% CI: 0.81-0.91), but mainly driven by selective serotonin reuptake inhibitors (AOR = 0.86; 95% CI:0.81-0.93). A reduced risk was also observed with trazodone (AOR = 0.76;95% CI: 0.64-0.91), and clomipramine (AOR = 0.62; 95% CI: 0.40-0.96), whereas no significant effect was observed with other antidepressants. A duration-dependent effect was suggested for selective serotonin reuptake inhibitors, trazodone and clomipramine, while there was no clear dose-dependency. CONCLUSION: This study suggests that current use of antidepressants interfering selectively with the reuptake of serotonin, and those antagonizing the 5-HT2A receptor, are associated with a decrease in AMI risk and should be the antidepressants of choice in patients at cardiovascular risk.