Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Cerebrovascular, Cardiovascular, and Mortality Events in New Users of Selective Serotonin Reuptake Inhibitors and Serotonin Norepinephrine Reuptake Inhibitors: A Propensity Score-Matched Population-Based Study

Leong, Christine BSc (Pharm), PharmD*; Alessi-Severini, Silvia PhD*; Enns, Murray W. MD; Nie, Yao MSc; Sareen, Jitender MD; Bolton, James MD; Prior, Heather J. MSc; Chateau, Dan PhD

Journal of Clinical Psychopharmacology: June 2017 - Volume 37 - Issue 3 - p 332–340
doi: 10.1097/JCP.0000000000000701
Original Contributions

Background Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) are widely prescribed for mood and anxiety disorders. However, it is not clear whether SNRIs are more strongly associated with cardiovascular and cerebrovascular events than SSRIs.

Methods This was a propensity score–matched, population-based, cohort study of Manitobans who started an SSRI or SNRI between April 1, 1998, and March 31, 2014. The primary outcome was a composite of acute myocardial infarction (AMI), stroke, or cardiovascular-related hospitalization within 1 year of drug initiation. Each component of the primary outcome and death were analyzed separately in secondary analyses.

Results A total of 225,504 and 54,635 patients initiated treatment on an SSRI and SNRI, respectively. After propensity score matching, a higher risk was observed for the primary outcome among SNRI users (weighted hazards ratio [HR], 1.13; 95% confidence interval [CI], 1.06–1.21). Secondary analyses showed that the risk of nonfatal stroke was higher among SNRI users (weighted HR, 1.20; 95% CI, 1.08–1.33). The risk of death was higher among SNRI users without mood and/or anxiety disorders (weighted HR, 1.17; 95% CI; 1.03–1.32). No differences were observed in the risk of AMI or fatal stroke between SSRI and SNRI use.

Conclusions New SNRI use was associated with a higher risk of nonfatal stroke relative to SSRI use. Further investigation is warranted regarding the higher risk of death observed in our subgroup analysis among incident SNRI users without mood and/or anxiety disorders.

Supplemental digital contents are available in the text.

From the *College of Pharmacy, Rady Faculty of Health Sciences, Apotex Centre; †Department of Psychiatry, and ‡Manitoba Centre for Health Policy; Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Received August 29, 2016; accepted after revision February 17, 2017.

Reprints: Christine Leong, BSc (Pharm), PharmD, College of Pharmacy, Rady Faculty of Health Science, University of Manitoba, Room 222, Apotex Centre, 750 McDermot Ave, Winnipeg, MB, Canada R3E 0T5 (e-mail:

This study was funded by the University of Manitoba Start-Up Funds.

Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.