Research report Antidepressant use and the risk of suicide: A population-based cohort study Kiki Cheung a , Nikkie Aarts a,b , Raymond Noordam a,b , Jan C. van Blijderveen a,c , Miriam C. Sturkenboom c , Rikje Ruiter a , Loes E. Visser a,d , Bruno H. Stricker a,e,n a Department of Epidemiology, Erasmus MC – University Medical Centre Rotterdam, The Netherlands b Department of Internal Medicine, Erasmus MC – University Medical Centre Rotterdam, The Netherlands c Department of Medical Informatics, Erasmus MC – University Medical Centre Rotterdam, The Netherlands d Apotheek Haagse Ziekenhuizen – HAGA, The Hague, The Netherlands e Inspectorate of Health Care, The Hague, The Netherlands article info Article history: Received 5 July 2014 Received in revised form 9 December 2014 Accepted 10 December 2014 Available online 18 December 2014 Keywords: Depression Selective Serotonin Reuptake Inhibitors Tricyclic Antidepressants Suicide abstract Background: The existing literature provides contradictory evidence on antidepressant use and risk of suicide. Some studies have shown that the use of Selective Serotonin Reuptake Inhibitors (SSRIs) is associated with an increased risk of suicide, especially during the first months of treatment, whereas other studies did not confirm this association. For this reason, our objective was to investigate the association between antidepressant use and risk of suicide in incident antidepressant users in relation to time since starting therapy. Methods: We conducted a population-based cohort study within the Dutch Integrated Primary Care Information (IPCI) database, in incident users of antidepressant therapy between 1994 and 2012 (n ¼27,712). Cox proportional hazard models were used to study the association between current use of SSRIs, tricyclic antidepressants (TCA) and other antidepressants and risk of suicide or attempted suicide. Results: During follow-up, a total of 280 incident antidepressant users attempted or committed suicide. Current use of SSRIs (hazard ratio (HR): 0.78, 95% CI: 0.57–1.07), TCAs (HR: 0.82, 95% CI: 0.48–1.42) or other antidepressants (HR: 0.75, 95% CI: 0.47–1.18) was not statistically significantly associated with suicide compared to past use of any of the antidepressants. Limitations: Although a large healthcare database was used, the number of reported cases of suicide (attempt) was low. Conclusions: This study did not indicate an increase in risk of suicide after starting treatment with SSRIs, TCAs or other antidepressants compared with past antidepressant use. & 2014 Elsevier B.V. All rights reserved. 1. Introduction Suicide accounts for almost one million deaths worldwide each year and is therefore a major problem in many countries (Goldsmith et al., 2002). Depression is the most important risk factor (Brent, 1993). From the various treatments that are available to treat depression, Selective Serotonin Reuptake Inhibitors (SSRIs) are prescribed most frequently (Usala et al., 2008). This preference to prescribe SSRIs, compared to tricyclic antidepressants (TCAs), is due to their milder adverse effect and toxicity profile (Anderson, 2000). Compared to non-use as well as compared to TCAs and other antidepressants, SSRIs were associated with an increased risk of suicidal behavior, especially in children and adolescents (Martinez et al., 2005; Hall and Lucke, 2006; Fergusson et al., 2005). The risk seems to be increased especially during the first month of therapy (Hall and Lucke, 2006; Juurlink et al., 2006). As a causal pathway, it is hypothesized that SSRIs may cause agitation and subsequently potential ill-considered behavior, before their beneficial effect relieves depression (Mihanovic et al., 2010). However, others could not confirm the increased risk of suicide during use of SSRIs (Isacsson et al., 2009; Arias et al., 2010; Gibbons et al., 2007). It therefore remains controversial whether SSRI use is associated with suicidal behavior. For studies comparing SSRIs and TCAs, findings might be influenced by confounding by indication, as indications for prescribing TCAs and SSRIs are different (Jick et al., 2004; Didham et al., 2005). Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jad Journal of Affective Disorders http://dx.doi.org/10.1016/j.jad.2014.12.032 0165-0327/& 2014 Elsevier B.V. All rights reserved. n Corresponding author at: Department of Epidemiology, Erasmus Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Tel.: þ31 10 70 44294; fax: þ31 10 70 44657. E-mail address: b.stricker@erasmusmc.nl (B.H. Stricker). Journal of Affective Disorders 174 (2015) 479–484