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Eur Neuropsychopharmacol. 2020 Mar;32:120-130. doi: 10.1016/j.euroneuro.2020.01.004. Epub 2020 Jan 27.

The effect of combined treatment with SSRIs and renin-angiotensin system (RAS) drugs: A propensity score matched cohort study.

Author information

1
Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Palle Juul-Jensens Boulevard 175, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark. Electronic address: karkoe@rm.dk.
2
National Centre for Register-Based Research (NCRR), Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Initiative for Integrated Research in Psychiatry, Aarhus, Denmark; Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark.
3
Deakin University, School of Medicine, IMPACT, the Institute for Mental and Physical Health and Clinical Translation, Geelong, Victoria, Australia; Orygen Youth Health Research Centre and the Centre of Youth Mental Health, The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Parkville, Victoria, Australia.
4
Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Palle Juul-Jensens Boulevard 175, 8200 Aarhus, Denmark; iPSYCH, The Lundbeck Initiative for Integrated Research in Psychiatry, Aarhus, Denmark; Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.
5
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; iPSYCH, The Lundbeck Initiative for Integrated Research in Psychiatry, Aarhus, Denmark; Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark.

Abstract

Drugs acting on the renin-angiotensin system (RAS) may have beneficial effects on mental health. We investigated whether use of drugs acting on the RAS, as add-on to selective serotonin reuptake inhibitors (SSRIs), was associated with a reduced risk of psychiatric hospital contacts. We identified all individuals initiating treatment with an SSRI between 1997 and 2012. Individuals using an SSRI without concomitant use of a RAS drug (SSRI-only users) were propensity score matched 1:1 to individuals using both an SSRI and a drug acting on the RAS (SSRI+RAS users). The SSRI-only and SSRI+RAS users were followed for up to three years or until December 31, 2013. We performed Cox proportional hazard regression analyses to calculate risks for psychiatric hospital contacts, hospital contacts due to depression, suicidal behavior, and all-cause mortality. We followed 30,311 SSRI-only users and 30,311 SSRI+RAS users for a total of 49,327 person-years. Compared to SSRI-only users, concomitant use of SSRI+RAS was associated with a significantly reduced risk for psychiatric hospital contacts (hazard rate ratio (HRR)=0.91; 95%-confidence intervals (95%-CI)=0.84-0.98) and lower mortality rate (HRR=0.70; 95%-CI=0.66-0.75). The associations between SSRI+RAS use and psychiatric hospital contacts for depression (HRR=0.92; 95%-CI=0.80-1.05) and suicidal behavior (HRR=1.06; 95%-CI=0.79-1.42) were not statistically significant. In this observational cohort study, concomitant use of an SSRI and a drug acting on the RAS was associated with a slightly reduced risk for psychiatric hospital contacts, when compared to use of an SSRI alone.

KEYWORDS:

Antidepressant; Depression; Inflammation; Renin-Angiotensin; SSRI

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