Cardiovascular adverse effects of newer antidepressants

Abstract

Newer antidepressants that are more selective in their neurotransmitter effects include the selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others (agomelatine, bupropion, mirtazapine, reboxetine, vilazodone, vortioxetine). This article systematically reviews data from a variety of sources regarding the potential adverse effects of these medications on various cardiovascular parameters. Potential biochemical mechanisms by which these antidepressants may adversely affect the cardiovascular system are also discussed. Antidepressants that are associated with higher cardiovascular risk (SNRIs, reboxetine), lower risk (SSRIs), and without current evidence of cardiovascular risk (agomelatine, mirtazapine, vilazodone, vortioxetine) are identified. The FDA’s recommendations regarding citalopram are organized and summarized, and situations with higher risk of cardiovascular adverse effects are identified.

Keywords::

• adverse effects
• antidepressants
• blood pressure
• cardiovascular
• electrocardiogram
• orthostatic hypotension
• QT interval
• side effects
• serotonin-norepinephrine reuptake inhibitors
• selective serotonin reuptake inhibitors

Financial & competing interests disclosure

R Mago has received grant/research or travel support from Forest Research Institute, Shire Development, LLC, Genomind, Bristol-Myers Squibb, Eli Lilly and Company, AstraZeneca, GlaxoSmithKline, and Otsuka Pharmaceutical Development & Commercialization, Inc. He has been a consultant or speaker for Bristol Myers-Squibb and GuidePoint Global. C. Andrade has received grant/research support from Indian Council of Medical Research, Department of Biotechnology, Government of India, Yale University, Intas Pharmaceuticals, GlaxoSmithKline, Gufic Limited, PhytoPharma, Aristo Pharmaceuticals, Cybele Laboratories, Himalaya Drug Company, Natural Remedies, Arya Vaidya Nilayam, Corcept Therapeutics, and Lupin Laboratories. He has consulted for AstraZeneca, Wyeth, and ClinPrax. His academic publications for free public dissemination are or have been supported by Sun Pharmaceuticals, Alkem Laboratories, Zydus Neurosciences, and the British Association for Psychopharmacology. N. Tripathi has no conflicts to disclose. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• In contrast to the tricyclic and monoamine oxidase inhibitor antidepressants, newer antidepressants have lower risks of cardiovascular adverse effects but are not devoid of them.

• The mechanisms by which the newer antidepressants may cause cardiovascular adverse effects have not been fully elucidated.

• While selective serotonin reuptake inhibitors have minimal cardiovascular risk, at high doses and in patients with other risk factors, they may be associated with prolongation of the QT interval and, very rarely, with ventricular arrhythmias.

• Antidepressants that enhance the central and peripheral effects of norepinephrine are generally associated with some risk of increased pulse and blood pressure. These include the serotonin-norepinephrine reuptake inhibitors and reboxetine.

• Mirtazapine, agomelatine, vilazodone and vortioxetine are not currently known to be associated with any significant cardiovascular risk, but data on this are limited.

• While newer antidepressants are admittedly quite safe in most situations, clinicians must be cautious in situations where multiple risk factors converge.

Notes

Data taken from [43].