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Case Reports in Medicine
Volume 2016 (2016), Article ID 5362485, 6 pages
Case Report

Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

1Department of Psychiatry, Hospital do Divino Espírito Santo de Ponta Delgada, Avenida D. Manuel I, Ponta Delgada, 9500-370 Azores, Portugal
2Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
3Ciclo Básico de Medicina, Department of Biology, University of the Azores, Rua da Mãe de Deus, 9501-801 Ponta Delgada, Portugal

Received 7 July 2016; Revised 18 September 2016; Accepted 19 September 2016

Academic Editor: Bernardo Carpiniello

Copyright © 2016 Rui Lopes et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice.