Antidepressant efficacy and side-effect burden: a quick guide for clinicians

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Prescribing of antidepressant treatment (ADT) for major depressive disorder (MDD) has increased in quantity and popularity over the last two decades. This is likely due to the approval of safer medications, better education of clinicians and their patients, direct-to-consumer marketing practices, and less stigma associated with those taking ADT. This trend has also been met with some controversy, however, as the ongoing safety and effectiveness of these treatments have at times been called into question. This paper discusses the differing levels of evidence that support the use of ADT based on (A) Food and Drug Administration approvals, (B) data from randomized controlled trials or meta-analyses and, where these are not available, the authors discuss and apply, (C) theoretical pharmacodynamic principles to justify antidepressant choice in the treatment of MDD patients. The final section discusses standard psychopharmacology guideline approaches to better alert the reader as to which practices are commonplace compared with those which are more outside of the standard of care.

Keywords: antidepressants, pharmacotherapy, psychotropics, efficacy, depression, pharmacodynamics, safety, effectiveness.

Abbreviations: ADT, antidepressant treatment; DLPFC, dorsolateral prefrontal cortex; ECT, electroconvulsive therapy; FDA, Food and Drug Administration; GI, gastrointestinal; HAM-D, Hamilton Rating Scale for Depression; ITT, intent-to-treat; MADRS, Montgomery–Asberg Depression Rating Scale; MAOI, monoamine oxidase inhibitor; MDD, major depressive disorder; MTD, minimum therapeutic dose; NaSSA, noradrenergic antagonist-specific serotonin antagonist; NDRI, norepinephrine–dopamine reuptake inhibitor; RCT, randomized controlled trial; SARI, serotonin antagonist and reuptake inhibitor; SMS, serotonin modulator and stimulator; SNRI, serotonin norepinephrine reuptake inhibitor; SPARI, serotonin partial agonist reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

Citation: Santarsieri D, Schwartz TL. Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs in Context 2015; 4: 212290. DOI: 10.7573/dic.212290

Contributions: TS conceived the idea, supervised the preparation of the manuscript, streamlined and provided longitudinal editing, and co-wrote the manuscript with DS, who additionally provided substantial contributions to literature review and editing of the final manuscript.

Potential conflict of interests: The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests forms for the authors are available for download at: The authors have no relationships to disclose.

Funding declaration and acknowledgement: The authors have declared that this is an unfunded study.

Copyright: Copyright © 2015 Santarsieri D, Schwartz TL. Distributed under the terms of the Creative Commons License Deed CC BY NC ND 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2015 Santarsieri D, Schwartz TL. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

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Correspondence: Thomas L Schwartz, Department of Psychiatry, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.

Provenance: Submitted; externally peer reviewed

Submitted: 22 August 2015; Peer review comments to author: 9 September 2015; Published: 8 October 2015

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