Safety and tolerability of edivoxetine as adjunctive treatment to selective serotonin reuptake inhibitor antidepressants for patients with major depressive disorder

Article Details

Authors
James M Martinez, Margaret B Ferguson, Beth A Pangallo, Tina M Oakes, JonDavid Sparks, Mary Anne Dellva, Qi Zhang, Peng Liu, Mark Bangs, Jonna Ahl, Celine Goldberger

Article Type
Original Research

DOI
10.7573/dic.212279

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Abstract

Objective: The aim of this analysis was to assess the safety profile of edivoxetine as adjunctive treatment to selective serotonin reuptake inhibitor (SSRI) antidepressants.

Methods: A pooled analysis was conducted on data obtained from the integrated safety database of edivoxetine as adjunctive treatment to SSRIs. Safety and tolerability assessments included discontinuation rates, spontaneously reported treatment-emergent adverse events (TEAEs), clinical laboratory tests, blood pressure (BP) and pulse, and electrocardiograms (ECGs).

Results: The analysis included 1260 patients treated with adjunctive edivoxetine and 806 treated with adjunctive placebo. Study completion rates were 85.2% and 84.5% (p=0.994), respectively. Discontinuations due to adverse events were 4.9% and 3.5% (p=0.07), respectively. Significantly more patients in the adjunctive edivoxetine group compared with adjunctive placebo group reported at least one TEAE (56.8 vs 43.7%, p<0.001). The most common TEAEs (occurred ≥5% frequency) were hyperhidrosis, nausea, and tachycardia. Mean changes in sitting BP and pulse at the last visit were increased significantly in patients treated with adjunctive edivoxetine compared with adjunctive placebo (SBP: 2.7 vs 0.5 mm Hg, p<0.001; DBP: 4.1 vs 0.8 mm Hg, p<0.001; pulse: 8.8 vs –1.3 bpm, p<0.001). There were no clinically significant changes in laboratory measures.

Conclusions: The tolerability and safety profile of edivoxetine as adjunctive treatment to SSRI antidepressants was consistent with its norepinephrine reuptake inhibitor mechanism of action, and was comparable with edivoxetine monotherapy treatment in patients with major depressive disorder.

Keywords: norepinephrine reuptake inhibitor, serotonin reuptake inhibitor, second-generation antidepressive agent, major depressive disorder, adjunctive therapy, drug safety, drug tolerability.

Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; ECG, electrocardiogram; MDD, major depressive disorder; SSRI, selective serotonin reuptake inhibitor; SBP, systolic blood pressure; TEAE, treatment-emergent adverse event.

Citation: Martinez JM, Ferguson MB, Pangallo BA, Oakes TM, Sparks J, Dellva MA, Zhang Q, Liu P, Bangs M, Ahl J, Goldberger C. Safety and tolerability of edivoxetine as adjunctive treatment to selective serotonin reuptake inhibitor antidepressants for patients with major depressive disorder. Drugs in Context 2015; 4: 212279. DOI: 10.7573/dic.212279

Contributions: JMM, MBF, BAP, TMO, MB, and CG made substantial contributions to the conception of the work and interpretation of the data and reviewed it for critically important intellectual content. JS, MAD, QZ, and PL made substantial contributions to the conception of the work, acquisition of the data, analysis, and interpretation of the data, and reviewed it for critically important intellectual content. JA drafted the work, revised it for critically important intellectual content, and made contributions to interpretation of the data. All authors approved the final version to be published, and agree to be accountable for all aspects of the work.

Potential conflicts of interest: The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests forms for the authors are available for download at: https://www.drugsincontext.com/wp-content/uploads/2015/05/dic.212279-COI.pdf. All authors are employees and stockholders in Eli Lilly and Company.

Funding declaration: This study was sponsored by Eli Lilly and Company, Indianapolis, IN, USA.

Trial registration numbers: NCT00840034, NCT01185340, NCT01187407, NCT01173601

Copyright: Copyright © 2015 Martinez JM, Ferguson MB, Pangallo BA, Oakes TM, Sparks J, Dellva MA, Zhang Q, Liu P, Bangs M, Ahl J, Goldberger C. 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 Martinez JM, Ferguson MB, Pangallo BA, Oakes TM, Sparks J, Dellva MA, Zhang Q, Liu P, Bangs M, Ahl J, Goldberger C. http://dx.doi.org/10.7573/dic.212279. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

Article URL: https://www.drugsincontext.com/safety-tolerability-edivoxetine-adjunctive-treatment-selective-serotonin-reuptake-inhibitor-antidepressants-patients-major-depressive-disorder

Correspondence: James M Martinez, MD, Eli Lilly and Company, Drop Code 1542, Indianapolis, IN 46285, USA. martinez_james_michael@lilly.com

Provenance: Submitted, externally peer reviewed

Submitted: 4 February 2015; Accepted, subject to peer review: 6 February 2015; Peer review comments to author: 23 February 2015; Revised manuscript submitted: 23 April 2015; Published: 13 May 2015

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