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Desvenlafaxine Versus Venlafaxine for the Treatment of Adult Patients with Major Depressive Disorder: a Review of the Comparative Clinical and Cost-Effectiveness

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Desvenlafaxine Versus Venlafaxine for the Treatment of Adult Patients with Major Depressive Disorder: a Review of the Comparative Clinical and Cost-Effectiveness CADTH RAPID RESPONSE REPORT: SUMMARY WITH CRITICAL APPRAISAL Desvenlafaxine versus Venlafaxine for the Treatment of Adult Patients with Major Depressive Disorder: A Review of the Comparative Clinical and Cost-Effectiveness Service Line: Rapid Response Service Version: 1.0 Publication Date: October 25, 2017 Report Length: 15 Pages Authors: Veronica Poitras, Sarah Visintini Cite As: Desv enlaf axine v ersus Venlaf axine for the Treatment of Adult Patients with Major Depressiv e Disorder: A Rev iew of the Comparativ e Clinical and Cost-Ef f ectiveness. Ottawa: CADTH; 2017 Oct. (CADTH rapid response report: summary with critical appraisal). Acknowledgments: ISSN: 1922-8147 (online) Disclaimer: The inf ormation in this document is intended to help Canadian health care decision-makers, health care prof essionals, health sy stems leaders, and policy -makers make well-inf ormed decisions and thereby improv e the quality of health care serv ices. While patients and others may access this document, the document is made av ailable f or inf ormational purposes only and no representations or warranties are made with respect to its f itness f or any particular purpose. The inf ormation in this document should not be used as a substitute f or prof essional medical adv ice or as a substitute f or the application of clinical judgment in respect of the care of a particular patient or other prof essional judgment in any decision-making process. The Canadian Agency f or Drugs and Technologies in Health (CADTH) does not endorse any inf ormation, drugs, therapies, treatments, products, processes, or serv ic es. While care has been taken to ensure that the inf ormation prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was f irst published by CADTH, CADTH does not make any guarantees to that ef f ect. CADTH does not guarantee and is not responsible f or the quality , currency , propriety , accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The v iews and opinions of third parties published in this document do not necessarily state or ref lect those of CADTH. CADTH is not responsible f or any errors, omissions, injury , loss, or damage arising f rom or relating to the use (or misuse) of any inf ormation, statements, or conclusions contained in or implied by the contents of this document or any of the source materials. This document may contain links to third-party websites. CADTH does not hav e control ov er the content of such sites. Use of third-party sites is gov erned by the third-party website owners’ own terms and conditions set out f or such sites. CADTH does not make any guarantee with respect to any inf ormation contained on such third-party sites and CADTH is not responsible f or any injury , loss, or damage suf f ered as a result of using such third-party sites. CADTH has no responsibility f or the collection, use, and disclosure of personal inf ormation by third-party sites. Subject to the af orementioned limitations, the v iews expressed herein are those of CADTH and do not necessarily represent the v iews of Canada’s f ederal, prov incial, or territorial gov ernments or any third party supplier of inf ormation. This document is prepared and intended f or use in the context of the Canadian health care sy stem. The use of this document outside of Canada is done so at the user’s own risk. This disclaimer and any questions or matters of any nature arising f rom or relating to the content or use (or misuse) of this document will be gov erned by and interpreted in accordance with the laws of the Prov ince of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusiv e jurisdiction of the courts of the Prov ince of Ontario, Canada. The copy right and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document f or non-commercial purposes only , prov ided it is not modif ied when reproduced and appropriate credit is giv en to CADTH and its licensors. About CADTH: CADTH is an independent, not-f or-prof it organization responsible f or prov iding Canada’s health care decision-makers with objectiv e ev idence to help make inf ormed decisions about the optimal use of drugs, medical dev ices, diagnostics, and procedures in our health care sy stem. Funding: CADTH receiv es f unding f rom Canada’s f ederal, prov incial, and territorial gov ernments, with the exception of Quebec. SUMMARY WITH CRITICAL APPRAISAL Desv enlaf axine v ersus Venlaf axine f or the Treatment of Adult Patients with Major Depressiv e Disorder 2 Context and Policy Issues Major Depressive Disorder (MDD) is a chronic, disabling disorder characterized by depressed mood or diminished interest or pleasure in activities of daily living, along with changes in weight, appetite and/or sleep, fatigue or loss of energy, feelings of worthlessness or inappropriate guilt, inability to concentrate, or recurrent thoughts of death or suicide that last at least two weeks and that affect normal functioning.1,2 In Canada, the annual prevalence of MDD is 4.7% and the lifetime prevalence is 11.3%.2 MDD is the second leading cause of disability worldwide, with considerable economic impact due to treatment costs and lost productivity.2 MDD is thus associated with substantial personal, societal, and economic burden.3 Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a first-line pharmacotherapy option in the treatment of MDD4 that function by inhibiting the neuronal reuptake of serotonin and norepinephrine, two neurotransmitters that play an important role in mood.5 Venlafaxine was the first-available SNRI and is considered to be one of the most effective antidepressants.6 Desvenlafaxine is the primary metabolite of venlafaxine,5 and administering desvenlafaxine directly has some theoretical advantages. For example, venlafaxine, like most antidepressants, is metabolized by the cytochrome P450 enzymatic pathway; this pathway exhibits marked genetic polymorphism and inter-individual variability in activity, which could lead to sub-therapeutic drug concentrations in those who have rapid P450 pathway metabolism.7 In contrast, desvenlafaxine is metabolized independently of this pathway (and is cleared primarily via the kidney), which may result in more stable plasma concentrations and fewer drug-drug interactions.7-9 In addition, the binding affinity for serotonin and norepinephrine reuptake pumps is higher for desvenlafaxine than venlafaxine, which theoretically could translate to greater efficacy.5,8 The clinical effectiveness of active metabolites should not be assumed however,6 and in 2009 a CADTH report of the Common Drug Review recommended not to list desvenlafaxine, because at that time there were no randomized controlled trials directly comparing desvenlafaxine and venlafaxine, and desvenlafaxine was more expensive at recommended doses.10 Both venlafaxine and desvenlafaxine are used in the treatment of MDD in Canada,11 however, and an updated examination of the comparative clinical effectiveness and cost-effectiveness is warranted. The purpose of this report is to examine the clinical effectiveness and cost-effectiveness of desvenlafaxine compared to venlafaxine for the treatment of adults patients with MDD. Research Questions 1. What is the comparative clinical effectiveness of desvenlafaxine versus venlafaxine for the treatment of adult patients with Major Depressive Disorder? 2. What is the comparative cost-effectiveness of desvenlafaxine versus venlafaxine for the treatment of adult patients with Major Depressive Disorder? SUMMARY WITH CRITICAL APPRAISAL Desv enlaf axine v ersus Venlaf axine f or the Treatment of Adult Patients with Major Depressiv e Disorder 3 Key Findings Limited evidence from three systematic reviews suggested there was no significant difference in the clinical effectiveness of desvenlafaxine versus venlafaxine for the treatment of adult patients with Major Depressive Disorder. However, the totality of the evidence across the reviews comprised only two head-to-head trials and an indirect meta- analysis based on comparisons with placebo; therefore, results should be interpreted with caution. No evidence regarding the comparative cost-effectiveness of desvenlafaxine versus venlafaxine for the treatment of adult patients with Major Depressive Disorder was identified. Methods Literature Search Methods A limited literature search was conducted on key resources including PubMed, The Cochrane Library, University of York Centre for Reviews and Dissemination (CRD), Embase, Medline, Canadian and major international health technology agencies, as well as a focused Internet search. No methodological filters were employed. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2012 and September 22, 2017. Selection Criteria and Methods One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1. Table 1: Selection Criteria Population Adult patients requiring treatment for Major Depressive Disorder Intervention Desvenlafaxine (e.g., Pristiq) Comparator Venlafaxine (e.g., Effexor) Outcomes Q1: Comparative clinical effectiveness, clinical benefit and harm Q2: Cost-effectiveness Study Designs Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non- randomized studies, economic evaluations Exclusion Criteria Articles were excluded if they did not meet the selection criteria outlined in Table 1, or if they were not published in English, were duplicate publications, or were published prior to 2012.
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